Potential impact of trained innate immunity on the pathophysiology of metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) occurs in a low-grade inflammatory milieu dependent on highly complex networks that span well-beyond the hepatic tissue injury. Dysfunctional systemic metabolism that characterizes the disease, is further induced in response to environmental cues that modify energy and metabolic cellular demands, thereby altering the availability of specific substrates that profoundly regulate, through epigenetic mechanisms, the phenotypic heterogeneity of immune cells and influence hematopoietic stem cell differentiation fate. This immuno-metabolic signaling drives the initiation of downstream effector pathways and results in the decompensation of hepatic homeostasis that precedes pro-fibrotic events. Recent evidence suggests that innate immune cells reside in different tissues in a memory effector state, a phenomenon termed trained immunity, that may be activated by subsequent exogenous (e.g., microbial, dietary) or endogenous (e.g., metabolic, apoptotic) stmuli. This process leads to long-term modifications in the epigenetic landscape that ultimately precondition the cells towards enhanced transcription of inflammatory mediators that accelerates MAFLD development and/or progression. In this mini review we aimed to present current evidence on the potential impact of trained immunity on the pathophysiology of MAFLD, shedding light on the complex immunobiology of the disease and providing novel potential therapeutic strategies to restrain the burden of the disease.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Effect of golimumab on health-related quality of life, other patient-reported outcomes and healthcare resource utilization in patients with moderate-to-severe ulcerative colitis: a real-world multicenter, noninterventional, observational study in Greece.

BACKGROUND AND AIMS: This real-world study assessed the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with ulcerative colitis over 12 months in Greece. METHODS: GO-LIFE was a noninterventional, prospective, multicenter, 12-month study. Patients who had moderately-to-severely active ulcerative colitis were naïve to antitumor necrosis factor (anti-TNFα) therapy and had failed previous conventional therapy. Patients received golimumab as per label. The primary endpoint was patients achieving inflammatory bowel disease questionnaire 32-item (IBDQ-32) remission at 12 months. Secondary endpoints, at 6 and 12 months, included patients achieving IBDQ-32 response; the mean change in the treatment satisfaction questionnaire for medication (TSQM) and the work productivity and activity impairment in ulcerative colitis (WPAI:UC) questionnaires; changes in healthcare utilization; patients achieving clinical response and remission; adherence rates and the percentage of patients who discontinued golimumab. RESULTS: IBDQ-32 remission was achieved by 76.9% of patients at 12 months. Mean changes in all TSQM and WPAI:UC domain scores at 12 months were statistically significant. Clinical remission was achieved by 49.4 and 50.6% of patients at 6 and 12 months, and clinical response by 59.3 and 56.8%, respectively. All patients but one (80/81) had high adherence (≥80%) to golimumab treatment over 12 months. Ulcerative colitis-related health care resource utilization was reduced during the follow-up period. CONCLUSIONS: In real-world settings, treatment with golimumab resulted in meaningful improvements in HRQoL and other PROs, and in disease activity at 6 and 12 months in patients with moderately-to-severely active ulcerative colitis who were naïve to anti-TNFa therapy.

Endoscopic treatment of a gastrocutaneous fistula using the over-the-scope-clip system: a case report.

The over-the-scope-clip (OTSC; Ovesco Endoscopy GmbH, Tuebingen, Germany) system is a newly designed method for the mechanical compression of large areas in the gastrointestinal tract. So far, indications for OTSC application are hemostasis of primary or postinterventional bleeding, closure of iatrogenic full-thickness or covered perforations. Recently closure of gastrointestinal tract fistulas using this device has been described. A 44-year-old man developed a gastrocutaneous fistula after surgical treatment for a perforated gastric ulcer. We describe the successful endoscopic closure of the fistula using the OTSC system. The patient's clinical followup was uneventful. Fistula closure was successfully implemented as it was documented by imaging and endoscopic examinations performed on the 2nd day and 6th week after the application of the clip. Endoscopic application of the OTSC device was safe and effective for the treatment of a gastrocutaneous fistula.

Adalimumab - an effective and promising treatment for patients with fistulizing Crohn's disease: a case series.

INTRODUCTION: Crohn's disease is a chronic inflammatory bowel disease of unknown etiology which may affect any part of the bowel. Fistulas are a common and often serious complication of Crohn's disease. The treatment for fistulizing Crohn's disease can be medical, surgical or a combination of the two. Recently, adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, has been suggested as a safe and effective treatment for the induction and maintenance of remission in adult patients with moderate to severe Crohn's disease, who are refractory to conventional therapy or intolerant to infliximab. However, large studies focusing on evaluating the efficacy of adalimumab in fistulizing Crohn's disease have not yet been published. CASE PRESENTATION: We report the cases of three patients, of European Caucasian ethnicity and Greek nationality, with active luminal and fistulizing Crohn's disease. All of the cases were treated successfully with adalimumab. Patient 1 (a 44-year-old man) and patient 2 (an 18-year-old woman) developed early post-surgical enterocutaneous fistulas, while patient 3 (a 20-year-old woman) had peri-anal fistulizing Crohn's disease. Adalimumab treatment (160 mg subcutaneously at week zero, 80 mg at week two, and 40 mg every other week) was used for three different indications: (1) after the failure of other conservative medical treatments for Crohn's disease (patient 1); (2) as a monotherapy in treating a naive patient (patient 2); (3) after an intolerance to infliximab (patient 3). A remission of the active luminal and fistulizing disease was achieved soon after the initiation of adalimumab and sustained thereafter with maintenance doses. No further surgical intervention was required and no adverse effects were observed in any of the cases. CONCLUSIONS: Fistulizing Crohn's disease remains a challenge in clinical practice. Adalimumab seems to be an effective, well-tolerated and safe treatment option for the induction and maintenance of remission in patients with moderate to severe peri-anal fistulizing Crohn's disease. Furthermore, adalimumab seems to be a promising treatment option for patients with moderate to severe fistulizing Crohn's disease with enterocutaneous fistulas. However, this clinical observation needs to be investigated in further clinical trials.

Evaluation of guide wire cannulation technique in elderly patients with choledocholithiasis.

AIMS: Post-ERCP pancreatitis is the most frequent complication of ERCP. We aimed to evaluate guide-wire cannulation as compared to conventional contrast-assisted cannulation with regard to the rate of post-ERCP pancreatitis (PEP) in elderly patients with choledocholithiasis. METHODS: Patients aged 80 years or over with known choledocholithiasis, who were referred to ERCP in one single district hospital from January 2005 to March 2008 were reviewed retrospectively. RESULTS: During this period, 246 ERCPs were performed in 217 patients. In 82 procedures (37.0%) deep cannulation of the biliary tree was achieved by means of a contrast-assisted procedure, whereas in the remaining 135 attempts a guide wire was used. Among the 64 patients older than 80 years, cannulation was accomplished in 25 by contrast visualization of the biliary tree and in 39 by means of the guide-wire. In the overall population of 217 patients, PEP occurred in 11 patients (5%), 10 and 1 case, respectively, for each of the two procedures (p = 0.00042). In the elderly patients, PEP occurred in 5 out of 25 patients after contrast filling of the bile duct, and in 1 out of 39 patients after the guide-wire utilization (p = 0.021). Cannulation was successful in 201 of 217 patients (92.6%), and in 57 of the 64 elderly patients (89%) (36 with guide wire, p = 0.42). Bleeding occurred in 5 patients (2.3%) and perforation in one (0.46%). CONCLUSION: The guide-wire seems to reduce the incidence of pancreatitis in the elderly compared to conventional contrast but does not improve the success rate for cannulation.

Endoscopic resection of large pedunculated colonic polyps and risk of postpolypectomy bleeding with adrenaline injection versus endoloop and hemoclip: a prospective, randomized study.

BACKGROUND: Postpolypectomy bleeding is a major complication, especially in large pedunculated colonic polyps. Several endoscopic techniques have been evolved for prevention of bleeding episodes. The aim of this study is to evaluate postpolypectomy bleeding rates in large (>2 cm) pedunculated colonic polyps using either adrenaline injection alone or loop and clip application as prophylactic methods. MATERIALS AND METHODS: Patients with one pedunculated colonic polyps (>2 cm) were included in a double-blind study and studied prospectively. Exclusion criteria were coexistence of other large polyps, antiplatelet, nonsteroidal anti-inflammatory drugs or aspirin. In group A (n = 32), adrenaline (1:10,000) was injected in the base of the stalk followed by conventional polypectomy using mixed coagulation and cutting current. In group B (n = 32), a detachable snare was placed at the base of the stalk followed by conventional polypectomy and clip application in the residual stalk above the snare. We evaluate the efficacy of combined endoscopic methods in early and late postpolypectomy bleeding rate in large pedunculated colonic polyps, severity of bleeding, days of hospitalization, and required transfusions. RESULTS: Overall, bleeding complications occurred in 5/64 patients (7.81%). In group A (adrenaline injection alone), four patients (12.5%) had a bleeding episode: two (6.25%) occurred during the first 24 h and two (6.25%) between days 7 and 14 from the procedure. In group B only one patient (3.12%) had a late bleeding episode (p = 0.02). Severity of late bleeding in group B patients (one moderate bleeding) versus group A patients (one moderate and one severe bleeding) and need for transfusions (1 versus 5 blood units) were lower (p = 0.02). Hospitalization days did not differ between the two groups, but colonoscopy time was significantly higher in group B versus group A (p = 0.04). CONCLUSION: Combined endoscopic techniques seem to be more effective in preventing postpolypectomy bleeding in large pedunculated colonic polyps.

Asymptomatic brain finding results on MRI in a patient with Crohn's disease: a case report.

The association of inflammatory bowel disease with neurological involvement is unusual and often controversial. We report the case of a 39-year old man with Crohn's disease and an intracranial benign primary tumor, detected on MRI scan. The patient had been suffering from extensive perianal fistulas for 8 years, before inflammatory bowel disease was diagnosed six months ago. The patient, being enrolled in a research protocol, underwent brain MRI examination. Despite the absence of neurological symptoms and electromyography abnormalities, a meningioma was evidenced. Whether this is an incidental finding on brain MRI or whether it might be linked to Crohn's disease development as an extraintestinal, neurological disorder remains unclear. This information is especially important in view of the ethical and practical issues involved in the management of incidental findings in CD. This report might provide further confirmation of the hypothesis that central neurological disorders occur during CD.

Enterobius Vermicularis infection of the appendix as a cause of acute appendicitis in a Greek adolescent: a case report.

Gastrointestinal infection due to Enterobius vermicularis occurs worldwide and is considered to be the most common helminth infection. The simple presence of E. vermicularis in the appendix usually produces symptoms of acute appendicitis. The association of this parasitic infestation with acute appendicitis varies from 0.2%-41.8% worldwide. We present a case of a 15 year old female with enterobiasis of appendix presented with clinical features of acute appendicitis. The appendix was surgically removed and the specimen was pathologically diagnosed to contain of E. vermicularis in non-inflamed and histologically normal appendix. Even if this condition is not uncommon in the Greek population, to the best of our knowledge this is the first report presented in the English literature.

Idiopathic portal hypertension in an "inactive" HBV carrier: a case report.

Idiopathic portal hypertension belongs to the group of non-cirrhotic portal hypertension, its etiology is still unknown but its prognosis is excellent. We report a case of 45 year old female with inactive hepatitis B virus (HBV) carrier status and persistently elevated alpha-fetoprotein (AFP), presented with features of portal hypertension and without evidence of cirrhosis or fibrosis on liver biopsy.

Migrated biliary stent predisposing to fatal ERCP-related perforation of the duodenum.

ERCP may be associated with very serious and even fatal complications. Internal drainage with endoscopical prostheses has been used as a palliative treatment for malignant bile duct obstruction. We report a rare case of subcutaneous emphysema with a fatal outcome. The emphysema resulted from a perforation of a duodenal ulcer during ERCP due to a migrated biliary stent that had been previously endoscopically placed.