Shining a light on the road towards conducting principle-based co-production research in rehabilitation.

Moving from participatory approaches incorporating co-design to co-production in health research involves a commitment to full engagement and partnership with people with lived experience through all stages of the research process-start to finish. However, despite the increased enthusiasm and proliferation of research that involves co-production, practice remains challenging, due in part to the lack of consensus on what constitutes co-production, a lack of guidance about the practical steps of applying this approach in respect to diverse research methods from multiple paradigms, and structural barriers within academia research landscape. To navigate the challenges in conducting co-produced research, it has been recommended that attention be paid to focusing and operationalising the underpinning principles and aspirations of co-production research, to aid translation into practice. In this article, we describe some fundamental principles essential to conducting co-production research (sharing power, relational resilience, and adopting a learning mindset) and provide tangible, practical strategies, and processes to engage these values. In doing so, we hope to support rehabilitation researchers who wish to engage in co-production to foster a more equitable, ethical, and impactful collaboration with people with lived experience and those involved in their circle of care.

Efficacy of Interventions to Improve Cognitive Function in Adults with Spinal Cord Injury: A Systematic Review.

Cognitive impairment is a common complication following spinal cord injury (SCI) and imposes a significant negative impact on adjustment, functional independence, physical and mental health, and quality of life. It is unclear whether interventions for cognitive impairment following SCI are effective. A systematic review of controlled trials was performed to evaluate the effect of interventions on cognitive functions in adults with SCI using search engines: Embase, The Cochrane Library, MEDLINE, Scopus, CINAHL, and Web of Science up to December 2023. Two reviewers independently screened the articles, and study findings were synthesized and summarized. The risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Eight moderate-quality studies were found that investigated the effects of physical exercise/activity-based therapy plus cognitive training or intermittent hypoxia, diet modification and dietary supplements, tibial nerve or cortical stimulation, and drug therapy on cognitive function in SCI. Physical exercise/activity-based therapy plus cognitive training showed most promise for improving cognitive functions, while drug therapy, diet modification, and dietary supplements showed potential for improving cognitive function. However, about half of the participants experienced heightened instability in blood pressure following the administration of midodrine, and one participant reported gastrointestinal side effects after taking omega-3 fatty acids. There was no evidence of improvement in cognitive function for stimulation techniques. The current review highlights the scarcity of research investigating the effectiveness of interventions that target cognitive function after SCI. Further, the effects of these eight studies are uncertain due to concerns about the quality of designs and small sample sizes utilized in the trials, as well as the employment of insensitive neurocognitive tests when applied to adults with SCI. This review highlights a significant gap in knowledge related to SCI cognitive rehabilitation.

Using the consolidated Framework for Implementation Research to integrate innovation recipients' perspectives into the implementation of a digital version of the spinal cord injury health maintenance tool: a qualitative analysis.

BACKGROUND: Despite advances in managing secondary health complications after spinal cord injury (SCI), challenges remain in developing targeted community health strategies. In response, the SCI Health Maintenance Tool (SCI-HMT) was developed between 2018 and 2023 in NSW, Australia to support people with SCI and their general practitioners (GPs) to promote better community self-management. Successful implementation of innovations such as the SCI-HMT are determined by a range of contextual factors, including the perspectives of the innovation recipients for whom the innovation is intended to benefit, who are rarely included in the implementation process. During the digitizing of the booklet version of the SCI-HMT into a website and App, we used the Consolidated Framework for Implementation Research (CFIR) as a tool to guide collection and analysis of qualitative data from a range of innovation recipients to promote equity and to inform actionable findings designed to improve the implementation of the SCI-HMT. METHODS: Data from twenty-three innovation recipients in the development phase of the SCI-HMT were coded to the five CFIR domains to inform a semi-structured interview guide. This interview guide was used to prospectively explore the barriers and facilitators to planned implementation of the digital SCI-HMT with six health professionals and four people with SCI. A team including researchers and innovation recipients then interpreted these data to produce a reflective statement matched to each domain. Each reflective statement prefaced an actionable finding, defined as alterations that can be made to a program to improve its adoption into practice. RESULTS: Five reflective statements synthesizing all participant data and linked to an actionable finding to improve the implementation plan were created. Using the CFIR to guide our research emphasized how partnership is the key theme connecting all implementation facilitators, for example ensuring that the tone, scope, content and presentation of the SCI-HMT balanced the needs of innovation recipients alongside the provision of evidence-based clinical information. CONCLUSIONS: Understanding recipient perspectives is an essential contextual factor to consider when developing implementation strategies for healthcare innovations. The revised CFIR provided an effective, systematic method to understand, integrate and value recipient perspectives in the development of an implementation strategy for the SCI-HMT. TRIAL REGISTRATION: N/A.

Special Issue-Spinal Cord Injuries: Advances in Rehabilitation.

Spinal cord injury (SCI) is a severe Kolling Institute, neurological disorder resulting from traumatic injury (such as a motor vehicle crash or fall) or non-traumatic injury associated with disease (such as cancer or infection) that results in impaired voluntary motor control and sensory function, usually leading to lifelong severe disability [...].

Co-design of the Spinal Cord Injury Health Maintenance Tool to Support Self-Management: A Mixed-Methods Approach.

Background: There is a lack of consumer-friendly tools to empower and support people living with spinal cord injury (SCI) to self-manage complex health needs in community. This article describes the co-design process of the new SCI Health Maintenance Tool (SCI-HMT). Methods: Co-design of the SCI-HMT using a mixed-methods approach included a rapid review, e-Delphi surveys with range of multidisciplinary health care professionals (n = 62), interviews of participants with SCI (n = 18) and general practitioners (n = 4), focus groups (n = 3 with 7, 4, and 4 participants with SCI, respectively), design workshops with stakeholders (n = 11, 8), and end-user testing (n = 41). Results: The SCI-HMT (healthmaintenancetool.com) was developed based on participatory research with data synthesis from multiple sources. Five priority health maintenance issues for bladder, bowel, skin, pain, and autonomic dysreflexia were originally covered. Best practice recommendations, red flag conditions, referrals, and clinical pathways were agreed on through an e-Delphi technique. Qualitative analysis identified six broad key concepts for self-management, including early symptom recognition, role of SCI peers, knowledge sharing with primary care, general practitioners as gatekeepers, and shared decision-making and highlighted a need to place much stronger emphasis on mental health and well-being. Design workshops and end-user testing provided key insights about user experience, functionality, and content for the SCI-HMT. Conclusion: The co-design process engaging end users, including people with SCI and general practitioners, enabled a shared understanding of the problem and identification of important needs and how to meet them. Informed by this process, the SCI-HMT is a freely accessible resource supporting SCI self-management, shared decision-making, and early problem identification.

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights.

T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) protein-coding genes-BAALC, HHEX, MEF2C, FAT1, LYL1, LMO2, LYN, and TAL1; (ii) epigenetic modifiers-DOT1L, EP300, EML4, RAG1, EZH2, and KDM6A; and (iii) long noncoding RNAs (lncRNAs)-XIST, PCAT18, PCAT14, LINC00202, LINC00461, LINC00648, ST20, MEF2C-AS1, and MALAT1 in an independent cohort of 99 patients with T-ALL. Principal component analysis revealed distinct clusters aligning with immunophenotypic subtypes, providing insights into the molecular heterogeneity of T-ALL. The identified signature genes exhibited associations with clinicopathologic features. Survival analysis uncovered several independent predictors of patient outcomes. Higher expression of MEF2C, BAALC, HHEX, and LYL1 genes emerged as robust indicators of poor overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). Higher LMO2 expression was correlated with adverse EFS and RFS outcomes. Intriguingly, increased expression of lncRNA ST20 coupled with RAG1 demonstrated a favorable prognostic impact on OS, EFS, and RFS. Conclusively, several hitherto unreported associations of gene expression patterns with clinicopathologic features and prognosis were identified, which may help understand T-ALL's molecular pathogenesis and provide prognostic markers.

COVID-19 and spinal cord injury: clinical presentation, clinical course, and clinical outcomes of people hospitalised.

STUDY DESIGN: Retrospective study OBJECTIVES: To describe the presenting symptoms/signs, clinical course and outcomes in hospitalised people with spinal cord injury (SCI) and symptomatic COVID-19 infections. SETTING: One university hospital and two SCI centres in Switzerland. METHODS: Descriptive analysis of symptoms/signs, clinical course and outcomes of people with SCI with symptomatic COVID-19 infections and need for hospitalisation. RESULTS: Twenty-two people with SCI were included, 15 (68%) were male, median age 64.5 years (interquartile range, IQR, 52-73 years). Nine (41%) had tetraplegia, and eight (36%) were classified with motor-complete lesions. Frequent clinical symptoms were fever (59%), coughing (54%), fatigue (50%), and dyspnoea (27%). Most frequent complications were bacterial pulmonary superinfection (18%), and acute respiratory distress syndrome (18%). Fifteen persons (68%) needed oxygen therapy during the course of hospitalisation, and 7 (32%) people were ventilated. Median length of stay (LOS) was 23 days (IQR 15-35), varying by age for people under 60 years with a median LOS of 9 days (IQR 8-27), and for those older than 60 years with a median of 34 days (IQR 17-39), respectively. In total, 3 persons (14%) died during hospitalisation, all older with paraplegia. CONCLUSIONS: Typical symptoms like fever and coughing were not present in all people. People with tetraplegia did not demonstrate worse outcomes, on the contrary, they had shorter LOS, no difference in ventilation needs, and no higher mortality compared to people with paraplegia. Older people showed longer LOS. This study recommends close supervision of the SCI population to detect early signs and symptoms of COVID-19 infection.

Analysis of SIGLEC12 expression, immunomodulation and prognostic value in renal cancer using multiomic databases.

Siglecs belong to a family of immune regulatory receptors predominantly found on hematopoietic cells. They interact with Sia, resulting in the activation or inhibition of the immune response. Previous reports have suggested that the SIGLEC12 gene, which encodes the Siglec-XII protein, is expressed in the epithelial tissues and upregulated in carcinomas. However, studies deciphering the role of Siglec-XII in renal cancer (RC) are still unavailable, and here we provide insights on this question. We conducted expression analysis using the Human Protein Atlas and UALCAN databases. The impact of SIGLEC12 on RC prognosis was determined using the KM plotter, and an assessment of immune infiltration with SIGLEC12 was performed using the TIMER database. GSEA was conducted to identify the pathways affected by SIGLEC12. Finally, using GeneMania, we identified Siglec-XII interacting proteins. Our findings indicated that macrophages express SIGLEC12 in the kidney. Furthermore, we hypothesize that Siglec-XII expression might be involved in the increase of primary RC, but this effect may not be dependent on the age of the patient. In the tumour microenvironment, oncogenic pathways appeared to be upregulated by SIGLEC12. Similarly, our analysis suggested that SIGLEC12-related kidney renal papillary cell carcinomas may be more suitable for targeted immunotherapy, such as CTLA-4 and PD-1/PD-L1 inhibitors. These preliminary results suggested that high expression of SIGLEC12 is associated with poor prognosis for RC. Future studies to assess its clinical utility are necessitated.

Heart Rate Variability Biofeedback in Adults with a Spinal Cord Injury: A Laboratory Framework and Case Series.

Heart rate variability biofeedback (HRV-F) is a neurocardiac self-regulation therapy that aims to regulate cardiac autonomic nervous system activity and improve cardiac balance. Despite benefits in various clinical populations, no study has reported the effects of HRV-F in adults with a spinal cord injury (SCI). This article provides an overview of a neuropsychophysiological laboratory framework and reports the impact of an HRV-F training program on two adults with chronic SCI (T1 AIS A and T3 AIS C) with different degrees of remaining cardiac autonomic function. The HRV-F intervention involved 10 weeks of face-to-face and telehealth sessions with daily HRV-F home practice. Physiological (HRV, blood pressure variability (BPV), baroreflex sensitivity (BRS)), and self-reported assessments (Fatigue Severity Scale, Generalised Anxiety Disorder Scale, Patient Health Questionnaire, Appraisal of Disability and Participation Scale, EuroQol Visual Analogue Scale) were conducted at baseline and 10 weeks. Participants also completed weekly diaries capturing mood, anxiety, pain, sleep quality, fatigue, and adverse events. Results showed some improvement in HRV, BPV, and BRS. Additionally, participants self-reported some improvements in mood, fatigue, pain, quality of life, and self-perception. A 10-week HRV-F intervention was feasible in two participants with chronic SCI, warranting further investigation into its autonomic and psychosocial effects.

Biologic Antiresorptive: Denosumab.

Background: Osteoporosis is an age-related common bone disorder characterized by low bone mineral density and increased fragility fracture risk. Various Antiresorptive medications are being used to target osteoclast mediated bone resorption to prevent bone loss and reduce fracture risk. About Denosumab: Denosumab is a novel biological antiresorptive drug that belongs to the class of monoclonal antibodies. It binds to and inhibits the cytokine receptor activator of nuclear factor kappa-B ligand (RANKL), which is requisite for osteoclast differentiation, function and survival. Effectiveness: Denosumab has been shown to be a potent and effective therapy for osteoporosis, with clinical trial data demonstrating significant improvement in bone mineral density (BMD) and reductions in fracture risk at various skeletal sites for more than 10 years of treatment. Safety Profile: Denosumab has a favourable benefit/risk profile, with low rates of complications such as infection, atypical femoral fracture and osteonecrosis of the jawbone. Challenges: However, denosumab treatment requires continuous administration, as discontinuation leads to rapid bone mineral loss and increased risk of multiple vertebral fractures due to rebound of bone turnover. Therefore, modification to another anti-osteoporosis drug therapy after denosumab discontinuation is required to maintain bone health. Conclusion: Denosumab is a promising biological antiresorptive therapy for osteoporosis that offers high efficacy and safety, but also poses challenges for long-term management.

Combination Therapy of Denosumab and Teriparatide in Osteoporosis.

Osteoporosis is a chronic disease that often requires long-term treatment for many years. The clinician should know about all the drugs that are currently being used for treatment in osteoporosis and their mechanism of action, efficacy, safety profile, mode of administration and number of years they can be given safely without causing significant adverse effects. The categories of drugs that are currently being used for osteoporosis are antiresorptives such as oral and intravenous bisphosphonates, denosumab, and anabolics like teriparatide. This article will focus on the combination therapy of denosumab and teriparatide and will discuss how this combination is better than other class of drugs when given alone or in combination in osteoporosis patients especially those who are at high risk of fragility fractures.

Complex lived experiences and hidden disability after spinal cord injury: a latent profile analysis of the Australian arm of the International Spinal Cord Injury (Aus-InSCI) Community Survey.

PURPOSE: To identify and examine subgroups of people with spinal cord injury (SCI) with different patterns of lived experience, and examine hidden impairments and disability among functionally independent and ambulant people. MATERIALS AND METHODS: Latent profile analysis of population-based data from the Australian arm of the International Spinal Cord Injury (InSCI) Community survey (n = 1579). RESULTS: Latent subgroups reflected levels of functional independence and extent of problems with health, activity/participation, environmental barriers, and self-efficacy. Quality of life (QoL), psychological profiles, and activity/participation were often as good or better in participants who reported lower (vs. higher) functional independence alongside comparable burden of health problems and environmental barriers. QoL, mental health, and vitality reflected self-efficacy and problem burdens more closely than functional independence. Ambulant participants reported a substantial burden of underlying, potentially hidden impairments, with QoL and mental health similar to wheelchair users. CONCLUSION: Hidden disability among more independent and/or ambulant people with SCI can affect well-being substantially. Early and ongoing access to support, rehabilitation, and SCI specialist services is important irrespective of cause, type, severity of injury, and level of functional independence. Improved access to SCI expertise and equity of care would help to improve early recognition and management of hidden disability. TRIAL REGISTRATION: Not applicable.

Hidden disability can substantially affect the well-being and quality of life of people with spinal cord injury (SCI) who appear to be functioning well and independently.Early and ongoing access to rehabilitation and SCI specialist services is important for people with SCI of any cause, type, severity, and level of functional independence.The potential for and implications of hidden disability are key considerations for the broader community of health practitioners who manage people with SCI, to ensure that appropriate referrals to specialist SCI services occur.Hidden disability is a key consideration in the design and implementation of disability support systems.

Cognitive Failure in Adults with Spinal Cord Injury: A Valuable Adjunct Measure for Enhancing Cognitive Assessment and Rehabilitation Outcomes.

Cognitive impairment is common in persons with spinal cord injury (SCI), impacting their daily functioning and rehabilitation. This study assesses the extent of self-reported cognitive failures in everyday life in persons with SCI and its relationships with objective neurocognitive measures and psychosocial factors, including depressive mood, anxiety, perceived control, and fatigue. The differences between forty-one adults with a chronic SCI and forty-one able-bodied controls were examined. The participants completed the Cognitive Failures Questionnaire (CFQ) to assess cognitive failure and neurocognitive tests assessing attention and executive functions, as well as a psychosocial assessment. The SCI group reported higher cognitive failure rates than the able-bodied group (31.7% versus 19%, p > 0.05). Objective neurocognitive tests did not significantly correlate with the CFQ scores in either group. However, the CFQ scores were positively associated with most psychosocial factors, even after controlling for covariates. The CFQ scores were significantly associated with depressive mood in persons with SCI. These findings highlight the importance of incorporating self-reported cognitive measures into neurocognitive assessments and rehabilitation planning for adults with SCI. Self-reports capture everyday cognitive challenges that objective tests may miss. Additionally, this study highlights the strong connections between cognitive failures and psychosocial issues, particularly mood disorders, emphasizing the need for comprehensive rehabilitation and psychosocial support post-SCI, addressing both cognitive and emotional wellbeing.

Effects of behaviour change interventions on physical activity in people with spinal cord injury: A systematic review and meta-analysis.

OBJECTIVES: This review investigated the effectiveness of behaviour-change interventions to improve physical activity (PA) participation in individuals with a spinal cord injury. Additionally, the review sought to analyse the change in PA behaviour that might be expected by utilising behaviour change in PA interventions and what specific intervention characteristics, application of behaviour change theories, and behaviour change techniques are most efficacious. METHODS: The protocol was prospectively registered on PROSPERO: CRD42021252744, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed in this review. Eight databases were comprehensively searched using a well-defined strategy developed in collaboration with an academic liaison librarian. Randomised, non-randomised controlled, and non-controlled studies were included in this review; however, controlled and non-controlled studies were analysed separately. Studies were included if participants were older than 16 years and had an SCI of any cause, level or severity, regardless of the time since injury. The behaviour change technique taxonomy version 1 was used to code the intervention characteristics for behaviour modification. The combined effects across studies were pooled in a meta-analysis, and the risk of bias was assessed using the Cochrane Risk of Bias 2 tool. RESULTS: The search retrieved 10,155 titles and abstracts. After duplicate removal and screening against the eligibility criteria, 23 studies were included. The overall effect estimate of the change in PA participation in the controlled trials post-intervention was medium (d = 0.50, 95% CI = 0.31-0.70) in favour of behaviour-targeted interventions. The mean difference in PA volume between pre- and post-intervention was an increase of 22 minutes per week (95% CI = 5.96-38.90). Interventions that provided practical support (d = 0.81, 95% CI = 0.46-1.16), which were individualised (d = 0.62, 95% CI = 0.34-0.90) and that utilised monitoring (d = 0.59, 95% CI = 0.34-0.83) had a greater effect on change to PA than those that were group-based and did not utilise those specific techniques. CONCLUSIONS: Interventions that target behaviour change to increase PA in people with SCI appear effective. Utilising behaviour change frameworks and specific behaviour change techniques augments PA uptake and levels, and interventions aimed at improving PA in people with SCI should incorporate a behaviour modification component. More research is needed on the isolated effect of intervention structure parameters and specific behaviour change techniques.

Translation, cross-cultural adaptation and reliability testing of the barriers to physical activity and Disability survey (B-PADS) for Thai people with Spinal Cord injury.

PURPOSE: The objectives of this study were to translate and culturally adapt the Barriers to Physical Activity and Disability Survey (B-PADS) into the Thai context and to assess its inter- and intra-rater reliability. METHODS: Participants were experts in the field of spinal cord injury (SCI, n = 3), linguistic experts (n = 7), Thai-English bilingual speakers (n = 40), Thai physiotherapists (n = 8), and people with SCI living in Thailand (n = 43). The translation and cross-cultural adaptation of the B-PADS into the Thai context was conducted using a 6-step process; forward translation, reconciliation of the two translated versions, backward-translation, harmonisation, backward-translation of the revised version, and cognitive debriefing with potential users and target population. The reliability of the translated tool was assessed using Cohen's kappa (K) and McNemar's test. RESULTS: The inter-rater reliability test demonstrated high-range agreement for the majority of statements (27 out of 38; Cohen's K > 0.60) in the Thai-B-PADS final version. The intra-rater reliability test revealed that the majority of the statements (29 out of 38) in the Thai-B-PADS final version obtained substantial (Cohen's K = 0.61-0.80, p < 0.05) to perfect agreement (Cohen's K = 1.0, p < 0.05). McNemar's test displayed no statistically significant differences amongst assessors (p > 0.05) for nearly all statements. CONCLUSION: The Thai-B-PADS final version was successfully translated and culturally adapted for people with SCI.

Multi-stakeholders, including academic experts, researchers, translators, clinicians, target users and clients, should be involved in developing health-related questionnaires' translation and cultural adaptation processes.The Thai version of Barriers to Physical Activity and Disability Survey (B-PADS) possessed high levels of inter- and intra-rater reliability to assess barriers related to undertaking physical activities or exercise in people with spinal cord injury.Interactional biases and perceived social status effects may not be avoided when deploying a face-to-face interview of health-related questionnaires in a culture where social hierarchy is present within the language.The translation and adaptation processes used in this study were thorough, systematic and comprehensive, providing a culturally competent exemplar for translating health-related questionnaires between languages of different root origins.

Involvement of DPP3 in modulating oncological features and oxidative stress response in esophageal squamous cell carcinoma.

Resistance to therapy in esophageal squamous cell carcinoma (ESCC) is a critical clinical problem and identification of novel therapeutic targets is highly warranted. Dipeptidyl peptidase III (DPP3) is a zinc-dependent aminopeptidase and functions in the terminal stages of the protein turnover. Several studies have reported overexpression and oncogenic functions of DPP3 in numerous malignancies. The present study aimed to determine the expression pattern and functional role of DPP3 in ESCC. DPP3 expression was assessed in normal and tumor tissues using quantitative real-time (qRT)-PCR and corroborated with ESCC gene expression datasets from Gene Expression Omnibus (GEO) and The cancer genome atlas (TCGA). DPP3 stable knockdown was performed in ESCC cells by shRNA and its effect on cell proliferation, migration, cell cycle, apoptosis, and activation of nuclear factor erythroid 2-related factor 2 (NRF2) pathway was assessed. The results suggested that DPP3 is overexpressed in ESCC and its knockdown leads to reduced proliferation, increased apoptosis, and inhibited migration of ESCC cells. Additionally, DPP3 knockdown leads to down-regulation of the NRF2 pathway proteins, such as NRF2, G6PD, and NQO1 along with increased sensitivity toward oxidative stress-induced cell death and chemotherapy. Conclusively, these results demonstrate critical role of DPP3 in ESCC and DPP3/NRF2 axis may serve as an attractive therapeutic target against chemoresistance in this malignancy.

Prognostic relevance of surface expression of cytokine receptor-like factor 2 in pediatric B-lineage acute lymphoblastic leukemia.

Overexpression of cytokine receptor-like factor 2 (CRLF2) resulting from its genomic rearrangement is the most frequent genetic alteration found in Philadelphia chromosome-like (Ph-like) B-cell acute lymphoblastic leukemia (B-ALL), a high-risk leukemia. Detection of CRLF2 expression by multiparameter flow cytometry has been proposed as a screening tool for the identification of Ph-like B-ALL. However, the prognostic relevance of flow cytometric expression of CRLF2 in pediatric B-ALL is not very clear. Additionally, its association with common copy number alterations (CNA) has not been studied in detail. Hence, in this study, we prospectively evaluated the flow cytometric expression of CRLF2 in 256 pediatric B-ALL patients and determined its association with molecular features such as common CNAs detected using Multiplex ligation-dependent probe amplification and mutations in CRLF2, JAK2 and IL7RA genes. Further, its association with clinicopathological features including patient outcome was assessed. We found that 8.59% (22/256) pediatric B-ALL patients were CRLF2-positive at diagnosis. Among CNAs, CRLF2 positivity was associated with presence of PAX5 alteration (P=0.041). JAK2 and IL-7R mutations were found in 9% and 13.6% CRLF2-positive patients, respectively. IGH::CRLF2 or P2RY8::CRLF2 fusions were each found in 1/22 individuals. CRLF2-positive patients were found to have inferior overall (hazard ratio (HR) =4.39, P=0.006) and event free survival (HR=2.62, P=0.045), independent to other clinical features. Furthermore, concomitant CNA of IKZF1 in CRLF2 positive patients was associated with a greater hazard for poor overall and event free survival, compared to patients without these alterations or presence of any one of them. Our findings demonstrate that the surface CRLF2 expression in association with IKZF1 copy number alteration can be used to risk stratify pediatric B-ALL patients.

Cognitive Reserve and Its Association with Cognitive and Mental Health Status following an Acute Spinal Cord Injury.

BACKGROUND: Mild cognitive impairment (MCI) is a common secondary condition associated with spinal cord injury (SCI). Cognitive reserve (CR) is believed to protect against cognitive decline and can be assessed by premorbid intelligence (pmIQ). Despite the potential utility of pmIQ as a complementary metric in the evaluation of MCI in SCI, this approach has been infrequently employed. The purpose of this study was to examine the association between MCI and pmIQ in adults with SCI with the aim of exploring the potential value of pmIQ as a marker of CR in this population. METHODS: Cognitive function was assessed on three occasions in adults with SCI over a 12-month period post-injury, and pmIQ was assessed once at baseline. Demographic and mental health measures were also collected, and logistic regression was conducted to determine the strength of association between pmIQ and MCI while adjusting for factors such as mental health and age. RESULTS: The regression analysis revealed that at the time of admission to SCI rehabilitation, the MCI assessed by a valid neurocognitive screen was strongly associated with pmIQ. That is, if a person has MCI, there was 5.4 greater odds (p < 0.01) that they will have poor pmIQ compared to a person without MCI after adjustment for age and mental health. CONCLUSIONS: The assessment of CR is an important area that should be considered to improve the process of diagnosing MCI in adults with an acute SCI and potentially facilitate earlier intervention to slow or prevent cognitive decline.

Health System's Role in Facilitating Health Service Access among Persons with Spinal Cord Injury across 22 Countries.

(1) Background: Despite efforts to improve access to health services, between- and within-country access inequalities remain, especially for individuals with complex disabling conditions like spinal cord injury (SCI). Persons with SCI require regular multidisciplinary follow-up care yet experience more access barriers than the general population. This study examines health system characteristics associated with access among persons with SCI across 22 countries. (2) Methods: Study data are from the International Spinal Cord Injury Survey with 12,588 participants with SCI across 22 countries. Cluster analysis was used to identify service access clusters based on reported access restrictions. The association between service access and health system characteristics (health workforce, infrastructure density, health expenditure) was determined by means of classification and regression trees. (3) Results: Unmet needs were reported by 17% of participants: lowest (10%) in Japan, Spain, and Switzerland (cluster 1) and highest (62%) in Morocco (cluster 8). The country of residence was the most important factor in facilitating access. Those reporting access restrictions were more likely to live in Morocco, to be in the lowest income decile, with multiple comorbidities (Secondary Conditions Scale (SCI-SCS) score > 29) and low functioning status (Spinal Cord Independence Measure score < 53). Those less likely to report access restriction tended to reside in all other countries except Brazil, China, Malaysia, Morocco, Poland, South Africa, and South Korea and have fewer comorbidities (SCI-SCS < 23). (4) Conclusions: The country of residence was the most important factor in facilitating health service access. Following the country of residence, higher income and better health were the most important facilitators of service access. Health service availability and affordability were reported as the most frequent health access barriers.