TET2 deficiency increases the competitive advantage of hematopoietic stem and progenitor cells through upregulation of thrombopoietin receptor signaling.

Ten-Eleven Translocation-2 (TET2) mutations drive the expansion of mutant hematopoietic stem cells (HSCs) in clonal hematopoiesis (CH). However, the precise mechanisms by which TET2 mutations confer a competitive advantage to HSCs remain unclear. Here, through an epigenetic drug screen, we discover that inhibition of disruptor of telomeric silencing 1-like (DOT1L), a H3K79 methyltransferase, selectively reduces the fitness of Tet2 knockout (Tet2) hematopoietic stem and progenitor cells (HSPCs).

ADTGP: correcting single-cell antibody sequencing data using Gaussian process regression.

Summary: We present ADTGP, an R package that uses Gaussian process regression to correct droplet-specific technical noise in single-cell protein sequencing data. ADTGP improves the interpretability of the data by modeling the distribution of protein expression, conditioned on equal isotype control counts across cells. ADTGP is written in R and needs only the protein raw counts, isotype control raw counts, and a design matrix to run.

Outcome of adolescents and young adult acute myeloid leukemia patients compared with middle-aged patients: A single centre retrospective experience.

Adult acute myeloid leukemia (AML) patients under the age of 60 often receive similar intensive treatments, while outcomes between the adolescent and young adult (AYA) age group (18-39) and middle-aged adults (40-60 years) were seldom reported. We aim to study the characteristics and outcomes of AYA patients in comparison to middle-aged adults. A retrospective analysis was performed on AYA patients treated at Princess Margaret Cancer Center between 2008 and 2018.

Body composition assessment by artificial intelligence can be a predictive tool for short-term postoperative complications in Hartmann's reversals.

Background: Hartmann's reversal, a complex elective surgery, reverses and closes the colostomy in individuals who previously underwent a Hartmann's procedure due to colonic pathology like cancer or diverticulitis. It demands careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery.

Outcomes and adverse events in older acute lymphoblastic Leukemia patients treated with a pediatric-inspired protocol with Pegylated or native Asparaginase.

This retrospective report presents the outcomes and adverse events (AEs) observed in 73 patients aged 60 years or older diagnosed with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (Ph-negative ALL) treated with a pediatric-inspired protocol incorporating either Pegylated (PEG-ASP) or Native Asparaginase (EC-ASP). Notably, 61% of patients experienced AEs of Grade III-IV severity. The most prevalent AEs included thrombosis (35.

Colorectal cancer treatment outcomes during the pandemic: Our experience of COVID-19 at a tertiary referral center.

Backgrounds: The coronavirus disease 2019 (COVID-19) has led to major shifts in the management of colorectal cancer (CRC). This study aims to identify the impact and early outcomes of COVID-19 following CRC management at a tertiary referral center in Victoria, Australia.

Methods: This was a retrospective study, utilizing the Australian Comprehensive Cancer Outcomes and Research Database and inpatient records.

Flow cytometry-based measurable residual disease (MRD) analysis identifies AML patients who may benefit from allogeneic hematopoietic stem cell transplantation.

Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry-based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes.

Outcomes of intensive and nonintensive blast-reduction strategies in accelerated and blast-phase MPN.

Transformation of BCR::ABL1-negative myeloproliferative neoplasms (MPN) to an accelerated or blast phase is associated with poor outcomes. The efficacy of acute myeloid leukemia (AML)-type intensive and nonintensive hypomethylating agent-based regimens is not well studied. We therefore performed a retrospective analysis of patients with MPN-AP/BP (N = 138) treated with intensive (N = 81) and nonintensive (N = 57) blast-reduction strategies.

Preclinical characterization and clinical trial of CFI-400945, a polo-like kinase 4 inhibitor, in patients with relapsed/refractory acute myeloid leukemia and higher-risk myelodysplastic neoplasms.

CFI-400945 is a selective oral polo-like kinase 4 (PLK4) inhibitor that regulates centriole duplication. PLK4 is aberrantly expressed in patients with acute myeloid leukemia (AML). Preclinical studies indicate that CFI-400945 has potent in vivo efficacy in hematological malignancies and xenograft models, with activity in cells harboring TP53 mutations.

The association of body composition on chemotherapy toxicities in non-metastatic colorectal cancer patients: a systematic review.

Background: In recent years, certain body composition measures, assessed by computed tomography (CT), have been found to be associated with chemotherapy toxicities. This review aims to explore available data on the relationship between skeletal muscle and adiposity, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intramuscular and intermuscular adipose tissue and their association with chemotherapy toxicity in non-metastatic colorectal cancer (CRC) patients.

Methods: A systematic literature search following PRISMA guidelines was conducted in Medline, Embase, Cochrane and Web of Science, for papers published between 2011 and 2023.

Patient and Provider Satisfaction with Asynchronous Versus Synchronous Telepsychiatry in Primary Care: A Secondary Mixed-Methods Analysis of a Randomized Controlled Trial.

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Can AI-based body composition assessment outperform body surface area in predicting dose-limiting toxicities for colonic cancer patients on chemotherapy?

Purpose: Gold standard chemotherapy dosage is based on body surface area (BSA); however many patients experience dose-limiting toxicities (DLT). We aimed to evaluate the effectiveness of BSA, two-dimensional (2D) and three-dimensional (3D) body composition (BC) measurements derived from Lumbar 3 vertebra (L3) computed tomography (CT) slices, in predicting DLT in colon cancer patients.

Methods: 203 patients (60.

Asynchronous Technologies in Mental Health Care and Education.

Purpose Of Review: Patients, providers, and trainees should understand the current types of asynchronous technologies that can be used to enhance the delivery and accessibility of mental health care. Asynchronous telepsychiatry (ATP) removes the need for real time communication between the clinician and patient, which improves efficiency and enables quality specialty care. ATP can be applied as distinct consultative and supervisory models in , , and settings.

Impact of Geographical Distance from Quaternary Treatment Center on Clinical Trial Participation, Intensive Induction Chemotherapy, and Outcomes in Patients with Newly Diagnosed Acute Myeloid Leukemia.

Introduction: Care for patients with acute myeloid leukemia (AML) is centralized in the Ontario single-payer public healthcare system, with intensive induction chemotherapy and clinical trials only offered at specialized cancer centers with large catchment areas.

Methods: We therefore conducted a retrospective single-center review of all AML patients assessed at a large specialized cancer center in Ontario, Canada.

Results: Between 2012 and 2017, 1,310 patients were assessed by our center for upfront AML therapy.

Can sarcopenia predict survival in locally advanced rectal cancer patients?

Background: There is mounting evidence that suggests sarcopenia can be used to predict survival outcomes in patients with colon cancer. However, the effect on locally advanced rectal cancer (LARC) is less clear. We sought to determine the association between sarcopenia on Overall Survival and Recurrence-free Survival (OS and RFS) in patients with LARC undergoing multimodal treatment.

Breakthrough Invasive Fungal Infection After Coadministration of Venetoclax and Voriconazole.

Venetoclax requires a 75% dose reduction when coadministered with voriconazole. In a 10-year historical cohort of treatment with venetoclax, we did not observe a worse hematologic outcome in patients who received voriconazole prophylaxis versus those who did not. Subtherapeutic voriconazole levels and a triazole exposure history may contribute to breakthrough invasive fungal infection.

Safety of re-challenging adults with acute lymphoblastic leukemia with PEG-asparaginase-induced severe hypertriglyceridemia when treated with a pediatric-inspired regimen.

PEG-asparaginase is used as a treatment for Philadelphia-negative acute lymphoblastic leukemia. In pediatric studies, triglycerides (TGs) were affected more by PEG-asparaginase than by native L-asparaginase (10.0% vs.

Venous thromboembolism incidence associated with pegylated asparaginase (ASP) compared to the native L-ASP: A retrospective analysis with an ASP-based protocol in adult patients with acute lymphoblastic leukaemia.

Venous thromboembolism (VTE) is a well-known complication in patients with acute lymphoblastic leukaemia (ALL) receiving asparaginase (ASP)-based chemotherapy, including the ASP-intensive Dana-Farber Cancer Institute (DFCI) 91-01 protocol for adults. Since 2019, native L-ASP is no longer available in Canada and was replaced by pegylated (PEG)-ASP. To determine whether the incidence of VTE has changed since switching from L-ASP to PEG-ASP, we conducted a single-centred retrospective cohort study.

Mutational profile, outcomes, and impact of allogeneic hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia and inconclusive cytogenetic analysis.

Background: Inconclusive cytogenetic analysis (IC) at baseline has been reported as a predictor of poor prognosis in patients with acute myeloid leukemia (AML). The mutational profile in this group of patients, and its impact on outcomes have not been reported.

Methods: We retrospectively analyzed adult patients (≥18 years) with newly diagnosed AML treated with intensive induction chemotherapy between 2015 and 2019.