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.

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.

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.

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.

[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.

Intestinal T-cell lymphoma not otherwise specified: a case report and literature review.

Intestinal T-cell lymphoma, not otherwise specified (ITCL, NOS), primarily affects the small bowel but can involve the stomach and large bowel. This report presents an uncommon case of ITCL, NOS in a patient affecting the large bowel, supported by a literature review. An 87-year-old female presented with abdominal pain, fever, vomiting and weight loss. Imaging revealed nodular thickening of the transverse and right colon, confirmed as polypoid mass lesions with ulceration through colonoscopy and biopsy, indicating ITCL, NOS. CT scan showed adrenal nodes classifying it as stage VI. The patient was referred for palliative care and passed away 40 days later, likely due to tumor progression. This case underscores the rarity of large bowel ITCL, NOS and the diagnosis challenge.

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.

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.

[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.

[Not Available]. / Y a-t-il intérêt à doser les métabolites de l'azathioprine chez les malades ayant une maladie inflammatoire chronique de l'intestin?

OBJECTIVE: The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population. METHOD: We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1year. Each patient had a dosage of azathioprine metabolites. RESULTS: We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients. CONCLUSION: Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule.

[Is there any interest to dose the azathioprine's metabolites during inflammatory bowel diseases?]. / Y a-t-il intérêt à doser les métabolites de l'azathioprine chez les malades ayant une maladie inflammatoire chronique de l'intestin ?

OBJECTIVE: The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population. METHOD: We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1 year. Each patient had a dosage of azathioprine metabolites. RESULTS: We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients. CONCLUSION: Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule.

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.

[Bone metabolism, biochemical markers of bone resorption and formation processes and interleukine 6 cytokin level during coeliac disease]. / Anomalies du métabolisme osseux et résultats des marqueurs biochimiques du remodelage osseux et de l'interleukine 6 au cours de la maladie coeliaque.

BACKGROUND: Celiac disease (CD) is characterized by a malabsorption syndrom. The bone anomalies are one of the principal complications of this disease. The osteoporosis frequency is high: 3.4% among patients having with CD versus 0.2% in the general population. AIM: To study the bone mineral density during the CD, to compare it to a control group and to determine the anomalies of biochemical markers of bone turn over and level of interleukin 6 cytokin (IL6) in these patients. METHODS: All patients with CD have a measurement of bone mineral density by dual-energy x-ray absorptiometry (DXA), a biological exam with dosing calcemia, vitamin D, parathormone (PTH), the osteoblastic bone formation markers (serum osteocalcin, ALP phosphates alkaline), bone osteoclastic activity (C Télopeptide: CTX) and of the IL6. RESULTS: 42 patients were included, with a median age of 33.6 years. 52. 8% of the patients had a low level of D vitamine associated to a high level of PTH. An osteoporosis was noted in 21.5% of patients. No case of osteoporosis was detected in the control group. The mean level of the CTX, ostéocalcine and the IL6 was higher among patients having an osteoporosis or ostéopenia compared to patients with normal bone (p = 0,017). The factors associated with an bone loss (osteopenia or osteoporosis) were: an age > 30 years, a weight <50 kg, a level of ALP phosphates alkaline > 90 UI/ml, an hypo albuminemia < 40 g/l and a level of CTX higher than 1.2. CONCLUSION: Our study confirms the impact of the CD on the bone mineral statute. The relative risk to have an osteopenia or an osteoporosis was 5 in our series. The measurement of the osseous mineral density would be indicated among patients having a CD.

[Post-infectious irritable bowel syndrome]. / Une nouvelle entité clinique: le syndrome de l'intestin irritable postinfectieux.

BACKGROUND: Post-infectious irritable bowel syndrome (PI-IBS) is a disorder wherein symptoms of IBS begin after an episode of acute gastroenteritis. AIMS: To determine epidemiology, clinical features and prognosis of PI-IBS and to precise its physiopathology and treatment. METHODS: Literature review. RESULTS: Published studies have reported an incidence of PI-IBS ranging from 4 to 32 % with a mean of 10 %. Bacterial infections are the most responsible agents. Risk factors for PI-IBS include patient's demographics, psychological disorders and the severity of enteric illness. The most common symptoms are those of diarrheapredominant IBS. The mechanisms underlying PI-IBS include especially changes in intestinal permeability and persistent mucosal inflammatory process. In fact, there is increase in lymphocytic, mast and enterochromaffin cells in the gut mucosa. Furthermore, increased inflammatory cytokines have been demonstrated. Treatment of PIIBS is similar to that idiopathic IBS. CONCLUSION: PI-IBS is a novel clinic entity that suggests a novel approaches to IBS.

[24-hour esophageal impedance-ph monitoring: technical aspects, indications and results]. / L'impédancemétrie couplée à la ph-mètrie oesophagienne des 24 heures: technique, indications et résultats.

BACKGROUND: Classical techniques like endoscopy and esophageal pH-metry are the gold standard to study patients with symptoms related to gastroesophageal reflux disease. Although these techniques have been useful over the years both for diagnosis and therapeutic guidance, there are still many patients with typical or atypical gastroesophageal reflux disease symptoms with normal endoscopy and pH-metry that do not respond adequately to antisecretory therapy. Ambulatory esophageal impedance-pH monitoring is a new technique that can be used to evaluate all types of gastroesophageal reflux, achieving higher rates of sensitivity and specificity than standard techniques. AIM: To precise the technical aspects of the esophageal impedancepH monitoring, indications and results of this technique in clinical practice. METHODS: Literature revue of the esophageal impedance - pH monitoring Results: Combined multichannel intraluminal impedance and pH monitoring is a new technique that can be used to evaluate both bolus transport and all types of reflux (acid, weakly acidic and weakly alkaline), without radiation hazards. With this technique, higher rates of sensitivity and specificity than standard techniques are obtained in the diagnosis of pathological gastroesophageal reflux. The technique has also been used in the evaluation of atypical gastroesophageal reflux symptoms, in the assessment of the association of different patterns of reflux with symptoms, and in the evaluation of therapeutic outcome mainly in patients with refractory gastroesophageal reflux disease. CONCLUSION: The esophageal impedance represents real progress in understanding the different mechanisms involved in the pathophysiology of gastroesophageal reflux. This technique should also allow a better understanding of the responsibility of non-acid reflux in special clinical situations, such as patients resistant to antisecretory or extra-intestinal manifestations of gastroesophageal reflux.

[Is APRI score a suitable tool for prediction of fibrosis in Tunisian patients with genotype 1 chronic viral hepatitis C?]. / Le score April est il fiable pour la prediction de la fibrose chez les patients Tunisiens atteints d'hepatite chronique virale C de genotype 1?

BACKGROUND: Therapeutic indications in chronic genotype 1 hepatitis C are based on severity of fibrosis. APRI score is a simple, cheap and reproducible biochemical test. Performances of APRI score in Tunisian population with chronic hepatitis C were not previously prospectively studied. AIM: To evaluate the performances of APRI score in prediction of severity of fibrosis in chronic genotype 1 hepatitis C based on a prospective study. METHODS: We prospectively include patients with chronic genotype 1 hepatitis C and positive viral load. Hepatic biopsy was performed in all included patients and abnormalities were classified according to METAVIR classification. In all patients, APRI score was calculated based on biochemical data collected within the 15 days before hepatic biopsy. RESULTS: We studied 140 patients (46 men, mean age 48.4 years (20 - 65 years)). Mean APRI score was 0.89 (0.18 - 3.72). Statistically significant correlation was observed between APRI score and fibrosis severity (r = 0.31 p < 0.0001). APRI score was higher in patients with severe fibrosis (F2, F3 or F4) compared to patients with moderate fibrosis (F0 or F1) (0.97 + 0.68 vs 0.62 + 0.44; p 0.009). Threshold value of APRI score of 0.72 was associated with area under the curve of 0.65 + 0.05 (0.57 - 0.73), sensitivity of 56.3% and specificity of 75.8% in prediction of severe fibrosis. APRI score was also higher in patients with cirrhosis (1.24 + 0.79 vs 0.85 + 0.61; p = 0.01). Threshold value of 0.86 was associated with area under the curve of 0.69 + 0.07 (0.61 - 0.77), sensitivity of 76.4% and specificity of 65.8% in prediction of cirrhosis. CONCLUSION: APRI score is not a good alternative to hepatic biopsy although a strong correlation with fibrosis severity, because of relatively low area under the curve, sensitivity and specificity in prediction of severe fibrosis and cirrhosis.

Dermatologic manifestations in inflammatory bowel disease in Tunisia.

BACKGROUND: Cutaneous manifestations are the most common extra intestinal manifestations associated with inflammatory bowel disease (IBD). AIM: To assess the epidemio-clinical profile of skin manifestations in IBD. METHODS: A prospective and descriptive study was conducted. We have examined skin, mucosa, hair and nails, of all patients with an IBD during one year. RESULTS: One hundred-ninety-five patients were included. Crohn's disease (CD) was noted in 154 cases (79.8%), ulcerous rectocolitis (UC) in 39 cases (21.2%) and inclassable IBD in 2 cases. Cutaneous manifestations were found in 91% of Crohn's patients and in 92% of UC patients. Granulomatous perianal skin lesions were the main cutaneous manifestations of CD (53%). The most common affected sites were ano-perineal fistulae, perianal and perineal fissures and oedematous and infiltrated perianal and genital plaques. Reactive lesions (Erythema nodosum, Pyoderma gangrenosum, Aphthous stomatitis) were noted in 14 cases. Skin manifestations due to malabsorption were also frequently observed (101 cases: 51.7%).Other dermatoses implicating various mechanisms such as psoriasis, alopecia areata, vitiligo, rosacea, lichen planus, were also noted. Adverse skin manifestations due to treatment (folliculitis, acne, macula-papular rash and DRESS syndrome) were present in 16 cases. CONCLUSION: Our series is characterized by a high frequency of cutaneous manifestations associated to IBD. A better recognition of these skin manifestations by the physician may improve their management.