Irit Chermesh

Failure of Synbiotic 2000 to Prevent Postoperative Recurrence of Crohn's Disease

Complications of Crohn’s disease (CD) lead to surgery in about 70–90% of patients. The majority of patients suffer from relapse of the disease. Colonic bacteria are essential to the development of CD. Therefore, a rationale exists in trying to prevent relapse by manipulation of gut microflora. This is feasible by treatment with probiotics or antibiotics. Synbiotic 2000 is a cocktail containing 4 probiotic species and 4 prebiotics. It is rational to pursue that it could be effective in preventing postoperative disease. We sought to check weather treatment with Synbiotic 2000 could prevent postoperative recurrence in patients with CD. This was a prospective multicenter, randomized study. Patients were randomized to active treatment or placebo in a 2:1 ratio. Follow-up consisted of endoscopic, clinical, and laboratory parameters. Thirty patients were enrolled. No differences were found between the 2 treatment groups regarding gender, age at diagnosis, age at surgery, weight, smoking status, type of disease, length of the resected segment, or medical treatment prior to surgery. No difference in either endoscopic or clinical relapse rate was found between patients treated with once daily dose of Synbiotic 2000 or placebo. In our small study, Synbiotic 2000 had no effect on postoperative recurrence of patients with CD. Larger studies in patients with the inflammatory type of CD undergoing surgery, using higher doses of probiotics cocktail might prove effective.

Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and clostridium difficile infection.

BACKGROUND & AIMS Management of Clostridium difficile infection in patients with flaring inflammatory bowel disease (IBD) has not been optimized. We investigated the effects of combination therapy with antibiotics and immunomodulators in patients with IBD and C difficile infection. METHODS We analyzed data from 155 patients (59% with ulcerative colitis [UC]) from a retrospective, European Crohns and Colitis organization, multi-center study comparing outcome of hospitalized IBD patients with C difficile infection who were treated with antibiotics (n = 51) or antibiotics and immunomodulators (n = 104). The primary composite outcome was death or colectomy within 3 months of admission, in-hospital megacolon, bowel perforation, hemodynamic shock, or respiratory failure. RESULTS The primary outcome occurred in 12% of patients given the combination treatment vs none of the patients given antibiotics alone (P = .01). UC, abdominal tenderness, or severe bloody diarrhea was more common among patients that received the combined therapy. However, multivariate analysis revealed that only the combination therapy maintained a trend for an independent association with the primary outcome (likelihood ratio = 11.9; CI, 0.9-157; P = .06). Treatment with 2 or 3 immunomodulators was correlated with the primary outcome, independent of disease severity at presentation (odds ratio [OR] = 17; CI, 3.2-91; P < .01). Acid-suppressing medications increased the risk of C difficile relapse (OR = 3.8; CI, 1.1-12.9; P = .03), whereas recent hospitalization correlated with increased rate of C difficile persistence (OR = 8; CI, 2.1-29; P = .002). CONCLUSIONS Patients with IBD that also have C difficile infection are frequently treated with a combination of antibiotics and immunomodulators. However, this combination tends to associate with a worse outcome than antibiotic therapy alone. Prospective controlled trials are urgently needed to optimize the management of these challenging patients.

Malnutrition in Surgical Wards: A Plea for Concern

Background. Malnutrition in hospitalized patients is underdiagnosed, with 30 to 60% of patients admitted being malnourished. The objective of this study was to investigate the nutritional status of patients in a general surgery ward and to define the correlation between the risk of malnutrition and the hospital course and clinical outcome. Study design. The study group included 100 consecutive patients admitted to a general surgery ward who were ambulant and could undergo the Malnutrition Universal Screening Tool (MUST). Results. Thirty-two patients (33%) had aMUST score of 2 or higher, and were therefore defined at high-malnutrition risk. The patients at risk had longer hospitalization and worse outcome. The length of stay of the malnourished patients was significantly longer than that of patients without malnutrition risk (18.8 ± 11.5 vs. 7 ± 5.3 days, P = .003). Mortality in the high-risk group was higher overall, in hospital, and after six months and one year of followup. Conclusions. Medical personnel must be aware that malnutrition afflicts even patients whose background is not suggestive of malnutrition. Best results are achieved when cooperation of all staff members is enlisted, because malnutrition has severe consequences and can be treated easily.

Thiopurine effectiveness in patients with Crohn's disease: a study of genetic and clinical predictive factors.

Background: Thiopurines are efficacious in the treatment of Crohns disease and were recently shown to induce T-cell apoptosis by modulation of Rac1 activation. To assess whether polymorphisms in Rac1 and other apoptosis-related genes, combined with clinical parameters, can predict response to thiopurines. Methods: A retrospective cohort of 156 thiopurine-treated patients with Crohns disease was genotyped for 11 single-nucleotide polymorphisms (SNPs): 9 SNPs in Rac1, 1 SNP in the Fas ligand −843 T>C, and 1 SNP in the Caspase-9 93 C>T. Clinical data were extracted from the medical charts. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between demographic, clinical, and genetic variables and thiopurine response rates were calculated. Results: The overall response rate to thiopurines was 74% (115/156). The Rac1 SNP rs34932801 heterozygote genotype GC was associated with a lower response rate compared with the wild-type GG genotype (46% versus 76%; OR = 0.26; 95% CI, 0.08–0.91; P = 0.036). Only wild-type homozygotes were found for 5 Rac1 SNPs. None of the other 3 Rac1 SNPs were associated with response to thiopurines. Patients with Montreal B3 behavior pattern responded worse than those with a B1 behavior pattern (59%, versus 80%; OR = 0.37; 95% CI, 0.17–0.83; P = 0.016). Sephardic Jews had a lower response rate to thiopurines compared with Jews of Ashkenazi or mixed ancestry (60% versus 82%; OR = 0.32; 95% CI, 0.15–0.69, P = 0.003). Conclusions: Rac1 SNP rs34932801carriage, Montreal B3 disease behavior, and a Sephardic Jewish origin were associated with unfavorable response to thiopurines. Corroboration of these associations in larger cohorts is warranted.

Capsule endoscopy in Crohn's disease - Indications and reservations 2008.

Capsule endoscopy (CE) was found to be an effective tool in diagnosis of small bowel pathology. This review will focus on its role in Crohns disease. Its role in patients with suspected Crohns disease (CD) is described. CE has an established role for diagnosing CD when other tests are negative, though it is not a first line investigative tool in these patients. Over diagnosis is of concern. Its use in established CD remains an open question. It can provide exact mapping of small bowel disease before surgery, and might have impact on the treatment of the disease. It may have role in monitoring mucosal healing, which is becoming a target of therapy, and may help establish the exact diagnosis in a limited group of patients with indeterminate colitis. Retention of CE might occur. It is of low rate in patients with suspected CD and higher in patients with known CD but clinical obstruction is extremely rare. Economic considerations are a limit to a wider application of the CE.

Dietary Therapy With the Crohn’s Disease Exclusion Diet is a Successful Strategy for Induction of Remission in Children and Adults Failing Biological Therapy

Background Loss of response [LoR] to biologics in Crohns disease [CD] is a significant clinical problem. Dietary therapy as a treatment strategy in this setting has not been previously reported. We report the use of dietary strategies using enteral nutrition coupled with the Crohns Disease Exclusion Diet [CDED] for LoR to infliximab or adalimumab as a single-centre experience. Methods Patients with LoR to a biologic despite dose escalation or combination therapy were treated with partial enteral nutrition [PEN] by a polymeric formula and the CDED for 12 weeks. Paediatric patients with severe flares received 14 days of exclusive enteral nutrition followed by PEN + CDED as above. All patients were seen at weeks 6 and 12 for follow up. Current and prior treatment, Harvey Bradshaw Index [HBI], C-reactive protein [CRP] and albumin were recorded. Remission was defined as HBI <5 at week 6. Results Twenty-one patients, mean age 22.1 ± 8.9 years [11 adults and ten children] met study criteria. Seventeen patients [81%] had used combination therapy, and 10/21 [47.6%] had failed a second biologic. Seven patients had a prior intestinal resection. Dose escalation had failed in 13/21 [62%] patients. Clinical remission by physicians global assessment and HBI after 6 weeks was obtained in 13/21 [61.9%]. Mean HBI decreased from 9.4 ± 4.2 to 2.6 ± 3.8 [p < 0.001], mean CRP decreased from 2.8 ± 3.4 to 0.7 ± 0.5 [p = 0.005] and mean albumin increased from 3.5 ± 0.6 to 3.8 ± 0.5 [p = 0.06]. Conclusion Dietary treatment combining PEN with the CDED may be a useful salvage regimen for patients failing biological therapy despite dose escalation.

Proactive screening in Israel identifies alarming prevalence of malnutrition among hospitalized patients—Action is needed

OBJECTIVE Malnourished patients suffer from higher morbidity and mortality rates than well-nourished patients do. However, few studies have controlled the outcomes for the underlying illnesses. Our aim was to determine the prevalence of malnutrition among patients admitted to the internal medicine ward and to determine whether malnutrition is an independent risk factor for adverse outcomes in these settings. METHODS Consecutive patients screened for malnutrition with the MUST (Malnutrition Universal Screening Tool), admitted to an internal medicine department, were included in this study. Demographic data, background disease, laboratory results, length of stay, and mortality rates were retrieved from the computerized file and Charlson Comorbidity Index (CCI) was calculated. Univariate and multivariate analyses were used to check for the association of malnutrition and outcome measures. RESULTS One thousand consecutive patients were included in the study. Mean age was 67.6 y; 25.4% of patients were found to be at high risk for malnutrition. Patients at high risk for malnutrition had significantly longer length of stay and mortality rates than well-nourished patients (9.7 d versus 6.2 d and 19.3% versus 3.2%; accordingly [P < 0.001]). On multivariate analyses, increased mortality was found to be associated with a high risk for malnutrition as well as pneumonia, acute myocardial infarction, acute renal failure, or shock on admission and a high CCI score. CONCLUSION The prevalence of malnutrition among hospitalized patients, as measured by the MUST score, is common. Malnutrition is prevalent and represents an independent and significant risk factor for in-hospital mortality and increased length of stay in patients admitted to the internal medicine ward.

Crohn’s Disease and SLC11A1 Promoter Polymorphism

Crohn’s disease (CD) is a chronic multifactorial inflammatory disease. The prevalence of CD in Ashkenazi Jews is higher than in Sephardic Jews. SLC11A1, also known as Nramp1, is a divalent cation antiporter essential for the elimination of intraphagosomal pathogens. SLC11A1 has seven alleles in the promoter region and previous studies have suggested an association between CD and SLC11A1. The aim of this study was to check for a possible association between SLC11A1 promoter alleles and CD in Ashkenazi Jewish patients. DNA samples from healthy Ashkenazi donors and Ashkenazi CD patients were obtained and analyzed for SLC11A1 promoter polymorphism by PCR and DNA sequencing. One hundred thirty-one samples from healthy donors and 131 samples from CD patients were analyzed. Four alleles were identified: ∼70% of the samples carried allele 3; ∼30%, allele 2; ∼1%, allele 1; and <1%, allele 5. There was no difference in allele frequencies between healthy donors and CD patients. No correlation was found between mutations in NOD2/CARD15 and the phenotype of CD. We conclude that the difference in SLC11A1 promoter polymorphism plays no role in CD in Ashkenazi Jews.

Outcome and Complications of Colonoscopy: A Prospective Multicenter Study in Northern Israel

Background. Colonoscopy for screening the population at an average risk of colorectal cancer (CRC) is recommended by many leading gastrointestinal associations. Objectives. The objective was to assess the quality, complications and acceptance rate of colonoscopy by patients. Methods. We prospectively gathered data from colonoscopies which were performed between October 2003 and September 2006. Patients were asked to return a follow-up form seven days after the procedure. Those who failed to do so were contacted by phone. Results. 6584 patients were included (50.4% males). The average age of subjects was 57.73 (SD 15.22). CRC screening was the main indication in 12.8%. Cecal intubation was achieved in 92% of patients and bowel preparation was good to excellent in 76.2%. The immediate outcome after colonoscopy was good in 99.4%. Perforations occurred in 3 cases—1 in every 2200 colonoscopies. Significant bleeding occurred in 3 cases (treated conservatively). 94.2% of patients agreed to undergo repeat colonoscopy in the future if indicated. Conclusions. The good quality of examinations, coupled with the low risk for complications and the good acceptance by the patients, encourages us to recommend colonoscopy as a primary screening test for CRC in Israel.

Malnutrition and Nutrition-Therapy: Our Neglected Responsibility

Around 30% of hospitalized patients in Europe are malnourished, and the figures for the community are also alarming. In certain diseases the proportion of malnourished patients can go up to 60%. The consequences of malnutrition are still neglected. The levels of knowledge and awareness of nutritional problems are low among all caregivers. Malnutrition is a heavy burden for the society, leading to increased morbidity, longer hospital stays, increased complications, decreased quality of life for the patients, and higher costs. Interventions to ensure appropriate nutritional care would be cost-effective. The impact of nutritional support is well known from many clinical trials. For each patient group specific nutritional recommendations are published in several reviews and guidelines. Although it is known how to do better, the nutritional support is often not regarded as an important therapeutic tool of the patients. In this issue several interesting papers summarize different important aspects related to malnutrition and nutritional support. The first paper describes the mechanism of cancer cachexia and the clinical implication and helps to understand why nutrition should be a central part in the management of cancer patients. It is well known that with an adequate nutritional support an increase of the quality of life can be achieved. Two further papers are dealing with nutritional aspects in the elderly. A large survey in Germany confirms the high prevalence of malnutrition in nursing homes. A significant number of orally and tube-fed patients were malnourished. The most important factors leading to malnutrition were analysed. Oropharyngeal dysphagia is a high prevalent problem in the elderly and is a leading factor for malnutrition and aspiration. The paper in this issue gives important information for diagnosing and the treatment for this clinically relevant problem. Three papers are related to surgical and ICU patients. Too often malnutrition is neglected in surgical patients. The clinical outcome is significantly different in malnourished patients compared to well-nourished controls. The paper on malnutrition in surgery wards confirms the importance of screening all surgical patients. 1/3 of the reported patients were malnourished, and the outcome was not as good compared to the patients not at nutritional risks. Elective surgery should be avoided until the nutritional deficits are corrected. In a further paper the perioperative nutritional support is described. Enteral nutrition was not given for long time to patients with acute pancreatitis because of the fear of worsening the outcome. This opinion has changed in the last decade. The importance and limits of enteral nutrition are well explained in this issue. In other three papers more general nutritional items are addressed. In the ICU hyperglycaemia is associated with poor outcome. Several interesting trials were published in the past on this specific problem. Until now the best blood sugar control is still debated. The review in this issue helps the reader to understand this controversial problem in more detail. In patients with severe malnutrition it is important to know that nutrition support can also be harmful if the refeeding syndrome is not considered. The paper on the refeeding syndrome is therefore very helpful for understanding and avoiding the refeeding problems. In nutritional practice the placing of a percutaneous endoscopy gastrostomy is very common. This procedure is done more and more on a propofol-based sedation. There are only few data on the safety of propofol-based sedation in the PEG procedure. The paper in this issue shows that propofol is a safe procedure if it is done according to the common guidelines. There is no significant difference in overall complication rates, sedation, and procedure-related complication. Obesity is also regarded as a form of malnutrition. Controlled weight loss is well recognized as to be beneficial to reduce complications in these patients. One paper in this issue reports data on a specific supplement on the effect on weight loss. The use of green coffee extract shows some promising effects but the available trials are of poor methodological quality. A general recommendation cannot be given now. The last paper is dealing with the important unhealthy Western diet. This diet is too high in n-6 polyunsaturated fatty acids (PUFA) and too low in n-3 PUFAs. We know that these diets can have negative effects on health. It is extremely important that all efforts should be undertaken to decrease this unhealthy diet in the future. Until now these important recommendations are not sufficiently implemented in the daily practice. This paper is therefore very important for promoting general health. We hope that the selected manuscripts help the readers to understand more the importance of recognizing the burden of malnutrition and to raise the awareness of the impact of nutritional support for the patients.  Irit Chermesh Lubos Sobotka Corina Hartman Remy Meier