AOH1996 targets mitochondrial dynamics and metabolism in leukemic stem cells via mitochondrial PCNA inhibition.

Cytoplasmic proliferating cell nuclear antigen (PCNA) is highly expressed in acute myeloid leukemia (AML) cells, supporting oxidative metabolism and leukemia stem cell (LSC) growth. We report on AOH1996 (AOH), an oral compound targeting cancer-associated PCNA, which shows significant antileukemic activity. AOH inhibited growth in AML cell lines and primary CD34 + CD38 - blasts (LSC-enriched) in vitro while sparing normal hematopoietic stem cells (HSCs).

Fludarabine melphalan reduced intensity conditioning vs radiation-based myeloablative conditioning in patients undergoing allogeneic transplantation for acute myeloid leukemia with measurable residual disease.

Patients with AML and measurable residual disease (MRD) undergoing allogeneic hematopoietic cell transplantation (HCT) may benefit from myeloablative conditioning (MAC) when feasible to reduce relapse risk. Fludarabine-Melphalan (FluMel) is a common reduced intensity conditioning (RIC) regimen; however, data in MRD+ patients is sparse. We performed a retrospective review of AML patients who underwent their first HCT (2016-2021) without morphologic disease at City of Hope who had pre-transplant marrow evaluated for MRD using multicolor flow cytometry (MFC) and received radiation-based MAC or FluMel conditioning.

Combined Cytokine Blockade Therapy (CCBT) Using Basiliximab and Infliximab for Treatment of Steroid-Refractory Graft-Versus-Host Disease (SR-GvHD).

Background: The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which have historically had limited responses. Combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker) has had limited discussion in the literature.

Methods: Sixty patients with steroid-refractory aGVHD were analyzed.

Venetoclax in combination with a pediatric-inspired regimen for the treatment of newly diagnosed adults with Philadelphia chromosome-negative acute lymphoblastic leukemia.

BCL-2 protein overexpression, common in B-cell acute lymphoblastic leukemia (B-ALL), including the Philadelphia (Ph)-like subtype, mediates leukemic cell survival. We treated 24 patients with 14 days of BCL-2 inhibitor, venetoclax, 400 mg daily (dose level 1) during induction and consolidation cycles combined with the CALGB 10403 regimen in newly diagnosed adults with Ph-negative B-ALL. Median age was 31 (range: 18-53) years, 92% were Hispanic, and 12 (50%) patients had Ph-like ALL.

Impact of spliceosome mutation on outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia patients undergoing allogeneic hematopoietic cell transplantation.

Introduction: Allogeneic Hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The impact of spliceosome mutations on allo-HCT outcome is unclear and further understanding is needed to assess the implications of this class of mutations on risk of relapse, overall survival (OS) and non-relapse mortality (NRM) in order to make decision regarding timing of allo-HCT. We examined the allo-HCT outcomes of MDS/CMML patients based on their spliceosome mutation profile to understand the impact of these mutations on transplant outcomes.

Comparing transplant outcomes in ALL patients after myeloablative conditioning in mismatch-related or unrelated donor settings.

The optimal myeloablative conditioning regimen for ALL patients undergoing hematopoietic cell transplant (HCT) with an alternative donor is unknown. We analyzed HCT outcomes ALL patients (n = 269) who underwent HCT at our center from 2010 to 2020 in complete remission (CR) after FTBI-etoposide and CNI-based GvHD prophylaxis for matched donor HCT (ETOP-package; n = 196) or FTBI-Fludarabine and post-transplant cyclophosphamide (PTCy)-based prophylaxis for HLA- mismatched (related or unrelated) donors (FLU-package; n = 64). Patients in FLU-package showed a significant delay in engraftment (p < 0.

Total Body Irradiation and Fludarabine with Post-Transplantation Cyclophosphamide for Mismatched Related or Unrelated Donor Hematopoietic Cell Transplantation.

Allogeneic hematopoietic cell transplantation (HCT) remains the sole curative treatment for most patients with hematologic malignancies. A well-matched donor (related or unrelated) remains the preferred donor for patients undergoing allogeneic HCT; however, a large number of patients rely on alternative donor choices of mismatched related (haploidentical) or unrelated donors to access HCT. In this retrospective study, we investigated outcomes of patients who underwent mismatched donor (related or unrelated) HCT with a radiation-based myeloablative conditioning MAC regimen in combination with fludarabine, and post-transplantation cyclophosphamide (PTCy) as higher-intensity graft-versus-host disease (GVHD) prophylaxis.

Reduced digit spans and ear dominance using dichotic digits in bimodal cochlear-implant users.

Bimodal stimulation, a cochlear implant (CI) in one ear and a hearing aid (HA) in the other, provides highly asymmetrical inputs. To understand how asymmetry affects perception and memory, forward and backward digit spans were measured in nine bimodal listeners. Spans were unchanged from monotic to diotic presentation; there was an average two-digit decrease for dichotic presentation with some extreme cases of decreases to zero spans.

Acute Onset of Mania and Psychosis in the Context of Long-COVID: A Case Study.

Acute phase COVID-19 has been associated with an increased risk for several mental health conditions, but less is known about the interaction of long COVID and mental illness. Prior reports have linked long COVID to PTSD, depression, anxiety, obsessive compulsive symptoms, and insomnia. This case report describes a novel presentation of mania arising in the context of long COVID symptoms with attention given to possible interacting etiological pathways.

Clinical management of a patient following a granulocyte transfusion from a donor positive for COVID-19.

Granulocyte transfusions are indicated for patients with severe neutropenia and evidence of bacterial or fungal infection who are unresponsive to standard antimicrobial therapy. With a limited expiration time of 24 hours after collection, granulocytes are often transfused before results of infectious-disease screening tests are available, and before a transfusion service can perform a risk assessment if postdonation information is provided after the collection. The case we describe herein demonstrates a clinical scenario meeting indications for granulocyte transfusion, coupled with the clinical management undertaken after the granulocyte donor disclosed a positive result for a COVID-19 self-test taken 1 day after donation.

Differences in Achilles tendon mechanical properties between professional ballet dancers and collegiate athletes utilizing shear wave elastography.

Purpose: To report normative stiffness parameters obtained using shear wave elastography in dorsiflexion from the Achilles tendons in asymptomatic professional ballet dancers and compare them with college-level athletes.

Methods: An Institutional Review Board (IRB)-approved study consists of 28 professional ballet dancers and 64 asymptomatic collegiate athletes. The athletes were further subdivided into runner and non-runner disciplines.

Development and implementation of natural killer cell simultaneous ADCC and direct killing assay.

Assays to quantify natural killer (NK) cell killing efficacy have traditionally focused on assessing either direct killing or antibody dependent cell-mediated cytotoxicity (ADCC) independently. Due to the probability that immunotherapeutic interventions affect NK cell-mediated direct killing and NK cell-mediated ADCC differently, we developed an assay with the capacity to measure NK cell-mediated direct killing and ADCC simultaneously with cells from the same human donor. Specifically, this design allows for a single NK cell population to be split into several experimental conditions (e.

Outcomes of a Remote Cardiac Rehabilitation Program for Patients Undergoing Atrial Fibrillation Ablation: Pilot Study.

Background: Risk factor modification, in particular exercise and weight loss, has been shown to improve outcomes for patients with atrial fibrillation (AF). However, access to structured supporting programs is limited. Barriers include the distance from appropriate facilities, insurance coverage, work or home responsibilities, and transportation.

Test Then Erase? Current Status and Future Opportunities for Measurable Residual Disease Testing in Acute Myeloid Leukemia.

Background: Measurable residual disease (MRD) test positivity during and after treatment in patients with acute myeloid leukemia (AML) has been associated with higher rates of relapse and worse overall survival. Current approaches for MRD testing are not standardized leading to inconsistent results and poor prognostication of disease. Pertinent studies evaluating AML MRD testing at specific times points, with various therapeutics and testing methods are presented.

Prevalence of Urinary Incontinence and Other Pelvic Floor-Related Symptoms in Female Professional Dancers.

Introduction: Urinary incontinence (UI) is a common issue in female athletes and is known to negatively impact quality of life and sport performance. However, the prevalence of UI in dancers has not been widely investigated. The purpose of this study was to assess the prevalence of UI as well as other symptoms of pelvic floor dysfunction in female professional dancers.

Tocilizumab for Cytokine Release Syndrome Management After Haploidentical Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis.

Cytokine release syndrome (CRS) is a common complication after haploidentical hematopoietic cell transplantation (HaploHCT). Severe CRS after haploHCT leads to higher risk of non-relapse mortality (NRM) and worse overall survival (OS). Tocilizumab (TOCI) is an interleukin-6 receptor inhibitor and is commonly used as first-line for CRS management after chimeric antigen receptor T cell therapy, but the impact of TOCI administration for CRS management on Haplo HCT outcomes is not known.

FLT3 Inhibitors as Maintenance Therapy after Allogeneic Stem-Cell Transplantation.

Mutations in the gene are associated with poor prognosis in patients with AML, even after consolidation with allogeneic hematopoietic cell transplantation (alloHCT) in first remission. Treatment failure in -mutated AML is largely driven by excessive risk of relapse compared to other genetic subtypes, including in patients post-alloHCT. As a result, there is substantial interest in studying posttransplant maintenance therapy in -mutated AML as an approach to optimize disease control and improve long-term outcomes.

A chromosomal-level reference genome of the widely utilized Coccidioides posadasii laboratory strain "Silveira".

Coccidioidomycosis is a common fungal disease that is endemic to arid and semi-arid regions of both American continents. Coccidioides immitis and Coccidioides posadasii are the etiological agents of the disease, also known as Valley Fever. For several decades, the C.

An update on acalabrutinib to treat chronic lymphocytic leukemia.

Acalabrutinib was approved by the U.S. Food and Drug Administration (FDA) for treatment-naive (TN) and relapsed/refractory (R/R) use for patients with chronic lymphocytic leukemia (CLL) in November 2019 following the phase III ASCEND and ELEVATE-TN registration trials.

Dry Needling and Acupuncture in Treatment of Dance-Related Injuries, MD, and PT Perspectives.

Dancers frequently present to health care professionals with musculoskeletal impairments. The role of the health care practitioner, whether physician, physical therapist, or acupuncturist, is to decrease pain and restore function in the short term and to restore adaptive potential and neural connectivity in the long term. When dysfunction is treated, pain improves.