Identifying advanced stage NSCLC patients who benefit from afatinib therapy using 18F-afatinib PET/CT imaging

Objectives: Non-small cell lung cancer (NSCLC) tumors harboring common (exon19del, L858R) and uncommon (e.g. G719X, L861Q) activating epidermal growth factor receptor (EGFR) mutations are best treated with EGFR tyrosine kinase inhibitors (TKI) such as the first-generation EGFR TKI erlotinib, second-generation afatinib or third-generation osimertinib. However, identifying these patients through biopsy is not always possible. Therefore, our aim was to evaluate whether 18F-afatinib PET/CT could identify patients with common and uncommon EGFR mutations. Furthermore, we evaluated the relation between tumor 18F-afatinib uptake and response to afatinib therapy.Materials and methods: 18F-afatinib PET/CT was performed in 12 patients: 6 EGFR wild type (WT), 3 EGFR common and 3 EGFR uncommon mutations. Tumor uptake of 18F-afatinib was quantified using TBR_WB60-90 (tumor-to-whole blood activity ratio 60-90 min post-injection) for each tumor. Response was quantified per lesion using percentage of change (PC): [(response measurement (RM)?baseline measurement (BM))/BM]?100. Statistical analyses were performed using t-tests, correlation plots and sensitivity/specificity analysis.Results: Twenty-one tumors were identified. Injected dose was 348 ? 31 MBq. Group differences were significant between WT versus EGFR (common and uncommon) activating mutations (p = 0.03). There was no significant difference between EGFR common versus uncommon mutations (p = 0.94). A TBR_WB60-90 cut-off value of 6 showed the best relationship with response with a sensitivity of 70 %, a specificity of 100 % and a positive predictive value of 100 %.Conclusion: 18F-afatinib uptake was higher in tumors with EGFR mutations (common and uncommon) compared to WT. Furthermore, a TBR_WB60-90 cut-off of 6 was found to best predict response to therapy. 18F-afatinib PET/ CT could provide a means to identify EGFR mutation positive patients who benefit from afatinib therapy.Pathogenesis and treatment of chronic pulmonary disease

Epidemiology, Prehospital Characteristics and Outcomes of Severe Traumatic Brain Injury in The Netherlands: The BRAIN-PROTECT Study

Objective: A thorough understanding of the epidemiology, patient characteristics, trauma mechanisms, and current outcomes among patients with severe traumatic brain injury (TBI) is important as it may inform potential strategies to improve prehospital emergency care. The aim of this study is to describe the prehospital epidemiology, characteristics and outcome of (suspected) severe TBI in the Netherlands. Methods: The BRAIN-PROTECT study is a prospective observational study on prehospital management of patients with severe TBI in the Netherlands. The study population comprised all consecutive patients with clinical suspicion of TBI and a prehospital GCS score ≤ 8, who were managed by one of the 4 Helicopter Emergency Medical Services (HEMS). Patients were followed-up in 9 trauma centers until 1 year after injury. Planned sub-analyses were performed for patients with “confirmed” and “isolated” TBI. Results: Data from 2,589 patients, of whom 2,117 (81.8%) were transferred to a participating trauma center, were analyzed. The incidence rate of prehospitally suspected and confirmed severe TBI were 3.2 (95% CI: 3.1;3.4) and 2.7 (95% CI: 2.5;2.8) per 100,000 inhabitants per year, respectively. Median patient age was 46 years, 58.4% were involved in traffic crashes, of which 37.4% were bicycle related. 47.6% presented with an initial GCS of 3. The median time from HEMS dispatch to hospital arrival was 54 minutes. The overall 30-day mortality was 39.0% (95% CI: 36.8;41.2). Conclusion: This article summarizes the prehospital epidemiology, characteristics and outcome of severe TBI in the Netherlands, and highlights areas in which primary prevention and prehospital care can be improved

Association between intraoperative tissue oxygenation, arterial blood pressure and noradrenaline use in urological patients

Background and Goal of Study: Inadequate tissue oxygenation should be prevented during surgery as it might cause postoperative morbidity. In this observational study we looked at factors that might influence tissue oxygenation (StO2) such as blood pressure and use of vasoactive drugs. Materials and Methods: In 159 urological patients receiving balanced anaesthesia and mechanical ventilation, we measured StO2 intraoperatively on the thenar eminescence (InSpectra, Hutchinson Tech., USA) along with (non)invasive blood pressure and recorded the use of noradrenaline. We correlated StO2 and MAP as recorded at defined moments during surgery. In addition, we looked at the effects of low blood pressure (as defined by the areas under the curve (AUC) while MAP was < 65 mmHg) on StO2. Furthermore, we related StO2 to different noradrenaline (NA) dosages: none, low (<0.03 mg/kg/min) and high dose (≥0.03 mg/kg/min). Results and Discussion: At the start and end of surgery, there was no correlation between StO2 and MAP. However, the lowest recorded MAP per patient did correlate with the corresponding StO2 (R=0.206, R2=0.043, p< 0.01; Pearson‘s correlation, 2-tailed). Similarly, a higher MAP AUC < 65 mmHg was associated with a lower average StO2 (R=-0.189, R2=0.036, p< 0.05; Spearman‘s correlation, 2-tailed). These results support the hypothesis of intact autoregulation of tissue blood flow to preserve StO2 in the normal range of blood pressure, whereas this autoregulation fails during lowest pressures. Furthermore, StO2 was higher without noradrenaline (no NA)(88.4%) than during high dose noradrenaline (85.2%) (p< 0.001; ANOVA, Bonferroni post hoc analysis). Possibly, the vasoconstrictive effect of noradrenaline decreases blood flow through the observed tissue (peripheral muscle). Conclusions: Tissue oxygenation is not influenced by blood pressure in the normal blood pressure range during anaesthesia, whereas it becomes dependent when MAP drops below the clinically relevant threshold of 65 mmHg. Noradrenaline use is associated with a decreased tissue oxygenation in the thenar eminescence. Further studies should identify other factors that may influence tissue oxygenation and assess the impact of tissue hypoxia on postoperative patients‘ outcome

Feasibility of pulse oximetry in the initial prehospital management of victims of drowning: A preliminary study

AbstractAimImmediate delivery of oxygen is the most important treatment for victims of drowning at the rescue site. Monitoring oxygen saturation with pulse oximetry is potentially useful, but its use may be limited by poor peripheral perfusion due to hypothermia. This preliminary study explores the feasibility of pulse oximetry in simulated minor drowning scenarios.Materials and methodsSix different pulse oximeters were tested on ten healthy volunteers after brief submersion, after ten minutes of swimming in a swimming pool (warm water, temperature 21°C), and in the sea (cold water, temperature 16°C). A measured oxygen saturation reading ≤94% was assumed to be incorrect.ResultsThere was considerable variability between each pulse oximeter. In warm water, 5.8% of measurements were outside the predicted range (8.3% after submersion, 3.3% after swimming), compared to 34% in cold water (20% after submersion, 48% after swimming). The spurious measurements came from two pulse oximeters in warm water, but from all six in cold water. The best and worst performing pulse oximeters showed 5% and 33% measurements respectively outside the predicted range.ConclusionThe performance of pulse oximeters varies considerably in healthy volunteers submersed or immersed in warm or cold water. Further studies are needed to understand these differences