Role of allogeneic hematopoietic cell transplantation in VEXAS syndrome.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a newly diagnosed syndrome comprising severe systemic inflammatory and hematological manifestations including myelodysplastic syndrome and plasma cell dyscrasia. Since its discovery four years ago, several groups have identified pleomorphic clinical phenotypes, but few effective medical therapies exist which include Janus Kinase (JAK) inhibitors, interleukin inhibitors (IL-1 and IL-6), and hypomethylating agents. Prospective trials are lacking at this time and most patients remain corticosteroid dependent.

What's age got to do with it? A study of the implementation of the discharge medicines service for paediatric patients.

Objectives: The discharge medicines service (DMS) was introduced as an essential service for all community pharmacies in England through the Community Pharmacy Contractual Framework (CPCF) in February 2021. This study aimed to describe the implementation of this service for paediatric patients and to identify any barriers to referrals.

Methods: The study was undertaken in a 24-bed paediatric ward in a District General Hospital from September 2022 to February 2023.

When to consider inherited marrow failure syndromes in adults.

The inherited bone marrow failure syndromes (IBMFS) are a heterogenous group of disorders caused by germline mutations in related genes and characterized by bone marrow failure (BMF), disease specific organ involvement, and, in most cases, predisposition to malignancy. Their distinction from immune marrow failure can often be challenging, particularly when presentations occur in adulthood or are atypical. A combination of functional (disease specific assays) and genetic testing is optimal in assessing all new BMF patients for an inherited etiology.

Clonal haematopoiesis across the age spectrum of vasculitis patients with Takayasu's arteritis, ANCA-associated vasculitis and giant cell arteritis.

Objectives: Ageing and inflammation are associated with clonal haematopoiesis (CH), the emergence of somatic mutations in haematopoietic cells. This study details CH in patients with systemic vasculitis in association with clinical, haematological and immunological parameters.

Methods: Patients with three forms of vasculitis were screened for CH in peripheral blood by error-corrected sequencing.

VEXAS syndrome, a new kid on the block of auto-inflammatory diseases: A hematologist's point of view.

The recently discovered VEXAS syndrome is caused by the clonal expansion of hematopoietic stem or progenitor cells with acquired mutations in UBA1 gene, which encodes for a key enzyme of the ubiquitylation proteasome system. As a result, a shorter cytoplasmic isoform of UBA1 is transcribed, which is non-functional. The disease is characterized by non-specific and highly heterogeneous inflammatory manifestations and macrocytic anemia.

Early activation of inflammatory pathways in UBA1-mutated hematopoietic stem and progenitor cells in VEXAS.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a pleiotropic, severe autoinflammatory disease caused by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. To elucidate VEXAS pathophysiology, we performed transcriptome sequencing of single bone marrow mononuclear cells and hematopoietic stem and progenitor cells (HSPCs) from VEXAS patients. HSPCs are biased toward myeloid (granulocytic) differentiation, and against lymphoid differentiation in VEXAS.

Conditional survival and standardized mortality ratios of patients with severe aplastic anemia surviving at least one year after hematopoietic cell transplantation or immunosuppressive therapy.

Immunosuppressive treatment (IST) and hematopoietic cell transplant (HCT) are standard therapies for severe aplastic anemia (SAA). We report on conditional survival and standardized mortality ratios (SMR), which compare the mortality risk with the general population adjusted for age, gender, and race/ethnicity, in patients with SAA alive for at least 12 months after treatment with IST or HCT between 2000 and 2018. Given changes to treatment regimens and differences in length of follow-up, two treatment periods were defined a priori: 2000-2010 and 2011-2018.

Alemtuzumab in relapsed immune severe aplastic anemia: Long-term results of a phase II study.

Immune severe aplastic anemia (SAA) is characterized by pancytopenia and immune-mediated bone marrow destruction. SAA may be treated with hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). However, 30% of patients treated with IST relapse.

Differential diagnosis of bone marrow failure syndromes guided by machine learning.

The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely, the misdiagnosis of inherited bone marrow failure (BMF) can expose patients to ineffectual and expensive therapies, toxic transplant conditioning regimens, and inappropriate use of an affected family member as a stem cell donor. To predict the likelihood of patients having acquired or inherited BMF, we developed a 2-step data-driven machine-learning model using 25 clinical and laboratory variables typically recorded at the initial clinical encounter.

Efficacy of JAK1/2 inhibition in murine immune bone marrow failure.

Immune aplastic anemia (AA) is a severe blood disease characterized by T-lymphocyte- mediated stem cell destruction. Hematopoietic stem cell transplantation and immunosuppression are effective, but they entail costs and risks, and are not always successful. The Janus kinase (JAK) 1/2 inhibitor ruxolitinib (RUX) suppresses cytotoxic T-cell activation and inhibits cytokine production in models of graft-versus-host disease.

Clinical outcomes and immune responses to SARS-CoV-2 vaccination in severe aplastic anaemia.

Patients with severe aplastic anaemia (SAA) are often not vaccinated against viruses due to concerns of ineffective protective antibody response and potential for pathogenic global immune system activation, leading to relapse. We evaluated the impact of COVID-19 vaccination on haematological indices and disease status and characterized the humoural and cellular responses to vaccination in 50 SAA patients, who were previously treated with immunosuppressive therapy (IST). There was no significant difference in haemoglobin (p = 0.

Somatic mutations in VEXAS Syndrome and Erdheim-Chester disease: Inflammatory myeloid diseases.

Somatic mutations have been increasingly identified as etiologic for many hematologic and autoinflammatory disorders. VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome and Erdheim-Chester disease (ECD), a type of histiocytosis, can be classified as inflammatory myeloid diseases, characterized by systemic inflammation and multi-organ disease with predisposition to myeloid malignancies. VEXAS is a novel disease caused by UBA1 mutations that was first discovered using a genotype-driven approach (genotype was used to identify patients with undiagnosed inflammatory diseases).

Selecting Portable Ankle/Toe Brachial Pressure Index Systems for a Peripheral Arterial Disease Population Screening Programme: a Systematic Review, Clinical Evaluation Exercise, and Consensus Process.

Objective: To provide an overview of systems available for peripheral arterial disease (PAD) screening, together with respective accuracies and a clinical evaluation to identify a system suitable for use in a community screening programme.

Methods: A systematic review of the diagnostic accuracy of six ankle brachial pressure index (ABPI) and toe brachial pressure index (TBPI) devices deemed to be portable, which were Conformité Européenne (CE) marked, and were automated or semi-automated was carried out compared with gold standard handheld Doppler and duplex ultrasound. The devices were MESI-ABPI-MD, Huntleigh Dopplex Ability, Huntleigh ABPI and TBPI systems, Systoe TBPI system, and BlueDop.

Anti-COX-2 autoantibody is a novel biomarker of immune aplastic anemia.

In immune aplastic anemia (IAA), severe pancytopenia results from the immune-mediated destruction of hematopoietic stem cells. Several autoantibodies have been reported, but no clinically applicable autoantibody tests are available for IAA. We screened autoantibodies using a microarray containing >9000 proteins and validated the findings in a large international cohort of IAA patients (n = 405) and controls (n = 815).