Publications by authors named "Diamond E"

Aim: All commercial chelating gels contain EDTA which reacts chemically with sodium hypochlorite (NaOCl). This research aimed to develop a non-EDTA clodronate gel and to measure physicochemical and functional gel properties of the novel and commercial gels.

Methodology: A 1.

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Endocrinopathies are frequently the initial presentation of histiocytic neoplasms, which are rare hematologic disorders affecting multiple organ systems. Langerhans cell histiocytosis and Erdheim-Chester disease are 2 such disorders known to infiltrate the hypothalamus and/or pituitary gland, leading to arginine vasopressin deficiency (AVP-D) and anterior pituitary dysfunction (APD) in 20% to 30% of cases, often as the first manifestation. Conversely, histiocytic disorders account for a notable proportion (10-15%) of all pituitary stalk lesions.

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Anxiety and depression are common in many cancers but have not been systematically studied in patients with histiocytic neoplasms (HN). We sought to estimate rates of anxiety and depression and identify clinical features and patient-reported outcomes (PROs) associated with anxiety and depression in patients with HN. A registry-based cohort of patients with HN completing PROs including the Hospital Anxiety and Depression Scale (HADS) from 2018-2023 was identified.

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Purpose: TRK fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients.

Experimental Design: We conducted an international retrospective cohort study of patients with TRK fusion-driven CNS tumors.

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Purpose: To evaluate choroidal findings in patients with histiocytosis, including subfoveal choroidal thickness (SFCT), and multimodal imaging in eyes with choroidal infiltrates visible by ophthalmoscopy and determine if abnormalities change with histiocytosis-directed (kinase inhibitor) therapy.

Design: Retrospective comparative study at single tertiary cancer referral center.

Participants: Ninety-one patients with histiocytosis and 41 age- and sex-matched controls.

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Recent advances in Rosai-Dorfman-Destombes disease (RDD), notably molecular testing, targeted therapy, and PET-CT imaging, hold promise for better recognition and improved outcomes. This study presents patients diagnosed and treated in a "real world" setting, where navigating limited resources must be considered. This retrospective single-center review includes 15 adult patients diagnosed with RDD at Vancouver General Hospital between November 2015 and October 2023.

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Article Synopsis
  • Langerhans cell Histiocytosis (LCH) and Erdheim-Chester disease (ECD) are linked to certain genetic mutations and pose a heightened risk for neurodegeneration, revealing microglia mutant clones in patients' brains.
  • These mutant clones lead to symptoms like microgliosis and neuronal loss, notably affecting specific brain regions, with symptoms correlating to the disease's duration and the size of these clones.
  • Research suggests that targeting these mutant microglia with a CSF1R-inhibitor could prevent neuronal loss, presenting a potential new treatment option distinct from current MAPK inhibitors.
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Article Synopsis
  • The study explores the potential of using circulating tumor DNA (ctDNA) found in plasma as a noninvasive diagnostic tool for ocular-involving histiocytosis, a condition marked by cancer-driven histiocyte expansion.
  • Conducted at a tertiary cancer center, the research involved 24 adult patients, focusing on detecting specific genetic mutations associated with histiocytosis through ctDNA sequencing methods.
  • Results showed that ctDNA sequencing successfully identified known driver mutations in 14 patients, demonstrating high concordance with mutations found via traditional tumor sequencing, which suggests ctDNA could streamline the diagnostic process.
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Erdheim-Chester Disease Masquerading as CLIPPERS.

Neurol Neuroimmunol Neuroinflamm

September 2024

Objectives: To present 4 patients with Erdheim-Chester disease (ECD) based on clinical, radiologic, histopathologic, and molecular genetic findings who had enhancing brainstem lesions and were initially believed to have chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

Methods: Case series.

Results: Although patients with ECD can demonstrate clinical and imaging features similar to CLIPPERS, refractoriness to corticosteroids, lack of fulfillment of specific MRI criteria (i.

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Objectives: To co-construct a sports medicine and exercise science research and translational agenda with Team USA elite female athletes serving as the experts on their health, performance and well-being.

Methods: 40 Team USA female athletes across sports disciplines participated in an online, anonymous, modified Delphi survey by ranking topics on a Likert scale (1='strongly disagree' and 5='strongly agree') and providing qualitative justification regarding whether they believed having more information and research on each topic would support their athletic performance, health and well-being. After each Delphi round, quantitative rankings of topics and qualitative justifications were analysed, informing revisions to the list of topics for review in the subsequent round.

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Purpose: Even though BRAF fusions are increasingly detected in standard multigene next-generation sequencing panels, few reports have explored their structure and impact on clinical course.

Experimental Design: We collected data from patients with BRAF fusion-positive cancers identified through a genotyping protocol of 97,024 samples. Fusions were characterized and reviewed for oncogenic potential (in-frame status, non-BRAF partner gene, and intact BRAF kinase domain).

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Introduction: Mitogen-activated protein kinase kinase (MEK) inhibitors are targeted anticancer agents that are prescribed to treat a broad range of cancers. Despite their strong efficacy profile, MEK inhibitors have been associated with ocular toxicities, most notably, self-limited serous detachments of the neurosensory retina. In this report, we outline 3 cases of a rarely documented toxicity, MEK inhibitor-associated ocular hypertension.

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Background/aims: Ocular manifestations of histiocytosis and their genetic underpinnings are poorly characterised. This study characterises ocular sites of histiocytosis, notate genetic alterations and correlates to histiocytosis clinical features including subtype and sites of disease.

Methods: Prospective registry-based study of predominantly adult histiocytosis patients at a single-institution tertiary referral centre.

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Article Synopsis
  • RAF inhibitors have improved treatment for BRAFV600-mutant cancers, but challenges like ERK signaling adaptation and poor brain penetration limit their effectiveness.
  • PF-07799933 is a new, brain-penetrant, selective pan-mutant BRAF inhibitor that shows promising results in preclinical trials by inhibiting dimer signaling and maintaining wild-type ERK signaling.
  • A clinical trial for PF-07799933 demonstrated it was well-tolerated and led to multiple positive responses in patients with treatment-resistant BRAF-mutant tumors, highlighting its potential as an effective therapy combined with MEK inhibitors.
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Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life-threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy.

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Article Synopsis
  • * This study focused on patients with mixed histiocytic neoplasms (MXH) and identified unique genetic mutations, while evaluating how well these patients responded to different treatments—both traditional and targeted therapies.
  • * Results showed that targeted therapies significantly improved treatment outcomes, leading to higher rates of response and lower likelihood of disease progression compared to conventional therapies.
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The flexibility of the motor system to adjust a planned action before or during the execution of the movement in response to sensory information is critical for preventing errors in motor control. As individuals age, this function declines, leading to an increased incidence of motor errors. Although sensory processing and cognitive decline are known contributors to this impairment, here, we test the hypothesis that repetition of context-specific planned actions interferes with the adjustment of feedforward motor commands.

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Introduction: Many cancers have derangement of the mitogen-activated pathway kinase (MAPK), making this pathway blockade a therapeutic target. However, inhibitors of MAPK can result in adverse effects including retinopathy. This study compares clinical and morphological characteristics of serous retinal disturbances in patients taking agents with variable inhibition of MAPK: either direct interference of mitogen-activated protein kinase kinase (MEK) or extracellular signal-regulated kinase (ERK) inhibitors or with indirect inhibition via interference with FGFR signaling.

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Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim-Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatment of ECD has been challenging.

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Effective tissue repair requires coordinated intercellular communication to sense damage, remodel the tissue, and restore function. Here, we dissected the healing response in the intestinal mucosa by mapping intercellular communication at single-cell resolution and integrating with spatial transcriptomics. We demonstrated that a risk variant for Crohn's disease, hepatocyte growth factor activator (HGFAC) ArgHis (R509H), disrupted a damage-sensing pathway connecting the coagulation cascade to growth factors that drive the differentiation of wound-associated epithelial (WAE) cells and production of a localized retinoic acid (RA) gradient to promote fibroblast-mediated tissue remodeling.

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Article Synopsis
  • * Recent studies have identified other mutations, like those in PIK3CA, which may also drive LCH independently from MAPK signaling, although their effects were not fully understood until now.
  • * New research using a mouse model shows that PIK3CA mutations can contribute to LCH, and a patient's LCH with this mutation successfully responded to a targeted treatment (alpelisib), highlighting the potential for personalized therapies in treating histiocytic neoplasms.
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