John Byrd

BACKGROUND: We evaluated the frequency of genomic testing and treatment patterns by age category in patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated in both academic- and community-based health systems within a single Midwestern State. METHODS: Retrospective analysis of data from the Indiana University Health System Enterprise Data Warehouse and two local cancer registries, of 629 patients aged ≥18 years with ND AML during 2011-2018...

Cellular senescence is a durable cell cycle arrest as a result of the finite proliferative capacity of cells. Senescence responds to both intrinsic and extrinsic cellular stresses, such as aging, mitochondrial dysfunction, irradiation, and chemotherapy. Here, we report on the use of mass cytometry (MC) to analyze multiple model systems and demonstrate MC as a platform for senescence analysis at the single-cell level. We demonstrate changes to p16 expression, cell cycling fraction, and histone tail modifications in several established senescent model systems and using isolated human T cells...

No abstract text is available yet for this article.

We evaluated outcomes of AML patients with central nervous system (CNS) involvement at two academic institutions.Fifty-two adult patients were identified. Neurologic symptoms were reported in 69%of patients, with headache the most common (33%). 84% ( n  = 42) of patients cleared their cerebrospinal fluid (CSF), with a median number of one dose ofintrathecal (IT)chemotherapy. Of these patients, 21% ( n  = 9) had a CSF relapse, with 67% ( n  = 6) of those experiencing CSF relapse also having concurrent bone marrow relapse...

Optimization of degrader properties is often a challenge due to their beyond-rule-of-5 nature. Given the paucity of known E3 ligases and the often-limited choice of ligands with varied chemical structures for a given protein target, degrader linkers represent the best position within the chimeric molecules to modify their overall physicochemical properties. In this work, a series of AT7519-based CDK9 degraders was assembled using click chemistry, facilitating the tuning of aqueous solubility and lipophilicity while retaining their linker type and molecular weight...

ELEVATE-RR demonstrated noninferior progression-free survival and lower incidence of key adverse events (AEs) with acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia. We further characterize AEs of acalabrutinib and ibrutinib via post hoc analysis. Overall and exposure-adjusted incidence rate was assessed for common Bruton tyrosine kinase inhibitor-associated AEs and for selected events of clinical interest (ECIs). AE burden scores based on previously published methodology were calculated for AEs overall and selected ECIs...

Neuroinvasive La Crosse virus disease remains the primary cause of pediatric arboviral encephalitis in the USA. In spite of the persistent public health burden, there are limited entomologic surveillance options that target both native and invasive La Crosse virus (LACV) vectors. In this study we used Reiter/Cummings tacklebox gravid traps to compare white oak (Quercus alba) and hay (predominately Festuca arundinacea) infusions within a LACV-endemic area of western North Carolina. Paired gravid traps (approximately 1,728 total trap-hours for each infusion) yielded 485 mosquitoes, with 3 species (Aedes japonicus [n = 265], Ae...

INTRODUCTION: Chronic lymphocytic leukemia (CLL) commonly affects older adults. However, few studies have examined the relationship between baseline geriatric domains and clinical outcomes in this population. Here, we aim to evaluate the use of a comprehensive geriatric assessment in older (>65 years) untreated patients with CLL to predict outcomes. MATERIALS AND METHODS: We conducted a planned analysis of 369 patients with CLL age 65 or older treated in a phase 3 randomized trial of bendamustine plus rituximab versus ibrutinib plus rituximab versus ibrutinib alone (A041202)...

PURPOSE: Acquired mutations in Bruton's tyrosine kinase (BTK) or phospholipase C-γ2 (PLCG2) genes are associated with clinical progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) treated with BTK inhibitors. Data on mutation rates in patients without PD on ibrutinib treatment are limited. EXPERIMENTAL DESIGN: We evaluated frequency and time to detection of BTK and PLCG2 mutations in peripheral blood samples from 388 patients (n=238) or relapsed/refractory (n=150) CLL across 5 clinical trials...

No abstract text is available yet for this article.

The 2022 International Society of Hip Preservation (ISHA) physiotherapy agreement on assessment and treatment of greater trochanteric pain syndrome (GTPS) was intended to present a physiotherapy consensus on the assessment and surgical and non-surgical physiotherapy management of patients with GTPS. The panel consisted of 15 physiotherapists and eight orthopaedic surgeons. Currently, there is a lack of high-quality literature supporting non-operative and operative physiotherapy management. Therefore, a group of physiotherapists who specialize in the treatment of non-arthritic hip pathology created this consensus statement regarding physiotherapy management of GTPS...

No abstract text is available yet for this article.

Survival of patients with acute myeloid leukemia (AML) is influenced by genetic factors, age, and race. Social deprivation is increasingly recognized as an important contributor to disparities in cancer outcomes, but studies of adult AML are lacking. We analyzed associations between social deprivation index (SDI) and outcome in 1,893 patients with AML treated on Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology frontline protocols. Patients with low (first quartile, lowest deprivation) and high (quartiles 2-4) SDI were analyzed for associations with baseline clinical, cytogenetic and molecular features, and outcomes...

New England Journal of Medicine, Volume 388, Issue 19, Page 1812-1813, May 2023.

OBJECTIVE: It is suggested that hidradenitis suppurativa (HS) is more prevalent and causes greater morbidity in Black patients than in White. Clinical data are however lacking. PATIENTS AND METHODS: We therefore describe HS risk factors, disease severity and clinical phenotypes in the Blacks and Whites. Patients referred for HS between 1984 and 2019 at the Johns Hopkins Hospital were identified using the Pathology Data System (PDS). Clinical and sociodemographic characteristics were extracted and the van der Zee & Jemec HS clinical phenotypes were recovered...

BACKGROUND: Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population. METHODS: This was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two-stage design...

BACKGROUND: Health services research can benefit from frontline clinician input across all stages of research, yet their key perspectives are often not meaningfully engaged. OBJECTIVE: How can we improve clinician engagement in research? DESIGN: Convenience sampling and semi-structured interviews followed by descriptive content analysis with an inductive approach, followed by group participatory listening sessions with interviewees to further contextualize findings...

Cyclin-dependent kinase 9 (CDK9) is a promising therapeutic target in multiple cancer types, including acute myeloid leukemia (AML). Protein degraders, also known as proteolysis targeting chimeras (PROTACs), have emerged as tools for the selective degradation of cancer targets, including CDK9, complementing the activity of traditional small-molecule inhibitors. These compounds typically incorporate previously reported inhibitors and a known E3 ligase ligand to induce ubiquitination and subsequent degradation of the target protein...

OBJECTIVES: As lifespans increase in people with HIV (PWH), there is concern that age-related neurodegenerative disorders may contribute to cognitive decline. We asked whether brain accumulation of Alzheimer's disease (AD)-associated proteins amyloid-beta (Aβ) and hyperphosphorylated tau (p-tau) predicted cognitive performance in middle-aged PWH. METHODS: In a prospectively followed, cognitively-characterized autopsy sample of 135 PWH, we used immunohistochemistry to assess Aβ plaques and neuronal p-tau in medial temporal and lateral frontal lobes...

No abstract text is available yet for this article.