An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment.

Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon’s diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances.

Results: Ten LC patients, 10?CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p?=?.02), but not during and after treatment (p?=?.09 and p?=?.33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p?<?.05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p?<?.01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p?=?.06) with no effect of treatment.

Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.     

Isotope Ratio Mass Spectrometry (IRMS) Versus Laser-Assisted Ratio Analyzer (LARA)

This study was carried out to compare the measurements and the diagnostic accuracy of the traditional expensive IRMS and the new economical LARA system using two doses of [¹³C]urea + two different test meals in patients undergoing upper gastrointestinal endoscopy, both before and after anti-Helicobacter treatment. A total of 354 dyspeptic patients underwent endoscopy with gastric biopsies to diagnose H. pylori infection by CLO-test and histology. No patients had taken antibiotics, bismuth, or antisecretory drugs in the 4 weeks before testing. After overnight fasting, breath samples were collected simultaneously in both plastic and glass tubes at baseline and at 30 and 60 min after urea ingestion. In 237 patients 100 mg [¹³C]urea + Ensure and in 117 patients 75 mg [¹³C]urea + citric acid were given. The test was also performed with the two urea dosages and meals in 67 and 64 infected patients, respectively, four weeks after anti-Helicobacter therapy. H. pylori was considered eradicated when both biopsy-based tests were negative. A value >5 was considered positive. Breath samples with insufficient CO₂ levels at both 30 and 60 min were excluded from final analysis (N = 37 in pre- and N = 8 in posttreatment). There was excellent agreement between overall values of the two machines with both [¹³C]urea 100 mg + Ensure and [¹³C]urea 75 mg + citric acid. The 95% CI of the difference against the mean was wider with the former (mean –1.3, +6.3, and –9.4) than with the latter urea dosage and test meal (mean –1.2, +5.2 and –8.1). LARA and IRMS were equally effective (P = NS) in distinguishing infected from uninfected patients before therapy using both doses of [¹³C]urea and test meals (sensitivity ranged from 95% to 99% and specificity from 95% to 97%). This good performance was maintained in the posttreatment phase (sensitivity ranged from 90% to 100% and specificity from 90% to 97%), without any statistical difference among the various combinations (P = NS). The LARA system is a valid alternative to IRMS in the diagnosis of H. pylori infection. Both machines provide highly reliable results after 30 min, so that the 60 min sample can be avoided. The dose of 75 mg + citric acid suffices to ensure an accurate UBT. The test performed with both devices and [¹³C]urea dosages is very effective also for posttherapy evaluation of H. pylori status.     

Lessons Learned about Implementing Research Evidence into Clinical Practice

The mission of the Veterans Health Administration's (VHA) quality enhancement research initiative (QUERI) is to enhance the quality of VHA health care by implementing clinical research findings into routine care. This paper presents lessons that QUERI investigators have learned through their initial attempts to pursue the QUERI mission. The lessons in this paper represent those that were common across multiple QUERI projects and were mutually agreed on as having substantial impact on the success of implementation. While the lessons are consistent with commonly recognized ingredients of successful implementation efforts, the examples highlight the fact that, even with a thorough knowledge of the literature and thoughtful planning, unexpected circumstances arise during implementation efforts that require flexibility and adaptability. The findings stress the importance of utilizing formative evaluation techniques to identify barriers to successful implementation and strategies to address these barriers.     

Socio-demographic,behavioral and functional characteristics of groups of community and institutionalized elderly Quechua Indians of Peru,and their association with nutritional status

Socio-demographic, behavioral, functional and anthropometric data for groups of elderly Quechua Indians of Peru were used to investigate the effects of gender and lifestyle patterns on nutritional status. Two community-dwelling samples were selected for study, representative of divergent lifestyles in terms of their combination of socio-economic, demographic and cultural contexts, plus an ad-hoc sample of institutionalized individuals with controlled food intake and reduced physical activity. Results suggest that differences in socio-demographic, behavioral and functional characteristics exist between the sexes and across settings (low- vs. highland) and lifestyles (institutionalized vs. community-dwelling; semi-urban vs. rural). These factors are likely to be related to diverging dietary and physical activity patterns, and have considerable effects on the nutritional status of the respondents.     

Serum leptin levels in women with systemic lupus erythematosus

The purpose of this study was to evaluate serum leptin levels in systemic lupus erythematosus (SLE). Forty-one women with SLE were compared with 23 healthy women of similar age and body mass index (BMI). Clinical characteristics and Mexican systemic lupus erythematosus disease activity index (Mex-SLEDAI) score were assessed. Serum leptin levels (ng/dl) were measured by enzyme-linked immunosorbent assay (ELISA). Comparisons of leptin levels were made with the Mann-Whitney U-test. In a multiple regression analysis, those factors that could influence the leptin levels were adjusted. Patients with SLE had higher leptin levels than the control group (SLE median 31 vs control median 15, P=0.023). After adjusting by other variables, the serum leptin levels remained higher in SLE than in controls (P=0.02). Patients with SLE had no association between leptin levels and Mex-SLEDAI score, age, duration of disease, or prednisone doses. Those with SLE had higher leptin levels than controls. Further longitudinal studies are required to evaluate the role of this hormone in the exacerbations of SLE.     

Influenza vaccine in chronic lymphoproliferative disorders and multiple myeloma

OBJECTIVE: Vaccination against influenza in patients with chronic lymphoproliferative disorders (CLPD) and multiple myeloma (MM) is still a matter of clinical uncertainty. The aim of this study was to determine the safety, immunogenicity and clinical response to a commercially available vaccine against influenza in a group of such patients. METHODS: Thirty-four patients with CLPD and MM and 34 immunologically normal subjects were vaccinated with the same vaccine against influenza. Patients were observed during the epidemic season from October 1999 to April 2000, and monitored for side-effects of the vaccine, seroprotection and seroconversion after vaccination. The prevaccination level of immunoglobulins was also determined. Occurrence of influenza episodes was demonstrated with the positive isolation of a viral strain from a pharyngeal swab. RESULTS: No patient had untoward reactions to the vaccine used. Seroconversion and seroprotection were up to the standard established by the European Agency for the Evaluation of Medicinal Products. Only one patient developed influenza during follow-up. CONCLUSIONS: Influenza vaccine is effective and well tolerated in patients with CLPD and MM. No contraindications exist for its use, and it should become a routine practice, in order to prevent serious complications during the influenza epidemic season.     

Beta3 integrin deficiency promotes atherosclerosis and pulmonary inflammation in high-fat-fed,hyperlipidemic mice

Hyperlipidemia promotes the chronic inflammatory disease atherosclerosis through poorly understood mechanisms. Atherogenic lipoproteins activate platelets, but it is unknown whether platelets contribute to early inflammatory atherosclerotic lesions. To address the role of platelet aggregation in diet-induced vascular disease, we studied beta3 integrin-deficient mice (lacking platelet integrin alphaIIbbeta3 and the widely expressed nonplatelet integrin alphavbeta3) in two models of atherosclerosis, apolipoprotein E (apoE)-null and low-density lipoprotein receptor (LDLR)-null mice. Unexpectedly, a high-fat, Western-type (but not a low-fat) diet caused death in two-thirds of the beta3-/-apoE-/- and half of the beta3-/-LDLR-/- mice due to noninfectious pneumonitis. In animals from both models surviving high-fat feeding, pneumonitis was absent, but aortic atherosclerosis was 2- to 6-fold greater in beta3-/- compared with beta+/+ littermates. Expression of CD36, CD40L, and CD40 was increased in lungs of beta3-/-LDLR-/- mice. Each was also increased in smooth muscle cells cultured from beta3-deficient mice and suppressed by retroviral reconstitution of beta3. These data show that the platelet defect caused by alphaIIbbeta3 deficiency does not impair atherosclerotic lesion initiation. They also suggest that alphavbeta3 has a suppressive effect on inflammation, the loss of which induces atherogenic mediators that are amplified by diet-induced hyperlipidemia.     

PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide

Plasmatic levels of PDGF-AB, TGFbeta1, and bFGF are increased in patients with essential thrombocythemia (ET) while intraplatelet levels are low for PDGF, normal for TGFbeta, and elevated for bFGF. To evaluate the contribution of gene expression to the dysregulated cytokine levels, we studied platelet PDGF-A, PDGF-B, TGFbeta1, and bFGF mRNA in ET patients before and during anagrelide treatment. We found decreased PDGF-A and PDGF-B, increased TGFbeta1, and normal bFGF mRNA levels. During treatment, mRNA levels remained decreased for PDGF-A, were increased for PDGF-B and normal for TGFbeta1. In untreated patients, protein expression of PDGF paralleled its mRNA levels while different patterns of RNA and protein were found for TGFbeta1 and bFGF.