Evidence of an Intracellular Reservoir in the Nasal Mucosa of Patients with Recurrent Staphylococcus aureus Rhinosinusitis

Severe infections due to Staphylococcus aureus require prolonged therapy for cure, and relapse may occur even years after the first episode. Persistence of S. aureus may be explained, in part, by nasal carriage of S. aureus which occurs in a large percentage of healthy humans and represents a major source of systemic infection. However, the persistence of internalized S. aureus within mucosal cells has not been evaluated in humans. Here, we provide the first in vivo evidence of intracellular reservoirs of S. aureus in humans, which were assessed in endonasal mucosa specimens from patients suffering from recurrent S. aureus rhinosinusitis due to unique, patient-specific bacterial clonotypes. Heavily infected foci of intracellular bacteria located in nasal epithelium, glandular, and myofibroblastic cells were revealed by inverted confocal laser scan fluorescence and electron microscopic examination of posttherapy intranasal biopsy specimens from symptom-free patients undergoing surgery on the sinuses. Intracellular residence may provide a sanctuary for pathogenic bacteria by protecting them from host defense mechanisms and antibiotic treatment during acute, recurrent S. aureus rhinosinusiti

Why do liver transplant patients so often become obese? The addiction transfer hypothesis

International audienceIn patients who receive transplantation for alcohol liver disease, obesity and metabolic syndrome are highly prevalent after transplantation and both contribute to a significant proportion of cardiovascular complications, late morbidity and mortality in this population. Although immunosuppressive medications have been hypothesised to explain some of these post-liver-transplantation (LT) metabolic complications, they cannot be considered the sole cause of obesity and metabolic syndrome, and the high prevalence of these illnesses remains unexplained. Given the significant overlap between the neurobiological, psychiatric and psychological factors that underlie alcohol addiction and reward-related behavioural dyscontrol disorders such as food addiction (FA), we hypothesised that the high prevalence of obesity and metabolic syndrome reported in patients who receive transplantation for alcohol liver disease could be explained at least partially by a switch in some individuals from a previous alcohol addiction to post-transplantation FA (i.e., addiction transfer = addiction switch). In our integrative model, we also speculate that an increased prevalence of FA or alcohol addiction may occur in patients with both specific psychobiological profiles and shared risk factors. We further hypothesise that in the subpopulation of patients who develop either alcohol addiction or FA after LT, those with high insight with regard to the consequences of alcohol use could be at higher risk for FA, whereas those with low insight could be at higher risk for alcohol addiction. We discuss here evidence for and against this hypothesis and discuss which patients could be more vulnerable to these two addictions after LT. Because it will not be either possible or ethical to test some of our hypotheses in humans, future studies should test these hypotheses using a translational strategy, using both clinical and preclinical approaches. If our hypotheses could account for the significant increase in obesity and metabolic syndrome after LT, this would lead to new avenues for research and preventive as well as therapeutic interventions for alcohol-related LT patients. All patients with previous or current alcohol addiction should be systematically screened for FA and followed up for subsequent risk of obesity and metabolic syndrome. Such strategies might be effective in improving survival, outcomes and quality of life after LT and also in the overall population of patients with alcohol addiction. By determining common risk factors for both alcohol addiction and FA using a translational approach, our model could help to find novel psychopharmacological and psychological strategies that might be effective in both FA and alcohol addiction

T Lymphocytes Promote the Antiviral and Inflammatory Responses of Airway Epithelial Cells

T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV)

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

peer reviewedBackground: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI –∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8–27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI −0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17–0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33–2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16–0·47] and 0·21 [0·13–0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health—Programme Hospitalier de Recherche Clinique 2010

Evénements cardio-vasculaires dans l'hépatite C chronique (valeur pronostique de l'évolution de l'élasticité hépatique)

Introduction : L'hépatite C chronique est aussi une maladie métabolique pouvant favoriser la survenue d'événements cardio-vasculaires. Le FibroScan® est un outil diagnostique de la fibrose et pronostique dans les complications de la cirrhose et la mortalité. L'objectif de notre étude est d'étudier la valeur pronostique de l'évolution de l'élasticité hépatique mesurée par FibroScan® dans la survenue d'événements cardio-vasculaires chez des patients porteurs d'une hépatite chronique virale C, ainsi que la valeur pronostique de l'élasticité initiale à la prise en charge. Patients et méthodes : Tous les patients majeurs suivis pour une hépatite C chronique dans un centre de référence ayant eu au moins deux mesures de l'élasticité hépatique (MEH) par FibroScan® valides entre 2006 et 2013 ont été inclus. En cas de suivi inférieur à 2 ans, de co-infection virale, de cirrhose décompensée, de transplantation hépatique, de maladie hépatique associée, les patients étaient exclus. Les évènements cardio-vasculaires survenus après la première évaluation par FibroScan® ont été recueillis rétrospectivement. Une progression lente de l'élasticité hépatique était définie par une évolution des MEH =0,3kPa/an. Une élasticité initiale élevée était définie par une MEH initiale >= 7kPa. Résultats : Sur les 561 patients VHC ayant eu une évaluation indirecte de l'élasticité par Fibroscan®,135 patients ont été inclus. Il s'agissait majoritairement d'hommes (n=75,56%), âgés de 55,3 ans, infectés par un génotype 1 (n=94,71%). Parmi les 89 patients traités (66%), 28 ont eu une réponse virologique soutenue dont 8 avant la MEH initiale. Sur les 135 patients, 27 étaient en surpoids (IMC>=25), 12 avaient un diabète de type 2 et 41 une stéatose échographique. Au cours du suivi, 7 patients (5%) ont présenté un événement cardio-vasculaire (4 infarctus du myocarde, 3 accidents vasculaires cérébraux). Une progression lente était notée chez 100 patients et une progression rapide chez 35. Un évènement cardio-vasculaire est survenu chez 5% des patients du groupe progression lente et 6% du groupe progression rapide (p=1,0). Parmi les 57 patients avec une élasticité initiale élevée, 11% (n=6) ont présenté un événement cardio-vasculaire comparé à 1% (n=1) des 78 patients ayant une élasticité initiale faible (p=0,04). La durée moyenne de suivi par FibroScan® était de 5,2 ans. La première MEH médiane était de 6,3 kPa (4,9 - 8,8) contre 5,9 kPa (4,8 - 7,9) pour la seconde. La médiane de l'évolution annuelle de l'élasticité était de -1,5 kPa/an. Conclusion : Chez les patients porteurs d'une hépatite chronique virale C, l'élasticité initiale >= 7kPa est associée à la survenue d'évènements cardio-vasculaires. La progression rapide de l'élasticité hépatique ne semble pas associée à la survenue de ces évènements.POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Traitement par interféron alpha de l'hépatite chronique virale C chez des malades hémophiles coinfectés ou non par la virus de l'immunodéficience humaine (étude prospective multicentrique chez 26 malades)

POITIERS-BU Médecine pharmacie (861942103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Le suivi des toxicomanes atteints d'hépatite C au Centre du Tourniquet à Poitiers

POITIERS-BU Médecine pharmacie (861942103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF