Vemurafenib in non-small-cell lung cancer patients with BRAFV600 and BRAFnonV600 mutations.

BACKGROUND: BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS: Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION: Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02304809.

Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia.

Processing of Precursor 1 (POP1) is a large protein common to the ribonuclease-mitochondrial RNA processing (RNase-MRP) and RNase-P (RMRP) endoribonucleoprotein complexes. Although its precise function is unknown, it appears to participate in the assembly or stability of both complexes. Numerous RMRP mutations have been reported in individuals with cartilage-hair hypoplasia (CHH) but, to date, only three POP1 mutations have been described in two families with features similar to anauxetic dysplasia (AD). We present two further individuals, one with severe short stature and a relatively mild skeletal dysplasia and another in whom AD was suspected. Biallelic POP1 mutations were identified in both. A missense mutation and a novel single base deletion were detected in proband 1, p.[Pro582Ser]:[Glu870fs*5]. Markedly reduced abundance of RMRP and elevated levels of pre5.8s rRNA was observed. In proband 2, a homozygous novel POP1 mutation was identified, p.[(Asp511Tyr)];[(Asp511Tyr)]. These two individuals show the phenotypic extremes in the clinical presentation of POP1-dysplasias. Although CHH and other skeletal dysplasias caused by mutations in RMRP or POP1 are commonly cited as ribosomal biogenesis disorders, recent studies question this assumption. We discuss the past and present knowledge about the function of the RMRP complex in skeletal development.

[Scrotal hair in infants]. / Vello escrotal en lactantes.

The presence of pubic hair is exceptional in healthy infants of both sexes. In most of the cases described in the literature, the process was self-limited and no etiology was found. Nevertheless, in some patients, this finding has been associated with other manifestations of hyperandrogenism related to potentially serious diseases such as congenital adrenal hyperplasia or virilizing tumors. In the present article, we describe seven infants followed-up in the Pediatric Endocrine Clinic because of scrotal hair. In all patients, the process was self-limited and resolved spontaneously and no hormonal or developmental alterations were observed. Key words: Scrotal hair, infants, virilization.

[Group therapy for the treatment of obesity in children and adolescents]. / Terapia de grupo para el tratamiento de la obesidad infantil.

THERAPY: Although obesity is one of the leading health problems in developed countries, effective treatment is lacking. The aim of the present study was to determine whether group therapy is more efficient in inducing weigh loss than individual therapy in the pediatric age group. EXPERIMENTAL DESIGN: Fifty obese patients, 15 preadolescents and 33 adolescents (12 boys and 23 girls) were studied. In all patients, dietary intake was modified to reduce calorie intake. Initially all patients were followed-up individually every 3 months (individual therapy) until the beginning of group therapy when the patients were seen monthly in groups of 10-15 patients with their parents (preadolescents) or alone (adolescents). In the group sessions, talks were given about diet and exercise. In each session, the patient who had shown the greatest improvement in habits and weight loss received a prize. The patients were followed-up for 2 years, with individual therapy in the first year and group therapy in the second. Differences in body mass index (BMI) z-score before the beginning of therapy and during therapy were analyzed using Student's paired T test. RESULTS: With individual therapy, no changes in BMI z-score were observed throughout the study. In contrast, with group therapy, BMI z-score decreased in all the groups studied. During the 1-year follow-up with individual therapy, 60 % of the patients gained more than 5 kg. With group therapy, only 10 % of patients gained more than 5 kg. CONCLUSIONS: In obese children and adolescents, group therapy was more efficient than individual therapy in inducing weight loss.

[Identification of yeasts of the Candida genus with a growth inhibition system: Microring YT]. / Identificación de levaduras del género Candida por un sistema de inhibición del crecimiento: Microring YT.

BACKGROUND: It has been observed an spectacular increasing of opportunistic Candida yeast infections. Many of them are fatal, and rapid and effective identification of the infecting species contributes to start the correct treatment. Several new methods for yeast identification have become available; Microring YT is one of these methods based on the growth inhibition by 6 different chemical products. The aim of this work is to study the performance of the test using representative clinical yeast isolates. METHODS: A total of 146 strains belonging to the 5 most common Candida species isolated in the clinical laboratory were identified using conventional methods (germ tube and chlamydospores production, and the standard API 20C AUX and 16 sugars auxonography; Institute Pasteur) and the Microring YT System. This test uses the differing susceptibilities of yeast to 6 discs mounted on a filter paper ring. The chemical products and dyes are: janus green, ethidium bromide, triphenyl tetrazolium chloride, brilliant green, cycloheximide and rhodamine 6G. The inhibition pattern of a 6 digit code is compared with a list of profiles. RESULTS: Using the Microring YT system 112 of the 146 studied strains were correctly identified with an overall concordance of 77% between this method and the standard one. The morphological study (germ tube production) increased 6% the identification of Candida albicans. Better results were obtained with C. krusei and C. parapsilosis (85% of concordance). With C. glabrata only 59% of concordance was found. CONCLUSIONS: In spite Microring YT is a simple method, easy to perform and read, it was considered inadequate for the identification of Candida species as a routine microbiological procedure.