Low value of inherited thrombophilia testing among patients with stroke or transient ischemic attack: A three-year retrospective study.

BACKGROUND/PURPOSE: Inherited thrombophilia testing in the acute inpatient setting is controversial and expensive, and rarely changes clinical management. We evaluated ordering patterns and results of inpatient inherited thrombophilia testing for patients who presented with an isolated acute ischemic stroke or transient ischemic attack (TIA) without concurrent venous thromboembolism. METHODS: We retrospectively analyzed patients admitted for acute ischemic stroke or TIA between January 1st, 2019 and December 31st, 2021 at Thomas Jefferson University Hospitals in Philadelphia, PA and who underwent inherited thrombophilia testing during the hospital admission. Charts were reviewed to determine stroke risk factors, test results, and clinical management. RESULTS: Among 2108 patients admitted for acute ischemic stroke or TIA (including branch and central retinal artery occlusions) during the study period, the study included 249 patients (median age 49.0 years, 50.2% female) who underwent inpatient testing for factor V Leiden, prothrombin G20210A variant, hyperhomocysteinemia, PAI-1 elevation, and deficiencies of protein C and S and antithrombin. 42.2% of patients had at least one abnormal test, and among the 1035 tests ordered, 14.3% resulted abnormal. However, 28% of abnormal tests were borderline positive antigen or activity assays that likely represented false positives. There was no significant difference in the likelihood of a positive test among patients without stroke risk factors vs those with risk factors (47.1% vs 40.9%, P = .428), nor any significant difference between those under vs over age 50 years (45.7% vs 38.3%, P = .237). No patients with an abnormal result had their clinical management changed as a result. Charges for the tests totaled $468,588 USD. CONCLUSIONS: Inherited thrombophilia testing in the hospital immediately following isolated acute arterial ischemic stroke or TIA was associated with high rates of likely false positive results and was expensive. Positive results did not change clinical management in a single case.

TOMM20 as a Potential Prognostic Biomarker in Chordoma: Results From a High-Volume, Single-Center Study.

OBJECTIVES: As few large studies identify correlative biomarkers in chordoma, our objective was to use our large, single-center chordoma tumor bank to identify novel signaling pathways. METHODS: Clinical and pathologic data for 73 patients with chordoma were retrospectively collected. Tumor microarrays were built from 61 archived chordoma specimens; immunohistochemistry for TOMM20, TIGAR, and MCT1 were performed; and semiquantitative analysis of staining intensity and percentage of positive tumor cells was performed. Average composite scores of MCT1, TIGAR, and TOMM20 expression were compared by disease status and anatomic location. RESULTS: Higher expression of TOMM20 was seen in recurrent and metastatic chordomas compared with primary lesions. Comparing composite scores of primary lesions in patients with primary disease only vs those with recurrent disease showed that TIGAR and TOMM20 expressions are significantly higher in primary lesions, followed by a history of recurrence. A TOMM20 composite score of greater than or equal to 3 significantly decreased overall survival (hazard ratio [HR], 5.83) and recurrence-free survival (HR, 8.95). CONCLUSIONS: Identifying novel signaling pathways that promote chordoma growth and recurrence is critical for developing targeted therapy for chordoma. TOMM20 may be a biomarker associated with chordoma disease progression.

Copper Deficiency Mimicking Myelodysplastic Syndrome: Zinc Supplementation in the Setting of COVID-19.

While copper deficiency is rare, it can have serious consequences, including pancytopenia and neuropathy. This treatable micronutrient deficiency can present very similarly to myelodysplastic syndrome (MDS), a group of myeloid neoplasms which can carry devastating prognoses. Copper deficiency is an essential differential diagnosis in suspected MDS, as it can present with similar laboratory findings, bone marrow biopsy, and clinical picture. While copper deficiency has multiple potential causes, it typically occurs in patients with a predisposing gastrointestinal pathology. One possible cause of copper deficiency is zinc overload. Interestingly, zinc over-supplementation has been prevalent during the COVID-19 pandemic, as some believe that zinc can help prevent COVID-19 infection. Multiple case reports have illustrated the similarities between copper deficiency and MDS. They have also highlighted zinc over-supplementation as a potential cause. The following case report is unique in that our patient lacked gastrointestinal pathology. He still presented with the clinical and laboratory findings of MDS in the setting of copper deficiency. These include anemia, leukopenia, fatigue, and neuropathy. Further, this deficiency was caused by zinc over-supplementation in efforts to prevent COVID-19. The deficiency and the accompanying symptoms were treated with copper supplementation and cessation of zinc intake.