Discontinuation of Infliximab in Patients With Ulcerative Colitis Is Associated With Increased Risk of Relapse: A Multinational Retrospective Cohort Study.

BACKGROUND & AIMS: Infliximab is a safe and effective therapy for ulcerative colitis (UC). We conducted a multicenter retrospective cohort study that included 7 European countries and Israel to examine whether infliximab discontinuation can be considered for patients who achieve sustained remission. METHODS: We performed a retrospective cohort study, collecting medical records from 13 tertiary care referral inflammatory bowel disease centers of all patients with UC treated with infliximab (n = 193). We compared the disease course of patients with at least 12 months of clinical remission who discontinued infliximab (n = 111) with that of patients who continued scheduled treatment (controls, n = 82). We examined the incidence rates of relapse, hospitalization and colectomy, the comparative effectiveness of different therapeutic strategies after discontinuation, and assessed the rates of response, remission, and adverse effects after infliximab re-initiation. Statistical analyses used time-to-event methods. RESULTS: In the entire cohort, 67 patients (34.7%) relapsed during the follow-up period. The incidence rate of relapse was significantly higher after discontinuation (23.3 per 100 person-years) compared with the control group (7.2 per 100 person-years) in univariable analysis (log-rank P < .001; hazard ratio, 3.41; 95% confidence interval, 1.88-6.20) and multivariable analysis (hazard ratio, 3.70; 95% confidence interval, 2.02-6.77). Rates of hospitalization and colectomy did not differ between groups. Thiopurines appeared to be the best treatment option after infliximab discontinuation (incidence of relapse: 15.0 per 100 person-years for thiopurines, 27.4 per 100 person-years for thiopurines plus aminosalicylates, and 31.2 per 100 person-years for aminosalicylates alone; log-rank P = .032). Response was regained in 77.1% of patients and remission in 51.4% of patients who re-initiated infliximab. However, 17.1% had infusion reactions and 17.1% reported other adverse events. CONCLUSIONS: In a multinational retrospective cohort study of patients with UC in sustained clinical remission, we associated discontinuation of infliximab with an increased risk of relapse. Treatment re-initiation is effective and safe.

An unusual site for calciphylaxis: a case report.

BACKGROUND: Calciphylaxis is a rare condition characterized by calcification of the tunica media of small arteries with or without endovascular fibrosis, extravascular calcification and vascular thrombosis, leading to tissue ischemia and hence necrosis of tissues supplied by respective vessel. CASE REPORT: An 83-year-old lady presented with a 2-week history of rapidly progressing painful necrotic vulval lesion. This patient was being treated medically with bisphosphonates for mild hypercalcaemia secondary to a parathyroid adenoma. The diagnosis of calciphylaxis was made by biopsy of lesion, revealing extensive necrotic areas and multiple abscesses with numerous thrombosed and calcified blood vessels. CONCLUSIONS: This case shows an unusual presentation of calciphylaxis, in a patient with primary hyperparathyroidism, in the absence of end stage renal failure. The pathogenesis of the condition is still relatively unknown. Particularly of note in this case is the presentation of the lesion 9 months after the start of treatment with bisphosphonate after the relative decrease of serum parathyroid levels and serum calcium levels. This leads to the question of initiation of the pathology - did the bisphosphonate treatment have an input in initiation of the lesion? The case under review adds a new differential diagnosis to necrotic vulval lesions, other than malignancy.

Identification of antibiotic resistance patterns in Helicobacter pylori strains isolated from gastric biopsies using real-time PCR and genotypic analysis.

BACKGROUND: Helicobacter pylori (H. pylori) is associated with dyspepsia, mucus-associated lymphoid tissue lymphoma, gastritis, and peptic ulcer disease. Treatment in Malta consists of triple therapy, which consists of a proton pump inhibitor and 2 of the antibiotics amoxicillin, clarithromycin, metronidazole and fluoroquinolones. We aimed to determine the resistance rates for clarithromycin and fluoroquinolones in patients with H. pylori, and its incidence, in patients undergoing an esophagogastroduodenoscopy (EGD) using real-time polymerase chain reaction (RT-PCR). METHODS: Patients undergoing an EGD were recruited. A rapid urease test (RUT) was performed, and 4 gastric biopsies were also taken (2 from antrum, 2 from corpus) and analyzed using RT-PCR. Positive samples were tested for antibiotic resistance using amplification and reverse hybridization techniques. RESULTS: Two hundred patients (mean age 53.6 [range 20-92] years; 53.1% female) were recruited; the majority were (78%) non-smokers. H. pylori was identified in 21.0% of the patients. Fluoroquinolone resistance was detected in 21.4% of the patients. Clarithromycin resistance was observed in 26.2%, with dual resistance identified in 4.8% of the patients. A high concordance was present with patients testing negative for H. pylori with both RUT and RT-PCR (94.3%). Only 57.6% of patients tested positive with both tests. However, 92.9% of RT-PCR positive patients had a positive genotype HelicoDR test. CONCLUSIONS: This data demonstrates a high rate of H. pylori resistance to both clarithromycin and fluoroquinolones. These should be avoided when treating H. pylori by utilizing different treatment regimes. Furthermore, we derived important data on the role of RT-PCR, which may be implemented in routine clinical practice.

The role of multimodal treatment in Crohn's disease patients with perianal fistula: a multicentre retrospective cohort study.

BACKGROUND: Treatment paradigms for Crohn's disease with perianal fistulae (CD-pAF) are evolving. AIMS: To study the impact of multimodality treatment in CD-pAF on recurrence rates and the need for re-interventions and to identify predictive factors for these outcomes. METHODS: This was a multinational multicentre retrospective cohort study. Multimodality approach was defined as using a combination of medical treatments (anti-TNFs ± immunomodulators ± antibiotics) along with surgical approach (examination under anaesthesia (EUA) ± seton drainage) at diagnosis of CD-pAF. Univariable and multivariable analyses were performed for variables indicative of the need for reintervention. RESULTS: A total of 253 patients were included. 65% of patients received multimodality approach. Multimodality treatment resulted in complete fistula healing in 52% of patients. Re-intervention was needed in 27% of patients with simple and in 40.3% of those with complex fistula. On multivariable analysis multimodality treatment (OR: 0.35, 95% CI: 0.17-0.57, P = 0.001), seton removal (OR: 0.090, 95% CI: 0.027-0.30, P = 0.0001, therapy with infliximab (OR: 0.19, 95% CI: 0.06-0.64, P = 0.007), and therapy with adalimumab (OR: 0.12, "95% CI: 0.026-0.56, P = 0.007) were predictive of avoiding repeat surgery. Proctitis (OR: 3.76, 95% CI: 1.09-12.96, P = 0.03) was predictive of the need for radical surgery (proctectomy, diverting stoma) while multimodality treatment reduced the need for radical surgery (OR: 0.21, 95% CI: 0.05-0.81, P = 0.02). CONCLUSIONS: Multimodality treatment, anti-TNFs use, and removal of setons after multimodality treatment can result in improved outcomes in CD patients with perianal fistulae and reduce the need for repeat surgery and radical surgery.

Clinical utility and diagnostic accuracy of faecal calprotectin for IBD at first presentation to gastroenterology services in adults aged 16-50 years.

BACKGROUND: Distinguishing inflammatory bowel disease (IBD) from functional gastrointestinal (GI) disease remains an important issue for gastroenterologists and primary care physicians, and may be difficult on the basis of symptoms alone. Faecal calprotectin (FC) is a surrogate marker for intestinal inflammation but not cancer. AIM: This large retrospective study aimed to determine the most effective use of FC in patients aged 16-50 presenting with GI symptoms. METHODS: FC results were obtained for patients presenting to the GI clinics in Edinburgh between 2005 and 2009 from the Edinburgh Faecal Calprotectin Registry containing FCs from >16,000 patients. Case notes were interrogated to identify demographics, subsequent investigations and diagnoses. RESULTS: 895 patients were included in the main analysis, 65% female and with a median age of 33 years. 10.2% were diagnosed with IBD, 7.3% with another GI condition associated with an abnormal GI tract and 63.2% had functional GI disease. Median FC in these three groups were 1251, 50 and 20 µg/g (p < 0.0001). On ROC analysis, the AUC for FC as a predictor of IBD vs. functional disease was 0.97. Using a threshold of ≥ 50 µg/g for IBD vs. functional disease yielded a sensitivity of 0.97, specificity of 0.74, positive predictive value of 0.37 and negative predictive value of 0.99. Combined with alarm symptoms, the sensitivity was 1.00. CONCLUSIONS: Implementation of FC in the initial diagnostic workup of young patients with GI symptoms, particularly those without alarm symptoms, is highly accurate in the exclusion of IBD, and can provide reassurance to patients and physicians.

Acute ischaemic ventricular inferoseptal defect in a pyretic patient: a diagnostic challenge.

A 78-year-old Caucasian male presented with a 5-day progressive history of fever, vomiting and dyspnoea. Initial clinical examination revealed fever, sinus tachycardia, hypotension, peripheral cyanosis and a systolic murmur. Investigations revealed a multiple organ dysfunction syndrome. A repeat trans-thoracic echocardiogram showed a basal inferoseptum aneurysm associated with an acquired ventricular septal defect not demonstrated on initial scan. An intra-aortic balloon pump was urgently inserted and he underwent surgical repair of the defect, 7 days after his initial presentation. He unfortunately died from postoperative complications.