Myeloma UK

Chordoma, a rare primary bone malignancy, currently lacks effective targeted therapies. Despite surgical resection and adjuvant radiotherapy, prognosis remains poor. Recent preclinical studies have highlighted potential therapeutic targets, including the transcription factor T-box transcription factor T (TBXT). However, clinical outcomes associated with therapies targeting TBXT remain underexplored or have been modest, warranting further investigation. In this study, we investigated the therapeutic potential of transfer RNA (tRNA) synthetase inhibitors in chordoma treatment. Focused compound screening identified distinct chemotypes targeting human glutamyl-prolyl-tRNA synthetase (EPRS) as being effective in reducing cell viability in chordoma cell lines through a cyclic AMP-dependent transcription factor (ATF4)-mediated stress response rather than through TBXT regulation. Mechanistically significant upregulation of ATF4 and associated stress response genes was identified with consecutive pro-apoptotic DNA damage-inducible transcript 3 protein (DDIT3)-mediated cell death. The prototypic EPRS inhibitor halofuginone demonstrated significant tumour growth inhibition in an in vivo patient-derived xenograft model. These results suggest that targeting metabolic stress pathways via ATF4 activation presents a novel therapeutic approach for chordoma, warranting further clinical investigation.

BackgroundDegenerative cervical myelopathy (DCM), a form of slow-motion and progressive spinal cord injury caused by spinal cord compression secondary to degenerative pathology, leads to high levels of disability and dependence, and may reduce quality of life. Myelopathy.org is the first global scientific and clinical charity for DCM, providing an accessible platform freely disseminating information relevant to the DCM diagnosis and its treatment. Significant transient and long-term change to earnings do occur and can thrust individuals into poverty. People with DCM face many challenges accessing state financial assistance. This can have a cumulative negative financial effect due to the association between DCM and low socioeconomic index. Financial support available to patients under pension age include Universal Credit (UC), a payment that helps with living costs, and Personal Independence Payment (PIP), which helps with extra living costs if someone has both a long-term health condition or disability and difficulty doing certain everyday tasks.ObjectiveThis study aimed to assess if delivering workshops centered around access to financial support could assist people with DCM living in the United Kingdom.MethodsA series of 2 internet-based workshops was targeted at accessing financial support for English patients under the state pension age, with an anonymized survey delivered to participants after each session. The first session was on UC and the second on PIP. The survey consisted of a mixture of Likert scales, free text and yes or no answers. Survey responses were analyzed using descriptive statistics and free text answers underwent inductive thematic analysis.ResultsThe average rating on the use of UC was 9.00/10. Presession self-rated confidence levels were 5.11/10 rising to 8.00/10. The mean score of wanting further similar sessions was 8.67/10 with 56% (5/9) of participants wanting one-to-one sessions. For PIP, the average session use rating was 10/10. Presession self-rated confidence levels were 4.43/10 rising to 9.57/10. The mean score of wanting further similar sessions was 8.71/10, with 43% (3/7) of participants wanting one-to-one sessions . Following inductive thematic analysis, themes regarding the usefulness of such sessions and the challenges to accessing financial support emerged. One participant gave negative feedback, which included the length of the session and perceived problems around confidentiality and data protection.ConclusionsThe pilot series was largely perceived as a success, with participants finding them useful and increasing their self-rated confidence in navigating the UK financial support system. Given the small sample size, it is hard to predict the success of future sessions. Finally, given that the hurdles in accessing financial support extend beyond DCM, such workshops may be relevant to other organizations.

Treatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a 'GP Myeloma diagnostic tool' and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost-effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis.

To describe determinants of persisting humoral and cellular immune response to the second COVID-19 vaccination among patients with myeloma. This is a prospective, observational study utilising the RUDYstudy.org platform. Participants reported their second and third COVID-19 vaccination dates. Myeloma patients had an Anti-S antibody level sample taken at least 21 days after their second vaccination and a repeat sample before their third vaccination. 60 patients provided samples at least 3 weeks (median 57.5 days) after their second vaccination and before their third vaccination (median 176.0 days after second vaccine dose). Low Anti-S antibody levels (<50 IU/mL) doubled during this interval (p = .023) and, in the 47 participants with T-spot data, there was a 25% increase negative T-spot tests (p = .008). Low anti-S antibody levels prior to the third vaccination were predicted by lower Anti-S antibody level and negative T-spot status after the second vaccine. Independent determinants of a negative T-spot included increasing age, previous COVID infection, high CD4 count and lower percentage change in Anti-S antibody levels. Negative T-spot results predict low Anti-S antibody levels (<50 IU/mL) following a second COVID-19 vaccination and a number of biomarkers predict T cell responses in myeloma patients.

Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this. The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes. Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders. Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway. This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community. DERR1-10.2196/46809.

IntroductionDegenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM.Methods and analysisRECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60–100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8–14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care.Study designClinical trial protocol V.2.2 October 2020.Ethics and disseminationEthical approval has been obtained from HRA—Wales.The results will be presented at an international and national scientific conferences and in a peer-reviewed journals.Trial registration numberISRCTN Number: ISRCTN16682024.

ObjectivesTo evaluate the measurement properties of outcome measures currently used in the assessment of degenerative cervical myelopathy (DCM) for clinical research.DesignSystematic reviewData sourcesMEDLINE and EMBASE were searched through 4 August 2020.Eligibility criteriaPrimary clinical research published in English and whose primary purpose was to evaluate the measurement properties or clinically important differences of instruments used in DCM.Data extraction and synthesisPsychometric properties and clinically important differences were both extracted from each study, assessed for risk of bias and presented in accordance with the Consensus-based Standards for the selection of health Measurement Instruments criteria.ResultsTwenty-nine outcome instruments were identified from 52 studies published between 1999 and 2020. They measured neuromuscular function (16 instruments), life impact (five instruments), pain (five instruments) and radiological scoring (five instruments). No instrument had evaluations for all 10 measurement properties and <50% had assessments for all three domains (ie, reliability, validity and responsiveness). There was a paucity of high-quality evidence. Notably, there were no studies that reported on structural validity and no high-quality evidence that discussed content validity. In this context, we identified nine instruments that are interpretable by clinicians: the arm and neck pain scores; the 12-item and 36-item short form health surveys; the Japanese Orthopaedic Association (JOA) score, modified JOA and JOA Cervical Myelopathy Evaluation Questionnaire; the neck disability index; and the visual analogue scale for pain. These include six scores with barriers to application and one score with insufficient criterion and construct validity.ConclusionsThis review aggregates studies evaluating outcome measures used to assess patients with DCM. Overall, there is a need for a set of agreed tools to measure outcomes in DCM. These findings will be used to inform the development of a core measurement set as part of AO Spine RECODE-DCM.

Study DesignSurvey.IntroductionAO Spine Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy (AO Spine RECODE-DCM) is an international initiative that aims to accelerate knowledge discovery and improve outcomes by developing a consensus framework for research. This includes defining the top research priorities, an index term and a minimum data set (core outcome set and core data elements set – core outcome set (COS)/core data elements (CDE)).ObjectiveTo describe how perspectives were gathered and report the detailed sampling characteristics.MethodsA two-stage, electronic survey was used to gather and seek initial consensus. Perspectives were sought from spinal surgeons, other healthcare professionals and people with degenerative cervical myelopathy (DCM). Participants were allocated to one of two parallel streams: (1) priority setting or (2) minimum dataset. An email campaign was developed to advertise the survey to relevant global stakeholder individuals and organisations. People with DCM were recruited using the international DCM charity Myelopathy.org and its social media channels. A network of global partners was recruited to act as project ambassadors. Data from Google Analytics, MailChimp and Calibrum helped optimise survey dissemination.ResultsSurvey engagement was high amongst the three stakeholder groups: 208 people with DCM, 389 spinal surgeons and 157 other healthcare professionals. Individuals from 76 different countries participated; the United States, United Kingdom and Canada were the most common countries of participants.ConclusionAO Spine RECODE-DCM recruited a diverse and sufficient number of participants for an international PSP and COS/CDE process. Whilst PSP and COS/CDE have been undertaken in other fields, to our knowledge, this is the first time they have been combined in one process.