Actinomyces in Chronic Granulomatous Disease: An Emerging and Unanticipated Pathogen

Background.Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system that causes defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections, mostly by catalase-producing organisms. We report for the first time, to our knowledge, chronic infections with Actinomyces species in 10 patients with CGD. Actinomycosis is a chronic granulomatous condition that commonly manifests as cervicofacial, pulmonary, or abdominal disease, caused by slowly progressive infection with oral and gastrointestinal commensal Actinomyces species. Treatment of actinomycosis is usually simple in immunocompetent individuals, requiring long-term, high-dose intravenous penicillin, but is more complicated in those with CGD because of delayed diagnosis and an increased risk of chronic invasive or debilitating disease. Methods.Actinomyces was identified by culture, staining, 16S ribosomal DNA polymerase chain reaction, and/or a complement fixation test in 10 patients with CGD. Results.All 10 patients presented with a history of fever and elevated inflammatory signs without evident focus. Diagnosis was delayed and clinical course severe and protracted despite high-dose intravenous antibiotic therapy and/or surgery. These results suggest an unrecognized and unanticipated susceptibility to weakly pathogenic Actinomyces species in patients with CGD because these are catalase-negative organisms previously thought to be nonpathogenic in CGD. Conclusions.Actinomycosis should be vigorously sought and promptly treated in patients with CGD presenting with uncommon and prolonged clinical signs of infection. Actinomycosis is a catalase-negative infection important to consider in CG

Mutations du transporteur rénal sodium/phosphate NPT2a associées à des lithiases rénales chez l'homme

Le co-transporteur sodium-phosphate NPT2a joue un rôle majeur dans la réabsorption rénale du phosphate (Pi). Deux mutations de NPT2a viennent d'être identifiées à l'état hétérozygote chez 2 patients présentant des lithiases rénales avec hyperphosphaturie. Nous avons caractérisé fonctionnellement ces mutations après expression hétérologue et étude électrophysiologique. Le courant (I) induit par le Pi est significativement inférieur dans les ovocytes exprimant le transporteur NPT2a muté que NPT2a sauvage, suggérant un déficit de fonction des NPT2a mutés. D'autre part, I est diminué dans les ovocytes coexprimant NPT2a muté et sauvage par rapport aux ovocytes exprimant NPT2a sauvage seul, montrant un effet dominant négatif des mutations. Les conséquences fonctionnelles de ces mutations de NPT2a peuvent rendre compte du phénotype des patients et confirment le rôle de mutations de NPT2a dans la formation de certaines lithiases rénales chez l'Homme, donc leur origine génétique.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Impact of percutaneous pulmonary valve implantation procedural steps on leaflets histology and mechanical behaviour: An in vitro study

International audienceBackground: Percutaneous pulmonary valve implantation (PPVI) using bovine jugular veinMelody valve is safe and effective. However, post-procedural complications have beenreported for unclear reasons.Objective: We sought to assess the impact of PPVI procedural steps on valvular histologyand leaflet mechanical behaviour.Methods: Three different valved stents (Melody valve, homemade stents with bovine andporcine pericardium) were tested in-vitro in 4 conditions: I) control group, II) crimping, III)crimping + inflation of low-pressure balloon and IV) condition III + post dilatation (highpressureballoon). For each condition, valvular leaflets (and venous wall sample for Melodystents) were taken for histological analysis and mechanical uniaxial tests of valve leaflets.Results: Among Melody valves, incidence of transverse fractures was significantly higher intraumatized samples compared with control group (p<0.05) whereas, incidence and depth oftransverse fractures were not statistically different between the 4 conditions for bovine andporcine pericardial leaflets. No significant modification in mechanical behaviour of in-vitrotraumatized Melody® valvular leaflets was observed. Bovine and porcine pericardia becamemore elastic and less resilient after balloon expansion and post-dilatation (condition III andIV), with a significant decrease of elastic modulus and stress at rupture.Conclusion: Valved stent implantation procedural steps induce histological lesions onMelody valve leaflets. Conversely, bovine and porcine pericardial valved stents were nothistologically altered by in vitro manipulations although their mechanical properties weresignificantly modified. These data could explain some of the long-term complicationsobserved with these substitutes

A three-gene expression signature associated with positive surgical margins in tongue squamous cell carcinomas: Predicting surgical resectability from tumour biology?

International audienceObjectives: Achieving complete tumour resection is one of the main goals of surgery for head and neck squamous cell carcinoma (HNSCC) tumours. Whether biological characteristics of tumours contribute to the surgical resectability and the presence of positive surgical margins (SM) after resection of HNSCC is unclear. We aimed to address this issue.Materials and methods: We used data from The Cancer Genome Atlas (TCGA) to relate the SM status of 356 HNSCC tumours covering five major primary locations (tongue, larynx, tonsils, floor of mouth and buccal mucosa) with data from multiple omics approaches (transcriptomic, genomic and proteomic analyses).Results: We identified three differentially expressed genes whose expression was significantly associated with the presence of positive SM in tongue tumours (n = 144). The three genes (CCDC66, ZRANB2 and VCPKMT) displayed significantly higher mRNA levels in tongue tumours with positive SM compared to tumours with negative SM. The corresponding gene expression signature identified tongue tumours with a positive SM with high sensitivity and specificity (85% and 76%, respectively, Area Under the Curve (AUC) = 0.84). Tongue tumours with this signature were characterised by a high grade, elevated proliferation levels and a tumour stroma with fewer fibroblasts and endothelial cells.Conclusion: Positive SM were found to be strikingly associated with tumour biology in tongue tumours. These findings offer interesting perspectives for biomarker identification and precision surgery in these tumours

Diagnostic Approach to Congenital Cystic Masses of the Neck from a Clinical and Pathological Perspective

Background: neck cysts are frequently encountered in pediatric medicine and can present a diagnostic dilemma for clinicians and pathologists. Several clinical items enable to subclassify neck cyst as age at presentation, anatomical location, including compartments and fascia of the neck, and radiological presentation. Summary: this review will briefly describe the clinical, imaging, pathological and management features of (I) congenital and developmental pathologies, including thyroglossal duct cyst, branchial cleft cysts, dermoid cyst, thymic cyst, and ectopic thymus; (II) vascular malformations, including lymphangioma. Key Messages: pathologists should be familiar with the diagnostic features and clinicopathologic entities of these neck lesions in order to correctly diagnose them and to provide proper clinical management

Mutation in the mitochondrial translation elongation factor EFTs results in severe infantile liver failure

Background & AimsMultiple respiratory chain deficiencies represent a common cause of mitochondrial diseases and often result in hepatic failure. A significant fraction of patients present mitochondrial DNA depletion but a number of cases remain unexplained. The aim of our study was to identify the disease causing gene in a kindred with intrauterine growth retardation, neonatal lactic acidosis, liver dysfunction and multiple respiratory chain deficiency in muscle.MethodsHomozygosity mapping was performed by 50K SNP genotyping and candidate genes were successively analyzed by direct sequencing on genomic DNA of the family members.ResultsSNP genotyping detected several regions of homozygosity in which we focused our attention to genes involved in mitochondrial translation. We sequenced the TSFM gene, encoding the mitochondrial translation factor EFTs and identified a homozygous mutation changing a highly conserved arginine into a tryptophan (R312W).ConclusionsThis mutation has been previously reported in two unrelated kindred presenting two distinct syndromes (fatal mitochondrial encephalomyopathy and hypertrophic cardiomyopathy respectively). The description of a third syndrome associated with a same TSFM mutation gives support to the broad clinical and genetic heterogeneity of mitochondrial translation deficiencies in human. It suggests that mitochondrial translation deficiency represents a growing cause of hepatic failure of mitochondrial origin in infants

Selective propensity of bovine jugular vein material to bacterial adhesions: An in-vitro study

International audienceBACKGROUND: Percutaneous pulmonary valve implantation (PPVI) using Melody valve made of bovine jugular vein is safe and effective. However, infective endocarditis has been reported for unclear reasons. We sought to assess the impact of valvular substrates on selective bacterial adhesion. METHODS: Three valved stents (Melody valve, homemade stents with bovine and porcine pericardium) were tested in-vitro for bacterial adhesion using Staphylococcus aureus and Streptococcus sanguinis strains. RESULTS: Bacterial adhesion was higher on bovine jugular venous wall for S. aureus and on Melody valvular leaflets for S. sanguinis in control groups and significantly increased in traumatized Melody valvular leaflets with both bacteria (traumatized vs non traumatized: p=0.05). Bacterial adhesion was lower on bovine pericardial leaflets. CONCLUSION: Selective adhesion of S. aureus and S. sanguinis pathogenic strains to Melody valve tissue was noted on healthy tissue and increased after implantation procedural steps