Hereditary Angioedema: a Challenging Diagnosis for the Gastroenterologist

Hereditary angioedema (HAE) caused by a deficiency of C1 esterase inhibitor enzyme (C1-INH) is a very rare, autosomal dominantly inherited genetic disorder, characterized by recurrent peripheral angioedema, painful abdominal attacks and episodes of laryngeal edema. Abdominal attacks are frequent symptoms in adult HAE patients, occurring in more than 90% of the cases. Angioedema in the bowel or abdomen can occur in the absence of cutaneous manifestations and may be easily misdiagnosed unless the clinician has a high degree of awareness to include HAE in the differential diagnosis. Misdiagnosis is associated with inadequate treatments, including unnecessary surgical procedures. Any patient who presents recurrent episodes of swelling should be evaluated for HAE caused by C1-INH deficiency. New therapies could save lives and dramatically improve their quality of life

The Current Knowledge on <em>Clostridioides</em><em> difficile</em> Infection in Patients with Inflammatory Bowel Diseases

Clostridioides difficile (C. difficile) represents a major health burden with substantial economic and clinical impact. Patients with inflammatory bowel diseases (IBD) were identified as a risk category for Clostridioides difficile infection (CDI). In addition to traditional risk factors for C. difficile acquisition, IBD-specific risk factors such as immunosuppression, severity and extension of the inflammatory disease were identified. C. difficile virulence factors, represented by both toxins A and B, induce the damage of the intestinal mucosa and vascular changes, and promote the inflammatory host response. Given the potential life-threatening complications, early diagnostic and therapeutic interventions are required. The screening for CDI is recommended in IBD exacerbations, and the diagnostic algorithm consists of clinical evaluation, enzyme immunoassays (EIAs) or nucleic acid amplification tests (NAATs). An increased length of hospitalization, increased colectomy rate and mortality are the consequences of concurrent CDI in IBD patients. Selection of CD strains of higher virulence, antibiotic resistance, and the increasing rate of recurrent infections make the management of CDI in IBD more challenging. An individualized therapeutic approach is recommended to control CDI as well as IBD flare. Novel therapeutic strategies have been developed in recent years in order to manage severe, refractory or recurrent CDI. In this article, we aim to review the current evidence in the field of CDI in patients with underlying IBD, pointing to pathogenic mechanisms, risk factors for infection, diagnostic steps, clinical impact and outcomes, and specific management

MicroRNA Modulation of Host Immune Response and Inflammation Triggered by <i>Helicobacter pylori</i>

Helicobacter pylori (H. pylori) remains the most-researched etiological factor for gastric inflammation and malignancies. Its evolution towards gastric complications is dependent upon host immune response. Toll-like receptors (TLRs) recognize surface and molecular patterns of the bacterium, especially the lipopolysaccharide (LPS), and act upon pathways, which will finally lead to activation of the nuclear factor-kappa B (NF-kB), a transcription factor that stimulates release of inflammatory cytokines. MicroRNAs (MiRNAs) finely modulate TLR signaling, but their expression is also modulated by activation of NF-kB-dependent pathways. This review aims to focus upon several of the most researched miRNAs on this subject, with known implications in host immune responses caused by H. pylori, including let-7 family, miRNA-155, miRNA-146, miRNA-125, miRNA-21, and miRNA-221. TLR–LPS interactions and their afferent pathways are regulated by these miRNAs, which can be considered as a bridge, which connects gastric inflammation to pre-neoplastic and malignant lesions. Therefore, they could serve as potential non-invasive biomarkers, capable of discriminating H. pylori infection, as well as its associated complications. Given that data on this matter is limited in children, as well as for as significant number of miRNAs, future research has yet to clarify the exact involvement of these entities in the progression of H. pylori-associated gastric conditions

MicroRNA Modulation of Host Immune Response and Inflammation Triggered by Helicobacter pylori

Helicobacter pylori (H. pylori) remains the most-researched etiological factor for gastric inflammation and malignancies. Its evolution towards gastric complications is dependent upon host immune response. Toll-like receptors (TLRs) recognize surface and molecular patterns of the bacterium, especially the lipopolysaccharide (LPS), and act upon pathways, which will finally lead to activation of the nuclear factor-kappa B (NF-kB), a transcription factor that stimulates release of inflammatory cytokines. MicroRNAs (MiRNAs) finely modulate TLR signaling, but their expression is also modulated by activation of NF-kB-dependent pathways. This review aims to focus upon several of the most researched miRNAs on this subject, with known implications in host immune responses caused by H. pylori, including let-7 family, miRNA-155, miRNA-146, miRNA-125, miRNA-21, and miRNA-221. TLR–LPS interactions and their afferent pathways are regulated by these miRNAs, which can be considered as a bridge, which connects gastric inflammation to pre-neoplastic and malignant lesions. Therefore, they could serve as potential non-invasive biomarkers, capable of discriminating H. pylori infection, as well as its associated complications. Given that data on this matter is limited in children, as well as for as significant number of miRNAs, future research has yet to clarify the exact involvement of these entities in the progression of H. pylori-associated gastric conditions

UTILITATEA ŞI SEMNIFICAŢIA MARKERILOR SEROLOGICI IMUNI AI INFLAMAŢIEI LA PACIENŢII CU COLITĂ ULCERATIVĂ

INTRODUCTION: The recent advance in the area of diagnostic testing is focusing on serologic immune markers: atypical perinuclear anti-neutrophil citoplasmic antibody (pANCA) and anti-Saccharomyces cervisiae antibody (ASCA), and her utility in differentiating between ulcerative colitis (UC), Crohn’s disease (CD) and indeterminate colitis (IC). The aim of this study was to investigate the diagnostic value of pANCA and ASCA in inflammatory bowel diasease (IBD) diagnosis and for the differential diagnosis of UC from CD.MATERIAL AND METHOD: A prospective study was conducted in 31 patients with new or established diagnoses of UC (n=15), CD (n=9) or IC (n=7) and also controls (n=7). Antibodies status has been measured with ELISA. A definitive diagnosis was reached using conventional techniques (colonoscopy or ileoscopy).RESULTS: Sensitivity and specificity of pANCA for UC diagnosis was 66.67% and 77.78%, respectively; and ASCA for CD: 20% and 22.22%, respectively. The combined use of these two markers gave changes in diagnosis accuracy: pANCA+/ASCA- in UC and pANCA-/ASCA+ in CD: 75% and 72.73%, respectively. In phase II, for 23 of 38 patients a definitive diagnosis was reached using conventional techniques (colonoscopy and ileoscopy). In IC group, after 1-year follow-up, a definitive diagnosis was reached in 5 of the 7 patients.CONCLUSION: The combined use of atypical pANCA and ASCA test results substantially affects pretest-posttest probability in distinguishing UC from CD in patients with IBD. This may be of help in patients in whom distinction between CD or UC is not obvious with the classic diagnostic tools. Key words: Ulcerative colitis, Crohn’s disease, Indeterminate colitis, perinuclear anti-neutrophil citoplasmic antibody , anti-Saccharomyces cervisiae antibody.INTRODUCERE: Progresele recente &icirc;n domeniul testelor de diagnostic se concentrează asupra markerilor serologici imuni: anticorpii anti-citoplasmatici neutrofilici perinucleari (pANCA) și anticorpii anti-Saccharomyces cervisiae (ASCA) precum și utilitatea lor &icirc;n diferențierea colitei ulcerative (CU), de boala Crohn (BC) și de colita nedeterminată (IC). SCOPUL acestui studiu a fost de a investiga valoarea diagnostică a pANCA și ASCA &icirc;n diagnosticul BII și diferențierea CU de BC.MATERIAL ȘI METODĂ: Am efectuat un studiu prospectiv pe un lot de 31 de pacienți nou-diagnosticați sau cu diagnostic stabilit de CU (n=15), BC (n=9) sau IC (n=7), precum și un grup de control (n=7). Determinarea anticorpilor a fost realizată cu teste ELISA. Diagnosticul definitiv a fost stabilit utiliz&acirc;nd metode convenționale (colonoscopie sau ileoscopie).RESULTATE: Sensibilitatea și specificitatea pANCA pentru diagnosticul de CU a fost 66,67%, respectiv 77,78%; pentru ASCA (&icirc;n BC): 20%, respectiv 22,22%. Determinarea combinată a celor 2 markeri a determinat modificări &icirc;n acuratețea stabilirii diagnosticului: pANCA+/ASCA- &icirc;n CU și pANCA-/ASCA+ &icirc;n BC: 75% și respectiv 72,73%. &Icirc;n faza II, la 23 din 38 pacienți diagnosticul difinitiv a fost stabilit utiliz&acirc;nd tehnici convenționale (colonoscopie și ileoscopie). &Icirc;n lotul cu IC, după 1 an de urmărire, diagnosticul difinitiv a fost stabilit la 5 din 7 pacienți.CONCLUZII: Utiliz&acirc;nd determinarea combinată a pANCA și ASCA, rezultatele testelor influențează substanțial probabilitatea pretest-postest pentru diferențierea CU de BC la pacienții cu BII. Aceste determinări ar putea fi utile la pacienții la care diferențierea dintre BC și CU nu poate fi stabilită prin metode clasice de diagnostic.&nbsp;Cuvinte cheie: Colită ulcerativă, Boala Crohn, Colită nedeterminată, Anticorpii anti-citoplasmatici neutrofilici perinucleari, Anticorpii anti-Saccharomyces cervisiae

Computer-Aided Diagnosis in Colorectal Cancer: Current Concepts and Future Prospects

Colorectal cancer is an important health issue, both in terms of the number of people affected and the associated costs. Colonoscopy is an important screening method that has a positive impact on the survival of patients with colorectal cancer. The association of colonoscopy with computer-aided diagnostic tools is currently under researchers’ focus, as various methods have already been proposed and show great potential for a better management of this disease. We performed a review of the literature and present a series of aspects, such as the basics of machine learning algorithms, different computational models as well as their benchmarks expressed through measurements such as positive prediction value and accuracy of detection, and the classification of colorectal polyps. Introducing computer-aided diagnostic tools can help clinicians obtain results with a high degree of confidence when performing colonoscopies. The growing field of machine learning in medicine will have a big impact on patient management in the future