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.

Differential effects of interleukin-1α and β on the arachidonic acid cascade in human synovial cells and chondrocytes in culture

The effects of interleukin-1 and were tested on the [³H]-arachidonic acid release and the prostaglandin synthesis by human cultured synovial cells and chondrocytes. Both forms of interleukin-1 stimulated the arachidonic acid release but interleukin-1 was more potent than IL-1. Human synovial cells and chondrocytes synthesized three types of prostaglandins upon stimulation with interleukin-1 or : prostaglandin E₂, F₂ and 6-keto-prostaglandin F₁. Regarding the synthesis of these prostaglandins, IL-1 was again more potent than IL-1. A comparison between interleukin-1-stimulated synovial cells and chondrocytes revealed neither significant quantitative nor qualitative differences in both the arachidonic acid release and the prostaglandin synthesis.     

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.

     

Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages

Alternatively activated macrophages (aaMphi) display molecular and biological characteristics that differ from those of classically activated macrophages (caMphi). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMphi, whereas in the late and chronic stages of infection, aaMphi develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMphi versus caMphi elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMphi as compared with caMphi. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-gamma antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMphi and establish FIZZ1 and Ym1 as markers for aaMphi.     

Using Metamodeling to Identify the Optimal Strategy for Colorectal Cancer Screening

ObjectivesMetamodeling can address computational challenges within decision-analytic modeling studies evaluating many strategies. This article illustrates the value of metamodeling for evaluating colorectal cancer screening strategies while accounting for colonoscopy capacity constraints.MethodsIn a traditional approach, the best screening strategy was identified from a limited subset of strategies evaluated with the validated Adenoma and Serrated pathway to Colorectal CAncer model. In a metamodeling approach, metamodels were fitted to this limited subset to evaluate all potentially plausible strategies and determine the best overall screening strategy. Approaches were compared based on the best screening strategy in life-years gained compared with no screening. Metamodel runtime and accuracy was assessed.ResultsThe metamodeling approach evaluated >40 000 strategies in <1 minute with high accuracy after 1 adaptive sampling step (mean absolute error: 0.0002 life-years) using 300 samples in total (generation time: 8 days). Findings indicated that health outcomes could be improved without requiring additional colonoscopy capacity. Obtaining similar insights using the traditional approach could require at least 1000 samples (generation time: 28 days). Suggested benefits from screening at ages <40 years require adequate validation of the underlying Adenoma and Serrated pathway to Colorectal CAncer model before making policy recommendations.ConclusionsMetamodeling allows rapid assessment of a vast set of strategies, which may lead to identification of more favorable strategies compared to a traditional approach. Nevertheless, metamodel validation and identifying extrapolation beyond the support of the original decision-analytic model are critical to the interpretation of results. The screening strategies identified with metamodeling support ongoing discussions on decreasing the starting age of colorectal cancer screening.     

Cell salvage in burn excisional surgery

BackgroundHemostasis during burn surgery is difficult to achieve, and high blood loss commonly occurs. Bleeding control measures are limited, and many patients require allogeneic blood transfusions. Cell salvage is a well-known method used to reduce transfusions. However, its evidence in burns is limited. Therefore, this study aimed to examine the feasibility of cell salvage during burn surgery.Study design and methodsA prospective, observational study was conducted with 16 patients (20 measurements) scheduled for major burn surgery. Blood was recovered by washing saturated gauze pads with heparinized saline, which was then processed using the Cell Saver. Erythrocyte concentrate quality was analyzed by measuring hemoglobin, hematocrit, potassium, and free hemoglobin concentration. Microbial contamination was assessed based on cultures at every step of the process. Differences in blood samples were tested using the Student’s t-test.ResultsThe red blood cell mass recovered was 29 ± 11% of the mass lost. Patients’ preoperative hemoglobin and hematocrit levels were 10.5 ± 1.8 g/dL and 0.33 ± 0.05 L/L, respectively. The erythrocyte concentrate showed hemoglobin and hematocrit levels of 13.2 ± 3.9 g/dL and 0.40 ± 0.11 L/L thus showing a concentration effect. The potassium level was lower in the erythrocyte concentrate (2.5 ± 1.5 vs. 4.1 ± 0.4 mmol/L, p < 0.05). The free hemoglobin level was low (0.16 ± 0.21 μmol/L). All cultures of the erythrocyte concentrate showed bacterial growth compared to 21% of wound cultures.ConclusionRecovering erythrocytes during burn excisional surgery using cell salvage is possible. Despite strict sterile handling, erythrocyte concentrates of all patients showed bacterial contamination. The consequence of this contamination remains unclear and should be investigated in future studies.     

Cadmium uptake and defense mechanism in insect cells

The uptake of cadmium and the defense mechanism against this heavy metal were studied in the Aedes albopictus C6/36 cell line. The internalization of cadmium was a very quick process and exhibited saturation kinetics over the metal concentration gradient (1.37 to 131 micromol/L). Cd toxicity and influx were both shown to be temperature dependent. The uptake was not influenced by a 2, 4-dinitrophenol pretreatment but was significantly decreased by the Ca2+ antagonist verapamil. These data suggest that cadmium is readily taken up through mediated transport, not requiring metabolic energy. A considerable amount of the metal passes through the Ca2+ channels, but probably (an)other transporting molecule(s) also play(s) an important role in the uptake process. The remarkable, nonsigmoid viability pattern of Cd-treated cultures suggests that CdCl2 concentrations above 33 micromol/L induce a cellular defense system. This phenomenon went together with increased protein synthesis. We found a major induction of a group consisting of 71-, 75-, and 78-kDa proteins, probably belonging to the HSP70 family, as similar proteins were induced by heat shock. A slight induction of a 120-kDa protein also occurred. At the highest Cd concentrations 98-, 108-, and 110-kDa proteins were induced. These data suggest that heat shock proteins may play an important role in the Aedes cell protection against Cd insult.     

Infliximab induces remission in cryptogenic multifocal ulcerous stenosing enteritis:First case

We present the case of a 29-year-old patient with a history of abdominal pain and vomiting.Based on wireless video capsule findings he was previously diagnosed with ileal Crohn’s disease at a different institution,although the clinical and radiological picture was not typical and the response to corticosteroids was poor.We performed a single-balloon enteroscopy showing a short,ulcerous stenosis 50 cm proximal from Bauhin’s valve.The endoscopic and clinical histopathological findings were compatible with cryptogenic multifocal ulcerous stenosing enteritis(CMUSE).High dose corticosteroids were again started,without effect.The monoclonal tumor necrosis factor-α(TNF-α) antibody infliximab was added to the medical therapy.After induction therapy,both clinical and endoscopic amelioration was obtained.Larger case studies are needed to confirm the efficacy of TNF-α inhibition in steroid refractory CMUSE.