Opioid Analgesics Do Not Improve Abdominal Pain or Quality of Life in Crohn's Disease.

BACKGROUND: Abdominal pain and opioid analgesic use are common in Crohn's disease (CD). AIMS: We sought to identify factors associated with abdominal pain in CD and evaluate the impact of opioid analgesics on pain and quality-of-life scores in this setting. METHODS: We performed a longitudinal cohort study using a prospective, consented IBD natural history registry from a single academic center between 2009 and 2013. Consecutive CD patients were followed for at least 1 year after an index visit. Data were abstracted regarding pain experience (from validated surveys), inflammatory activity (using endoscopic/histologic findings), laboratory studies, coexistent psychiatric disorders, medical therapy, opioid analgesic, and tobacco use. RESULTS: Of 542 CD patients (56.6% women), 232 (42.8%) described abdominal pain. Individuals with pain were more likely to undergo surgery and were more frequently prescribed analgesics and/or antidepressants/anxiolytics. Elevated ESR (OR 1.79; 95%CI 1.11-2.87), coexistent anxiety/depression (OR 1.87; 95%CI 1.13-3.09), smoking (OR 2.08; 95%CI 1.27-3.40), and opioid use (OR 2.46; 95%CI 1.33-4.57) were independently associated with abdominal pain. Eighty patients (14.8%) were prescribed opioids, while 31 began taking them at or after the index visit. Patients started on opioids demonstrated no improvement in abdominal pain or quality-of-life scores on follow-up compared to patients not taking opioids. CONCLUSIONS: Abdominal pain is common in CD and is associated with significant opioid analgesic utilization and increased incidence of anxiety/depression, smoking, and elevated inflammatory markers. Importantly, opioid use in CD was not associated with improvement in pain or quality-of-life scores. These findings reinforce the limitations of currently available analgesics in IBD and support exploration of alternative therapies.

The natural history of COVID-19 in vaccinated inflammatory bowel disease patients.

AIM: Assess the characteristics of break through COVID-19 in Inflammatory Bowel Disease (IBD) patients, despite complete vaccination. METHODS: Patients who reported a COVID-19 at least 3 weeks after complete vaccination were asked to answer an on-line anonymous questionnaire which included patient and disease characteristics, vaccination history, and the evolution of COVID-19. RESULTS: Among 3240 IBD patients who reported complete vaccination between 1st May 2021 and 30thJune 2022, 402 (12.4%) were infected by SARS Cov-2 [223 male, 216 Crohn's disease (CD), 186 Ulcerative Colitis (UC), mean (SD) age 42.3 (14.9) years, mean (SD) IBD duration 10.1 (9.7) years]. Three hundred and sixty-nine patients (91.8%) were infected once and 33 (8.2%) twice. The mean (SD) time between last vaccination and infection was 4.1 (1.6) months. Overall, 351 (87.3%) patients reported mild constitutional and/or respiratory symptoms, 34 (8.4%) were asymptomatic and only 17 patients (4.2%) required hospitalization. Of hospitalized patients, 2 UC patients died of COVID-19 pneumonia. The remaining hospitalized patients did not need high flow oxygen supply or ICU admission. CONCLUSIONS: A minority of completely vaccinated IBD patients developed COVID-19 which evolved with mild symptoms and a favorable outcome. These results reinforce the importance of vaccination especially in vulnerable populations.

Inflammatory Bowel Disease [IBD] and Physical Activity: A Study on the Impact of Diagnosis on the Level of Exercise Amongst Patients With IBD.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] can impair patients' functional capacity with significant negative effects on their quality of life. Our aim was to determine the impact of IBD diagnosis on fitness levels and to assess the levels of engagement in physical activity and fatigue in IBD patient before and after diagnosis. METHODS: A prospective multi-centre cross-sectional study was performed. Patients diagnosed with IBD in the previous 18 months were recruited. Inclusion criteria included clinical remission and/or no treatment changes within the previous 6 months. Physical exercise levels were assessed by the Godin score and fatigue levels was assessed by the functional assessment of chronic illness therapy [FACIT] score. RESULTS: In total, 158 patients (100 Crohn's disease [CD]) were recruited. Mean age was 35.1 years (95% confidence interval [CI] ± 2.0). Gender distribution was approximately equal [51.3% male]. The Mean Harvey Bradshaw and Simple Clinical Colitis Activity indices were 2.25 [95% CI ± 0.40] and 1.64 [95% CI ± 0.49], respectively. The mean Godin score difference before and after IBD diagnosis was 6.94 [p = 0.002]. Patients with ulcerative colitis [UC] [41.8%] were more likely than patients with CD [23.0%] to reduce their exercise levels [p = 0.04]. FACIT scores were lower in patients who had experienced relapses [p = 0.012] and had severe disease [p = 0.011]. Approximately one-third of patients reduced their activity level following IBD diagnosis. CONCLUSIONS: Patients were significantly less physically active after a diagnosis of IBD and this was more apparent in UC. Identification of the risk factors associated with loss of fitness levels would help to address the reduced patient quality of life.

Genetic risk factors in patients with inflammatory bowel disease and vascular complications: case-control study.

BACKGROUND: Inherited risk factors have been suggested to play an important role in the pathogenesis of vascular complications of inflammatory bowel disease (IBD). The aim of the present study was to investigate the role of mutations associated with cardiovascular disease in IBD patients with or without vascular complications compared with thrombotic and healthy controls (HC). METHODS: Twelve polymorphisms of thrombophilic and vasoactive genes were evaluated in a group of 30 IBD patients with vascular complications (IBD-VC) compared with 60 IBD patients without vascular complications, 30 thrombotic controls (TC), and 54 healthy controls, using a commercially available kit. RESULTS: No significant differences between IBD-VC and TC concerning the carriage of these mutations were found. The frequencies of the factor V (FV) 506 RQ (Leiden) genotype and the 506Q allele were significantly higher in these groups than in HC (P < 0.05) but not IBD controls (P > 0.05). The allele frequency of the mutant 4G allele of the plasminogen activator inhibitor (PAI) polymorphism, similar in the IBD-VC and TC groups, was significantly higher in these groups compared with the IBD group (P = 0.03) and the HC (P = 0.001). It is noteworthy that there was a trend of association of FV R506Q polymorphism with venous thrombosis and PAI-1 gene polymorphism with arterial thrombosis. CONCLUSIONS: Our results suggest that the investigated gene polymorphisms do not differ in patients with IBD-VC and TC. FV R506Q and PAI-1 gene polymorphisms might be associated with the increased risk of development of vascular complications in IBD.

Serum laminin and collagen IV in inflammatory bowel disease.

BACKGROUND: / AIMS: Laminin and collagen IV have been proposed as extracellular matrix serum markers. Because fibrosis is a major complication of inflammatory bowel disease, serum concentrations of laminin and collagen IV were measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared with inflammatory and healthy controls. METHODS: Laminin and collagen IV serum concentrations were measured in 170 patients with inflammatory bowel disease (86 UC and 84 CD), in 23 patients with other causes of intestinal inflammation, and in 80 matched healthy controls using commercially available enzyme linked immunosorbent assays. Laminin and collagen IV concentrations were correlated with disease activity, type, localisation, and treatment. RESULTS: Mean (SD) serum laminin concentrations were 281.0 (110.1) ng/ml in patients with UC, 275.6 (106.7) ng/ml in patients with CD, 192.0 (17.8) ng/ml in healthy controls, and 198.5 (32.5) ng/ml in inflammatory controls. Mean (SD) serum collagen IV concentrations were 72.8 (22.9) ng/ml in patients with UC, 71.0 (18.2) in patients with CD, 79.8 (12.2) ng/ml in healthy controls, and 88.9 (24.6) ng/ml in inflammatory controls. There was a significant difference among the four groups (p < 0.0001) for both markers. There was a strong correlation between serum laminin, but not collagen IV, and disease activity in both diseases. No significant association was found between these markers and disease localisation or disease type. CONCLUSIONS: Serum concentrations of laminin are increased, whereas serum concentrations of collagen IV are decreased, in patients with inflammatory bowel disease. They may be useful surrogate markers for sustained inflammation and tissue remodelling.

Somatostatin for acute severe bleeding from portal hypertensive gastropathy.

OBJECTIVES: To investigate the effect of somatostatin in acute severe bleeding from portal hypertensive gastropathy in 26 cirrhotic patients. METHODS: All patients with signs of acute gastrointestinal bleeding and an upper GI endoscopy (during the first 24 h) indicating overt bleeding from portal hypertensive gastropathy were included in the study. Somatostatin (or the synthetic tetradecapeptide, octreotide) was administered in all cases. Eleven patients received somatostatin and 15 patients received octreotide. An initial injection of 250 microg bolus somatostatin was followed by a continuous infusion of 250 microg/h for 3 days (100 microg and 50 microg/h for octreotide). RESULTS: Somatostatin arrested bleeding in all 26 patients and in 23 there was no hospital relapse. In the remaining three patients the bleeding recurred each time somatostatin infusion was discontinued and arrested again on reinstitution of treatment. In two there was a control of haemorrhage, while the third required a total gastrectomy after repeated episodes. The rebleeding rate in our study is much lower compared to untreated patients of other series. There were no differences between the somatostatin and octreotide group. There were no significant side effects. Gastroscopy at the end of the therapy showed improvement of the endoscopic appearance. CONCLUSIONS: This open study suggests that somatostatin is a safe and effective treatment of acute severe bleeding from portal hypertensive gastropathy.

Idiopathic fibrosing pancreatitis and Crohn's disease: an interesting association.

Idiopathic fibrosing pancreatitis is an uncommon condition in children and adolescents of unknown aetiology. This syndrome has been reported in 36 cases so far. To our knowledge none of these cases was definitively associated with Crohn's disease. In this report we describe a young female patient who developed Crohn's disease of the colon 5 years after having been diagnosed with idiopathic fibrosing pancreatitis. The differential diagnosis between this syndrome associated with Crohn's disease and pancreatic Crohn's disease or fibrosing colonopathy, an entity related to pancreatic enzyme therapy, is discussed.

Increased levels of lipoprotein (a) in Crohn's disease: a relation to thrombosis?

OBJECTIVE: Lipoprotein (a) is recognized as a risk factor for arterial and venous thrombosis, a property that might be related to its structural similarity to plasminogen. Since patients with inflammatory bowel disease frequently suffer from thromboembolic events, we studied the role of lipoprotein (a) in conjunction with lipids and apolipoproteins in Greek patients with ulcerative colitis and Crohn's disease. METHODS: Lipoprotein (a), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1 and apolipoprotein B-100 were determined in sera from 129 consecutive fasting Greek patients with inflammatory bowel disease (66 with ulcerative colitis and 63 with Crohn's disease) and from 66 matched healthy controls. RESULTS: In Crohn's disease patients, the mean serum lipoprotein (a) level was significantly higher than in control patients (41.2 mg/dl vs 22.9 mg/dl; P = 0.005). Mean apolipoprotein A-1 and apolipoprotein B-100 levels were significantly lower in Crohn's disease patients than in the controls. In ulcerative colitis patients the mean levels of lipoprotein (a) and apolipoprotein A-1 were not significantly different to the controls, but the levels of apolipoprotein B-100 were significantly lower. Raised levels of lipoprotein (a) of > 30 mg/dl were found in 29 Crohn's disease patients (46%), 15 ulcerative colitis patients (23%) and 11 control patients (17%). Patients with active Crohn's disease had significantly higher mean lipoprotein (a) and lower apolipoprotein A-1 than patients with non-active disease. CONCLUSIONS: Our results suggest that Crohn's disease patients have different lipoprotein (a) and apolipoprotein patterns compared to ulcerative colitis patients and healthy controls. These changes in Crohn's disease patients may possibly expose them to a higher risk of thrombosis.

Association between ulcerative colitis and systemic lupus erythematosus: report of two cases.

BACKGROUND: Common aetiopathogenic factors may explain the association of ulcerative colitis with autoimmune disorders such as systemic lupus erythematosus. PATIENTS: We report two cases of ulcerative colitis associated with idiopathic systemic lupus erythematosus: one patient who developed ulcerative colitis 11 years after having been diagnosed as a case of systemic lupus erythematosus and one case of simultaneous appearance of the two diseases. The lupus clinical manifestations were in neither case correlated with the treatment of ulcerative colitis. CONCLUSION: The association between ulcerative colitis and systemic lupus erythematosus is rare. Although a chance occurrence cannot be excluded it is possible that both conditions share some genetic or immunological defects.

Assaying of tumor necrosis factor alpha, complement factors, and alpha-1-antitrypsin in the diagnosis of malignant serous effusions.

The objective of this study was to measure the concentrations of tumor necrosis factor-alpha (TNFalpha) in pleural and peritoneal effusions of different causes and to verify whether TNFalpha, alpha-1-antitrypsin (alpha1AT), and complement factors C3 and C4 can be used in the differential diagnosis of serous effusion. One hundred forty-five serous effusions of various origins were analyzed. TNFalpha, alpha1AT, and complement factors C3 and C4 concentrations were measured simultaneously in blood and serous effusion using commercially available methods. Serous effusions were classified as follows: 102 exudates and 43 transudates. All variables were found to have good diagnostic value in the differential diagnosis of serous effusion. In the stepwise discriminant analysis, four variables were selected, producing a significant discriminant function (p < 0.001). Their order of selection was alpha1AT effusion, C4 serum, TNFalpha-effusion, and C3 effusion. Combined use of these variables increased remarkably the diagnostic value (in diagnosing exudates versus transudates) giving sensitivity = 93.14%; specificity = 90.70%; positive predictive value = 95.96%; negative predictive value = 84.78%. Determination of TNFalpha, complement factors C3 and C4, and alpha1AT may be a significant parameter in the differential diagnosis of serous effusions, particularly in those patients with malignant disease. Moreover, the combination of them significantly increased their diagnostic power.

Increased expression of VEGF and CD146 in patients with inflammatory bowel disease.

BACKGROUND: Angiogenesis has been suggested as an integral part of inflammatory bowel disease pathology. Vascular endothelial growth factor has long been considered to play a central, specific role in angiogenesis. Endothelial junction adhesion molecules, such as CD146, have recently been suggested to play a potent role in angiogenesis. CD34 is expressed on vascular endothelium, and it has been reported to be upregulated on endothelium in IBD. We investigated the expression of tissue vascular endothelial growth factor, CD34 and CD146 in the inflamed mucosa of patients with active inflammatory bowel disease compared with no inflamed mucosa of healthy controls. METHODS: Forty-two IBD patients [23 ulcerative colitis, 19 Crohn's disease] and ten healthy controls were included in the study. In colonoscopically obtained biopsies, CD34, CD146 and vascular endothelial growth factor expression were evaluated by immunohistochemistry. RESULTS: Vascular endothelial growth factor was detected in the mucosa of all groups, and its expression was significantly higher in both Crohn's disease and ulcerative colitis compared with controls (p<0.05). Immunohistochemical staining for CD146 in the inflamed mucosa was significantly higher in both Crohn's disease and ulcerative colitis compared with controls (p=0.002). A trend of higher CD34 expression in Crohn's disease and ulcerative colitis compared with controls was also found, but the difference among the three groups was not statistically significant (p=0.09). CONCLUSIONS: Inflamed mucosa of patients with active Crohn's disease and ulcerative colitis showed a markedly enhanced expression of VEGF and CD146, than normal mucosa of controls, indicating a possible role of angiogenesis in the pathogenesis of inflammatory bowel disease.

Potential role of soluble angiopoietin-2 and Tie-2 in patients with inflammatory bowel disease.

BACKGROUND: Angiogenesis has been suggested to play an important role in inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD). MATERIALS AND METHODS: Serum Ang-2 and Tie-2 serum levels were measured in 160 IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2 levels were correlated with the disease activity, as well as the type, localization and treatment of the disease. RESULTS: Median serum Ang-2 and Tie-2 levels were significantly higher in both the UC patients and the CD patients compared with the healthy controls (P < 0.05 and P < 0.001, respectively). The IBD patients with early disease (diagnosis < 2 years) had significantly higher (P = 0.04) median serum Ang-2 levels but significantly lower (P = 0.02) median serum Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2 years). The CD patients with active disease had significantly higher levels of Ang-2 compared with non-active disease (P = 0.02). Serum levels of both Ang-2 and Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood cell count, platelet count and albumin. CONCLUSIONS: Serum Ang-2 and Tie-2 levels are elevated in patients with IBD. These markers may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD.

The spectrum of segmental colitis associated with diverticulosis.

BACKGROUND: Segmental colitis associated with diverticulosis (SCAD) has been defined as chronic colonic inflammation surrounding diverticula with rectal sparing. Distinguishing this condition from inflammatory bowel disease may be difficult. Our aim was to evaluate the epidemiological and clinical characteristics of SCAD in our area. METHODS: Retrospective case identification with prospective follow-up was done. Patients with endoscopic findings suggestive of SCAD were enrolled. The epidemiological, clinical, and histological characteristics of these patients were analyzed. RESULTS: Out of 605 patients with diverticulosis, 23 cases of SCAD were identified (3.8%). Four patients had histological characteristics suggestive of ulcerative colitis, in 1 case the histology was suggestive of ischemic colitis, 6 patients had histology compatible with SCAD, and the remaining patients had either transitional mucosa or minimal lesions. Four cases were refractory to conservative treatment (mesalamine and antibiotics) and surgery was required. No cases of extension of colonic inflammation in diverticula-free areas were found. CONCLUSIONS: Segmental colitis associated with diverticulosis is not a rare disorder. It may occur with a spectrum of clinical and histologic features and may be confused with ulcerative colitis. The majority of the cases respond to medical therapy with antibiotics and/or mesalamine, whereas few cases are refractory and need surgery. No evolution to inflammatory bowel disease was observed.

Role of thrombotic vascular risk factors in inflammatory bowel disease.

Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). It is recognized that a hypercoagulable state exists in IBD which involves all components of the clotting system. It has been suggested that this hypercoagulable state is closely linked to the disease pathogenesis. Recent studies have shown that genetic defects such as factor V Leiden mutation and C677T methylenetetrahydrofolate reductase polymorphism associated with hyperhomocysteinemia seem to interfere in the thrombotic manifestations of IBD. Acquired factors such as antiphospholipid antibodies could also participate in the development of the thrombotic process. Deficiencies of other anticoagulant factors play a less important role in the thrombosis, and therefore it is not surprising that the results on these factors in IBD are contradictory. In conclusion the resultant gene-gene and gene-environment interactions between risk factors are the key to the understanding of why an IBD patient develops thrombosis at a specific point in time.

Appendectomy and the development of ulcerative colitis: results of a metaanalysis of published case-control studies.

OBJECTIVE: Numerous epidemiological studies have been performed to determine risk factors that might contribute to the development of ulcerative colitis (UC). Recent studies have focused on the role of appendectomy in the disease's pathogenesis. This report aims to review and analyze the degree of evidence from recent published studies. METHODS: Medline and Embase databases were scrutinized for studies published between 1987 and January 1999. Reference lists from published articles, reviews, and abstracts from major gastrointestinal (GI) meetings were also reviewed. All studies specifically designed to evaluate the association between appendectomy and UC were selected. Thirteen studies that satisfied our selection criteria were evaluated by metaanalysis. RESULTS: The 13 case-control studies collectively gathered evidence from 2770 patients with UC and 3352 controls. Combining the results of the individual studies gave an overall odds ratio of 0.307 (95% confidence interval [CI] = 0.249-0.377) in favor of appendectomy (p<0.0001). This suggests that appendectomy gives a 69% reduction in the risk of developing UC (95% CI = 62%-75%). The test for heterogeneity (of all 13 studies) was not significant (chi2 = 16.213, d.f. = 12, p>0.10). The influence of potential confounding factors (mainly smoking) on these results could be excluded. CONCLUSIONS: The review of the literature and the metaanalysis of the selected studies suggest that the inverse association between appendectomy and UC is strong and consistent. Further studies are needed to establish whether a causal relationship exists.

Role of acquired and hereditary thrombotic risk factors in colon ischemia of ambulatory patients.

BACKGROUND & AIMS: Hypercoagulable states may play an important role in the pathogenesis of colon ischemia. Aim of this study was to assess this hypothesis investigating the role of acquired and hereditary thrombotic risk factors in patients with definite diagnosis of colon ischemia. METHODS: We compared the frequency of antiphospholipid antibodies, protein C, protein S, and antithrombin deficiencies, factor V Leiden, prothrombin gene mutation G20210GA, and methylenetetrahydrofolate reductase C677T in 36 patients (23 men, 13 women; mean age, 64.8 years) with colon ischemia, 18 patients with diverticulitis, and 52 healthy controls. RESULTS: The prevalence of antiphospholipid antibodies was significantly higher in patients with colon ischemia compared with inflammatory and healthy controls (19.4% vs. 0% and 1.9%). Among genetic factors, only factor V Leiden was significantly associated with colon ischemia (22.2% vs. 0% and 3.8%). A combination of thrombophilic disorders was found in 25% of the cases. Overall, one or several prothrombotic abnormalities were present in 26 patients (72%). CONCLUSIONS: A comprehensive thrombophilic screening in colon ischemia reveals a congenital or acquired thrombophilic state in 72% of patients. Hereditary and acquired thrombotic risk factors may play an important role in the disease pathogenesis.

Anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Anti-cardiolipin (aCL) antibodies have been shown to be associated with thrombosis. Recently, the antibodies against the anti-cardiolipin cofactor beta2-glycoprotein I (a(beta2)GPI) have been found with higher specificity for thrombosis. The presence of these antibodies was assessed in 128 patients with IBD [83 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)] and 100 healthy controls (blood donors). Patients with UC and CD had a significantly higher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (HC) (3%). Eleven IBD patients (8.6%) but no HC had a(beta2)GPI. None of the IBD patients with a history of thrombosis had aCL and only one of them (a UC patient with deep vein thrombosis of the right leg) had a high titer of IgG a(beta2)GPI. In conclusion, these data show that both aCL and a(beta2)GPI are significantly associated with IBD but further studies are needed to determine the significance of our findings.