Crohn’s disease of the appendix

Although appendectomy is often the first surgical procedure in patients with Crohn's disease (CD), only few data exist on appendiceal CD. The aim of this study was to analyze appendices of CD patients undergoing surgery. We analyzed 149 specimens from consecutive patients with CD who underwent primary right ileocolonic or (sub)total colonic resection. The appendix was present in 90 resection specimens. Histologic findings were compared with those of 180 age and sex matched controls. Thirty-six appendices showed histologic signs of CD (40%): A transmural inflammation was found in 24 cases (67%), and a mucosal inflammation in 12 cases (33%). Histologic hallmarks of mucosal involvement were focal or discontinuous inflammation with crypt distortion and a histiocytic and lymphocytic predominant inflammation. Furthermore, epitheloid granulomas and erosions or ulcers with abundant histiocytes at the lesions base were observed. In comparison to controls luminal obliteration was significantly overrepresented in CD whereas acute phlegmonous appendicitis was underrepresented ( P<0.01). Patients with CD of the appendix showed a more widespread colonic involvement than those without ( P<0.01). This study shows that CD of the appendix exhibits specific histologic features that allow a differentiation from non-CD-associated appendicitis. CD-associated appendicitis is a frequent event, probably signifying a more widespread colonic involvement.     

Adalimumab in Crohn’s Disease

Adalimumab is a subcutaneously administered, recombinant, human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). The clinical efficacy and safety of adalimumab in patients with moderate to severe Crohn's disease has been demonstrated in four pivotal, randomized, double-blind trials (CLASSIC-I, GAIN, CHARM, and CLASSIC-II) that included a total of >1400 patients. In the CLASSIC-I trial, adalimumab was significantly more effective than placebo for induction of remission in patients who had not previously received anti-TNF therapy. Adalimumab was also more effective than placebo for induction of remission in the GAIN study in patients who had either lost responsiveness or developed intolerance to infliximab. The CHARM trial showed that, among patients who responded to open-label adalimumab induction, maintenance therapy with adalimumab 40 mg weekly or every other week for up to 1 year was associated with significantly greater remission rates than placebo at weeks 26 and 56. In addition, significantly more adalimumab than placebo recipients achieved corticosteroid-free remission and had complete fistula closure. In CLASSIC-II, an extension of the CLASSIC-I trial, patients who were in remission after a short course of adalimumab and were randomized to receive up to 1 year's treatment with adalimumab 40 mg weekly or every other week were significantly more likely to remain in remission than those randomized to receive placebo. In general, the tolerability profile of adalimumab in patients with Crohn's disease was similar to that in patients with rheumatoid arthritis or other approved indications.     

Oxidative stress and regulated cell death in Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Motor deficits usually associated with PD correlate with dopaminergic axonal neurodegeneration starting at the striatum, which is then followed by dopaminergic neuronal death in the substantia nigra pars compacta (SN), with both events occurring already at the prodromal stage.We will overview the main physiological characteristics responsible for the higher susceptibility of the nigrostriatal circuit to mitochondrial dysfunction and oxidative stress, as hinted by the acting mechanisms of the PD-causing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Then, we will present multiple lines of evidence linking several cell death mechanisms involving mitochondria and production of reactive oxygen species to neuronal loss in PD, namely intrinsic and extrinsic apoptosis, necroptosis, ferroptosis, parthanatos and mitochondrial permeability transition-driven necrosis. We will focus on gathered data from postmortem PD samples and relevant in vivo models, especially MPTP-based models.     

Natalizumab for the treatment of Crohn’s disease

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disorder characterized by immune-mediated destruction of the salivary and lacrimal glands with unknown etiology. Due to recent research utilizing human subjects as well as laboratory animal models, our understanding of the pathophysiological and immunological mechanisms of pSS has made great strides. As a consequence, targeted, immune-based therapies are gaining increased attention as the ideal way to conquer autoimmune diseases like pSS. Currently, however, there is no effective treatment to target specific immunological events or effector immune cells in the pathogenesis of pSS (discussed in other reviews of the current issue). Here, we summarize our current understanding and knowledge of the roles of monocytes/macrophages in the pathogenesis of pSS. Human studies, especially utilizing salivary gland biopsies, demonstrate the infiltration of macrophages and its correlation with disease severity. Moreover, animal model studies have shown the functional involvement of macrophages in promoting the ocular component of pSS.     

Vedolizumab for the treatment of Crohn’s disease

Introduction: Crohn’s disease (CD) is an immune-mediated condition characterized by inflammation of the gut tissue, associated with progressive damage of the affected intestinal tract and possible complications. A treat-to-target approach is strongly advocated, consisting of early and aggressive inflammatory control. However, a great proportion of affected subjects lack response or are intolerant to conventional therapy. Even though the first-line biologic therapy targeting tumor necrosis factor-alfa (TNF-α) is associated with improvement of inflammation in some patients, others do not respond at first or lose response over time. These findings brought about the possibility of different mechanisms being involved in perpetuating the chronic inflammatory state. Novel drugs targeting different inflammatory pathways have been studied in CD, specifically addressed to leucocyte trafficking.

Areas covered: We aim to review the relevant data available in the literature and briefly summarize the efficacy and safety profile of vedolizumab in the treatment of CD.

Expert commentary: Vedolizumab has shown, from pivotal and real-life data, significant clinical benefit among CD patients, in addition to a singular safety profile. Future studies will provide helpful data concerning its use in special situations.     

Antibiotic Use in Crohn’s Disease

On the assumption that bacteria in the gut may be a cause of symptoms and/or complications of Crohn's disease, various antibiotics are efficaciously employed in some affected patients. However, we do not know exactly why and how they are helpful. A possible explanation is that one or several bacterial species may have a primary role in the aetiology of Crohn's disease, but this is not supported by the data in our possession. Another hypothesis is that intestinal bacteria may cause flare-up of the disorder, either by inducing intestinal lesions or by an interaction with the immune system, but we know today that specific pathogens can cause flares only in a minority of cases. On the contrary, there is considerable evidence that the intestinal microflora and its products may amplify and perpetuate inflammation in Crohn's disease. Despite the fact that few controlled trials have been conducted, and have shown inconclusive results, antibiotics are widely employed for improving symptoms and for inducing remission of active phases. At present, a combination of metronidazole and ciprofloxacin, active against many enteric bacteria, has proved to be effective in the treatment of Crohn's disease complications. This therapy also seems to be effective in acute flares as an alternative to, or in combination with, corticosteroids.     

Certolizumab Pegol in Crohn’s Disease

Certolizumab pegol is a pegylated humanized Fab' fragment of an anti-tumor necrosis factor-alpha (TNFalpha) monoclonal antibody, which binds with high affinity to both membrane-bound and soluble TNFalpha and demonstrates high neutralizing potency for these factors. The elimination half-life of certolizumab in humans has been extended to approximate/= 2 weeks through pegylation, allowing subcutaneous administration of this agent once every 4 weeks. Subcutaneous certolizumab pegol 400mg once every 4 weeks (with an additional 400mg dose at week 2) was effective as induction and maintenance therapy in patients with moderate to severe Crohn's disease in whom baseline serum C-reactive protein levels were >/=10 mg/L, according to data from two well designed, randomized phase III trials. Certolizumab pegol was, in general, well tolerated, and adverse events associated with the drug were of a mild to moderate nature; no instances of lupus were reported in any of the trials.     

Cardiac and autonomic function in patients with Crohn’s disease during remission

Purpose

The aim of the study was to assess cardiac and autonomic function in patients with Crohn’s disease and explore their relation to disease duration using cardiovascular reflex tests.

Significant association of strictures and internal fistula formation in Crohn’s disease

Intestinal inflammation in Crohn’s disease (CD) may be complicated by the occurrence of strictures and fistulae. The pathogenesis of fistula formation is unknown. We therefore wanted to determine whether mechanical factors might contribute to the development of fistulae. Furthermore, we tried to define the path of internal fistulae through the muscular layer. For this purpose, surgical resection specimens from 42 consecutive patients with CD were prospectively studied. In gross examination the whole bowel was cut into circumferential cross sections 0.3 cm thick. Abnormal areas were histologically examined. Strictures were found in 38 patients (90.5%), and fistulae were observed in 27 (64.3%) patients. In 11 (40.7%) specimens fistulae were found within a stricture, in 15 (55.6%) at the proximal end, and in 1 (3.7%) no stricture was found. In 7 (25.9%) cases with fistulae, herniated mucosa was found within the muscularis propria or the subserosa. In 7 (25.9%) cases a blood vessel was identified near a fistula traversing the muscularis propria. From these findings we conclude that that mechanical factors may contribute to fistula formation. This is further supported by the fact that fistulae appear to traverse the muscular layer along piercing vessels. Received: 21 January 2000 / Accepted: 7 March 2000     

Certolizumab pegol for the treatment of Crohn’s disease

Certolizumab pegol is a polyethylene glycolated FAb’ fragment of a humanized anti-TNF-α monoclonal antibody. This pegylated molecule binds with circulating TNF-α and forms an inactive complex that is then eliminated from the body. The drug has been shown to be better than placebo in the treatment of Crohn’s disease and maintaining a clinical response in adult patients with moderate-to-severe active disease who have had an inadequate response to conventional therapy, and the treatment of adults with moderately to severely active rheumatoid arthritis. Comparative trials with an active control group are lacking. The most common adverse reactions include abdominal pain, diarrhea, injection site reactions and infection. All necessary live and attenuated vaccines should be given prior to the initiation of certolizumab pegol therapy, patients should be evaluated for TB risk factors and tested for latent TB prior to initiating therapy, and the initiation of therapy should be avoided if the patient has an active infection. Concomitant use with anakinra is not recommended because of the increased risk of serious infections and neutropenia. Therapy should be discontinued if the patient develops a serious infection during therapy.     

Natalizumab: a promising treatment for Crohn’s disease

A primary feature contributing to the pathology of Crohn’s disease (CD) is inappropriate and persistent recruitment and migration of circulating leukocytes from the bloodstream to affected tissues and organs. These processes are mediated by interactions between α₄ integrin adhesion molecules expressed on leukocyte surfaces and cognate receptors on vascular endothelial cells. Natalizumab is a humanized immunoglobulin G₄ monoclonal antibody against α₄ integrins. Natalizumab has demonstrated efficacy in inducing and maintaining sustained remission in patients with moderately to severely active CD, including those intolerant of or unresponsive to infliximab. Maintenance therapy with natalizumab in adult patients allowed elimination of steroids in a significant number of patients and sustained patients’ quality of life. Natalizumab has been well tolerated in the majority of patients. However, progressive multifocal leukoencephalopathy, a rare opportunistic infection associated with the JC polyomavirus, occurred in three natalizumab-treated patients; two multiple sclerosis patients and one CD patient. This article reviews the properties of natalizumab and addresses its potential benefits and risks in the treatment of CD.     

Effect of fuzzy partitioning in Crohn’s disease classification: a neuro-fuzzy-based approach

Crohn’s disease (CD) diagnosis is a tremendously serious health problem due to its ultimately effect on the gastrointestinal tract that leads to the need of complex medical assistance. In this study, the backpropagation neural network fuzzy classifier and a neuro-fuzzy model are combined for diagnosing the CD. Factor analysis is used for data dimension reduction. The effect on the system performance has been investigated when using fuzzy partitioning and dimension reduction. Additionally, further comparison is done between the different levels of the fuzzy partition to reach the optimal performance accuracy level. The performance evaluation of the proposed system is estimated using the classification accuracy and other metrics. The experimental results revealed that the classification with level-8 partitioning provides a classification accuracy of 97.67 %, with a sensitivity and specificity of 96.07 and 100 %, respectively.