Publications by authors named "William Sewell"

Introduction: Flow cytometry (FCM) is widely used in the diagnosis of mature B-cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B-cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM.

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Article Synopsis
  • Heterozygous mutations in PIK3R1 cause activated PI3Kδ syndrome 2 (APDS2), which shares symptoms with APDS1 caused by PIK3CD mutations.
  • Research using a CRISPR/Cas9 mouse model and patient immune cells revealed that PIK3R1 mutations lead to unique cellular defects, including issues with B cell function and survival of pups.
  • The study found important differences in how PIK3R1 loss-of-function (LOF) and PIK3CD gain-of-function (GOF) mutations affect immune cell signaling and function, highlighting distinct genetic impacts on immune health.
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Background: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone.

Objective: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS.

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The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers.

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Article Synopsis
  • The overview discusses the upcoming 5th edition of the WHO Classification of Haematolymphoid Tumours, specifically focusing on lymphoid neoplasms, while myeloid and histiocytic neoplasms will be covered separately.
  • Key changes from the previous 4th edition include a hierarchical reorganization of entities, modifications in their nomenclature, and revisions to diagnostic criteria and subtypes.
  • The new edition will also see the deletion of certain entities, the introduction of new ones, and the inclusion of tumour-like lesions and germline predisposition syndromes related to lymphoid neoplasms.
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Millions of people worldwide have disabling hearing loss because one of their genes generates an incorrect version of some specific protein the ear requires for hearing. In many of these cases, delivering the correct version of the gene to a specific target cell within the inner ear has the potential to restore cochlear function to enable high-acuity physiologic hearing. Purpose: In this review, we outline our strategy for the development of genetic medicines with the potential to treat hearing loss.

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Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model.

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Introduction: The myelodysplastic syndromes (MDSs) are heterogeneous myeloid malignancies, conventionally diagnosed by cytomorphology and cytogenetics, with an emerging role for flow cytometry. This study compared the performance of a 4-parameter flow cytometry scoring system, the Ogata Score, with other modalities in the diagnosis of MDS.

Methods: Bone marrow aspirate and trephine biopsies from 238 patients performed to assess for possible MDS were analysed, and the flow cytometry score was retrospectively applied.

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Purpose: Deficiency of adenosine deaminase type 2 (ADA2) (DADA2) is a rare inborn error of immunity caused by deleterious biallelic mutations in ADA2. Clinical manifestations are diverse, ranging from severe vasculopathy with lacunar strokes to immunodeficiency with viral infections, hypogammaglobulinemia and bone marrow failure. Limited data are available on the phenotype and function of leukocytes from DADA2 patients.

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Sterile α motif domain-containing protein 9-like (SAMD9L) is encoded by a hallmark interferon-induced gene with a role in controlling virus replication that is not well understood. Here, we analyze SAMD9L function from the perspective of human mutations causing neonatal-onset severe autoinflammatory disease. Whole-genome sequencing of two children with leukocytoclastic panniculitis, basal ganglia calcifications, raised blood inflammatory markers, neutrophilia, anemia, thrombocytopaenia, and almost no B cells revealed heterozygous de novo mutations, p.

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Background: Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor.

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Importance: Eosinophilic chronic rhinosinusitis (eCRS), contemporarily classified as diffuse type 2 dominant chronic rhinosinusitis (CRS), is characterized by eosinophil-dominant mucosal inflammation. Contemporary management of eCRS as an inflammatory airway condition is multimodal with corticosteroid irrigations after the surgical creation of a neosinus cavity.

Objectives: To assess long-term treatment outcomes in patients with primary diffuse type 2 CRS or eCRS receiving multimodal treatment.

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Background: The epidemiological features and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) have been described; however, the temporal progression and medical complications of disease among hospitalized patients require further study. Detailed descriptions of the natural history of COVID-19 among hospitalized patients are paramount to optimize health care resource utilization, and the detection of different clinical phenotypes may allow tailored clinical management strategies.

Methods: This was a retrospective cohort study of 305 adult patients hospitalized with COVID-19 in 8 academic and community hospitals.

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Background: Solitary extramedullary plasmacytoma (SEP) is a localised proliferation of monoclonal plasma cells involving soft tissue with no or minimal bone marrow involvement and no other systemic evidence of multiple myeloma. Intraocular involvement is exceedingly rare.

Case Presentation: We report a 78-year-old man who was referred with glaucoma in the right eye.

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Article Synopsis
  • The study examined predictors of poor outcomes from COVID-19 among 297 hospitalized adults in Georgia, highlighting the importance of data collected during admission.
  • Older age significantly increased the risk of invasive mechanical ventilation and death, with those aged 65 and older at the highest risk.
  • Comorbidities like end-stage renal disease and coronary artery disease were linked to higher mortality, while certain antihypertensive medications showed unexpected associations with death.
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Background: There is limited data on outcomes in patients with coronavirus disease 2019 (Covid-19) in rural United States (US). This study aimed to describe the demographics, and outcomes of hospitalized Covid-19 patients in rural Southwest Georgia.

Methods: Using electronic medical records, we analyzed data from all hospitalized Covid-19 patients who either died or survived to discharge between 2 March 2020 and 6 May 2020.

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SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages.

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Background: Eosinophilic chronic rhinosinusitis (eCRS) is an inflammatory endotype of CRS. Contemporary treatment includes creation of a "neo-sinus" cavity and postoperative corticosteroid irrigations. Not all patients gain control with local therapy.

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Allergen specific immunoglobulin E (spIgE) in the nasal mucosa is a biomarker for local allergic rhinitis. Inferior turbinate tissue biopsy is a sensitive method to detect nasal spIgE but is invasive. Nasal brushing is a relatively noninvasive method to detect nasal spIgE that may be of comparable diagnostic utility.

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Background: Specific immunoglobulin E (sIgE) within the nasal airway is likely to be the most ideal marker of allergic status, but little is known of the normative values in asymptomatic patients and those with rhinitis.

Objective: The aim of this study was to assess the diagnostic characteristics of inferior turbinate tissue biopsy sIgE in asymptomatic and rhinitic patients.

Methods: A diagnostic cross-sectional study was undertaken, involving patients who underwent inferior turbinate surgery with or without other surgical interventions.

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Background: Chronic rhinosinusitis (CRS), in particular with nasal polyps (CRSwNP), has been linked with skewed T-helper 2 and immunoglobulin E (IgE)-mediated allergic responses. The role of atopy in CRS, however, remains unclear. Correlations between immunological allergic markers and patient-reported outcomes measures (PROMs) were investigated.

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Background: Allergen specific immunoglobulin can be present in the nasal mucosa of patients with non-allergic rhinitis (NAR). This condition is defined as local allergic rhinitis. However, the reported presence of nasal specific immunoglobulin E (nspIgE) among NAR is variable.

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