Publications by authors named "Elizabeth Lightbody"

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.

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Detection of light chain (LC) monoclonal gammopathies (MG) traditionally relies on serum free LC (FLC) κ, λ, and their ratio (κ/λ) reference ranges based on a mostly White population. We investigated FLC values in a racially diverse population by screening 10,035 individuals for heavy chain MG, identifying 9,028 negative cases whose FLC were measured. Participants included 4,149 from the PROMISE Study (US, n=2,383; South Africa, n=1,766) and 4,879 from the Mass General Brigham Biobank, with 44% self-identifying as Black.

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Background: Early therapeutic intervention in high-risk SMM (HR-SMM) has demonstrated benefit in previous studies of lenalidomide with or without dexamethasone. Triplets and quadruplet studies have been examined in this same population. However, to date, none of these studies examined the impact of depth of response on long-term outcomes of participants treated with lenalidomide-based therapy, and whether the use of the 20/2/20 model or the addition of genomic alterations can further define the population that would benefit the most from early therapeutic intervention.

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Background: Dehydration and malnutrition are common in hospitalised patients following stroke leading to poor outcomes including increased mortality. Little is known about hydration and nutrition care practices in hospital to avoid dehydration or malnutrition, and how these practices vary in different countries. This study sought to capture how the hydration and nutrition needs of patients' post-stroke are assessed and managed in the United Kingdom (UK) and Australia (AUS).

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  • - The study highlights the challenge in creating targeted therapies for Multiple Myeloma (MM) due to the rarity of genetic abnormalities, with the common amplification of chromosome 1q (Amp1q) linked to poorer outcomes for patients.
  • - Researchers used large-scale screening methods to identify that MM patients with Amp1q have increased sensitivity to a combination of MCL1 and PI3K inhibitors, which could potentially lead to more effective treatments.
  • - Further analysis through single-cell RNA sequencing revealed differences in the PI3K pathway's activity between cancer cells with and without Amp1q, suggesting that targeting this pathway along with MCL1 could enhance treatment efficacy for affected patients.
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Background: Depression is an important morbidity associated with stroke that impacts on recovery, yet is often undetected or inadequately treated.

Objectives: To evaluate the benefits and harms of pharmacological intervention, non-invasive brain stimulation, psychological therapy, or combinations of these to treat depression after stroke.

Search Methods: This is a living systematic review.

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  • Research focused on activating the STING pathway to improve chemotherapy effectiveness and overall survival, particularly in tumors lacking PTEN.
  • Results showed that PTEN-deficient tumors had worse survival rates and a more immunosuppressed environment, but STING activation alongside chemotherapy led to improved survival in animal models.
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Background: Patients with precursors to multiple myeloma are dichotomised as having monoclonal gammopathy of undetermined significance or smouldering multiple myeloma on the basis of monoclonal protein concentrations or bone marrow plasma cell percentage. Current risk stratifications use laboratory measurements at diagnosis and do not incorporate time-varying biomarkers. Our goal was to develop a monoclonal gammopathy of undetermined significance and smouldering multiple myeloma stratification algorithm that utilised accessible, time-varying biomarkers to model risk of progression to multiple myeloma.

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Unlabelled: Multiple myeloma (MM) develops from well-defined precursor stages; however, invasive bone marrow (BM) biopsy limits screening and monitoring strategies for patients. We enumerated circulating tumor cells (CTC) from 261 patients (84 monoclonal gammopathy of undetermined significance, 155 smoldering multiple myeloma, and 22 MM), with neoplastic cells detected in 84%. We developed a novel approach, MinimuMM-seq, which enables the detection of translocations and copy-number abnormalities through whole-genome sequencing of highly pure CTCs.

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Article Synopsis
  • Patients with smoldering multiple myeloma usually wait for their condition to get worse before starting treatment, but treating them early might help them live better.
  • A study tested a combination of three medicines (elotuzumab, lenalidomide, and dexamethasone) on patients with a more serious form of the disease and looked at their blood samples to see how their immune cells changed.
  • The results showed that early treatment was safe and might help, and how similar a patient’s immune system is to healthy people can help predict how well they will do with the treatment.
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Objectives: Low-middle income countries, such as Vietnam have a greater burden from stroke than high-income countries. Few health professionals have stroke specialist training, and the quality of care may vary between hospitals. To support improvements to stroke care, we aimed to gain a better understanding of the resources available in hospitals in Vietnam to manage acute stroke.

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Article Synopsis
  • - The study investigates the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in high-risk U.S. populations, particularly focusing on individuals of African descent and those with a family history of related diseases, using advanced mass spectrometry techniques.
  • - Out of 7,622 participants screened, 6,305 (83%) were identified as high risk based on their race or family history of hematological conditions, ensuring a diverse representation beyond previous estimates relying on predominantly White populations.
  • - The research also highlights the importance of utilizing new screening technology and emphasizes longitudinal follow-up data to better understand the clinical implications of monoclonal gammopathies in these high-risk groups over time.
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  • This protocol outlines a staining technique for analyzing immune cells in human bone marrow using mass cytometry.
  • It addresses challenges like low cell viability and fragile cell samples to help obtain viable single cells for analysis.
  • The assay is useful for studying immune cell characteristics, including activation and cytotoxicity, enhancing the understanding of human bone marrow in clinical contexts.
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Multiple myeloma (MM) is a haematological malignancy of plasma cells characterized by substantial intraclonal genetic heterogeneity. Although therapeutic advances made in the past few years have led to improved outcomes and longer survival, MM remains largely incurable. Over the past decade, genomic analyses of patient samples have demonstrated that MM is not a single disease but rather a spectrum of haematological entities that all share similar clinical symptoms.

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Background: Stroke can affect people's ability to swallow, resulting in passage of some food and drink into the airway. This can cause choking, chest infection, malnutrition and dehydration, reduced rehabilitation, increased risk of anxiety and depression, longer hospital stay, increased likelihood of discharge to a care home, and increased risk of death. Early identification and management of disordered swallowing reduces risk of these difficulties.

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Aims: To examine current practice, perceptions of healthcare professionals and factors affecting provision for oral care post-stroke in the UK and Australia.

Background: Poor oral care has negative health consequences for people post-stroke. Little is known about oral care practice in hospital for people post-stroke and factors affecting provision in different countries.

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Article Synopsis
  • The treatment landscape for multiple myeloma is rapidly changing with new agents allowing for minimal residual disease (MRD) negativity to be more achievable across all stages of the disease.
  • Advanced technologies like next-generation flow and sequencing are enhancing the detection and monitoring of MRD, while promising liquid biopsy techniques are being developed to deepen our understanding of it.
  • Clinicians are increasingly considering MRD status to inform treatment decisions, as ongoing studies highlight its potential importance for improving patient outcomes and guiding future research and clinical trials.
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Background: The role of stroke nurses in patient selection and administration of recombinant tissue plasminogen activator (rt-PA) for acute ischaemic stroke is evolving.

Objectives: To compare differences in stroke nurses' practices related to rt-PA administration in Australia and the United Kingdom (UK) and to examine whether these differences influence rt-PA treatment rates.

Methods: A cross-sectional, self-administered questionnaire administered to a lead stroke clinician from hospitals known to provide rt-PA for acute ischaemic stroke.

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Objective: To evaluate the effect of a dialogue-based intervention targeting psychosocial well-being at 12 months post-stroke.

Design: Multicenter, prospective, randomized, assessor-blinded, controlled trial with two parallel groups.

Setting: Community.

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Background and Purpose- Identifying the etiology of acute ischemic stroke is essential for effective secondary prevention. However, in at least one third of ischemic strokes, existing investigative protocols fail to determine the underlying cause. Establishing etiology is complicated by variation in clinical practice, often reflecting preferences of treating clinicians and variable availability of investigative techniques.

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Background: Strict criteria for recombinant tissue plasminogen activator (rtPA) eligibility are stipulated on licences for use in ischaemic stroke; however, practitioners may also add non-standard rtPA criteria. We examined eligibility criteria variation in 3 English-speaking countries including use of non-standard criteria, in relation to rtPA treatment rates.

Methods: Surveys were mailed to 566 eligible hospitals in Australia (AUS), the UK, and the USA.

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Excessive proliferation and apoptosis-resistance are hallmarks of cancer. Increased dynamin-related protein 1 (Drp1)-mediated mitochondrial fission is one of the mediators of this phenotype. Mitochondrial fission that accompanies the nuclear division is called mitotic fission and occurs when activated Drp1 binds partner proteins on the outer mitochondrial membrane.

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Background: Stroke is a leading cause of death and disability worldwide. Identifying the aetiology of ischaemic stroke is essential in order to initiate appropriate and timely secondary prevention measures to reduce the risk of recurrence. For the majority of ischaemic strokes, the aetiology can be readily identified, but in at least 30% of cases, the exact aetiology cannot be determined using existing investigative protocols.

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