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.

Comparison between ankle and toe index in patients with peripheral arterial disease

In contrast to the systolic blood pressure at the posterior tibial artery, the evaluation of pressure at the digital artery of the foot before and after exercise in patients with peripheral arterial disease is not well known. Twenty three patients with peripheral vascular disease were examined. The systolic pressure was measured by means of an ultrasound velocity detector at the brachial and posterior tibial artery. Digital artery pressure was determined with photoplethysmography. Pressures were measured before and within 5 and 10 minutes after a treadmill test. Ankle and toe index was calculated. At rest the toe index is lower than the ankle index and after a treadmill test the decrease in toe index occurs in parallel to the ankle index.     

Cell proliferation in human cerebral tumors. In vivo study of 45 cases by incorporation of 5-iododesoxyuridine

A method to study the proliferation of human brain tumors, is presented. Non radioactive 5-Iododeoxyuridine (2.4 gr) infused over a 24 hours period is detected in situ on histologic section by an immunological technique (peroxidase-anti-peroxidase) using a specific anti-Iododeoxyuridine antibody. This exploration utilised in 45 patients is easy, reliable and harmless. All cells which enter in S phase of cellular cycle during the infusion are labelled. So the cellular kinetics of all the brain tumor cells (malignant cells, inflammatory stroma reaction cells, reactive astrocytes, endothelial and muscular cells of the vessels) are detected on the same histological section, as well as all the others proliferative cells of the body (leukocytes, primitive tumor of the metastatic brain localisation...) if multiples biopsies are done. 8 of 9 gliomas of low histological malignancy (grade I and II) have a slow cellular kinetic. The 23 astrocytomas of different histological malignancy (grade III and IV) have variable proliferative speed (7 very fast, 8 fast and 8 slow). Only the large cells of the pinealoma are very proliferative, the lymphoid stroma is quiescent. The 5 metastasis have a slow to very fast kinetic without correlation with the cellular differentiation except in one case (important differentiation and slow cellular proliferation). The 5 lymphoma cells kinetics are well correlated with the histologic differentiation (3 large cells poor differentiated lymphomas and very fast kinetic, 2 better differentiated and slower proliferation). The 2 meningiomas proliferate slowly. The biochemical and histopathological grounds of the presented method and the limits of quantification are discussed. This method is compared with this using Bromodeoxyuridine. The correlation between proliferation and histologic malignancy is analysed. The use of cytokinetic results for therapeutic and prognosis need further statistical anatomoclinical studies.     

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.

     

Cell-mediated anti-tumor response in the RLmale 1 system. I. T nature, H-2Dd involvement and antigenic specificity of the effector cells.

After in vivo priming and in vitro secondary stimulation by the radio-induced RL♂ 1 lymphoma cells, syngeneic BALB/c splenic lymphocytes evidenced a specific but very weak cytolytic activity against RL♂ 1 target cells. Under the same experimental conditions, spleen cells from (B6 x BALB/c)F₁ were at least 100 times more efficient. In both cases, the effector cells were cytolytic T lymphocytes (CTL). Normal H-2D^d antigens of the tumor cell surface were involved in the effector-to-target cell interaction since anti-H-2 or anti-H-2D^d antisera abolished the RL♂ 1 cytolysis by immune syngeneic CTL, whereas anti-H-2K^d were devoid of blocking activity. The testing of a series of lymphoma cells, either virus-induced or not, belonging to different H-2 haplotypes, show that the immune CTL were highly specific for RL♂ 1 target cells. Only with the P815 mastocytoma cells was a weak cross-reactivity detected by both direct tests and competition experiments. Allogeneic (H-2^k) AKR lymphoma cells which share the X1 antigen with RL♂ 1 do not react, possibly due to an H-2 restriction of the CTL activity. The CTL-reacting antigen cannot be definitely identified, since several specificities, including the serologically defined X1 antigen, are possibly involved simultaneously. The Hh antigens which could have accounted for the F₁ anti-parent reaction, appear irrelevant.     

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.     

Time dependence of serial diffusion-weighted imaging features in a case of pyogenic brain abscess

Both signal intensity on trace images and apparent diffusion coefficient measurements on mapped images evolved rapidly on serial diffusion-weighted sequences in a case of pyogenic brain abscess that was monitored primarily by MRI before a biopsy was performed. Considering only the signal intensities on the trace images would have led to an underestimation of the intrinsic tissue changes.