Browsing by Subject "Hematologic malignancy"

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    Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study
    (Oxford University Press, 2024) Bergin, Stephen P.; Chemaly, Roy F.; Dadwal, Sanjeet S.; Hill, Joshua A.; Lee, Yeon Joo; Haidar, Ghady; Luk, Alfred; Drelick, Alexander; Chin-Hong, Peter V.; Benamu, Esther; Khawaja, Fareed; Nanayakkara, Deepa; Papanicolaou, Genovefa A.; Butkus Small, Catherine; Fung, Monica; Barron, Michelle A.; Davis, Thomas; McClain, Micah T.; Maziarz, Eileen K.; Madut, Deng B.; Bedoya, Armando D.; Gilstrap, Daniel L.; Todd, Jamie L.; Barkauskas, Christina E.; Bigelow, Robert; Leimberger, Jeffrey D.; Tsalik, Ephraim L.; Wolf, Olivia; Mughar, Mona; Hollemon, Desiree; Duttagupta, Radha; Lupu, Daniel S.; Bercovici, Sivan; Perkins, Bradley A.; Blauwkamp, Timothy A.; Fowler, Vance G., Jr.; Holland, Thomas L.; Pathology and Laboratory Medicine, School of Medicine
    Background: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. Methods: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. Results: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%). Conclusions: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing.
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    Role of epigenetic in cancer biology, in hematologic malignancies and in anticancer therapy
    (Frontiers Media, 2024-09-06) Nwabo Kamdje, Armel Hervé; Dongmo Fogang, Hervet Paulain; Mimche, Patrice N.; Dermatology, School of Medicine
    Major epigenetic changes are associated with carcinogenesis, including aberrant DNA methylations and post-translational modifications of histone. Indeed evidence accumulated in recent years indicates that inactivating DNA hypermethylation preferentially targets the subset of polycomb group (PcG) genes that are regulators of developmental processes. Conversely, activating DNA hypomethylation targets oncogenic signaling pathway genes, but outcomes of both events lead in the overexpression of oncogenic signaling pathways that contribute to the stem-like state of cancer cells. On the basis of recent evidence from population-basedclinical and experimental studies, we hypothesize that factors associated with risk for developing a hematologic malignancy (HM), such as metabolic syndrome and chronic inflammation, may trigger epigenetic mechanisms to increase the transcriptional expression of oncogenes and activate oncogenic signaling pathways. Signaling pathways associated with such risk factors include but are not limited to pro-inflammatory nuclear factor κB (NF-κB) and mitogenic, growth, and survival Janus kinase (JAK) intracellular non-receptor tyrosine kinase-triggered pathways. The latter includes signaling pathways such as transducer and activator of transcription (STAT), Ras GTPases/mitogen-activated protein kinases (MAPKs)/extracellular signal-related kinases (ERKs), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and β-catenin pathways. Recent findings on epigenetic mechanisms at work in the biology of cancer and in HMs and their importance in the etiology and pathogenesis of these diseases are herein summarized and discussed. Furthermore, the role of epigenetic processes in the determination of biological identity, the consequences for interindividual variability in disease clinical profile, and the potential of epigenetic drugs in HMs are also considered.