Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).

Since 2014, programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors. Of these approved drug/disease combinations, a subset also has regulatory agency-approved, commercially available companion/complementary diagnostic assays that were clinically validated using data from their corresponding clinical trials. The objective of this document is to provide evidence-based guidance to assist clinical laboratories in establishing fit-for-purpose PD-L1 biomarker assays that can accurately identify patients with specific tumor types who may respond to specific approved immuno-oncology therapies targeting the PD-1/PD-L1 checkpoint. These recommendations are issued as 38 Guideline Statements that address (i) assay development for surgical pathology and cytopathology specimens, (ii) reporting elements, and (iii) quality assurance (including validation/verification, internal quality assurance, and external quality assurance). The intent of this work is to provide recommendations that are relevant to any tumor type, are universally applicable and can be implemented by any clinical immunohistochemistry laboratory performing predictive PD-L1 immunohistochemistry testing.

Pediatric near-drowning events: do they warrant trauma team activation?

BACKGROUND: The purpose of this study was to determine the incidence of traumatic injuries, factors associated with mortality, and need for pediatric trauma surgery involvement for drowning and near-drowning events in children. MATERIALS AND METHODS: An institutional review board-approved, retrospective chart review was performed at three American College of Surgeons-verified Pediatric Trauma Centers (2011-2014). Patients with International Classification of Diseases, Ninth Revision, codes or E-codes for fatal-nonfatal drowning, fall into water, accidental drowning, or submersion were included. Bivariate analysis using chi-square or Fisher exact test for nominal variables and Mann-Whitney U test for continuous variables was performed. RESULTS: A total of 363 patients (median 3.17 y [18 d-17 y]) met the inclusion criteria. Drowning sites included pool (81.5%), bathtub (12.9%), and natural water (5.2%). A witnessed fall or dive was reported in 34.9%, 57.9% did not fall or dive, and 7% had an unwitnessed event. Most patients did not undergo cervical spine (83%) or brain imaging (75.5%). Seven patients (1.92%) had associated soft tissue injuries. Two patients (0.006%) received surgical intervention (bronchoscopy and extracorporeal membrane oxygenation) within 24 h of presentation. Only 2.2% were admitted to the pediatric trauma service. The percentage of patients discharged home from the emergency department was 10.2%. Overall mortality was 12.4%. Factors associated with mortality included transfer from outside hospital (P = 0.016), presence of hypothermia on arrival (P < 0.0001), Glasgow Coma Scale of 3 on arrival (P < 0.0001), drowning in a pool (P = 0.013), or undergoing brain cooling at admission (P = 0.011). CONCLUSIONS: This is the largest reported series of pediatric near-drowning events. Only rarely did patients require immediate surgical attention and the majority were admitted to nonsurgical services. These data suggest that routine pediatric trauma surgery service involvement in patients with near-drowning events may be unnecessary.

Noninvasive hemoglobin measurement in pediatric trauma patients.

INTRODUCTION: Hemorrhage is a major cause of preventable death secondary to traumatic injury. Diagnosis often requires multiple blood draws, which are psychologically stressful in pediatric patients. The Pronto device is a pulse co-oximeter that measures the total hemoglobin level using multiple wavelengths of light. The purpose of this study was to evaluate the accuracy of the noninvasive hemoglobin measurements relative to current invasive and point of care testing methods in pediatric trauma patients. METHODS: We performed a prospective observational trial involving patients younger than 17 years presenting to a Level I pediatric trauma center. Following admission, blood was sampled from each patient for testing using an i-Stat device (point-of-care hemoglobin) and a complete blood count within our core laboratory (invasive hemoglobin). Noninvasive hemoglobin analysis was performed within 15 minutes of phlebotomy. Data were evaluated using Spearman correlation and Bland-Altman analysis. RESULTS: Over 2 years, 114 patients had attempted noninvasive hemoglobin measurements, with a success rate of 89%. Mean ± SD age was 9.2 ± 5.1 years. Ninety percent of admissions were for blunt injury, 3% penetrating, 5% near drowning, and 1% burns. Mean invasive hemoglobin was 12.6 ± 1.9 g/dL, mean point-of-care hemoglobin was 12.2 ± 2.0 g/dL, and mean noninvasive hemoglobin was 12.3 ± 1.6 g/dL. Noninvasive hemoglobin values were strongly correlated with both invasive and point of care measurements (R = 0.672 and R = 0.645, respectively; p < 0.001). Bland-Altman analysis comparing noninvasive to point-of-care and invasive hemoglobin levels resulted in an estimated bias of -0.39 and -0.49, respectively. CONCLUSION: Noninvasive hemoglobin values had excellent correlation with both invasive and point-of-care hemoglobin measurements, although the device was not successful for all patients. Given the rapid availability of results and the lack of requirement of venipuncture, noninvasive hemoglobin monitoring may be a valuable adjunct in the initial evaluation and monitoring of pediatric trauma patients. LEVEL OF EVIDENCE: Diagnostic test study, level II.

Guidelines from the Canadian Association of Pathologists for establishing a telepathology service for anatomic pathology using whole-slide imaging.

The use of telepathology for clinical applications in Canada has steadily become more attractive over the last 10 years, driven largely by its potential to provide rapid pathology consulting services throughout the country regardless of the location of a particular institution. Based on this trend, the president of the Canadian Association of Pathologists asked a working group consisting of pathologists, technologists, and healthcare administrators from across Canada to oversee the development of guidelines to provide Canadian pathologists with basic information on how to implement and use this technology. The guidelines were systematically developed, based on available medical literature and the clinical experience of early adopters of telepathology in Canada. While there are many different modalities and applications of telepathology, this document focuses specifically on whole-slide imaging as applied to intraoperative pathology consultation (frozen section), primary diagnosis, expert or second opinions and quality assurance activities. Applications such as hematopathology, microbiology, tumour boards, education, research and technical and/or standard-related issues are not covered.

Suggested guidelines for immunohistochemical techniques in veterinary diagnostic laboratories.

This document is the consensus of the American Association of Veterinary Laboratory Diagnosticians (AAVLD) Subcommittee on Standardization of Immunohistochemistry on a set of guidelines for immunohistochemistry (IHC) testing in veterinary laboratories. Immunohistochemistry is a powerful ancillary methodology frequently used in many veterinary laboratories for both diagnostic and research purposes. However, neither standardization nor validation of IHC tests has been completely achieved in veterinary medicine. This document addresses both issues. Topics covered include antibody selection, fixation, antigen retrieval, antibody incubation, antibody dilutions, tissue and reagent controls, buffers, and detection systems. The validation of an IHC test is addressed for both infectious diseases and neoplastic processes. In addition, storage and handling of IHC reagents, interpretation, quality control and assurance, and troubleshooting are also discussed. Proper standardization and validation of IHC will improve the quality of diagnostics in veterinary laboratories.

Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets.

Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus (SARS-CoV) is a serious emerging human infectious disease. In this report, we immunized ferrets (Mustela putorius furo) with recombinant modified vaccinia virus Ankara (rMVA) expressing the SARS-CoV spike (S) protein. Immunized ferrets developed a more rapid and vigorous neutralizing antibody response than control animals after challenge with SARS-CoV; however, they also exhibited strong inflammatory responses in liver tissue. Inflammation in control animals exposed to SARS-CoV was relatively mild. Thus, our data suggest that vaccination with rMVA expressing SARS-CoV S protein is associated with enhanced hepatitis.