JULY 2024

July 2024—Like a long-awaited second act, the FDA’s final rule regulating laboratory-developed tests as medical devices took the stage this spring. As with any FDA performance, this one opened to mixed reviews. The spring curtain-raising followed the earlier proposed rule from last October, which drew some 6,500 responses during the public comment period. If that was an out-of-town tryout, no one quite knew what to expect from the rewrite, or if there would even be one. As it turns out, there were indeed changes, but they didn’t necessarily bring clarity. As Jane Pine Wood, counsel for McDonald Hopkins, puts it, the final rule “certainly raised a whole lot more questions than it answered.” The rule calls for a four-year, five-stage phaseout policy with the FDA enacting greater oversight of in vitro diagnostic products that are offered as LDTs. Stage one, beginning on May 6, 2025, calls for labs to comply with medical device reporting requirements, correction and removal reporting requirements, and quality system requirements regarding complaint files.

July 2024—With the Food and Drug Administration approval in May of two HPV self-collection devices for use in clinic settings, physicians in and out of the laboratory are optimistic the approach can reach underscreened patients, even if FDA approval is only a first step.

July 2024—A Mayo Clinic project is “democratizing artificial intelligence,” its leaders say, by enabling pathologists with varying levels of AI expertise—most of whom had never before participated in an AI project—to create and implement algorithms.

July 2024—Earlier this year the laboratory at King Salman Armed Forces Hospital joined more than 120 other Saudi labs in achieving CAP accreditation. And it did so with a boost from LEAP. The 665-bed hospital needed to adopt standards for nearly all technical specialties and comply with more than 1,000 CAP requirements.

July 2024—In patients with advanced non-small cell lung cancer, a validated PD-L1 immunohistochemistry expression assay should be used, with other targetable genomic biomarker assays where appropriate, for the selection of immune checkpoint inhibitor therapies. And the appropriate validation should be performed on all specimen types and fixatives. Those are two of the six recommendations of the CAP, Association for Molecular Pathology, International Association for the Study of Lung Cancer, Pulmonary Pathology Society, and LUNGevity Foundation, released in April and now in print in their PD-L1 and tumor mutation burden testing guideline for the selection of such therapies.

July 2024—The term value-based care is spoken of often, but what part do laboratories play in it and how can they be paid for it? What is Medicare 2030, and what does it mean for laboratories? How can AI be used to practice the medicine of tomorrow? Myra Wilkerson, MD, in speaking in May at the Pathology Informatics Summit, answered these and other questions. She is chair of the Department of Laboratory Medicine and of the Diagnostic Medicine Institute at Geisinger Health in Danville, Pa. She is a founding member of the Project Santa Fe Foundation, for which she serves on its board and as treasurer. She opened her talk in May about Project Santa Fe’s Clinical Lab 2.0 model—what it looks like now and the work they’re doing. We bring to you here what she shared there.

July 2024—The CAP’s hematopathology online education program, HPATH, is now in its 10th year, with real-world cases for which there’s real-time feedback and hundreds enrolled each year. Interesting cases, ones every hematopathologist should have experience with or be familiar with, are what the expert authors of the cases provide, says Kyle Bradley, MD, chair of the CAP Hematopathology Committee and associate professor of hematopathology at Emory University School of Medicine. Each case includes laboratory data, whole slide images, images of ancillary studies, feedback about the case and test results, and self-assessment questions. “And some of the high quality comes from brevity,” Dr. Bradley says. “We whittle down a lot of information into something very manageable and high yield for busy pathologists.”

July 2024—The University of Maryland Medical Center is one of many sites using low titer O whole blood in trauma cases. As of May, 720 patients at UMMC had received whole blood, and that number of patients treated since the program’s start in 2021 speaks for itself, says Bryon P. Jackson, MD, MHA, Midtown Campus laboratory director and director of blood management and associate director of transfusion medicine services.

July 2024—Instruments, assays, patient flow, and IT were some of what laboratory directors and IVD company representatives spoke of when CAP TODAY publisher Bob McGonnagle convened the group online on May 3. Here’s what they said about what instruments and assays are deployed where and the considerations that come into play in large health systems.

July 2024—Remote sign-out has become a major issue for pathologists, spurred in large part by the COVID-19 pandemic and the CAP’s advocacy efforts that led to our ability to sign out cases from other locations. The Centers for Medicare and Medicaid Services has allowed remote sign-out to continue long after the public health emergency was declared over and is considering making this a permanent rule. I recognize how popular remote sign-out has become and have enjoyed many of its advantages in my own practice. However, I also see a few possible unintended consequences that I think are very important for us to consider before we let things get too far.

July 2024—People with sickle cell disease may undergo treatment with the medication voxelotor, which can increase hemoglobin levels and help reduce hemolysis. A clinician treating a sickle cell disease patient with voxelotor may want to know the whole blood concentration of the drug to better monitor the patient’s treatment response, inform therapy, or confirm the patient is complying with the directions for use of the drug. Voxelotor binds to the alpha subunit of hemoglobin and results in the hemoglobin molecule being more likely to stay in the oxygenated conformation. In vivo concentrations of voxelotor cannot be measured in most clinical settings. However, voxelotor has been found to cause peak splitting in common forms of hemoglobin measurement, such as capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC)—that is, the classic peaks for each hemoglobin species split into a peak that has bound drug and a peak that does not.

July 17, 2024—Diasorin announced that the FDA has granted de novo authorization for the Simplexa C. auris Direct kit to test patients suspected of Candida auris colonization and aid in preventing potential spread in health care settings.

July 2024—The 2022 International Society of Urological Pathology consensus conference on urinary bladder cancer working group two was tasked with providing evidence-based proposals on applying grading to noninvasive urothelial carcinoma with mixed grades; invasive urothelial carcinoma, including subtypes and divergent differentiations; and pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has an intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component.

July 2024—Telomeres are repetitive DNA sequences at the end of a chromosome that protect the chromosome from damage. They are maintained in equilibrium, as continual shortening at each round of DNA replication is counterbalanced by the de novo addition of telomere sequence repeats by telomerase. Failure to maintain the length distribution leads to short telomere syndromes that manifest as age-related degenerative diseases, such as pulmonary fibrosis, immunodeficiency, and bone marrow failure. In contrast, long telomeres can predispose people to cancer. Mutations that increase telomerase expression are one of the most common cancer-associated molecular findings.

July 2024—The integration of machine learning models into pathology has revolutionized the field, offering new functionalities and workflows. Numerous machine learning (ML) models are commercially available, and organizations with computational pathology resources can develop their own. These models, whether or not they are imaging based, are intended to enhance clinical practice. However, no formal guidelines pertaining to verifying or validating such systems are available. Therefore, the authors proposed recommendations for evaluating ML systems that are based on evidence and literature that address, among other factors, the scope, strengths, and limitations of the technology.

July 2024 Q. Insulin assays traditionally have been used to work up hypoglycemia, but we are noticing more and more requests for insulin and C-peptide testing. Is there a reason for this shift? Read answer. Q. How should a lot-to-lot formalin comparison be done? Read answer.

July 2024—Earlier this summer, Danbury Hospital completed its first academic year using an integrated pathology informatics curriculum that introduced informatics exercises into seven of the pathology residency program’s 18 rotations. “The goal is for residents to learn informatics alongside the pathology workflows where they can apply it,” says Samuel Barasch, MD, medical director of cytopathology at the Danbury, Conn.-based hospital, part of the Nuvance Health Network.

July 2024—The CAP, Association for Molecular Pathology, and Society for Immunotherapy of Cancer released in June their recommendations for tumor mutational burden assay validation and reporting. The joint publication summarizes the existing knowledge and challenges related to TMB testing. The authors make 13 recommendations related to testing, reporting, and publications on TMB assays.

July 16, 2024—T-Neuro Pharma announced the publication of a landmark research article in Proceedings of the National Academy of Sciences (Panwar A, et al. Proc Natl Acad Sci USA. 2024;121(29):e2401420121).