Mucosal gene expression changes induced by anti-TNF treatment in inflammatory bowel disease patients.

In the last two decades anti-tumor necrosis factor (anti-TNF) therapy for inflammatory bowel disease (IBD) has been widely used to induce and maintain clinical and endoscopical remission, completely changing management of the disease. In this study, we aimed to identify gene expression changes in inflamed mucosa from Crohn's disease and ulcerative colitis patients treated with 5-aminosalicylic acid (5-ASA) (N = 25) or anti-TNF agents (N = 12) compared to drug-free IBD patients (N = 12) and non-IBD control subjects (N = 18). The mucosal expression of 84 genes previously associated with IBD was evaluated by qPCR. We found that both therapeutic regimens induce a decrease in LCN2, NOS2, and TFF1, the levels of which are overexpressed in drug-free patients compared to non-IBD control subjects. Interestingly, a stronger effect of anti-TNF drugs was observed on LCN2 and TFF1 levels. However, 5-ASA seems to induce a more robust reduction of NOS2 expression. Moreover, we found that anti-TNF treatment significantly increased ABCB1, leading to levels similar to those found in non-IBD control subjects.

Massive Hematochezia Secondary to Rectal Enema Injury: The Role of Sengstaken-Blakemore Tube for Hemostasis When Endoscopy Fails.

In rare instances, rectal cleansing enemas may cause rectal injury, precipitating lower gastrointestinal hemorrhage (LGIH). In a subset of LGIH cases, the bleeding diathesis may fail to respond to traditional treatment modalities and can be life-threatening. We present a case of an 84-year-old female with cleansing enema induced rectal bleeding - she was a poor surgical candidate and due to lack of access to in-house interventional radiology teams, hemostasis was attempted with sui generis use of the Sengstaken-Blakemore tube. Our transanal application of the Sengstaken-Blakemore tube for the management of LGIH contributes further evidence supporting the use of balloon tamponade in achieving hemostasis in select patients when traditional therapeutic modalities are unavailable.

Capecitabine-Induced Terminal Ileitis: Case Report and Literature Review.

Capecitabine is a well-established agent for adjuvant chemotherapy in breast and colorectal cancers. However, one of the limiting adverse events of this therapy is severe diarrhea, which is reported with increasing frequency as of late. Capecitabine-induced ileitis should be suspected in cases with severe, treatment-refractory diarrhea. We present a case of capecitabine-induced terminal ileitis in a patient who received the medication as adjuvant therapy for previously resected colon adenocarcinoma. Capecitabine-induced diarrhea secondary to ileitis is a severe adverse drug event, which occurs during adjuvant chemotherapy and does not respond to conservative treatment with antidiarrheals, often necessitating permanent drug withdrawal. A high index of suspicion is critical as the complications, such as dehydration and the associated electrolyte derangements, may be life-threatening if diagnosis and cause-specific treatment are delayed.

Preliminary Study Regarding the Association between Tumor Necrosis Factor Alpha Gene Polymorphisms and Childhood Idiopathic Nephrotic Syndrome in Romanian Pediatric Patients.

BACKGROUND: Childhood idiopathic nephrotic syndrome (INS) is one of the most common glomerular diseases, characterized by heavy proteinuria, hypoalbuminemia, dyslipidemia and generalized edema. Although some progresses were made regarding the pathogenesis of this disease, there are a lot of questions still left unanswered. Some of them involve the implications of several cytokines, including tumor necrosis factor alpha (TNF-alpha), in the development and clinical course of INS. OBJECTIVE: Our objective was to analyze the role of two single nucleotide polymorphisms of TNF-alpha gene in the development of pediatric INS and their implication in the response to corticosteroid therapy. MATERIAL AND METHODS: Seventy patients with INS and 159 healthy controls were included in this study. They were analyzed for TNF-alpha gene polymorphisms by using polymerase chain reaction. The two SNPs (rs1799724/-857C/T and rs1800629/-308G/A) were genotyped by TaqMan Genotyping Assays, association tests were performed and p values <0.05 were considered significant. RESULTS: Minor alleles frequencies were 15.72% in INS patients versus 18.55% in controls for 857*T allele and 11.43% in INS versus 13.2% in controls for 308*A allele. Although the minor alleles were more frequent in controls than in patients, the difference was not statistically significant (p=0.46, OR=0.818 and p=0.59, OR=0.848).Analyzing the response to corticosteroid therapy, we found a low frequency of 857*T allele in steroid resistant patients (9.09%) compared to steroid sensitive patients (16.95%) and controls (18.55%). Regarding 308*A allele, the frequencies were 18.18% in the corticoresistant group and 10.17% in the corticosensitive one. None of them was statistically significant (p>0.05). CONCLUSIONS: We conclude that neither -857C/T, nor-308G/A polymorphisms of TNF-alpha gene are associated with the susceptibility and response to steroid treatment of INS in our population. Given the small sample size used, future studies are necessary to clarify the results observed in the present study.