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.

Fluconazole and amphotericin B antifungal susceptibility testing by National Committee for Clinical Laboratory Standards broth macrodilution method compared with E-test and semiautomated broth microdilution test.

A comparative study of fluconazole and amphotericin B susceptibility testing was performed with 68 clinical Candida species isolates and three test methods. The methods used were an agar diffusion method (E-test) and two broth dilution methods, the National Committee for Clinical Laboratory Standards (NCCLS) reference broth macrodilution method and an in-house-prepared semiautomated broth microdilution method based on the Bioscreen turbidometer. In the microdilution method, growth of the yeasts was measured continuously by the automatic turbidometer (Bioscreen), which permitted precise and objective determination of endpoints. MIC endpoints were read after 24 h for the microdilution method and the E-test. Amphotericin B susceptibility testing with the NCCLS method and the E-test yielded comparable results in 89% of the tests, meaning that the endpoints obtained were identical or differed by no more than 2 twofold dilutions. The NCCLS and broth microdilution tests scored 97% comparable results, and the E-test and the broth microdilution test yielded 90% comparable results. Fluconazole susceptibility testing produced 96% comparable results with the NCCLS test and the E-test, 100% comparable results with the NCCLS and the microdilution methods, and 98.5% comparable results with the microdilution method and the E-test. We conclude that the E-test and the Bioscreen microdilution method are valuable alternatives to the NCCLS reference method for routine susceptibility testing of Candida species with fluconazole and amphotericin B.     

Use of confirmatory factor analysis for the identification of new components of the metabolic syndrome: the role of plasminogen activator inhibitor-1 and Haemoglobin A1c

BACKGROUND AND AIM: This study was aimed to identify additional components of metabolic syndrome from a set of cardiovascular risk markers. METHODS AND RESULTS: The homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, homocysteine, Haemoglobin A1c (HbA1c), and lipoprotein(a) were assessed in a population-based sample of 902 nondiabetic adult subjects. Those biomarkers that were associated with metabolic syndrome were evaluated by multiple regression analysis, along with other traditional cardiovascular risk factors. Confirmatory factor analysis (CFA) was used to test the hypothesis that both the established components of metabolic syndrome and the novel variables identified by the regression analysis were associated with a single underlying factor. HOMA-IR, PAI-1 and HbA1c were the only biomarkers independently related to metabolic syndrome. CFA validated a one-factor model that included these variables. Moreover, the indices of goodness of fit were better for this expanded model than those obtained for a previously validated one-factor model that was restricted to the conventional elements of the syndrome. CONCLUSIONS: These findings show that PAI-1 and HbA1c are singularly linked to metabolic syndrome. Their elevation is presumably another manifestation of the same pathophysiological mechanism that underlies the recognized traits of the syndrome.     

Infection of the thyroid gland caused by Campylobacter fetus subsp. fetus

We report what we consider to be the first case of an abscess of the thyroid gland due to Campylobacter fetus subsp. fetus (C. fetus) in a patient suffering from hyperthyroidism. C. fetus is known as a rare and opportunistic pathogen in humans, causing a broad variety of systemic infections. Acquisition by humans is thought to occur through contact with animals or animal products and to start as a gastro-intestinal colonization. The detection of C. fetus in stool is challenging, since culture efforts are generally directed in order to fulfil growth requirements of C.jejuni, a much more common enteric pathogen. Detection of C. fetus in non-stool samples is even more challenging since routine culture doesn't imply prolonged incubation (>72h), selective media and microaerophilic conditions. It is therefore not unlikely that human infections caused by C. fetus occur more often than generally assumed.     

Glucose-6-phosphate dehydrogenase variants: reexamination of G6PD Chicago and Cornell and a new variant (G6PD Pea Ridge) resembling G6PD Chicago

Two large and unrelated families were investigated for hereditary nonspherocytic hemolytic anemia associated with deficiency of erythrocyte glucose-6-phosphate dehydrogenase (G6PD). In both families, the kinetic and electrophoretic features of the G6PD variants resembled those of G6PD Chicago. Further investigation revealed that members of one of these families previously had been characterized as having the G6PD variants Chicago and Cornell. However, it is clear that each of these terms has been applied to the same variant in this single large kindred. In the second family, we describe a newly identified variant with unique characteristics, which we have designated G6PD Pea Ridge. G6PD Pea Ridge resembles G6PD Chicago but differs in electrophoretic mobility and in a few kinetic parameters. It exhibits an unusually high Ki for NADPH and thus appears to be insensitive to product inhibition. As other cases previously considered to be the Chicago variant become more fully characterized, this probably will be shown to be a heterogeneous group of variants.     

The hypereosinophilic syndrome after residence in a tropical country: report of 4 cases

Severe eosinophilia may be complicated by acute or chronic visceral damage. The underlying origin of the hypereosinophilia may be infectious, allergic, toxic, malignant or systemic (the secondary or reactive hypereosinophilic syndrome), but in a number of cases no cause can be found (the idiopathic hypereosinophilic syndrome). We describe 4 cases with hypereosinophilia and secondary visceral damage after residence in a tropical region. In three cases a helminthic infection was the obvious cause, the brain and the heart were the target organs. After treatment of the infection both the hypereosinophilia and the neurological and cardiac lesions disappeared. The fourth patient died of multi-organ disease. No definite trigger of the hypereosinophilia could be found. We discuss clinical findings, necessary investigations and therapeutic strategies.     

Surveillance of antibiotic resistance in clinical isolates of Streptococcus pneumoniae collected in Belgium during winter 2000-2001

A total of 314 isolates of Streptococcus pneumoniae collected by 10 different laboratories were tested for their susceptibility by using a microdilution technique following NCCLS recommendations. The following antibiotics were included: penicillin, ampicillin, amoxicillin, amoxicillin/clavulanate, cefaclor, cefuroxime, cefotaxime, imipenem, ciprofloxacin, gemifloxacin, levofloxacin, erythromycin, clarithromycin, azithromycin, miocamycin, clindamycin and tetracycline. The insusceptibility rate (IR) to penicillin was 21.0% [10.8% intermediate (> or = 0.12-1 microgram/mL) and 10.2% high-level (> or = 2 micrograms/mL)], to cefotaxime 7.3% [3.5% intermediate (> or = 1 microgram/mL) and 3.8% high-level (> or = 2 micrograms/mL)], to imipenem 3.8% [3.8% intermediate (> or = 0.25-0.5 microgram/mL) and 0% high-level (> or = 1 microgram/mL)], to ciprofloxacin 11.2% [8.3% intermediate (2 micrograms/mL) and 3.9% high-level (> or = 4 micrograms/mL)], to erythromycin 30.3% [3.5% intermediate (0.5 microgram/mL) and 26.8% high-level (> or = 1 microgram/mL)] and to tetracycline 38.5% [0.9% intermediate (4 micrograms/mL) and 37.6% high-level (> or = 8 micrograms/mL)]. No decreased susceptibility was found for gemifloxacin (> or = 0.5 microgram/mL). This compound was the most active with MIC50, MIC90 and an IR of 0.015 microgram/mL, 0.03 microgram/mL and 0% respectively, followed by amoxicillin/clavulanate, amoxicillin and imipenem (MIC50, MIC90 and IR: 0.015 microgram/mL, 1 microgram/mL, 1.6%/0.015 microgram/mL, 1 microgram/mL, 1.9%/0.008 microgram/mL, 0.12 microgram/mL, 3.8% respectively). Compared to the 1999 surveillance, penicillin and tetracycline-insusceptibility increased with 4.9% and 15.6% respectively, while cefotaxime, erythromycin and ciprofloxacin insusceptibility decreased with 5.4%, 5.8% and 4.4% respectively. MICs of all beta-lactams rose with those of penicillin for penicillin-insusceptible isolates. Imipenem, cefotaxime, amoxicillin and amoxicillin/clavulanate were generally 4, 2, 1 and 1 doubling dilutions respectively more potent than penicillin on these isolates while ampicillin, cefuroxime and cefactor were generally 1, 2 and 4 dilutions respectively [table: see text] less potent. Most penicillin-insusceptible isolates remained fully susceptible to amoxicillin/clavulanate (92.4%), amoxicillin (90.9%) and imipenem (81.8%). Erythromycin-tetracycline insusceptibility was the most common resistance phenotype (14.3%). Three- and four-fold resistance was found in 12.4% and 1.6% respectively of the isolates. Most penicillin-insusceptible isolates were of capsular types 14 (22.7%), 23 (21.2%), 6 (18.2%), 9 (13.6%) and 19 (12.1%).