Epameinondas V. Tsianos

The new global map of human brucellosis

The epidemiology of human brucellosis, the commonest zoonotic infection worldwide, has drastically changed over the past decade because of various sanitary, socioeconomic, and political reasons, together with the evolution of international travel. Several areas traditionally considered to be endemic--eg, France, Israel, and most of Latin America--have achieved control of the disease. On the other hand, new foci of human brucellosis have emerged, particularly in central Asia, while the situation in certain countries of the Near East (eg, Syria) is rapidly worsening. Furthermore, the disease is still present, in varying trends, both in European countries and in the USA. Awareness of this new global map of human brucellosis will allow for proper interventions from international public-health organisations.

The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations.

Principal changes with respect to the 2004 ECCO guidelines Ileocolonoscopy is recommended within the first year after surgery where treatment decisions may be affected (Statement 8C). Thiopurines are more effective than mesalazine or imidazole antibiotics alone in post-operative prophylaxis (Statement 8F). ### 8.1 Epidemiology of post-operative Crohns disease In the natural history of CD, intestinal resection is almost unavoidable since about 80% of patients require surgery at some stage. Surgery is unfortunately not curative as the disease inexorably recurs in many patients. The post-operative recurrence rate varies according to the definition used: clinical, endoscopic, radiological, or surgical. It is lowest when the repeat resection rate is considered, intermediate when clinical indices are used and highest when endoscopy is employed as the diagnostic tool.1–10 Data from endoscopic follow-up of patients after resection of ileo-caecal disease have shown that in the absence of treatment, the post-operative recurrence rate is around 65–90% within 12 months and 80–100% within 3 years of the operation. The clinical recurrence without therapy is about 20–25%/year.1,10 It has been demonstrated that the post-operative clinical course of CD is best predicted by the severity of endoscopic lesions. Symptoms, in fact, appear only when severe lesions are present and it is not uncommon to observe patients with fairly advanced recurrent lesions at endoscopy who remain asymptomatic.1 For these reasons, clinical indices such as the CDAI have low sensitivity at discriminating between patients with or without post-operative recurrence.11 These data mandate strategies aimed at interrupting or delaying the natural course of post-operative recurrence. Several medications have been tried in an attempt to prevent post-operative recurrence, mostly with disappointing results. The aim of this Consensus was therefore critically to evaluate the optimal strategies for the management of post-operative recurrence in CD. Most, if not all, of the evidence available deals with …

Differential Effects of NOD2 Variants on Crohn's Disease Risk and Phenotype in Diverse Populations: A Metaanalysis

OBJECTIVES:Three variants of the CARD15/NOD2 gene (SNP8, SNP12, and SNP13) have been associated with Crohns disease (CD). We assessed the impact of NOD2 variants on the CD risk across diverse populations and examined possible associations with disease phenotype.METHODS:We performed a metaanalysis searching MEDLINE and EMBASE (last search 05/2004) and contacting field experts.RESULTS:Forty-two eligible studies contributed data on 206 comparisons. No variants were detected in Asians. In non-Jewish descent Caucasians carriage of SNP8, SNP12, or SNP13 had an odds ratio (OR) for CD of 2.20 (95% CI: 1.84–2.62), 2.99 (95% CI: 2.38–3.74), and 4.09 (95% CI: 3.23–5.18), respectively. For Jewish descent patients the corresponding ORs were 1.74, 1.93, and 2.45, respectively. The OR in carriers of at least two alleles was 17.1 (95% CI: 10.7–27.2). Large studies tended to yield more conservative estimates than smaller studies, so publication or other bias cannot be excluded. Among CD patients, carrying at least one high-risk variant increased slightly the risk for familial disease (OR = 1.49, (95% CI: 1.18–1.87)), modestly the risk of stenosing CD (OR = 1.94, (95% CI: 1.61–2.34)), and more prominently the risk of small bowel involvement (OR = 2.53, (95% CI: 2.01–3.16)).CONCLUSIONS:SNP8, SNP12, and SNP13 have differential effects on CD risk, with SNP13 having the strongest genetic effect. These NOD2 variants are also significant risk factors for CD phenotype, in particular ileal location.

East–West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort

Objective The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East–West gradient in the incidence of IBD in Europe exists. Design A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. Results 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohns disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100 000 in 2010 for CD were 6.5 (range 0–10.7) in Western European centres and 3.1 (range 0.4–11.5) in Eastern European centres, for UC 10.8 (range 2.9–31.5) and 4.1 (range 2.4–10.3), respectively, and for IBDU 1.9 (range 0–39.4) and 0 (range 0–1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. Conclusions An East–West gradient in IBD incidence exists in Europe. Among this inception cohort—including indolent and aggressive cases—international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Does pregnancy change the disease course? A study in a European cohort of patients with inflammatory bowel disease

BACKGROUND AND AIMS:Inflammatory bowel disease (IBD) often affects patients in their fertile age. The aim of this study was to describe pregnancy outcome in a European cohort of IBD patients. As data are limited regarding the effect of pregnancy on disease course, our second objective was to investigate whether pregnancy influences disease course and phenotype in IBD patients.METHODS:In a European cohort of IBD patients, a 10-yr follow-up was performed by scrutinizing patient files and approaching the patients with a questionnaire. The cohort comprised 1,125 patients, of whom 543 were women. Data from 173 female ulcerative colitis (UC) and 93 Crohns disease (CD) patients form the basis for the present study.RESULTS:In all, 580 pregnancies, 403 occurring before and 177 after IBD was diagnosed, were reported. The rate of spontaneous abortion increased after IBD was diagnosed (6.5% vs. 13%, p = 0.005), whereas elective abortion was not significantly different. 48.6% of the patients took medication at the time of conception and 46.9% during pregnancy. The use of cesarean section increased after IBD diagnosis (8.1% vs 28.7% of pregnancies). CD patients pregnant during the disease course, did not differ from patients who were not pregnant during the disease course regarding the development of stenosis (37% vs 52% p = 0.13) and resection rates (mean number of resections 0.52 vs 0.66, p = 0.37). The rate of relapse decreased in the years following pregnancy in both UC (0.34 vs 0.18 flares/yr, p = 0.008) and CD patients (0.76 vs 0.12 flares/yr, p = 0.004).CONCLUSIONS:Pregnancy did not influence disease phenotype or surgery rates, but was associated with a reduced number of flares in the following years.

Crohn’s disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort

Background: No previous correlation between phenotype at diagnosis of Crohn’s disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. Methods: Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. Results: Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30–2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10–3.14)) and males (SMR 1.79 (95% CI 1.11–2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32–3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80–2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. Conclusions: This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.

Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response

Background: Intensifying infliximab therapy is often practiced in Crohns disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval‐halving compared with dose‐doubling. Methods: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose‐doubling (10 mg/kg/8 weeks). Results: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose‐doubling and 56 received interval‐halving strategy. Early response to dose‐escalation was experienced by 86/112 (77%) patients in the dose‐doubling group compared with 37/56 patients (66%) in the interval‐halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8–3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose‐doubling group compared with 39% in the interval‐halving group (OR 1.5, 95% CI 0.8–2.9, P = 0.2). On multivariate analysis, predictors of long‐term response to escalation were a nonsmoking status, CD diagnosis between 16–40 years of age, and normal C‐reactive protein (CRP). Conclusions: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose‐doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose‐doubling strategy may be preferable to the interval‐halving strategy. (Inflamm Bowel Dis 2012;)

Axillary hidradenitis suppurativa successfully treated with infliximab in a Crohn’s disease patient

Accident and Emergency department after a road traffic accident. He reported that, 2 days earlier, he had started to hear male voices talking about him in a derogatory manner. He also described visual hallucinations taking the form of strangers sitting in his room conversing with him. He was unaware that these experiences could be related to his recent steroid therapy, and he refused to leave his house. On the day of the accident, he started taking alcohol to combat the hallucinations. Some time later, he reported hearing a knock at his door and described seeing a group of unknown men on his doorstep commanding him to rob a nearby petrol station. He described being distracted by seeing the intruders follow him in a car and, as a consequence, he crashed into a disused railway line. Surprisingly, he escaped with relatively minor injuries. He was admitted to the hospital and continued to experience both complex visual and auditory hallucinations, constantly needing reassurance from nursing staff. There was no evidence of any mood disturbance, disorientation or alteration of consciousness. Psychiatric assessment established a diagnosis of steroid-induced psychosis. He was commenced on haloperidol 2.5 mg t.i.d., lorazepam 2 mg as required, and his steroids were reduced. He responded rapidly and was completely free of psychotic symptoms within a week. He was discharged on prednisolone 15 mg daily and had remained well at 1-month follow-up. This case illustrates the potentially serious nature of psychiatric symptoms arising from steroid therapy. There is some evidence of a dose-related effect but little information regarding other risk factors. In one study, psychiatric symptoms were recorded in 1.3% of patients receiving more than 40 mg of steroids, 4.6% of those receiving 40 – 80 mg daily, and 18.4% in patients on doses higher than 80 mg daily (3). However, reports also exist of adverse effects after exposure to very low doses, and there does not appear to be a correlation between dose and time of onset or type of disorder (4). Moreover, there is no evidence to suggest that past psychiatric history, previous steroid induced psychiatric disorder, or specific medical disorders help to identify individuals at risk (5). Clearly, identifying risk factors and measures to prevent steroid-related psychiatric disorders require further study. However, in the absence of clear clinical predictors, physicians need to be aware of the range of psychiatric disorders arising in the context of steroid use. We would strongly recommend that all patients treated with steroids, particularly at higher doses, are educated as to possible psychiatric symptoms associated with steroid use. Ideally, assessment of mental state including cognitive assessment should be carried out at baseline and repeated once the patient commences therapy. If there is evidence of emerging psychopathology, then a psychiatric consultation may be indicated. Information facilitating informed consent in the usage of these drugs might obviate the level of distress arising for patients developing psychiatric symptoms and avoid potentially fatal outcomes.

Role of Surgery in the Prophylaxis of Hereditary Cancer Syndromes

Conventional surgery in the treatment of solid tumors suggests a recently declining trend. Endoscopic and laparoscopic techniques are increasingly replacing traditional surgery as both rates of early detection and minimal invasive treatment are steadily increasing. Premalignant lesions and early-stage small cancers confined to the mucosal layer along the whole gastrointestinal tract, from esophagus and stomach to the colorectum, can now curatively be resected by minimally invasive techniques substantially improving the quality of life of many patients. In contrast, traditional surgical resection of specific organs for the protection of individuals at very high risk of developing inherited cancer in the breast, colon, and stomach is increasingly receiving considerable attention. However, although surgery is the only preventive intervention able to eliminate the risk of cancer at a specific organ, surgical prophylaxis has been controversial, for a numerous amount of reasons and questions have been raised. Here we discuss the benefits and obstacles of prophylactic surgery. Hereditary cancer syndromes are rare. They account for less than 5% of all cases because most breast, colon, or gastric adenocarcinomas occur sporadically. These syndromes include hereditary nonpolyposis colon cancer syndrome, Peutz-Jeghers syndrome, Cowden syndrome, and some kindreds affected with Li-Fraumeni syndrome and familial adenomatous polyposis. 1 Mutations in BRCA1 and BRCA2 genes have been identified, 8 years

Value of anti-HBc screening of blood donorsfor prevention of HBV infection: results of a 3-year prospective study in Northwestern Greece

BACKGROUND: The risk of infection with transfusion‐transmitted viruses has been reduced remarkably. However, a zero‐risk blood supply remains a popular goal. Some authorities have introduced the screening for antibody to HBc (anti‐HBc) as a surrogate test for the presence of several infectious agents. A 3‐year prospective study was conducted in the Epirus region of Greece to determine the prevalence of several blood‐borne viruses. One component of the study was the prevalence of HBV infection markers and the potential value of anti‐HBc testing of donors in this area.