TP53 and p53 statuses and their clinical impact in diffuse low grade gliomas.

TP53 is a pivotal gene frequently mutated in diffuse gliomas and particularly in astrocytic tumors. The majority of studies dedicated to TP53 in gliomas were focused on mutational hotspots located in exons 5-8. Recent studies have suggested that TP53 is also mutated outside the classic mutational hotspots reported in gliomas. Therefore, we have sequenced all TP53 coding exons in a retrospective series of 61 low grade gliomas (LGG) using high throughput sequencing technology. In addition, TP53 mutational status was correlated with: (i) p53 expression, (ii) tumor type, (iii) chromosome arms 1p/19q status and (iv) clinical features of patients. The cohort included 32 oligodendrogliomas (O), 21 oligoastrocytomas (M) and 8 astrocytomas (A). TP53 mutation was detected in 52.4% (32/61) of tumors (34% of O, 71.4% of M and 75% of A). All mutations (38 mutations in 32 samples) were detected in exons 4, 5, 6, 7, 8 and 10. Missense and non-missense mutations, including seven novel mutations, were detected in 42.6 and 9.8% of tumors respectively. TP53 mutations were almost mutually exclusive with 1p/19q co-deletion and were associated with: (i) astrocytic phenotype, (ii) younger age, (iii) p53 expression. Using a threshold of 10% p53-positive tumor cells, p53 expression is an interesting surrogate marker for missense TP53 mutations (Se = 92%; Sp = 79.4%) but not for non-missense mutation (18.4% of mutations). TP53 and p53 statuses were not prognostic in LGG. In conclusion, we have identified novel TP53 mutations in LGG. TP53 mutations outside exons 4-8 are rare. Although it remains imperfect, p53 expression with a threshold of 10% is a good surrogate marker for missense TP53 mutations and appears helpful in the setting of LGG phenotype diagnosis.

Lipoprotein-associated phospholipase A2 during the hyperacute stage of ischemic and hemorrhagic strokes.

BACKGROUND: The objectives of the study were to compare lipoprotein-associated phospholipase A2 (Lp-PLA2) levels in a prospective cohort including both ischemic and hemorrhagic strokes at the hyperacute phase, and to investigate if these levels were associated with stroke severity. MATERIALS AND METHODS: Lp-PLA2 mass and activity were measured during the first 6 hours of symptom onset before any therapeutic intervention. The Lp-PLA2 level was analyzed by comparing the mass and activities in ischemic strokes and spontaneous intracerebral hemorrhages (ICH). Correlations between Lp-PLA2 levels and clinical scores as well as stroke volumes were made. The temporal evolution of Lp-PLA2 during the first week was analyzed in ischemic stroke patients. RESULTS: Lp-PLA2 mass was higher in ICH than in ischemic stroke (P = .001). Lp-PLA2 activity at admission correlated with initial and follow-up stroke volume in ICH (P = .003 and P = .004, respectively) but not in ischemic stroke. None of the measurements correlated with clinical severity for either diagnosis. Lp-PLA2 mass decreased during the first week after the use of statins in ischemic stroke, whereas the activity remained stable. CONCLUSIONS: Lp-PLA2 mass is higher in ICH compared with ischemic stroke during the hyperacute stage. Lp-PLA2 activity is associated with stroke volume in ICH but not in ischemic stroke. This suggests that Lp-PLA2 mass and activity could provide different information in the hyperacute stage of stroke.

The Surface Microbiome of Clinically Unaffected Skinfolds in Hidradenitis Suppurativa: A Cross-Sectional Culture-Based and 16S rRNA Gene Amplicon Sequencing Study in 60 Patients.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin associated with specific lesional dysbiotic features. We studied the microbiome of clinically unaffected typical HS sites (armpits, inguinal folds, and gluteal clefts) in 60 patients with HS and 17 healthy controls. A total of 192 samples obtained by swabbing were analyzed by bacterial cultures. Of these, 116 randomly selected samples were studied by 16S rRNA gene amplicon sequencing. Patients and controls showed similar characteristics, except for smoking (87% vs. 6%, respectively). HS skinfolds were characterized by an increased abundance of anaerobes, predominantly Prevotella, but also Actinomyces, Campylobacter ureolyticus, and Mobiluncus, contrasting with a lower abundance of skin commensals such as Staphylococcus epidermidis, a major component of the skin microbiome; Kocuria; and Micrococcus luteus. The following three independent factors were associated with an abundance of high anaerobes by multivariate analysis: samples originating from patients with HS patients (P = 2.1 × 10-4); body mass index (P = 5 × 10-5); and the sampling site, the gluteal cleft being the most anaerobic area, followed by inguinal folds and axilla (P = 3 × 10-6). The microbiome of clinically unaffected HS skinfolds is reminiscent, albeit to a minor extent, of the microbiome of chronic suppurative HS lesions and may fuel inflammation at a preclinical stage of the disease.