Pembrolizumab treatment of inflammatory progressive multifocal leukoencephalopathy: a report of two cases.

Progressive multifocal leukoencephalopathy (PML) is a rare but devastating neurological disease caused by reactivation of the JC virus in susceptible individuals. The illness has classically been associated with the human immunodeficiency virus (HIV) and multiple sclerosis (MS) patients who are treated with natalizumab. It is also associated with haematological malignancies, organ transplantation, autoimmune disease and immunodeficiency. Aside from natalizumab, a range of other immunomodulators including obinutuzumab and rituximab have been associated with PML. The nature of these associations is unclear due to the overall low incidence of PML associated with these drugs and the fact that most patients will have other confounding risk factors for developing the disease. There is no known effective treatment available for PML in the non-HIV, non-MS cohort. Recent case studies and series have proposed that pembrolizumab, an anti-PD-1 immune checkpoint inhibitor, may be a potentially efficacious option for these patients. We present two cases of non-HIV, non-MS patients with PML who were treated with pembrolizumab with little clinical benefit. The literature surrounding pembrolizumab use in PML is discussed, with a focus on potential indicators of successful outcomes for patients who receive this therapy.

The Development of Expertise in Radiology: In Chest Radiograph Interpretation, "Expert" Search Pattern May Predate "Expert" Levels of Diagnostic Accuracy for Pneumothorax Identification.

Purpose To investigate the development of chest radiograph interpretation skill through medical training by measuring both diagnostic accuracy and eye movements during visual search. Materials and Methods An institutional exemption from full ethical review was granted for the study. Five consultant radiologists were deemed the reference expert group, and four radiology registrars, five senior house officers (SHOs), and six interns formed four clinician groups. Participants were shown 30 chest radiographs, 14 of which had a pneumothorax, and were asked to give their level of confidence as to whether a pneumothorax was present. Receiver operating characteristic (ROC) curve analysis was carried out on diagnostic decisions. Eye movements were recorded with a Tobii TX300 (Tobii Technology, Stockholm, Sweden) eye tracker. Four eye-tracking metrics were analyzed. Variables were compared to identify any differences between groups. All data were compared by using the Friedman nonparametric method. Results The average area under the ROC curve for the groups increased with experience (0.947 for consultants, 0.792 for registrars, 0.693 for SHOs, and 0.659 for interns; P = .009). A significant difference in diagnostic accuracy was found between consultants and registrars (P = .046). All four eye-tracking metrics decreased with experience, and there were significant differences between registrars and SHOs. Total reading time decreased with experience; it was significantly lower for registrars compared with SHOs (P = .046) and for SHOs compared with interns (P = .025). Conclusion Chest radiograph interpretation skill increased with experience, both in terms of diagnostic accuracy and visual search. The observed level of experience at which there was a significant difference was higher for diagnostic accuracy than for eye-tracking metrics. (©) RSNA, 2016 Online supplemental material is available for this article.

The impact of headache disorders: a prospective analysis of headache referrals to outpatient and inpatient neurology and emergency services in an Irish University teaching hospital.

BACKGROUND: Headache represents a significant proportion of disability globally in general practice, neurology outpatient settings, and emergency departments. There is scant literature regarding the impact of headache on healthcare services in Ireland. AIMS: We aimed to investigate headache burden across the emergency department, inpatient stays, and neurology outpatient department referrals in an Irish University teaching hospital. METHODS: We prospectively collected data regarding emergency department presentations, inpatient neurology consultations, and neurology outpatient referrals for patients with headache between 13th January and 8th March 2020. Data were analyzed using descriptive statistics. RESULTS: There were 180 emergency department attendances, 50 inpatient consultations, and 76 outpatient referrals with headache. Neurological examinations were often incomplete; neuroimaging was commonly employed. Migraine was the most frequent headache diagnosis at discharge in the emergency department and among inpatients after neurology review. Diagnostic uncertainty was identified-33% of patients left the emergency department with no diagnosis, and "unknown/unspecified headache" was recorded on 49% of outpatient referrals and 30% of inpatient consult requests. Medication overuse headache coexisted with migraine in nine patients in the inpatient group. Prophylaxis had been trialed in 56% of patients with migraine referred to outpatients. CONCLUSIONS: Primary headache disorders have a large impact on hospital services. Diagnostic uncertainty is common; neuroimaging is relied upon. Appropriate care pathways, education, and resource allocation should be prioritized.

Decision Making and Variation in Radiation Exposure Factor Selection by Radiologic Technologists.

The goal of radiographic imaging is to produce a diagnostically useful image while minimizing patient radiation dose. This study aimed to review variations in exposure factor selection by radiologic technologists for virtual patients with varying body mass index characteristics. Eleven technologists were asked to assign exposure parameters (kVp, mAs, source-to-image receptor distance, and grid use) to 10 computer-generated patient images for each of four radiographic examinations (anteroposterior [AP] shoulder; AP lumbar spine; lateral lumbar spine; AP portable chest). The virtual patients represented five body mass index categories-underweight, healthy weight, overweight, obese, and superobese. As participants assigned exposures, their visual patterns were recorded by a Tobii TX300 eye-tracker. Significant (P < .05) correlation was found between radiographer age/experience and assignment of mAs for AP shoulder and lumbar examinations. Greater age/experience correlated with higher mAs for the AP shoulder examination, but with lower values for lumbar examinations. Strong correlations also existed between times to first fixations on relevant anatomic areas, and kVp/mAs values existed for the AP portable chest examination. Exposure selection differences related to age/experience highlight inconsistencies in the practice of exposure parameter setting. The reason for these inconsistencies requires further investigation, and how to address deficiencies in practice requires consideration to optimize safe patient care. Because of the small sample size used, further research into the relationship between visual factors and individual examinations is suggested, after the findings regarding the AP portable chest examination.