Abnormal expression of oxylipins and related synthesizing/signaling pathways in inflammatory bowel diseases.

We investigated selected oxylipins and related synthesizing/signaling pathways in 28 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and 39 controls. Plasma and mucosal PUFA/oxylipin profiles were analyzed by LC-MS/MS. mRNA expression of 5, 12 and 15-lipooxygenases, FPR2/ALXR, FFAR4/GPR120, annexin A1, and interleukin-10 were analyzed by qRT-PCR. Oxylipin profile and related metabolic pathways were altered in both CD and UC patients. The patterns were characterized by increased prostaglandins, leukotrienes, and lipoxins and overexpression of 5-lipoxygenase, FPR2/ALXR, annexin A1, and interleukin-10 genes, but decreased n-3 PUFAs and 18-hydroxyeisapentaenoic acid. The gene of 15-lipoxygenase was under-expressed mainly in UC patients. CD and UC are associated with unbalanced n-6 ​​and n-3 derivatives and pro-inflammatory and anti-inflammatory/pro-resolving mediators favoring the former compounds. The findings suggest that oxylipins engage in the pathophysiology of the diseases. Targeting oxylipin's metabolic pathways would be a promising therapy for inflammatory bowel diseases.

Overlap syndrome of seronegative primary biliary cholangitis and small duct primary sclerosing cholangitis: a first case report and literature review.

Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) are distinct liver diseases. Cases combining PBC and PSC, are extremely rare. Here, we present a case of a 39-year-old woman with a history of colonic Crohn's disease treated with azathioprine. Discontinuation of the medication was prompted by abnormal liver function tests, but subsequent evaluations revealed persistent liver injury. Extensive diagnostic investigations, including imaging, serological tests, and liver biopsy, were conducted leading to a diagnosis of PBC-PSC overlap syndrome based on the presence of concentric lamellar fibrosis and chronic non-suppurative destructive cholangitis. The patient responded well to ursodeoxycholic acid treatment. This case emphasizes the importance of recognizing and diagnosing rare overlap syndromes, particularly those involving PBC and PSC, to ensure appropriate management and improve patient outcomes.

Altered mucosal and plasma polyunsaturated fatty acids, oxylipins, and endocannabinoids profiles in Crohn's disease.

Selected mucosal and plasma polyunsaturated fatty acids (PUFAs) and related oxylipins and endocannabinoids were determined in 28 Crohn's disease (CD) patients and 39 controls. Fasting blood and colonic biopsies were collected in all participants, during a disease flare for the patients. Thirty-two lipid mediators including PUFAs, oxylipins, and endocannabinoids were assessed by LC-MS/MS. The pattern of lipid mediators in CD patients is characterized by an increase in arachidonic acid-derived oxylipins and endocannabinoids and a decrease in n-3 PUFAs and related endocannabinoids. A model combining increased 6-epi-lipoxin A4 and 2-arachidonyl glycerol with decreased docoasapentaenoic acid in plasma fairly discriminates patients from controls and may represent a lipidomic signature for CD flare. The study findings suggest that lipid mediators are involved in CD pathophysiology and may serve as biomarkers for disease flare. Further research is required to confirm the role of these bioactive lipids and test their therapeutic potential in CD.

Esophageal motor abnormalities on high-resolution manometry in patients with scleroderma.

BACKGROUND: Systemic sclerosis (SS) is an autoimmune disorder that may result in diverse esophageal motor disorders. Typical manometric disorders include decreased lower esophageal sphincter (LES) pressure, absent contractility and ineffective peristalsis. AIMS: The aims of the study were to assess esophageal motor abnormalities in SS patients using high resolution manometry and to evaluate clinical and endoscopic features that are associated with manometric findings. METHODS: Patients with SS who underwent esophageal high-resolution manometry (HRM) between December 2016 and August 2020 were enrolled in the study. Data regarding demographics and symptom frequency were obtained through a questionnaire. Chicago classification criteria (V3.0.) were used for defining esophageal dysmotility. RESULTS: A total of 49 patients were enrolled in the study. Median age was 56 ±13.4 years. High-resolution manometry showed that absent contractility (n= 24; 49%) and ineffective motility (n=14; 28.6%) were the most frequent motor abnormalities. One case of esophageal gastric junction (EGJ) outflow obstruction was observed in a female patient. A hypotensive LES was observed in 18 patients (36.7%). Absent contractility was associated with regurgitations (=0.013), and erosive esophagitis (p=0.003). CONCLUSION: Absent contractility and ineffective motility were the most common esophageal contractile patterns among our patients. Patients with absent contractility experienced more frequently regurgitations and had more often erosive esophagitis.

Toxicity profile of thiopurines in inflammatory bowel disease: a retrospective cohort analysis.

BACKGROUND: Thiopurines have proven efficacy in inflammatory bowel disease. However, their use is limited by adverse effects in a subset of patients. AIMS: The present study aimed to evaluate toxicity profile and identify clinical predictive factors of thiopurine adverse effects in inflammatory bowel disease patients. METHODS: A retrospective longitudinal study was conducted among inflammatory bowel disease patients treated with thiopurines. Multiple logistic regression was used to identify risk factors for thiopurine adverse effects. RESULTS: A total of  210 patients were enrolled in the study. Mean age at disease onset was 29.8±11.4 years.  One hundred sixty-nine (169) patients had Crohn's disease, 29 had ulcerative colitis and 12 had indeterminate colitis. During a median follow-up of 28.5 ± 20 months, 56 patients (26.6%) had thiopurine-related adverse effects including digestive intolerance (n=14; 6.6%), immunoallergic reactions (n=8; 3.8%), myelotoxicity (n=25; 11.9%) and hepatotoxicity (n=8; 3.8%). Treatment withdrawal was reported in 19 patients (9%).  The only independent predictive factor for thiopurine adverse effects found in this study was steroid-dependence (OR= 3.96; 95% CI: 1.07- 14.53; p= 0.038). CONCLUSIONS: Almost a quarter of inflammatory bowel disease patients treated with thiopurines developed adverse effects. These adverse effects lead to drug withdrawal in almost 9% of patients either as monotherapy or as in combination with biologic therapies.  Steroid-dependent patients were significantly at higher risk for thiopurine-related toxicity.

Complex perianal fistulas in Crohn's disease: An anti-TNF α based medico-surgical treatment with magnetic imaging assessment.

BACKGROUND: Anti-TNFα associated to seton drainage has a central role in the treatment of complex perineal Crohn's fistulas (PAF). A precise treatment protocol is lacking. AIMS: to evaluate the results of this combined treatment and identify predictive factors of response. METHODS: It was a retrospective study which included all patients with complex PAF treated with Anti-TNFα. RESULTS: We included 49 patients, mean age of 31.6 years. 17 patients had an active rectal involvement. 35 patients had azathioprin. After the induction, 43 patients had a clinical response. Maintenance therapy was started in 45 cases. After a median of 19 months of Anti-TNFα, 24 patients had a clinical remission (with radiological remission in 20), 17 a partial clinical response, and 4 were in failure. After clinico-radiologic remission setons were removed in all patients, 46% of patients who stopped Anti-TNFα treatment after clinico-radiologic remission relapsed. Absence of rectal involvement and Clinical remission after induction were the independent predictive factors of achieving a clinical remission under maintenance therapy with Anti-TNFα (p=0.016) and clinico-radiological remission (p=0.028). CONCLUSION: An Anti-TNFα based treatment combined with long term loose seton drainage have contributed to the high rates of both clinical and radiological responses in this study. Obtaining a "deep" clinico-radiological remission should be the target of the treatment. Stopping the Anti-TNFα should be avoided even after obtaining such response.

Dietary habits associated with internal hemorrhoidal disease: a case-control study.

BACKGROUND: Pathophysiology of the internal hemorrhoidal disease is poorly understood but seems to be multifactorial. Some types of food and lifestyle have been assumed to increase the risk of internal hemorrhoidal disease.  Aims: To identify alimentary habits that are associated with internal hemorrhoidal disease. METHODS: Fifty patients and 50 healthy controls matched for age and sex were enrolled in a case-control study. Food intake of patients and controls was assessed by a nutritionist using the 72-hour recall method and the food frequency questionnaire. Data regarding their eating behavior were also collected using an eating behavior questionnaire. RESULTS: Mean age of patients was 42 ± 11.8 years with a female to male ratio of 1.17. Prolapse and anal pain were the most common presenting symptoms. Constipation was found in almost all patients. High-fiber foods were less often consumed by patients than by controls with the difference being significant for vegetables, fruits and cereals. Regarding spicy aliments, consumption of pepper and chili powder was found to be significantly less frequent in patients than in controls.  Multivariate analysis revealed daily fiber intake < 12 g (OR 7.08; 95%CI 1.24 - 40.30; p=0.027) and daily water intake < 2L (OR 8.68; 95%CI 3.07 - 24.51; p<0.001) significantly increase the risk of internal hemorrhoidal disease. CONCLUSIONS: Internal hemorrhoidal disease was more frequently observed in patients with low-fiber diet and a reduced water intake. These dietary habits were described as precipitating factors of constipation which was found in almost all patients.

The relationship between coagulation disorders and the risk of bleeding in cirrhotic patients.

INTRODUCTION AND OBJECTIVES: For long, bleeding in cirrhotic patients has been associated with acquired coagulation disorders. The aim of our study was to investigate the impact of acquired coagulation disorders on bleeding risk in cirrhotic patients. MATERIALS AND METHODS: Blood samples were collected from 51 cirrhotic patients with (H+) or without (H-) bleeding events and 50 controls matched by age and sex. Thrombin generation was assessed as endogenous thrombin potential (ETP). Hemostatic balance was assessed by means of ratios of pro- to anticoagulant factors and by ETP ratio with/without protein C (PC) activator (ETP ratio). RESULTS: Bleeding events occurred in 9 patients (17.6%). Compared with controls, VIII/anticoagulant factors, VII/PC and XII/PC were significantly higher in (H+) patients. No significant difference as regards all ratios across patient groups was detected. ETP ratio was significantly higher in (H+) patients than in controls (p=0.017). However, there was no significant difference between patient groups as regards ETP ratio. CONCLUSION: Hemostatic balance is shifted toward a hypercoagulability state even in cirrhotic patients who experienced bleeding. These findings provide evidence against traditional concept of hemostasis-related bleeding tendency in cirrhotic patients.

Health-related quality of life in cirrhotic patients: a case-control study.

BACKGROUND: Assessment of health-related quality of life (HRQOL) in patients with cirrhosis has been increasingly reported in literature.  Aims: To compare quality of life scores between cirrhotic patients and healthy controls and to assess factors associated with the impairment of quality of life in cirrhotic patients. METHODS: HRQOL was measured in cirrhotic patients by the Tunisian version of MOS 36-item short-form health survey (SF-36) and the Arabic version of the Liver Disease Symptom index 2.0 (LDSI2.0). Age-and sex- matched controls were asked to complete only the SF36. The SF36 scores were compared between cirrhotic patients and controls and LDSI2.0 scores were compared across cirrhotic patients according to the characteristics of cirrhosis. Factors associated with poor perceived health status were identified by logistic regression. RESULTS: Fifty cirrhotic patients and fifty controls were enrolled in the study. The cirrhotic group had significantly lower SF36 scores than healthy controls in all 8 dimensions (p<0.001). Most impaired LDSI items were severity of fear of complications (item 8), change in use of time (item 13), decreased sexual interest (item 14) and decreased sexual activity (item 15). Multiple logistic regression analysis showed that female sex (p=0.009), diabetes (p=0.046), treatment with diuretics (p=0.022), increased levels of serum bilirubin (p=0.045) and prolonged prothrombin time (p=0.041) were associated with poorer HRQOL. CONCLUSIONS: HRQOL was significantly more impaired in cirrhotic patients than controls. Female sex, diabetes, treatment with diuretics, increased levels of serum bilirubin and prolonged prothrombin time were important factors in reducing HRQOL.

Radiation exposure in Crohn's disease patients.

Introudction Crohn's disease (CD) is a lifelong condition. Multiple imaging investigations are often performed during follow-up. This could cause overexposure to radiation. The aim of our study was to determine mean radiation dose in patients  with  at least a 5-year course of CD and to determine possible risk factors associated with exposure to high doses of radiation. Methods We conducted a retrospective study including patients whose CD was diagnosed between 1998 and 2005. Epidemiologic features of patients, characteristics of the disease,  types of imaging investigations that were performed during follow-up and cumulative radiation effective dose were determined. Risk factors associated with exposure to high doses of radiation were then determined. Results One hundred sixty seven patients were included.  There were 92 males (55.1%) and 75 females (44.9%) with mean age at dianosis of 31.4±12.3years. Global radiation dose was 18.8±18.9 mSv. Twenty seven patients (16,2%) were exposed to more than  35 mSv and 4 patients (2.4%) had an exposure  of more than  75 mSv. Use of Infliximab, age at disease onset ≤ 24 years old and number of flares ≥ 8  were independent risk factors of radiation exposure more than 35 mSv with adjusted Odds ratios (OR) : 2.5 [2.1- 5.3]; 1.6 [1.2- 4.7] and 3.2 [2.1- 7.8] respectively. Similarly,  use of Infliximab and number of flares ≥ 8  were independent risk factors of radiation exposure more than 75 mSv with adjusted OR : 4.3 [2.8-9.5] and 7 [3.2-11.2] respectively. Conclusion Radiation risk seems to be increased with severe course of  CD. Both referring physicians and radiologists have the responsibility to minimise radiation exposure. Entero-magnetic resonance imaging (Entero-MRI)  may reduce this risk.

Changes of Crohn's disease phenotype over time.

Background - Crohn's disease is a clinically heterogeneous condition. Our aim was to identify the phenotype evolution of Crohn's disease over time according to the Montreal Classification and to precise predictive factors of the need for immunosuppressant treatment or surgery. Methods - We included Crohn's disease patients who were followed up for at least 5 years. We excluded patients who were lost to follow up before five. Patients were classified according to the Montreal classification for phenotype at diagnosis and five years later. The evolution of phenotype over time and the need for surgery, immunosuppressive or immunomodulatory drugs were evaluated. Results - One hundred twenty consecutive patients were recruited: 70 males and 50 females. At diagnosis, 68% of patients belong to A2 as determined by the Montreal classification. Disease was most often localized in the colon. The disease location in Crohn's disease remains relatively stable over time, with 93.4% of patients showing no change in disease location. Crohn's disease phenotype changed during follow up, with an increase in stricturing and penetrating phenotypes from 6% to 11% after 5 years. The only predictive factor of phenotype change was the small bowel involvement (OR=3.7 [1.2-7.6]). During follow-up, 82% of patients have presented a severe disease as attested by the use of immunosuppressive drugs or surgery. The factors associated with the disease severity were: small bowel involvement (L1), the stricturing (B2) and penetrating (B3) phenotypes and perineal lesions (OR=17.3 [8.4-19.7]; 12 [7.6-17.2]; 3[1.7-8.3] and 2.8 [2.2-5.1] respectively), without association with age, sex or smoking habits. Conclusion - Crohn's disease evolves over time: inflammatory diseases progress to more aggressive stricturing and penetrating phenotypes. The ileal location, the stricturing and penetrating forms and perineal lesions were predictive of surgery and immunosuppressant or immunomodulatory treatment.

[Dietary intake in Crohn's disease: results of a prospective comparative study]. / Enquête alimentaire au cours de la maladie de Crohn : résultats d'une étude prospective comparative.

BACKGROUND: Diet is thought to have an important role in the etiopathogenesis of Crohn's disease. In the other hand, Crohn's disease is frequently associated with nutritional deficiencies probably as result of disease activity and poor oral intake. AIMS: To investigate the dietary intake in patients with Crohn's disease in comparison with matched population controls and to assess the correlation between the results of the dietary enquete, nutritional status and disease activity. METHODS: We conducted a prospective case control study in patients with Crohn's disease and matched controls. All subjects were evaluated in respect of dietary intake (based on "NUTISTAR" logiciel) and nutritional status. RESULTS: We studied 23 patients and 23 controls. There was no statistical difference between patients and controls according to the proportion of carbohydrates, fat and protein intakes. Energy intakes were significantly lower in patients with Crohn's disease (1991 + 678 kcal/j) compared to controls (2537 + 345 kcal/j) (p=0.007) ; and in active disease (1353 + 308 kcal/j) compared to inactive disease patients (2481 + 415 kcal/j) (p<0.0001). In Crohn's disease patients, correlation study showed that energy intakes were correlated with CDAI (p<0.0001 ; r = - 0.74) and BMI (p=0.03 ; r = 0.45). CONCLUSION: In Crohn's disease, an inadequate dietary intake is correlated with nutritional status and disease activity.

Stem cell transplantation as rescue therapy for refractory Crohn's disease: a sytematic review.

BACKGROUND: Crohn's disease is a chronic relapsing- remitting affection. It has a strong immunologic component which represent the target of standard therapies including immunosppressants and biological therapies. However, many patients remain refracory or intolerant to these therapies. AIM: The aim of this review is to determine the effects of stem cell transplantation in patients with refractory Crohn's disease. METHODS: Systematic review of observational studies, clinical trials and case reports that focused on the effectiveness and safety of stem cell transplantation in patients with refractory Crohn's disease. RESULTS: Hematopoietic stem cell transplantation seems to be efficient in maintaining clinical and endoscopic remission in patients with Crohn's disease refractory or intolerant to current therapies. However, it has been associated to high morbidity and mortality due to chemotherapy. Mesenchymal stem cell transplantation could induce remission in patients with fistulising refractory Crohns disease with no severe side effects. Its impact on luminal Crohns disease is still controversial. CONCLUSION: Stem cell transplantation seems to hold promising in patients with refractory Crohn's disease. However, because of the high morbidity and mortality related to chemotherapy, hematopoietic stem cell transplantation should be used as last resort to control this disease. Effectiveness of mesenchymal stem cell transplantation in luminal Crohn's disease has yet to be proven.

[Epithelial cell in intestinal homeostasis and inflammatory bowel diseases]. / Rôle de la cellule épithéliale dans l'homéostasie intestinale et les maladies inflammatoires chroniques de l'intestin.

Crohn's disease (CD) and ulcerative colitis (UC) are the principal inflammatory bowel diseases (IBD) which physiopathology is currently poorly elucidated. During these diseases, the participation of the epithelial cell in the installation and the perpetuation of the intestinal inflammation is now clearly implicated. In fact, the intestinal epithelium located at the interface between the internal environment and the intestinal luminal, is key to the homeostatic regulation of the intestinal barrier. This barrier can schematically be regarded as being three barriers in one: a physical, chemical and immune barrier. The barrier function of epithelial cell can be altered by various mechanisms as occurs in IBD. The goal of this article is to review the literature on the role of the epithelial cell in intestinal homeostasis and its implication in the IBD.

Diagnosis and management of refractory celiac disease: a systematic review.

BACKGROUND: Refractory celiac disease is defined by persisting malabsorptive symptoms in spite of a strict gluten free diet for at least 6 to 12 months. Alternatives to gluten free diet seem to be still controversial. AIM: To describe the clinical and epidemiologic aspects of refractory celiac disease, and to identify therapeutic options in this condition. METHODS: Systematic review and critical analysis of observational studies, clinical trials and case reports that focused on diagnosis and management of refractory celiac disease. RESULTS: Refractory celiac disease can be classified as type 1 or type 2 according to the phenotype of intraepithelial lymphocytes. Great complications such as enteropathy-associated T-cell lymphoma may occur in a subgroup of these patients mainly in refractory celiac disease type 2. Curative therapies are still lacking. CONCLUSION: Refractory celiac disease remains a diagnosis of exclusion. Its prognosis remains still dismal by the absence yet of curative therapies. However, some new treatments seem to hold promise during few cohort-studies.