Tuberculosis is a leading cause of infectious disease–related death worldwide; however, only 10% of people infected with Mycobacterium tuberculosis develop disease. Factors that contribute to protection could prove to be promising targets for M. tuberculosis therapies. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify potential human candidate markers of host defense by studying gene expression profiles of macrophages, cells that, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene coexpression network analysis revealed an association between the cytokine interleukin-32 (IL-32) and the vitamin D antimicrobial pathway in a network of interferon-γ– and IL-15–induced “defense response” genes. IL-32 induced the vitamin D–dependent antimicrobial peptides cathelicidin and DEFB4 and to generate antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. In addition, the IL-15–induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent compared with active tuberculosis or healthy controls and a coexpression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15–induced gene network. As maintaining M. tuberculosis in a latent state and preventing transition to active disease may represent a form of host resistance, these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis.
PURPOSE Performance status (PS) is a key factor in oncologic decision making, but conventional scales used to measure PS vary among observers. Consumer-grade biometric sensors have previously been identified as objective alternatives to the assessment of PS. Here, we investigate how one such biometric sensor can be used during a clinic visit to identify patients who are at risk for complications, particularly unexpected hospitalizations that may delay treatment or result in low physical activity. We aim to provide a novel and objective means of predicting tolerability to chemotherapy. METHODS Thirty-eight patients across three centers in the United States who were diagnosed with a solid tumor with plans for treatment with two cycles of highly emetogenic chemotherapy were included in this single-arm, observational prospective study. A noninvasive motion-capture system quantified patient movement from chair to table and during the get-up-and-walk test. Activity levels were recorded using a wearable sensor over a 2-month period. Changes in kinematics from two motion-capture data points pre- and post-treatment were tested for correlation with unexpected hospitalizations and physical activity levels as measured by a wearable activity sensor. RESULTS Among 38 patients (mean age, 48.3 years; 53% female), kinematic features from chair to table were the best predictors for unexpected health care encounters (area under the curve, 0.775 ± 0.029) and physical activity (area under the curve, 0.830 ± 0.080). Chair-to-table acceleration of the nonpivoting knee ( t = 3.39; P = .002) was most correlated with unexpected health care encounters. Get-up-and-walk kinematics were most correlated with physical activity, particularly the right knee acceleration ( t = −2.95; P = .006) and left arm angular velocity ( t = −2.4; P = .025). CONCLUSION Chair-to-table kinematics are good predictors of unexpected hospitalizations, whereas the get-up-and-walk kinematics are good predictors of low physical activity.
This case report aimed to review the bone marrow features of patients with acute myeloid leukemia (AML) treated with isocitrate dehydrogenase 1/2 (IDH1/2) inhibitors. Five patients with AML treated with an IDH1/2 inhibitor were identified and retrospectively reviewed. We described the morphologic and immunophenotypic findings in the bone marrow, as well as ancillary study results. Two patients showed a hypercellular bone marrow with morphologic and immunophenotypic differentiation of blasts. The bone marrow of one patient displayed a hypoplastic phase. Four of the five patients demonstrated unusual morphologic and/or immunophenotypic populations, including basophilia with mild alterations on the myeloid blasts, a small subset of blasts with expression of T-cell markers not seen in the original immunophenotype, a cluster of differentiation 117 (CD117)-positive progenitor population with erythroid differentiation, and another population reminiscent of erythroid differentiation. Unusual morphologic and immunophenotypic populations can be seen in the bone marrows of patients treated with IDH1/2 inhibitors in the presence or absence of definite residual disease. The significance of these populations is uncertain, but further studies could be helpful to understand the meaning of these findings.
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