Avelumab: A Review in Metastatic Merkel Cell Carcinoma

Avelumab (Bavencio^®) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200. In Part A of the study, confirmed objective responses were observed in approximately one-third of patients with chemotherapy-refractory metastatic MCC treated with avelumab. The responses were observed early and appeared to be durable, with an estimated 74% of responses having a duration ≥?12 months. Furthermore, interim results from a separate cohort of patients (Part B) indicate an objective response rate for avelumab of >?60% in patients who were chemotherapy-naïve in the metastatic disease setting. Avelumab is associated with a risk of immune-related adverse events but, overall, has an acceptable and manageable safety and tolerability profile. In conclusion, currently available data suggest that avelumab presents a clinically beneficial new treatment option for metastatic MCC, a rare but aggressive cancer associated with a poor prognosis.     

Electrophysiological Biomarkers of Epilepsy

In patients being evaluated for epilepsy and in animal models of epilepsy, electrophysiological recordings are carried to capture seizures to determine the existence of epilepsy. Electroencephalography recordings from the scalp, or sometimes directly from the brain, are also used to locate brain areas where seizure begins, and in surgical treatment help plan the area for resection. As seizures are unpredictable and can occur infrequently, ictal recordings are not ideal in terms of time, cost, or risk when, for example, determining the efficacy of existing or new anti-seizure drugs, evaluating potential anti-epileptogenic interventions, or for prolonged intracerebral electrode studies. Thus, there is a need to identify and validate other electrophysiological biomarkers of epilepsy that could be used to diagnose, treat, cure, and prevent epilepsy. Electroencephalography recordings in the epileptic brain contain other interictal electrophysiological disturbances that can occur more frequently than seizures, such as interictal spikes (IIS) and sharp waves, and from invasive studies using wide bandwidth recording and small diameter electrodes, the discovery of pathological high-frequency oscillations (HFOs) and microseizures. Of IIS, HFOs, and microseizures, a significant amount of recent research has focused on HFOs in the pathophysiology of epilepsy. Results from studies in animals with epilepsy and presurgical patients have consistently found a strong association between HFOs and epileptogenic brain tissue that suggest HFOs could be a potential biomarker of epileptogenicity and epileptogenesis. Here, we discuss several aspects of HFOs, as well as IIS and microseizures, and the evidence that supports their role as biomarkers of epilepsy.     

“Yes,and …” Exploring the Future of Learning Analytics in Medical Education

This Conversations Starter article presents a selected research abstract from the 2017 Association of American Medical Colleges Northeastern Region Group on Educational Affairs annual spring meeting. The abstract is paired with the integrative commentary of three experts who shared their thoughts stimulated by the study. Commentators brainstormed “what's next” with learning analytics in medical education, including advancements in interaction metrics and the use of interactivity analysis to deepen understanding of perceptual, cognitive, and social learning and transfer processes.     

REBOA by a non-surgeon as an adjunct during MASCAL

Use of Resuscitative endovascular balloon occlusion of the aorta (REBOA) for control of non-compressible hemorrhage is a re-emerging technology that historically is employed by surgeons. We present a case in which REBOA was successfully placed by an emergency physician in a critical mass casualty patient awaiting transfer to the operating table. This case is an example in which emergency physicians, in collaboration with the surgeon, can utilize REBOA to temporize non-compressible hemorrhage when a surgeon is not immediately available.     

Perception or reality: Can thermal perceptions inform management of firefighters in the heat?

Accurately assessing the physiological status of firefighters during work in the heat is critical to ensuring their safety. Evaluating core temperatures (T_c) in the field is problematic due to cost and limitations in technology and accuracy. As such, fire services rely on individual perceptions of wellbeing. The present study aimed to establish whether perceptual responses measured using the perceptual strain index (PeSI), calculated from rate of perceived exertion (RPE) and thermal sensation (TS), could reliably predict the physiological strain (PSI) encountered by experienced firefighters working in a hot environment. We conducted two firefighting simulations (set-pace and self-paced) in a purposefully built heat chamber (100 ± 5°C) comprised of two 20-min periods separated by a 10-min recovery outside the chamber. Physiological strain was measured via heart rate (HR) and gastrointestinal temperature (T_gi) and compared with PeSI at 5-min intervals. To evaluate the predictive ability of the PeSI for PSI, mean differences and the 95% limits of agreement (LOA) were established, along with correlation coefficients at each 5-min interval. Moderately significant correlations occurred in the second work bout of the self-paced trial only (10 min: r = 0.335, 15 min: r = 0.498, 20 min r = 0.439) with no other correlations observed at any other time during either trial or during the rest periods. Bland-Altman analysis revealed mean differences of ?0.74 ± 2.70 (self-paced) and +0.04 ± 2.04 (set-paced) between PeSI and PSI with the 95% LOA being ?4.77 to 3.28 (self-paced) and ?4.01 to 2.01 (set-paced). The wide LOA and lack of correlations observed between perceptual and physiological strain in both self-paced and set-paced work trials indicate that PeSI is not sufficiently reliable as a sole measure of wellbeing for firefighters working in the heat. Hence, we recommend that fire services prioritise the development of reliable and effective monitoring tools for use in the field.