Computerized adaptive test strategies for the matrix reasoning subtest of the Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV).

OBJECTIVE: Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test - the 26-item Matrix Reasoning subtest of the WAIS-IV - might be used more efficiently if it were administered using computerized adaptive testing (CAT). METHOD: Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model. Simulated CAT results were generated to examine optimal short forms using fixed-length CATs of 3, 6, and 12 items and scores were compared to the original full subtest score. CAT models further explored how many items were needed to achieve a selected precision of measurement (standard error ≤ .40). RESULTS: The fixed-length CATs of 3, 6, and 12 items correlated well with full-length test results (with r = .90, .97 and .99, respectively). To achieve a standard error of .40 (approximate reliability = .84) only 3-7 items had to be administered for a large percentage of individuals. CONCLUSIONS: This proof-of-concept investigation suggests that the widely used Matrix Reasoning subtest of the WAIS-IV might be shortened by more than 70% in most examinees while maintaining acceptable measurement precision. If similar savings could be realized in other tests, the accessibility of neuropsychological assessment might be markedly enhanced, and more efficient time use could lead to broader subdomain assessment.

Bone marrow Ki-67 index is of prognostic value in newly diagnosed multiple myeloma.

BACKGROUND: Ki-67 is an index of proliferative activity and is an established predictive and prognostic marker in multiple malignancies. However, its prognostic relevance in multiple myeloma (MM) is unclear. We investigated the relationship between Ki-67 expression and survival outcomes in MM in the era of novel therapies. METHODS: We interrogated our database to identify patients with MM, newly diagnosed between July 1, 2013 and December 31, 2020, with Ki-67 expression assessed by immunohistochemistry (IHC) on bone marrow biopsies. Using an established threshold of 5% we defined Ki-67low (≤5%) and Ki-67high (>5%) subgroups for association with progression-free survival (PFS) and overall survival (OS). RESULTS: Of 167 patients included: 53 (31.7%) had Ki-67high and 114 had Ki-67low. More patients with R-ISS 3 had Ki-67high (22.2% vs. 9.7%). The gain of 1q21 was overrepresented in the Ki-67high group (28% vs. 8%). Median PFS in the Ki-67low group was 3.1 years, and in the Ki-67high group 1.6 years (log-rank p < .001, HR: 1.9). Median OS was not reached in the Ki-67low vs. 4.8 years in the Ki-67high cohort (HR: 1.9; log-rank test: p = .018). In the multivariable modeling, after adjusting for other risk factors, HR for Ki-67high versus Ki-67low was 2.4 (p < .001) for PFS and 2.1 (p = .026) for OS. CONCLUSIONS: Our results demonstrate that a high Ki-67 index (>5%) is an independent prognostic marker associated with worse OS and PFS in newly diagnosed MM. IHC staining for Ki-67 on bone marrow biopsies could be easily adopted as a prognostic biomarker for MM in economically constrained healthcare settings.

Peripheral blood smear findings in a kidney transplant recipient with disseminated histoplasmosis and elevated Aspergillus galactomannan.

We report a case of disseminated histoplasmosis in a renal transplant recipient who presented with a nodular pulmonary lesion and elevated serum and bronchoalveolar lavage (BAL) Aspergillus galatomannan. This almost led to an erroneous diagnosis of invasive aspergillosis since the donor respiratory tract was known to be colonized with Aspergillus terreus. However, distinctive intracelluar Histoplasma yeasts on peripheral blood smear led to early diagnosis and appropriate treatment. The cross-reactivity between Aspergillus galactomannan and Histoplasma antigen is discussed further.

ALK Fusions in a Wide Variety of Tumor Types Respond to Anti-ALK Targeted Therapy.

BACKGROUND: Genomic fusions of the anaplastic lymphoma kinase gene (ALK) are a well-established therapy target in non-small cell lung cancer (NSCLC). From a survey of 114,200 clinical cases, we determined the prevalence of ALK rearrangements (rALK) in non-NSCLC tumors and report their responsiveness to therapies targeting ALK. MATERIALS AND METHODS: Comprehensive genomic profiling of 114,200 relapsed and metastatic malignancies, including both solid tumors and hematolymphoid cancers, was performed using a hybrid-capture, adaptor ligation-based next-generation sequencing assay. RESULTS: Of 114,200 clinical samples, 21,522 (18.8%) were NSCLC and 92,678 (81.2%) were other tumor types. Of the 876 (0.8%) cases with ALK fusions (fALK) or rALK, 675 (77.1%) were NSCLC and 201 (22.9%) were other tumor types. ALK fusions were significantly more frequent in NSCLC (3.1%) than non-NSCLC (0.2%; p < .0001). Patients with non-NSCLC tumors harboring fALK were significantly younger (p < .0001) and more often female (p < .0001) than patients with fALK-positive NSCLC. EML4 was more often the fusion partner in NSCLC (83.5%) versus non-NSCLC tumors (30.9%; p < .0001). CONCLUSION: ALK rearrangements can be identified in a wide variety of epithelial and mesenchymal malignancies beyond NSCLC. Anti-ALK therapies can be effective in non-NSCLC tumors driven by fALK, and further study of therapies targeting ALK in clinical trials involving a wider variety of cancer types appears warranted. IMPLICATIONS FOR PRACTICE: Rearrangements involving the ALK gene have been detected in dozens of cancer types using next-generation sequencing. Patients whose tumors harbor ALK rearrangements or fusions respond to treatment with crizotinib and alectinib, including tumors not normally associated with ALK mutations, such as non-Langerhans cell histiocytosis or renal cell carcinoma. Comprehensive genomic profiling using next-generation sequencing can detect targetable ALK fusions irrespective of tumor type or fusions partner.

Hypotensive Transfusion Reaction Treated With Vasopressin in a Patient Taking an Angiotensin-Converting Enzyme Inhibitor: A Case Report.

Hypotensive transfusion reactions, which account for almost 3% of all transfusion reactions, are associated with patients treated with angiotensin-converting enzyme inhibitors. The current hypothesis suggests that they are caused by bradykinin-induced vasodilation in the absence of allergic, hemolytic, or septic mechanisms. The hypotension observed frequently is unresponsive to conventional therapy with catecholamines. The suggested intraoperative management includes cessation of transfusion and washing red blood cells before blood replacement. We present a patient experiencing a severe intraoperative hypotensive transfusion reaction, unresponsive to epinephrine and norepinephrine, in whom we were able to restore blood pressure and continue the transfusion of blood and plasma by infusing vasopressin.

Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms.

UNLABELLED: Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (non-LCH), respectively. The discovery of BRAF(V600E) mutations in approximately 50% of these patients provided the first molecular therapeutic target in histiocytosis. However, recurrent driving mutations in the majority of patients with BRAF(V600E)-wild-type non-LCH are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole-exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in patients with BRAF(V600E)-wild-type non-LCH. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of patients with MAP2K1- and ARAF-mutated non-LCH using MEK and RAF inhibitors, respectively, resulted in clinical efficacy, demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders. SIGNIFICANCE: We provide the first description of kinase fusions in systemic histiocytic neoplasms and activating ARAF and MAP2K1 mutations in non-Langerhans histiocytic neoplasms. Refractory patients with MAP2K1- and ARAF-mutant histiocytoses had clinical responses to MEK inhibition and sorafenib, respectively, highlighting the importance of comprehensive genomic analysis of these disorders.