Cytomegalovirus viral load in the colon and risk of colectomy in hospitalized patients with inflammatory bowel diseases

To the Editor: We read with interest the article of Lee et al1 describing the risk factors for adverse outcomes in hospitalized patients with ulcerative colitis (UC) with concurrent cytomegalovirus (CMV) colitis. CMV reactivation and resolution can be spontaneous in patients with UC regardless of antiviral therapy; however, inconsistencies between CMV detection methods of various studies and criteria for defining CMV positivity may be leading to these disparate findings.2,3 In the study by Lee et al, CMV colitis was defined by the presence of 1 or more inclusion bodies on hematoxylin and eosin staining or CMV immunohistochemistry on colonic biopsies. The most accurate approach for detection of clinically significant CMV infection has not been firmly established and guidelines differ in their recommendations.3,4 A recent study using quantitative colonic PCR in consecutive patients with UC undergoing endoscopy in the setting of a moderate to severe flare demonstrated a correlation between higher viral load and resistance to immunosuppressive therapy with significant differences found when using a cutoff viral load of .250 per milligram tissue.

Stagnant Loop Syndrome: A Rare Cause of Severe Malabsorption

Background: Intestinal bacterial overgrowth as a consequence of postsurgical anatomical abnormalities as well as other small bowel diseases can lead to malabsorption. Case Report: A female patient had several abdominal operations due to recurrent intestinal obstructions. Initially, she presented with severe megaloblastic anaemia. Subsequently, she suffered from weight loss, diarrhoea, oedema, recurrent anaemia (despite vitamin B12 substitution), and severe malabsorption of proteins, lipids, iron, and vitamins. Vague information about the performed surgeries, an anatomy of the bowel that was difficult to interpret, and an unusual cholestasis made it difficult to reach the diagnosis of bacterial overgrowth due to a stagnant loop syndrome. Treatment with antibiotics only temporarily improved the condition of the patient. After restoring bowel continuity and after the resection of an enteroenteric fistula as well as of a bowel conglomerate, the patient did not show any further symptoms. Conclusion: The history of this patient indicates that the diagnosis of a stagnant loop syndrome may be difficult. The primary goal regarding surgically created small intestinal bacterial overgrowth should be the correction of the underlying small intestinal abnormality, whenever possible

Ion therapy within the trimodal management of superior sulcus tumors: the INKA trial

Background: The standard trimodal treatment concept in locally advanced and non-metastasized non-small-cell superior sulcus tumors consists of a preoperative chemoradiation followed by surgical resection. High linear energy transfer (LET) radiation as, for example, C12 heavy-ion beam therapy theoretically offers biological advantages compared to high energy x-ray therapy as, for example, higher biological efficiency. Methods/Design: In the present prospective, single-armed, open pilot study performed at the Heidelberg Ion-Beam Therapy Center (HIT) in Heidelberg, the radiation treatment within the standard trimodal concept will be exchanged against C12 heavy-ion beam treatment and apply 39GyE in 13 single fractions in combination with a chemotherapy consisting of cisplatin and vinorelbine (local standard). The primary endpoint is feasibility and safety measured by the incidence of NCI-CTCAE grade 3/4 toxicity and/or discontinuation due to any reason. Secondary endpoint is the degree of regression in the histological specimen. The main inclusion criteria are histologically confirmed non-small-cell superior sulcus tumor, nodal disease stage ≤ N2, Karnofsky performance score ≥70%, patient age between 18 and 75 years as well as written informed consent. The main exclusion criteria include medical contraindications against elements of the trimodal treatment concept, PET confirmed nodal disease stage N3, stage IV disease, prior thoracic irradiation and decompensated diseases of the lung, cardio-vascular system, metabolism, hematopoietic and coagulation system and renal function. Furthermore, patients with implanted active medical devices without certification for ion-beam therapy are not allowed to take part in the study. Trial registration number: DRKS00006323 (www.drks.de)

Modulation of the Intestinal Microbiota Alters Colitis-Associated Colorectal Cancer Susceptibility

It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) collectively referred to as inflammatory bowel disease (IBD). Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC). However, the impact of the microbiota on the development of colitis-associated cancer (CAC) remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM)-exposed, conventionalized-Il10−/− mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62%) of AOM-Il10−/− mice developed colon tumors compared to only 3/15 (20%) of AOM- wild-type (WT) mice. Conventionalized AOM-Il10−/− mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10−/− mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10−/− mice. Germ-free AOM-treated Il10−/− mice showed normal colon histology and were devoid of tumors. Il10−/−; Myd88−/− mice treated with AOM displayed reduced expression of Il12p40 and Tnfα mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma

Evaluation of a Non-invasive Method to Detect Cytomegalovirus (CMV)-DNA in Stool Samples of Patients with Inflammatory Bowel Disease (IBD): A Pilot Study

A severe flare of colitis in patients with IBD treated with immunosuppressive therapy may be complicated by an underlying CMV infection. The aim of this pilot study was to investigate the diagnostic efficacy of quantitative polymerase chain reaction (PCR) to detect CMV DNA in stool samples of IBD patients

Multiple courses of stereotactic re-irradiation in recurrent oligodendroglioma: a case report

INTRODUCTION: High grade gliomas are an insidious disease associated with an extremely poor prognosis. The role of re-irradiation for recurrent gliomas is unclear but several retrospective studies have indicated mild toxicity and modest outcomes with this regimen. With subsequent progression, it is unclear what options remain and more radiotherapy is rarely offered for fear of surpassing normal central nervous system tissue tolerance and causing significant side effects without significant benefit. CASE PRESENTATION: In this report, we describe a 37-year-old Caucasian male initially diagnosed with a grade IV oligodendroglioma, who received multiple courses of re-irradiation and experienced a survival of 10 years with minimal cognitive or neurologic deficits. CONCLUSION: Significant toxicity with multiple courses of radiation does not always occur. Re-irradiation should be considered in a salvage setting

Lactobacillus GG in inducing and maintaining remission of Crohn's disease

Background Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders such as Crohn's disease and ulcerative colitis. Alteration of the intestinal microflora by antibiotic or probiotic therapy may induce and maintain remission. The aim of this randomized, placebo-controlled trial was to determine the effect of oral Lactobacillus GG (L. GG) to induce or maintain medically induced remission. Methods Eleven patients with moderate to active Crohn's disease were enrolled in this trial to receive either L. GG (2 × 109 CFU/day) or placebo for six months. All patients were started on a tapering steroid regime and received antibiotics for the week before the probiotic/placebo medication was initiated. The primary end point was sustained remission, defined as freedom from relapse at the 6 months follow-up visit. Relapse was defined as an increase in CDAI of >100 points. Results 5/11 patients finished the study, with 2 patients in each group in sustained remission. The median time to relapse was 16 ± 4 weeks in the L. GG group and 12 ± 4.3 weeks in the placebo group (p = 0.5). Conclusion In this study we could not demonstrate a benefit of L. GG in inducing or maintaining medically induced remission in CD

Modulation of the Intestinal Microbiota Alters Colitis-Associated Colorectal Cancer Susceptibility

It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) collectively referred to as inflammatory bowel disease (IBD). Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC). However, the impact of the microbiota on the development of colitis-associated cancer (CAC) remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM)-exposed, conventionalized-Il10−/− mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62%) of AOM-Il10−/− mice developed colon tumors compared to only 3/15 (20%) of AOM- wild-type (WT) mice. Conventionalized AOM-Il10−/− mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10−/− mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10−/− mice. Germ-free AOM-treated Il10−/− mice showed normal colon histology and were devoid of tumors. Il10−/−; Myd88−/− mice treated with AOM displayed reduced expression of Il12p40 and Tnfα mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

<p>Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.</p> <p>Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.</p> <p>Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.</p> <p>Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.</p> <p>Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.</p> <p>Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.</p&gt