Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

Switching to the bingeing/purging subtype of anorexia nervosa is frequently associated with suicidal attempts

OBJECTIVE: Anorexia nervosa has the highest suicide mortality ratio of psychiatric disorders, suicide being associated with many factors. We assessed the first lifetime occurrence of these factors taking into account their possible overlap. METHOD: Three hundred and four in- and out-patients with anorexia nervosa (DSM-IV) were systematically recruited in three hospitals of Paris suburbs, between December 1999 and January 2003. Patients were assessed by a face-to-face interview (DIGS). Current eating disorder dimensions were measured, and patients interviewed by a trained clinician to assess minimal BMI and, retrospectively, the age at which anorexia nervosa, major depressive disorder, anxiety disorders and switch to bingeing/purging type occurred for the first time, if applicable. RESULTS: Major depressive disorder (p<0.001) and subtype switch from the restrictive to the bingeing/purging type (p<0.001) were the two factors significantly more frequently occurring before suicidal attempts, and remained involved when a multivariate analysis is performed, whether syndromic or dimensional measures are being used. Taking into account lifetime occurrence with a survival analysis, the switch to bingeing/purging type of anorexia appears as a major predictive factor, with a large increase of the frequency of suicidal attempts (OR=15) when compared to patients with neither major depressive disorder nor bingeing/purging type. CONCLUSIONS: Bingeing/purging type of anorexia nervosa is largely associated with suicidal attempts, and may deserve specific attention. If confirmed on a prospectively designed study, these results would argue for early detection and/or more intensive and specific therapeutic intervention on this aspect of bingeing and purging behaviors.     

The external laryngeal nerve: surgical and anatomic considerations. Report of 50 total thyroidectomies

This surgical anatomy study aimed to evaluate the possibility of identifying the external laryngeal nerve during thyroid surgery and the possible variations of nerves at risk. Fifty patients underwent total thyroidectomies during a period of 12 months. Using a neurostimulator, the distal motor branch of the external laryngeal nerve was searched. Electrical stimulation of a nervous branch aimed to provoke a global contraction of the cricothyroid in order to identify with certitude the external laryngeal nerve. The external laryngeal nerve was identified in 20% of cases. Its course was, with almost equal frequency, either (1) between the vessels of the superior thyroid pedicle or (2) superficial and anterior to the fascia of the cricothyroid muscle. The external laryngeal nerve is hard to find during thyroid surgery, even with a neurostimulator. It can be vulnerable during thyroid surgery but only in cases of anatomic variations. Searching for the nerve systematically during thyroid surgery does not seem to be useful. Several precautions when dissecting the superior pole of the thyroid gland seem to be necessary and sufficient to respect the external laryngeal nerve.     

Prevalence of fragilysin gene in Bacteroides fragilis isolates from blood and other extraintestinal samples

Of 166 Bacteroides fragilis isolates, 26.2% of 103 isolates from blood and 20.6% of 63 extraintestinal isolates harbored the fragilysin gene (difference not statistically significant). Clinical characteristics and evolution were comparable in patients with B. fragilis bacteremia with or without this enterotoxin. Fragilysin seems not to be an important virulence factor in B. fragilis disease.     

Adolescents'' opinions about genetic risk information, prenatal diagnosis, and pregnancy termination

Advances in genetics create increasing possibilities of diagnosing and preventing genetic disease. In most countries, the community is poorly informed about the role of genetic factors in human disease and about genetic testing and its social, emotional, and ethical implications. School education about genetics may improve this situation. Students are, of course, the adults of the future and the potential users of the new genetic tests. To gain further insight into the perception of genetic risk of adolescents and their perception of the new genetic techniques and as a starting point for setting up an adequate information campaign in Flanders, we assessed the opinions and beliefs of students with regard to health, genetic diseases, genetic risk, and genetic testing.

A standardised interview and questionnaire were administered within the scope of the two yearly medical check up of 166 fifth grade students. They were randomly selected from the group of all fifth grade high school students in seven different schools.

This paper focuses on the attitudes of adolescents towards obtaining genetic information, towards prenatal diagnosis and pregnancy termination. Adolescents in Flanders are interested in being informed about genetic risks and genetic diseases and in making use of prenatal diagnosis because they want to make informed reproductive decisions in the future and to be emotionally prepared for the birth of an affected child. They adopt a critical attitude towards pregnancy termination. The association between these attitudes and several relevant factors was investigated. This showed significant correlations between some attitudes and general health related prevention, perceived burden of genetic diseases, the importance of the value “own health”, the perceived role of society, and the regularity of religious practice. Some points for special attention were formulated with regard to information campaigns for adolescents.

     

Involvement of SHV-12 and SHV-2a encoding plasmids in outbreaks of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a Tunisian neonatal ward

Previous genotypic investigations of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae recovered in a Tunisian neonatal ward revealed the spread of two epidemic strains and a high number of genetically unrelated isolates. The aim of the present study was to determine the role of the dissemination of self-transferrable plasmids harboring bla genes in the outbreaks experienced by the ward. The 49 previously identified clinical isolates of ESBL-producing K. pneumoniae were examined for relationships between their enzymes and plasmids. Analysis of crude extracts by isoelectric focusing showed four beta-lactamase-activities at pI 8.2, 7.6, 6, and 5.4. Clinical isolates contained large plasmids that could be transferred by conjugation and transformation conferring resistance to expanded-spectrum cephalosporins. DNA amplification and sequencing were performed to confirm the identities of transferred beta-lactamases. Nucleotide sequence analysis of SHV-specific PCR products from six isolates identified two bla(SHV) genes corresponding to SHV derived ESBLs, SHV-12 and SHV-2a. PstI digestion of plasmid DNA from transformants revealed six restriction patterns. The occurrence of the prevalent plasmid pattern in both epidemic strains and unrelated isolates indicated that diffusion and endemic persistence of the bla(SHV-ESBL) genes in the ward were due to concomitant spread of epidemic strains and plasmid dissemination among unrelated strains.     

Multiple exostoses,mental retardation,hypertrichosis, and brain abnormalities in a boy with a de novo 8q24 submicroscopic interstitial deletion

Multiple exostoses represent a genetically heterogeneous disorder that may occur isolated or as part of a complex contiguous gene syndrome such as Langer-Giedion syndrome on chromosome 8 and the proximal 11p deletion syndrome on chromosome 11. Here we describe a boy with multiple exostoses, hypertrichosis, mental retardation, and epilepsy due to a de novo deletion on chromosome 8q24. Molecular analysis revealed that the deletion interval overlaps with the Langer-Giedion syndrome and involves the EXT1 gene and additional genes located distal to EXT1, but probably not encompassing the TRPS1 gene located proximal to EXT1.