Novelties and Perspectives of Intestinal Ultrasound in the Personalised Management of Patients with Inflammatory Bowel Diseases-A Systematic Review.

Inflammatory bowel diseases (IBDs) affect over 4.9 million individuals worldwide. Colonoscopy (CS) is the gold-standard technique for diagnosis. The remissive-recurrent pattern of evolution raises the need for non-invasive techniques to monitor disease activity. This review aims to present the advantages of intestinal ultrasound (IUS) in managing IBDs. Our search was conducted on the PubMed, Embase, and Cochrane (CENTRAL) databases, selecting original studies comparing IUS with other imaging and invasive monitoring methods. Our search yielded 8654 results, of which 107 met the inclusion criteria. Increased bowel wall thickness (BWT) and colour Doppler signal (CDS) are discriminative for disease activity. IUS can predict disease outcomes and detect response to treatment or postoperative recurrence. Contrast-enhanced ultrasound (CEUS) and elastography help differentiate fibrotic from inflammatory stenoses. The difficult rectal assessment limits the use of IUS in ulcerative colitis (UC). Transmural healing may develop as a therapeutic target as it is associated with better outcomes. Patients are compliant with this technique, and its results correlate well with CS and other imaging methods. In conclusion, IUS proves to be essential in assessing IBD activity and treatment response, predicting outcomes and detecting complications. CEUS and elastography are researched to improve the diagnostic values of IUS.

Ischemic Heart Disease in Patients with Inflammatory Bowel Disease: Risk Factors, Mechanisms and Prevention.

According to new research, a possible association between inflammatory bowel disease (IBD) and an increased risk of ischemic heart disease (IHD) has been demonstrated, but this concern is still debatable. The purpose of this review is to investigate the link between IHD and IBD, as well as identify further research pathways that could help develop clinical recommendations for the management of IHD risk in IBD patients. There is growing evidence suggesting that disruption of the intestinal mucosal barrier in IBD is associated with the translocation of microbial lipopolysaccharides (LPS) and other endotoxins into the bloodstream, which might induce a pro-inflammatory cytokines response that can lead to endothelial dysfunction, atherosclerosis and acute cardiovascular events. Therefore, it is considered that the long-term inflammation process in IBD patients, similar to other chronic inflammatory diseases, may lead to IHD risk. The main cardiovascular risk factors, including high blood pressure, dyslipidemia, diabetes, smoking, and obesity, should be checked in all patients with IBD, and followed by strategies to reduce and manage early aggression. IBD activity is an important risk factor for acute cardiovascular events, and optimizing therapy for IBD patients should be followed as recommended in current guidelines, especially during active flares. Large long-term prospective studies, new biomarkers and scores are warranted to an optimal management of IHD risk in IBD patients.

Hereditary Hemorrhagic Telangiectasia and Arterio-Venous Malformations-From Diagnosis to Therapeutic Challenges.

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant vascular disease defined by the presence of mucosal and cutaneous telangiectasia and visceral arterio-venous malformations. The latter are abnormal capillary-free direct communications between the pulmonary and systemic circulations with the following consequences: arterial hypoxemia caused by right-to-left shunts; paradoxical embolism with transient ischemic attack or stroke and brain abscess caused by the absence of the normally filtering capillary bed; and hemoptysis or hemothorax due to the rupture of the thin-walled arterio-venous malformations (particularly during pregnancy). It is frequently underdiagnosed, commonly presenting as complications from shunting through arterio-venous malformations: dyspnea, chronic bleeding, or embolism. Arterio-venous malformations are present not only in the lungs, but can also be found in the liver, central nervous system (mainly in the brain), nasal mucosa, or the gastrointestinal tract. The first choice of therapy is embolization of the afferent arteries of the arterio-venous malformations, a minimally invasive procedure with a high efficacy, a low morbidity, and low mortality. Other therapeutic modalities are surgery (resection) or stereotactic radiosurgery (using radiation). Routine screening for arterio-venous malformations is indicated in patients diagnosed with this condition and can prevent severe complications such as acute hemorrhages, brain abscesses, or strokes. Clinicians should provide a long-term follow-up for patients with arterio-venous malformations, in an effort to detect their growth or reperfusion in case of previously treated malformations. In spite of two experts' consensuses, it still possesses multiple therapeutic challenges for physicians, as several aspects regarding the screening and management of arterio-venous malformations still remain controversial. Multidisciplinary teams are especially useful in complex cases.

New onset severe ulcerative colitis following Ixekizumab therapy.

Ixekizumab is one of the three biologic agents including Secukinumab and Brodalumab that targets the Interleukin-17 (IL-17) pathway to reduce inflammation in psoriasis and ankylosing spondylitis. In this report we present the case of 42-year-old woman, who was diagnosed with psoriasis and psoriatic arthritis. One week after first administration of Ixekizumab, she developed diffuse abdominal pain, bloody diarrhea (7-8 stools/day) and fever. Following imaging (colonoscopy, computed tomography) and laboratory investigations, she was diagnosed with acute severe ulcerative colitis complicated with toxic megacolon. The medical treatment (first corticotherapy, then infliximab) has failed and the patient needed emergency colectomy. Based on the immunological mechanisms and the observation from other studies, Ixekizumab should be considered an etiology for new-onset inflammatory bowel disease.

Role of PNPLA3 in the Assessment and Monitoring of Hepatic Steatosis and Fibrosis in Patients with Chronic Hepatitis C Infection Who Achieved a Sustained Virologic Response.

Background and Objectives: Hepatic diseases are an important public health problem. All patients with chronic hepatitis C virus (HCV) infection receive treatment, regardless of hepatic fibrosis severity. However, evaluation of hepatic fibrosis and steatosis is still useful in assessing evolution, prognosis and monitoring of hepatic disease, especially after treatment with direct-acting antivirals (DAAs). The aim of this study was to assess the link between patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism and the degree of hepatic steatosis and fibrosis in patients with chronic HCV infection, as well as changes in steatosis and fibrosis three monthsafter obtaining a sustained viral response (SVR). Materials and Methods:Ourstudy included 100 patients with chronic hepatitis C (CHC) infection and compensated cirrhosis who received DAA treatment and who were evaluated using Fibromax prior to and 3 months after SVR. The influence of PNPLA3 (CC, CG, GG) genotype among these patients on the degree of post-treatment regression of steatosis and fibrosis was assessed. Results: Regression was noticed in the degree of both hepatic steatosis and hepatic fibrosis post-DAA treatment (three months after SVR). Analysis of the correlation between PNPLA3 genotype and fibrosis indicated that the average level of fibrosis (F) before DAA treatment was higher in patients with the GG genotype than in patients with the CC or CG genotype. Three months after SVR, the average level of fibrosis decreased; however, it remained significantly increased in GG subjects compared to that in CC or CG patients. The degree of hepatic steatosis before treatment was not significantly different among patients with different PNPLA3 genotypes, and no significant correlations were observed three months after SVR. Conclusions: The genetic variants of PNPLA3 influence the evolution of hepatic fibrosis. The GG subtype plays an important role in the degree of hepatic fibrosis both before and after treatment (three months after SVR)and could be a prognostic marker for assessment of post-SVR evolution.

Anemia in Crohn's Disease-The Unseen Face of Inflammatory Bowel Disease.

Background and Objectives: Anemia is the most frequent complication of inflammatory bowel diseases. Clinically, anemia can affect important quality-of-life (QoL) components, such as exercise capacity, cognitive function, and the ability to carry out social activities. The disease activity has a significant impact on QoL, mainly due to clinical manifestations, which are more severe during the periods of disease activity. Our aim was to estimate the impact of anemia on QoL in patients with Crohn's disease. Material and Methods. We made a prospective study on 134 patients with Crohn's disease (CD) in a Romanian tertiary center. The CD diagnosis was established by colonoscopy and histopathological examination. In particular cases, additional examinations were required (small bowel capsule endoscopy, computed tomography enterography, and magnetic resonance enterography). Anemia was defined according to the World Health Organization's definition, the activity of the disease was assessed by Crohn's disease activity index (CDAI) score, and the QoL was evaluated by Inflammatory Bowel Disease Questionnaire 32 (IBDQ 32). Results: 44.8% patient had anemia, statistically related to the activity of the disease and corticoids use. We found a strong association between QoL and disease activity on all four sub-scores: patients with more severe activity had a significantly lower IBDQ (260.38 ± 116.96 vs. 163.85 ± 87.20, p = 0.001) and the presence of anemia (127.03 vs. 148.38, p = 0.001). In multiple regression analyses, both disease activity and anemia had an impact on the QoL. Conclusions: Anemia has high prevalence in the CD in northeastern region of Romania. Anemia was more common in female patients, in patients undergoing corticosteroid treatment, and in those with active disease. Both anemia and disease activity had a strong negative and independent impact on QoL.

Looking beyond gut inflammation in inflammatory bowel disease.

Patients diagnosed with inflammatory bowel disease (IBD) often develop one or more extraintestinal manifestations (EIM). We performed a prospective study that included 517 patients with IBD (Crohn's disease - CD, ulcerative colitis - UC or undifferentiated colitis - CN) diagnosed between 1975 and 2016 in the Northeastern region of Romania. The patients were extracted from the national database (IBD Prospect). UC cases predominated compared to CD cases (n=368 vs. n=135). Only 10 patients were diagnosed with CN. In the study group, 51 cases with IBD and EIM were identified, having a prevalence of 9.9%. Musculoskeletal manifestations were the most common EIM. Peripheral involvement - arthritis (n=26, 68.42%) predominated, followed by axial damage - sacroiliitis/ankylosing spondylitis (SI∕AS) (n=12, 31.58%) (p=0.001). Patients with CD had a 3.48-fold greater risk of developing joint manifestations [p<0.001, odds ratio (OR)=3.478, 95% confidence interval (CI) 1.779-6.801]. In both CD and UC patients, arthritis cases were the most frequent observed (68.42% vs. 31.58%). Patients with CD had a 5-fold higher risk of developing arthritis (p<0.001, OR=5.009, 95% CI 2.21-11.34). Neither CD, nor UC patients, had a confirmed risk of developing SI∕AS (p=0.468, OR=1.565, 95% CI 0.463-5.293 for CD) (p=0.586, OR=0.714, 95% CI 0.211-2.413 for UC). Cases of arthritis and CD (n=16) mainly correlated with the colonic localization of inflammation (n=7, p=0.723) followed by ileo-colonic form of CD (n=7, p=0.321). Patients with arthritis and UC (n=10) initially correlated with pancolitis (n=5, p=0.072, OR=3.023, 95% CI 0.855-10.69) then with proctitis (n=3, p=0.392) and left-sided colitis (n=2, p=0.024, OR=0.196, 95% CI 0.041-0.938).

A rapid test for assessing disease activity in ulcerative colitis.

BACKGROUND/AIMS: Direct assessment by endoscopic examination has become a "gold standard" in monitoring patients with ulcerative colitis. However, it is an invasive method, with risks and discomfort for the patients. The aim is therefore to identify a less invasive method of assessing ulcerative colitis activity compared to colonoscopy. MATERIALS AND METHODS: A prospective study was conducted among 103 patients with ulcerative colitis. Calprotectin was measured by a semi-quantitative rapid test. For each patient, a complete blood count was performed; liver and kidney functions, glycaemia, serum proteins, and inflammatory markers were also evaluated. RESULTS: The Mayo score showed direct correlations with fecal calprotectin, C-reactive protein, and the erythrocyte sedimentation rate (p<0.05) and indirect correlations with hemoglobin (p=0.139). The sensitivity and specificity of calprotectin were 98.0% and 76.7%, respectively. Subsequently, combined analysis of the markers' sensitivity/specificity was conducted. CONCLUSION: The semi-quantitative rapid test proved to be a good predictor for differentiating the endoscopic active disease from the inactive one. The individual use of fecal calprotectin presents the highest sensitivity in determining the endoscopic activity. Nevertheless, in monitoring patients, combined determination of the three inflammatory markers studied [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), calprotectin] is more useful in reducing unnecessary colonoscopies.

QUALITY OF LIFE IN CROHN'S DISEASE PATIENTS.

UNLABELLED: The aim of the study is to assess the impact of Crohn's Disease (CD) on quality of life (QoL) patients with and to identify the significant modifications in QoL, depending on both the development particularities of CD and the epidemiologic parameters. MATERIAL AND METHODS: a prospective study was conducted at the Institute of Gastroenterology and Hepathology Iasi, between October 2011 and August 2014. The study enrolled 63 patients with CD. The CD diagnosis was based on clinical, biological, endoscopic and histological criteria. QoL was assessed by means of the IBDQ-32 questionnaire (Inflammatory Bowel Disease Questionnaire). RESULTS: The total IBDQ score varied from 70 to 200, registering a slightly higher value in female patients. Parameters such as age, sex and smoking/non-smoking status did not present significant differences in the IBDQ score. The values of the IBDQ score were in indirect, mild correlation with the CDAI score; over 49% of the subjects with higher CDAI had a lower IBDQ score. CONCLUSIONS: Except for the disease activity periods, the results of the studies investigating the impact of the various factors on the QoL in patients with CD are contradictory. Further research is needed in order to define the subgroups of patients likely to suffer from poorer QoL.

ARE THERE ANY PARTICULARITIES IN CROHN'S DISEASE IN NORTH-EASTERN ROMANIA?

UNLABELLED: Crohn's disease is an inflammatory disease of the gastro-intestinal tract with an evolution marked by activity and remission periods. Lately, the incidence and evolution models of Crohn's disease significantly changed, an increasing number of patients presenting more severe forms. The aim of the study is to analyze Crohn's disease in its phenotypic classification and to establish correlation between the localization, the behavior and the activity of Crohn's disease. MATERIAL AND METHODS: A transversal study on 53 patients with Crohn's disease was conducted. RESULTS: from the 53 patients, 56.6% were males, 85% from the urban areas. Under the phenotype aspect, the colonic localization (49.1%) and the inflammatory behavior (52.8%) were predominant. More severe forms of activity were discovered to patients with ileal localization (57.1%) or with penetrant phenotype (33.3%). CONCLUSIONS: Male patients from urban areas were predominant. The most frequent forms are the colonic and ileocolonic forms. From a behavioral point of view, we observed an obvious predominance of the inflammatory phenotype. The moderate--severe activity was predominant for the ileal localization and the mild-- moderate activity for the colonic and ileocolonic localization. A mild--moderate activity is present for the stenosing forms and a moderate--severe one for the penetrant forms.

Serum 25-hydroxyvitamin D concentration and inflammatory bowel disease characteristics in Romania.

AIM: To describe the relationship between vitamin D levels and inflammatory bowel disease (IBD) characteristics in northeastern Romanian patients. METHODS: This was a prospective study of 47 consecutive IBD patients admitted to The Institute of Gastroenterology and Hepatology in Iasi, Romania between March 2011 and June 2012. The diagnosis of IBD was established based on endoscopic, histologic and radiologic findings. Demographic data, disease characteristics, ongoing treatments and biological parameters of patients (including markers of inflammation: C-reactive protein level, fibrinogen level, and erythrocyte sedimentation rate) were recorded. Serum vitamin D levels were measured and compared with age- and sex-matched healthy volunteers from the same geographic area. Vitamin D levels were defined as sufficient (> 30 ng/mL), insufficient (20-30 ng/mL), or severely deficient (< 20 ng/mL). RESULTS: Thirty-three of the IBD patients included in this study had ulcerative colitis (UC) and 14 had Crohn's disease (CD). Only 24% of the UC patients and 21% of the CD patients had sufficient vitamin D levels. The vitamin D levels were significantly lower in the CD patients with moderate to severe disease activity compared to the CD patients in remission or with mild disease activity (16 ± 6 ng/mL vs 26 ± 7 ng/mL; 16 ± 6 ng/mL vs 31 ± 9 ng/mL, respectively, P < 0.05). Vitamin D levels in the UC patients were not influenced by disease activity and no correlation was observed with the inflammation markers tested (C-reactive protein, fibrinogen, and erythrocyte sedimentation rate). No association was observed between vitamin D levels and smoking status or ongoing medication (5ASA, steroids, and anti-TNFα). Newly diagnosed IBD patients had lower vitamin D levels than patients with established cases, though these differences were not significant (UC: 22 ± 9 ng/mL vs 26 ± 12 ng/mL; CD: 18 ± 6 ng/mL vs 27 ± 11 ng/mL, respectively). Although no association was found between the season during which the visit was scheduled and vitamin D levels, the UC patients assessed during the winter tended to have lower levels than those assessed during the summer (22 ± 9 ng/mL vs 28 ± 13 ng/mL, respectively). CONCLUSION: Vitamin D levels are significantly reduced in IBD patients in northeastern Romania, with the lowest levels occurring in CD patients with moderate to severe disease activity.

Bone mineral density in patients with inflammatory bowel disease from north-eastern Romania.

UNLABELLED: Inflammatory bowel disease (IBD) is associated with increased prevalence of bone demineralization. One of the risk factors for low bone density is the inadequate level of 25-OH vitamin D. AIM: To determine the degree of bone demineralization in patients with IBD and the main causes leading to this condition. MATERIAL AND METHODS: A prospective study was carried out between April, 2011 and October, 2012 in 143 patients diagnosed with IBD at the Gastroenterology and Hepatology Centre of Iasi.The IBD diagnosis was made on clinical, biological, and endoscopic criteria and confirmed histologically. The diagnosis of osteopenia/osteoporosis was based on World Health Organization criteria. RESULTS: Osteopenia was found in 48.07% of the patients with ulcerative colits (UC) and in 56.41% of the patients with Crohn's disease (CD); osteoporosis was present in 18.26% of the patients with UC and 15.38% of those with CD. The main causes identified were inadequate vitamin D level, extended high-dose corticotherapy in patients with CD, BMI < 18.5 kg/m2, and smoking, especially in the patients with UC. CONCLUSIONS: Bone demineralization and hypovitaminosis D are frequently associated with IBD and require specific treatment.

The semi-quantitative calprotectin rapid test--is it useful in inflammatory bowel disease?

AIM: To assess the efficiency of the dosage of the semi-quantitative calprotectin rapid test in evaluating the activity of inflammatory bowel diseases. MATERIAL AND METHODS: The prospective study included 87 patients with BII (50 with ulcerative colitis, 37 with Crohn disease) hospitalized between January 2011 - May 2012. The diagnosis was confirmed by colonoscopy and histological examination. Fecal calprotectin was measured by means of a semi-quantitative rapid test. RESULTS: There were 50 patients with UC and 37 with BC. 96% of the UC patients were evaluated during the active disease. 21 of them had a severe episode of active disease, 16 had a moderate one, while 10 had a mild activity episode. The correlation between the calprotectin values and lesions localization was analyzed, without finding any statistical differences. The data have shown a very strong correlation between the severity of the active disease, assessed through the UCDAI (Mayo) score, and the calprotectin value. Patients with CD manifested a linear correlation between the severity of the active disease and the calprotectin value. CONCLUSIONS: The rapid test for assessing calprotectin could be a useful non-invasive marker in appreciating the severity of clinical and biological disease activity.

The prevalence of anaemia in patients with inflammatory bowel diseases in North-Eastern Romania.

UNLABELLED: Anemia is a frequent complication of inflammatory bowel diseases (IBD). The main incriminated mechanisms are the iron deficiency and the chronic inflammation. The aim of this study was to determine the prevalence of anemia in IBD patients and to identify the main causes. MATERIAL AND METHODS: A prospective study was carried out between April 1st 2011 and April 30th 2012 on a batch of 144 IBD patients diagnosed in the Gastroenterology and Hepatology Center of lasi. The IBD diagnosis was based on clinical, biological, endoscopic and histological criteria. The anemia diagnosis was based on the World Health Organization criteria. RESULTS: Anemia was present in 40.27 % of IBD patients. The main cause identified was mixed type anemia, followed by iron deficiency and inflammation. Iron deficiency anemia was present especially in patients with ulcerative colitis with long evolution, frequent activity spurts and extended forms of diseases; an inflammatory anemia emerged mainly in patients with exterided and moderate-severe forms of the diseases. CONCLUSIONS: Anemia remains a frequently associated pathology to the inflammatory bowel disease that requires specific management.