Both Disease Activity and HLA-B27 Status Are Associated With Gut Microbiome Dysbiosis in Spondyloarthritis Patients.

OBJECTIVE: Gut microbiome dysbiosis has previously been reported in spondyloarthritis (SpA) patients and could be critically involved in the pathogenesis of this disorder. The objectives of this study were to further characterize the microbiota structure in SpA patients and to investigate the relationship between dysbiosis and disease activity in light of the putative influence of the genetic background. METHODS: Shotgun sequencing was performed on fecal DNA isolated from stool samples from 2 groups of adult volunteers: SpA patients (n = 102) and healthy controls (n = 63). A subset of the healthy controls comprised the age-matched siblings of patients whose HLA-B27 status was known. Changes in gut microbiota composition were assessed based on species diversity, enterotypes, and taxonomic and functional differences. RESULTS: Dysbiosis was confirmed in SpA patients as compared to healthy controls. The restriction of microbiota diversity was detected in patients with the most active disease, and the abundance of several bacterial species was correlated with Bath Ankylosing Spondylitis Disease Activity Index score. Among healthy controls, significant differences in microbiota composition were also detected between the HLA-B27-positive and the HLA-B27-negative siblings of SpA patients. We highlighted a decreased abundance of several species of bacteria in SpA patients, especially those bacteria belonging to the Clostridiales order. Among the few species of bacteria showing increased abundance, Ruminococcus gnavus was one of the top differentiating species. CONCLUSION: These findings reveal that genetic background and level of disease activity are likely to influence the composition of the gut microbiota of patients with SpA. It may be appropriate for further research on chronic arthritis to focus on these key parameters.

Effects of Low FODMAP Diet on Symptoms, Fecal Microbiome, and Markers of Inflammation in Patients With Quiescent Inflammatory Bowel Disease in a Randomized Trial.

BACKGROUND & AIMS: There is limited evidence that a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) reduces gut symptoms in quiescent inflammatory bowel disease (IBD). We performed a randomized, controlled trial to investigate the effects of a low FODMAP diet on persistent gut symptoms, the intestinal microbiome, and circulating markers of inflammation in patients with quiescent IBD. METHODS: We performed a single-blind trial of 52 patients with quiescent Crohn's disease or ulcerative colitis and persistent gut symptoms at 2 large gastroenterology clinics in the United Kingdom. Patients were randomly assigned to groups that followed a diet low in FODMAPs (n = 27) or a control diet (n = 25), with dietary advice, for 4 weeks. Gut symptoms and health-related quality of life were measured using validated questionnaires. Stool and blood samples were collected at baseline and end of trial. We assessed fecal microbiome composition and function using shotgun metagenomic sequencing and phenotypes of T cells in blood using flow cytometry. RESULTS: A higher proportion of patients reported adequate relief of gut symptoms following the low FODMAP diet (14/27, 52%) than the control diet (4/25, 16%, P=.007). Patients had a greater reduction in irritable bowel syndrome severity scores following the low FODMAP diet (mean reduction of 67; standard error, 78) than the control diet (mean reduction of 34; standard error, 50), although this difference was not statistically significant (P = .075). Following the low FODMAP diet, patients had higher health-related quality of life scores (81.9 ± 1.2) than patients on the control diet (78.3 ± 1.2, P = .042). A targeted analysis revealed that in stool samples collected at the end of the study period, patients on the low FODMAP diet had significantly lower abundance of Bifidobacterium adolescentis, Bifidobacterium longum, and Faecalibacterium prausnitzii than patients on control diet. However, microbiome diversity and markers of inflammation did not differ significantly between groups. CONCLUSIONS: In a trial of the low FODMAP diet vs a control diet in patients with quiescent IBD, we found no significant difference after 4 weeks in change in irritable bowel syndrome severity scores, but significant improvements in specific symptom scores and numbers reporting adequate symptom relief. The low FODMAP diet reduced fecal abundance of microbes believed to regulate the immune response, compared with the control diet, but had no significant effect on markers of inflammation. We conclude that a 4-week diet low in FODMAPs is safe and effective for managing persistent gut symptoms in patients with quiescent IBD. www.isrctn.com no.: ISRCTN17061468.

Prediction of the intestinal resistome by a three-dimensional structure-based method.

The intestinal microbiota is considered to be a major reservoir of antibiotic resistance determinants (ARDs) that could potentially be transferred to bacterial pathogens via mobile genetic elements. Yet, this assumption is poorly supported by empirical evidence due to the distant homologies between known ARDs (mostly from culturable bacteria) and ARDs from the intestinal microbiota. Consequently, an accurate census of intestinal ARDs (that is, the intestinal resistome) has not yet been fully determined. For this purpose, we developed and validated an annotation method (called pairwise comparative modelling) on the basis of a three-dimensional structure (homology comparative modelling), leading to the prediction of 6,095 ARDs in a catalogue of 3.9 million proteins from the human intestinal microbiota. We found that the majority of predicted ARDs (pdARDs) were distantly related to known ARDs (mean amino acid identity 29.8%) and found little evidence supporting their transfer between species. According to the composition of their resistome, we were able to cluster subjects from the MetaHIT cohort (n = 663) into six resistotypes that were connected to the previously described enterotypes. Finally, we found that the relative abundance of pdARDs was positively associated with gene richness, but not when subjects were exposed to antibiotics. Altogether, our results indicate that the majority of intestinal microbiota ARDs can be considered intrinsic to the dominant commensal microbiota and that these genes are rarely shared with bacterial pathogens.

Early identification of patients at risk for difficult intubation in the intensive care unit: development and validation of the MACOCHA score in a multicenter cohort study.

RATIONALE: Difficult intubation in the intensive care unit (ICU) is a challenging issue. OBJECTIVES: To develop and validate a simplified score for identifying patients with difficult intubation in the ICU and to report related complications. METHODS: Data collected in a prospective multicenter study from 1,000 consecutive intubations from 42 ICUs were used to develop a simplified score of difficult intubation, which was then validated externally in 400 consecutive intubation procedures from 18 other ICUs and internally by bootstrap on 1,000 iterations. MEASUREMENTS AND MAIN RESULTS: In multivariate analysis, the main predictors of difficult intubation (incidence = 11.3%) were related to patient (Mallampati score III or IV, obstructive sleep apnea syndrome, reduced mobility of cervical spine, limited mouth opening); pathology (severe hypoxia, coma); and operator (nonanesthesiologist). From the ß parameter, a seven-item simplified score (MACOCHA score) was built, with an area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.85-0.94). In the validation cohort (prevalence of difficult intubation = 8%), the AUC was 0.86 (95% CI, 0.76-0.96), with a sensitivity of 73%, a specificity of 89%, a negative predictive value of 98%, and a positive predictive value of 36%. After internal validation by bootstrap, the AUC was 0.89 (95% CI, 0.86-0.93). Severe life-threatening events (severe hypoxia, collapse, cardiac arrest, or death) occurred in 38% of the 1,000 cases. Patients with difficult intubation (n = 113) had significantly higher severe life-threatening complications than those who had a nondifficult intubation (51% vs. 36%; P < 0.0001). CONCLUSIONS: Difficult intubation in the ICU is strongly associated with severe life-threatening complications. A simple score including seven clinical items discriminates difficult and nondifficult intubation in the ICU. Clinical trial registered with www.clinicaltrials.gov (NCT 01532063).

Impact of a recent chemotherapy on the duration and intensity of the norepinephrine support during septic shock.

The objective of this study was to compare the dose and the duration of vasopressor during septic shock in recently treated cancer patients, untreated cancer patients, and patients without malignancy. This was a retrospective single-center study. This study was performed on a 12-bed medical intensive care unit at a teaching hospital. There were 147 patients admitted to the intensive care unit with septic shock: 82 cancer patients recently treated (TCPs), 20 untreated cancer patients (UCPs), and 45 without malignancy (NPs). The primary outcomes were the maximal dose and the duration of vasopressor support. Treated cancer patients were younger (P < 0.0001) and compared with NPs had less comorbidity (P = 0.003), had more frequently an intra-abdominal source of sepsis (P = 0.011), less frequently a gram-positive bacteria (P = 0.036), and a shorter delay for antibiotics (P = 0.029). All patients received norepinephrine with similar maximal doses (0.66 [0.29-1.5] µg · kg(-1) · min(-1) in TCPs vs. 0.82 [0.41-1.4] µg · kg(-1) · min(-1) in NPs and 0.79 [0.48-1.7] µg · kg(-1) · min(-1) in UCPs; P = 0.61) and duration in the three groups (2 [2-4] days in TCPs vs. 3 [2-4] days in NPs and 3 [2-5] days in UCPs; P = 0.13). Mechanical ventilation (P = 0.11), renal replacement therapy (P = 0.19), and 28-day mortality (43% in TCPs vs. 49% in NPs, and 50% in UCPs; P = 0.77) were similar between the three groups. Cancer patients recently treated with chemotherapy had similar needs in vasopressor support during septic shock compared with untreated cancer patients and patients without malignancy. Mortality was not different in cancer and noncancer patients with septic shock.

Primary cardiac lymphoma and complete atrio-ventricular block: case report and review of the literature.

Primary cardiac lymphoma (PCL) is a rare and extremely aggressive malignancy, which can express itself by damaging the cardiac conduction system (complete atrio-ventricular block), the myocardium and the pericardium. Histology confirms the diagnosis. Chances of survival depend on early diagnosis and treatment. We present the case of a female patient admitted for severe deterioration of her general state of health who had a complete atrio-ventricular block caused by a tumour of the atrial septum, a B-cell lymphoma stage I. The diagnosis was suggested by combined PET/CT imaging and confirmed by histology of a cardiac biopsy. Her general clinical condition, including the cardiac parameters, significantly improved following chemotherapy induction.

[From Alport syndrome to benign familial hematuria: clinical and genetic aspect]. / Du syndrome d'Alport à l'hématurie familiale bénigne: aspects cliniques et génétiques.

Alport syndrome (AS) is a hereditary glomerulonephritis variably associated with neural hearing loss and ocular abnormalities. The prevalence of the disease is estimated at approximately 1 in 50,000 live births. AS arises from mutations in genes encoding alpha chains constituting type IV collagen. In 85% of patients, the disease results from mutations in the COL4A5 gene located on X chromosome. In the hemizygous male, persistent microhematuria is present from early life, then proteinuria and renal insufficiency occur with time, leading to end-stage renal failure before age 40. In the heterozygous female, clinical manifestations vary from completely healthy state to end-stage renal failure, most often reached after the age of 40. In 15% of patients, the disease results from mutations in either the COL4A3 or the COL4A4 gene, both located on chromosome 2. When both alleles are mutated (autosomal recessive form), the phenotype is constantly severe, resembling that of the hemizygous male in the X-linked form. In the heterozygous individual, the clinical spectrum vary from the absence of any manifestation to the development of proteinuria - the so-called autosomal-dominant AS -, and even renal insufficiency, sometimes reaching end-stage (after the age of 40) through the most frequently encountered phenotype, i.e. a persistently isolated microhematuria, accounting for the so-called benign familial hematuria (or healthy carrier state). The determinants of the phenotype remain largely unknown, so that it may be risky to predict renal prognosis in the individual with a single COL4A3/A4 mutation and an isolated microhematuria at the time of examination.