Enzymatic Dissociation of DNA-Histone Condensates in an Electrophoretic Setting: Modulating DNA Patterning and Hydrogel Viscoelasticity.

Development of an energy-driven self-assembly process is a matter of interest for understanding and mimicking diverse ranges of biological and environmental patterns in a synthetic system. In this article, first we demonstrate transient and temporally controlled self-assembly of a DNA-histone condensate where trypsin (already present in the system) hydrolyzes histone, resulting in disassembly. Upon performing this dynamic self-assembly process in a gel matrix under an electric field, we observe diverse kinds of DNA patterning across the gel matrix depending on the amount of trypsin, incubation time of the reaction mixture, and gel porosity. Notably, here, the micrometer-sized DNA-histone condensate does not move through the gel and only free DNA can pass; therefore, transport and accumulation of DNA at different zones depend on the release rate of DNA by trypsin. Furthermore, we show that the viscoelasticity of the native gel increases in the presence of DNA and a pattern over gel viscoelasticity at different zones can be achieved by tuning the amount of enzyme, i.e., the dissociation rate of the DNA-histone condensate. We believe enabling spatiotemporally controlled DNA patterning by applying an electric field will be potentially important in designing different kinds of spatiotemporally distinct dynamic materials.

Recent Advances in the Treatment Strategies of Friedreich's Ataxia: A Review of Potential Drug Candidates and their Underlying Mechanisms.

BACKGROUND: Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder characterized by progressive ataxia, cardiomyopathy, and diabetes. The disease is caused by a deficiency of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and iron metabolism. OBJECTIVE: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action. METHODS: A comprehensive literature search was conducted using various authentic scientific databases to identify studies published in the last decade that investigated potential treatment strategies for FRDA. The search terms used included "Friedreich's ataxia," "treatment," "drug candidates," and "mechanisms of action." RESULTS: To date, only one drug got approval from US-FDA in the year 2023; however, significant developments were achieved in FRDA-related research focusing on diverse therapeutic interventions that could potentially alleviate the symptoms of this disease. Several promising drug candidates have been identified for the treatment of FRDA, which target various aspects of frataxin deficiency and aim to restore frataxin levels, reduce oxidative stress, and improve mitochondrial function. Clinical trials have shown varying degrees of success, with some drugs demonstrating significant improvements in neurological function and quality of life in FRDA patients. CONCLUSION: While there has been significant progress in the development of treatment strategies for FRDA, further research is needed to optimize these approaches and identify the most effective and safe treatment options for patients. The integration of multiple therapeutic strategies may be necessary to achieve the best outcomes in FRDA management.

Cognitive domains affected post-COVID-19; a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This review aims to characterize the pattern of post-COVID-19 cognitive impairment, allowing better prediction of impact on daily function to inform clinical management and rehabilitation. METHODS: A systematic review and meta-analysis of neurocognitive sequelae following COVID-19 was conducted, following PRISMA-S guidelines. Studies were included if they reported domain-specific cognitive assessment in patients with COVID-19 at >4 weeks post-infection. Studies were deemed high-quality if they had >40 participants, utilized healthy controls, had low attrition rates and mitigated for confounders. RESULTS: Five of the seven primary Diagnostic and Statistical Manual of Mental Disorders (DSM-5) cognitive domains were assessed by enough high-quality studies to facilitate meta-analysis. Medium effect sizes indicating impairment in patients post-COVID-19 versus controls were seen across executive function (standardised mean difference (SMD) -0.45), learning and memory (SMD -0.55), complex attention (SMD -0.54) and language (SMD -0.54), with perceptual motor function appearing to be impacted to a greater degree (SMD -0.70). A narrative synthesis of the 56 low-quality studies also suggested no obvious pattern of impairment. CONCLUSIONS: This review found moderate impairments across multiple domains of cognition in patients post-COVID-19, with no specific pattern. The reported literature was significantly heterogeneous, with a wide variety of cognitive tasks, small sample sizes and disparate initial disease severities limiting interpretability. The finding of consistent impairment across a range of cognitive tasks suggests broad, as opposed to domain-specific, brain dysfunction. Future studies should utilize a harmonized test battery to facilitate inter-study comparisons, whilst also accounting for the interactions between COVID-19, neurological sequelae and mental health, the interplay between which might explain cognitive impairment.

The impact of psychiatric comorbidity on Parkinson's disease outcomes: a systematic review and meta-analysis.

Background: The burden of psychiatric symptoms in Parkinson's disease includes depression, anxiety, apathy, psychosis, and impulse control disorders. However, the relationship between psychiatric comorbidities and subsequent prognosis and neurological outcomes is not yet well understood. In this systematic review and meta-analysis, in individuals with Parkinson's disease, we aimed to characterise the association between specific psychiatric comorbidities and subsequent prognosis and neurological outcomes: cognitive impairment, death, disability, disease progression, falls or fractures and care home admission. Methods: We searched MEDLINE, Embase, PsycINFO and AMED up to 13th November 2023 for longitudinal observational studies which measured disease outcomes in people with Parkinson's disease, with and without specific psychiatric comorbidities, and a minimum of two authors extracted summary data. Studies of individuals with other parkinsonian conditions and those with outcome measures that had high overlap with psychiatric symptoms were excluded to ensure face validity. For each exposure-outcome pair, a random-effects meta-analysis was conducted based on standardised mean difference, using adjusted effect sizes-where available-in preference to unadjusted effect sizes. Study quality was assessed using the Newcastle-Ottawa Scale. Between-study heterogeneity was assessed using the I2 statistic and publication bias was assessed using funnel plots. PROSPERO Study registration number: CRD42022373072. Findings: There were 55 eligible studies for inclusion in meta-analysis (n = 165,828). Data on participants' sex was available for 164,514, of whom 99,182 (60.3%) were male and 65,460 (39.7%) female. Study quality was mostly high (84%). Significant positive associations were found between psychosis and cognitive impairment (standardised mean difference [SMD] 0.44, [95% confidence interval [CI] 0.23-0.66], I2 30.9), psychosis and disease progression (SMD 0.46, [95% CI 0.12-0.80], I2 70.3%), depression and cognitive impairment (SMD 0.37 [95% CI 0.10-0.65], I2 27.1%), depression and disease progression (SMD 0.46 [95% CI 0.18-0.74], I2 52.2), depression and disability (SMD 0.42 [95% CI 0.25-0.60], I2 7.9%), and apathy and cognitive impairment (SMD 0.60 [95% CI 0.02-1.19], I2 27.9%). Between-study heterogeneity was moderately high. Interpretation: Psychosis, depression, and apathy in Parkinson's disease are all associated with at least one adverse outcome, including cognitive impairment, disease progression and disability. Whether this relationship is causal is not clear, but the mechanisms underlying these associations require exploration. Clinicians should consider these psychiatric comorbidities to be markers of a poorer prognosis in people with Parkinson's disease. Future studies should investigate the underlying mechanisms and which treatments for these comorbidities may affect Parkinson's disease outcomes. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at University College London Hospitals NHS Foundation Trust, National Brain Appeal.

Primary care micro-teams: an international systematic review of patient and healthcare professional perspectives.

BACKGROUND: International trends have shifted to creating large general practices. There is an assumption that interdisciplinary teams will increase patient accessibility and provide more cost-effective, efficient services. Micro-teams have been proposed to mitigate for some potential challenges of practice expansion, including continuity of care. AIM: To review available literature and examine how micro-teams are described, and identify opportunities and limitations for patients and practice staff. DESIGN AND SETTING: This was an international systematic review of studies published in English. METHOD: Databases (MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus) and grey literature were searched. Studies were included if they provided evidence about implementation of primary care micro-teams. Framework analysis was used to synthesise identified literature. The research team included a public contributor co-applicant. The authors conducted stakeholder discussions with those with and without experience of micro-team implementation. RESULTS: Of the 462 studies identified, 24 documents met the inclusion criteria. Most included empirical data from healthcare professionals, describing micro-team implementation. Results included characteristics of the literature; micro-team description; range of ways micro-teams have been implemented; reported outcomes; and experiences of patients and staff. CONCLUSION: The organisation of primary care has potential impact on the nature and quality of patient care, safety, and outcomes. This review contributes to current debate about care delivery and how this can impact on the experiences and outcomes of patients and staff. This analysis identifies several key opportunities and challenges for future research, policy, and practice.

A Rare Presentation of Thyroid Mass- A case report.

Background-Respiratory symptoms are not uncommon in thyroid diseases and can be overlooked and misdiagnosed as acute exacerbation of asthma or COPD. Case report- A 58 years old female presented to emergency department with complaints of fever, shortness of breath from last 3-4 days for which she intubated in emergency department and shifted to ICU. Next day patient was absolutely fine and extubated and was planned to be shifted out surprisingly the same episode was repeated following which patient was intubated again and was found to be absolutely normal after 3-4 h and extubated again. The same episode was repeated next day as well. Eventually she was diagnosed to have cystic thyroid swelling. Immediate aspiration of the cyst done to relieve the symptoms and total thyroidectomy was done subsequently and patient was cured of the symptoms. Conclusion- Acute airway obstruction can occur in asymptomatic goitre patients. The anaesthetic management is crucial for airway till definitive surgery is done. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03179-x.

The role of the electroencephalogram (EEG) in determining the aetiology of catatonia: a systematic review and meta-analysis of diagnostic test accuracy.

Background: Catatonia is a psychomotor syndrome that has a wide range of aetiologies. Determining whether catatonia is due to a medical or psychiatric cause is important for directing treatment but is clinically challenging. We aimed to ascertain the performance of the electroencephalogram (EEG) in determining whether catatonia has a medical or psychiatric cause, conventionally defined. Methods: In this systematic review and meta-analysis of diagnostic test accuracy (PROSPERO CRD42021239027), Medline, EMBASE, PsycInfo, and AMED were searched from inception to May 11, 2022 for articles published in peer-reviewed journals that reported EEG findings in catatonia of a medical or psychiatric origin and were reported in English, French, or Italian. Eligible study types were clinical trials, cohort studies, case-control studies, cross-sectional studies, case series, and case reports. The reference standard was the final clinical diagnosis. Data extraction was conducted using individual patient-level data, where available, by two authors. We prespecified two types of studies to overcome the limitations anticipated in the data: larger studies (n ≥ 5), which were suitable for formal meta-analytic methods but generally lacked detailed information about participants, and smaller studies (n < 5), which were unsuitable for formal meta-analytic methods but had detailed individual patient level data, enabling additional sensitivity analyses. Risk of bias and applicability were assessed with the QUADAS-2 tool for larger studies, and with a published tool designed for case reports and series for smaller studies. The primary outcomes were sensitivity and specificity, which were derived using a bivariate mixed-effects regression model. Findings: 355 studies were included, spanning 707 patients. Of the 12 larger studies (5 cohort studies and 7 case series), 308 patients were included with a mean age of 48.2 (SD = 8.9) years. 85 (52.8%) were reported as male and 99 had catatonia due to a general medical condition. In the larger studies, we found that an abnormal EEG predicted a medical cause of catatonia with a sensitivity of 0.82 (95% CI 0.67-0.91) and a specificity of 0.66 (95% CI 0.45-0.82) with an I 2 of 74% (95% CI 42-100%). The area under the summary ROC curve offered excellent discrimination (AUC = 0.83). The positive likelihood ratio was 2.4 (95% CI 1.4-4.1) and the negative likelihood ratio was 0.28 (95% CI 0.15-0.51). Only 5 studies had low concerns in terms of risk of bias and applicability, but a sensitivity analysis limited to these studies was similar to the main analysis. Among the 343 smaller studies, 399 patients were included, resulting in a sensitivity of 0.76 (95% CI 0.71-0.81), specificity of 0.67 (0.57-0.76) and AUC = 0.71 (95% CI 0.67-0.76). In multiple sensitivity analyses, the results were robust to the exclusion of reports of studies and individuals considered at high risk of bias. Features of limbic encephalitis, epileptiform discharges, focal abnormality, or status epilepticus were highly specific to medical catatonia, but features of encephalopathy had only moderate specificity and occurred in 23% of the cases of psychiatric catatonia in smaller studies. Interpretation: In cases of diagnostic uncertainty, the EEG should be used alongside other investigations to ascertain whether the underlying cause of catatonia is medical. The main limitation of this review is the differing thresholds for considering an EEG abnormal between studies. Funding: Wellcome Trust, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust.

Clozapine as a treatment for catatonia: A systematic review.

Catatonia is a neuropsychiatric disorder characterised by altered movement, speech, and behaviour. Clozapine is an established therapy for treatment-resistant schizophrenia, but its role in catatonia has not been systematically examined. In this systematic review, we aimed to assess the evidence for clozapine as a treatment for catatonia. Full text original research articles in English where at least one patient with catatonia was treated with clozapine were included, provided catatonia did not occur solely in the context of neuroleptic malignant syndrome. Results were tabulated with calculations of summary statistics presented. Risk of bias was assessed with the Tool for Evaluating the Methodological Quality of Case Reports and Case Series. 182 patients were included, 81 from cohort studies and 101 from case reports or case series. 119/182 patients (65 %) had a specified underlying diagnosis of schizophrenia. Over 80 % of reported patients with catatonia had at least partial remission following treatment with clozapine across both cohort studies and case reports and case series. Among the case reports and series, 24/101 patients (23.8 %) followed clozapine withdrawal. Overall, 25 studies were of low quality, 60 of moderate quality and 8 of high quality. Our findings should be interpreted with caution, as the reliance on case reports, case series and small cohort studies is susceptible to reporting biases, regression to the mean and confounding by other treatments. Future research could use large healthcare databases to ascertain outcomes in those on clozapine with a history of catatonia given the difficulty and expense of conducting randomised controlled trials.

Primary care micro-teams: a protocol for an international systematic review to describe and examine the opportunities and challenges of implementation for patients and healthcare professionals.

INTRODUCTION: There has been a recent trend towards creating larger primary care practices with the assumption that interdisciplinary teams can deliver improved and more cost-effective services to patients with better accessibility. Micro-teams have been proposed to mitigate some of the potential challenges with practice expansion, including continuity of care. We aim to review the available literature to improve understanding of how micro-teams are described and the opportunities which primary care micro-teams can provide for practice staff and patients and limitations to their introduction and implementation. Our review asks: how is micro-team implementation described? What are the experiences of healthcare professionals and patients concerning micro-teams in primary care? What are the reported implications of micro-teams for patient care? METHODS AND ANALYSIS: CINAHL, Cochrane Library, Embase, MEDLINE and Scopus will be searched for studies in English. Grey literature will be sourced from Google Scholar, government websites, CCG websites, general practice directives and strategies with advice from stakeholders. Included studies will give evidence regarding the implementation of micro-teams. Data will be synthesised using framework analysis. We will use iterative stakeholder and public and patient participation to embed the perspectives of those whom micro-teams could impact. Included studies will be quality assessed using the Mixed Methods Appraisal Tool. The quality assessment will not be used to exclude any evidence but rather to develop a narrative discussion evaluating included literature. ETHICS AND DISSEMINATION: Ethical approval will not be necessary for this systematic review as there will only be a secondary analysis of data already available in scientific databases and the grey literature. This protocol has been submitted for registration to be made available on a review database (PROSPERO). Findings will be disseminated widely through peer-reviewed publication and in various media, for example, conferences, congresses or symposia. PROSPERO REGISTRATION NUMBER: CRD42021225367.

Persistent neuropsychiatric symptoms after COVID-19: a systematic review and meta-analysis.

The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection and in control groups where available. For each study, a minimum of two authors extracted summary data. For each symptom, we calculated a pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I 2. Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 unique titles, we included 51 studies (n = 18 917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14-182 days). Study quality was most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 21.4-34.4%)], followed by fatigue [24.4% (17.5-32.9%)], objective cognitive impairment [20.2% (10.3-35.7%)], anxiety [19.1% (13.3-26.8%)] and post-traumatic stress [15.7% (9.9-24.1%)]. Only two studies reported symptoms in control groups, both reporting higher frequencies in COVID-19 survivors versus controls. Between-study heterogeneity was high (I 2 = 79.6-98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing but indicates a particularly high prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection.

Inflammatory and blood gas markers of COVID-19 delirium compared to non-COVID-19 delirium: a cross-sectional study.

OBJECTIVES: We aimed to find the association of inflammation and respiratory failure with delirium in COVID-19 patients. We compare the inflammatory and arterial blood gas markers between patients with COVID-19 delirium and delirium in other medical disorders. METHODS: This cross-sectional study used the CHART-DEL, a validated research tool, to screen patients for delirium retrospectively from clinical notes. Inflammatory markers C-reactive protein (CRP) and white cell count (WBC), and the partial pressures of oxygen (PO2) and carbon dioxide (PCO2) were compared between patients with COVID-19 delirium and delirium in other medical disorders. RESULTS: In bivariate analysis, CRP (mg/L) was significantly higher in the COVID-19 group, (81.7 ± 80.0 vs. 58.8 ± 87.7, p = 0.04), and WBC (109/L) was significantly lower (7.44 ± 3.42 vs. 9.71 ± 5.45, p = 0.04). The geometric mean of CRP in the COVID-19 group was 140% higher in multiple linear regression (95% CI = 7-439%, p = 0.03) with age and sex as covariates. There were no significant differences in pO2 or pCO2 across groups. CONCLUSION: The association between higher CRP and COVID-19 in patients with delirium may suggest an inflammatory basis for delirium in COVID-19. Our findings may assist clinicians in establishing whether delirium is due to COVID-19, which may improve management and outcomes of infected patients.

Applications of 3D Bioprinting in Tissue Engineering and Regenerative Medicine.

Regenerative medicine is an emerging field that centers on the restoration and regeneration of functional components of damaged tissue. Tissue engineering is an application of regenerative medicine and seeks to create functional tissue components and whole organs. Using 3D printing technologies, native tissue mimics can be created utilizing biomaterials and living cells. Recently, regenerative medicine has begun to employ 3D bioprinting methods to create highly specialized tissue models to improve upon conventional tissue engineering methods. Here, we review the use of 3D bioprinting in the advancement of tissue engineering by describing the process of 3D bioprinting and its advantages over other tissue engineering methods. Materials and techniques in bioprinting are also reviewed, in addition to future clinical applications, challenges, and future directions of the field.

Emerging approaches to pre-hospital hemorrhage control: a narrative review.

In the United States, trauma claims the lives of over 150,000 civilians each year. In military settings, trauma and exsanguination result in 50% of combat related deaths. The majority of these deaths result from uncontrolled non-compressible hemorrhage. Non-compressible hemorrhage often results from deep vascular injuries within the torso, however can also occur secondary to penetrating injuries that involve the extremities. Given the high mortality rates for non-compressible hemorrhage, rapid and effective management of patients suffering from hemorrhage is essential to good patient outcomes. Consequently, there has been increasing interest in solutions for point-of-injury hemorrhage control in trauma and military medicine. Undoubtedly there is a great need for prehospital hemostatic interventions that can be deployed by trained and untrained personnel. Since 2001, various hemostatic agents have been developed, each with its advantages based upon the type and severity of injury, wound size, wound location, accessibility to injury site, and the coagulation status of the patient. These agents are often used in the military setting as a temporizing measure prior to definitive therapy and include techniques such as resuscitative endovascular balloon occlusion of the aorta (REBOA) and bioengineered agents including ResQFoam, RevMedx's XSTAT, Tranexamic acid (TXA), and QuikClot Combat Gauze (QCG). Here, we review the indications, composition, technique, efficacy, and outcomes of these hemostatic agents.

Endovascular interventions in the management of acute extremity trauma: a narrative review.

Minimally invasive endovascular interventions including stenting and embolization have been widely adopted for the treatment of emergent and traumatic thoracoabdominal injuries. In recent years, these techniques have been utilized in the setting of extremity vascular trauma with promising outcomes. By allowing for the rapid diagnosis and subsequent treatment of penetrating or blunt vascular extremity trauma, these techniques can help to minimize blood loss, reduce operative complications, and potentially prevent limb amputation. Here, we present a narrative review of the ever-increasing role of minimally invasive interventions in the management of extremity trauma and compare its use and outcomes to open surgical repair. A special focus is placed on diagnostic imaging modalities in trauma and the role of interventional radiologists in the work-up and treatment of extremity trauma. We discuss diagnostic imaging modalities that aid in the triaging of extremity trauma, such as Doppler sonography, CT angiography, and catheter-based angiography. We present an overview on the literature related to endovascular interventions such as embolotherapy and stent grafting as well as the technical challenges associated with each technique. Finally, we present our own cases on the workup and endovascular treatment of extremity trauma, including CT angiography, particulate and coil embolization, and stent graft placement.

A Descriptive Correlational Study to Evaluate Three Measures of Assessing Upper Extremity Function in Individuals with Multiple Sclerosis.

BACKGROUND: Activities of daily living and quality of life (QOL) are hindered by upper extremity (UE) impairments experienced by individuals with multiple sclerosis (iMS). The Nine-Hole Peg Test (9-HPT) is most frequently used to measure UE function. However, it does not measure peoples' ability to perform routine tasks in daily life and may not be useful in iMS who cannot pick up the pegs utilized in the 9-HPT. Therefore, we evaluated three measures to explore a more comprehensive assessment of UE function: Upper Extremity Function Scale (UEFS), Action Research Arm Test (ARAT), and the 9-HPT. The objectives were to quantitatively assess the relationship between these measures of UE function, understand if the measures correlate with QOL as calculated by the MS Quality of Life-54 (MSQOL-54), and to determine differences in the measures based on employment status. METHODS: 112 (79 female) iMS were prospectively recruited for this descriptive correlational study. Inclusion criteria were as follows: confirmed diagnosis of MS or clinically isolated syndrome, age ≥ 18 years, and ability to self-consent. All statistical analyses including Spearman's correlation coefficient (r s ) and Kruskal-Wallis tests were performed using SPSS. RESULTS: A moderate correlation (r s = -0.51; p < 0.001) was found between the ARAT and 9-HPT scores for the more impaired hand. Likewise, a moderate correlation was found between UEFS and the physical health composite scores (PHCSs) of MSQOL-54 (r s = -0.59; p < 0.001). Finally, performances on ARAT, 9-HPT, and UEFS differed between the employed individuals and those on long-term disability (p = 0.007, p < 0.001, and p = 0.001). CONCLUSION: The UEFS moderately correlated with the QOL measure, and considering the UESF is a patient-reported outcome, it could be used to complement routinely captured measures of assessing UE function. Further study is warranted to determine which measure, or combination of measures, is more sensitive to changes in UE function over time.

A Tripartite Knowledge Translation Program: Innovative Patient-Centered Approach to Clinical Research Participation for Individuals with Multiple Sclerosis.

BACKGROUND: Knowledge translation (KT) models that represent an individual's perspective are a sign of effective KT. Some common challenges in KT include participant engagement, organization of the team, and time demands of the participants. We implemented a unique tripartite KT program to (1) share current research, (2) inform persons living with multiple sclerosis (pwMS) about the clinical research process, and (3) invite pwMS to immediately participate in clinical research. The primary aim was to determine participants' perspectives on the value and acceptability of an experiential research program offered at a patient and family educational conference. METHODS: A team of researchers identified factors that would impact the logistics of hosting an experiential research program at a conference and designed a unique tripartite KT program. The local multiple sclerosis (MS) society was engaged to select an appropriate location and invite stakeholders to the conference. A survey to determine participants' perspectives on the value and acceptability of the experiential research program was developed and analyzed. RESULTS: 65 pwMS attended the conference, and 44 (67.7%) participated in the on-site experiential research program. 72.7% of the participants completed the survey, of which 93.8% stated that they strongly agree or agree with the following statements: "Did you feel like participating in research today was a valuable experience to you?" and "Did you feel like you were contributing to MS research?" 100% of the participants agreed or strongly agreed when asked "would you like to see more research activities taking place at these kinds of events?" CONCLUSIONS: This paper describes the logistics and challenges of conducting an experiential KT program, which proved to be rewarding for pwMS. The majority of pwMS attending the conference agreed to participate in the on-site experiential research program and an overwhelming majority of participants felt the experience was valuable.

Diagnostic Dilemma: An Atypical Case of Astrocytoma in a Patient with Relapsing-Remitting Multiple Sclerosis.

Distinguishing between tumefactive demyelinating lesions (TDLs) and brain tumors in multiple sclerosis (MS) can be challenging. A progressive course is highly common with brain tumors in MS and no single neuroimaging technique is foolproof when distinguishing between the two. We report a case of a 41-year-old female with relapsing-remitting multiple sclerosis, who had a suspicious lesion within the left frontal hemisphere, without a progressive course. The patient experienced paresthesias primarily to her right hand but remained stable without any functional decline and new neurological symptoms over the four years she was followed. The lesion was followed with brain magnetic resonance imaging (MRI) scans, positron emission tomography-computed tomography scans, and magnetic resonance spectroscopy. Together, these scans favored the diagnosis of a TDL, but a low-grade tumor was difficult to rule out. Examination of serial brain MRI scans showed an enlarging lesion in the left middle frontal gyrus involving the deep white matter. Neurosurgery was consulted and an elective left frontal awake craniotomy was performed. Histopathology revealed a grade II astrocytoma. This case emphasizes the importance of thorough and continuous evaluation of atypical MRI lesions in MS and contributes important features to the literature for timely diagnosis and treatment of similar cases.

Magnetic Resonance Imaging of Spinal Cord Lesions in Patients with Multiple Sclerosis in Saskatchewan, Canada.

BACKGROUND: Spinal cord lesions (SCLs) contribute to disability in multiple sclerosis (MS). Data in Saskatchewan, Canada, concerning SCLs and their association with disability levels in patients with MS are lacking. The study objectives were to identify clinicodemographic profiles of patients with MS with respect to spinal cord magnetic resonance imaging (MRI) involvement; determine the frequency of individuals with MRI SCLs; and explore differences between patients with MS with and without SCLs with respect to disability and disease-modifying therapy status. METHODS: A monocentric, cross-sectional, retrospective review of prospectively collected data from 532 research-consented patients seen at Saskatoon MS Clinic was performed. Data were collected from a database and electronic medical records. RESULTS: Of the 356 patients (66.9%) with an SCL, 180 (50.6%) had only cervical cord lesions. Median Expanded Disability Status Scale (EDSS), ambulation, and pyramidal scores of patients with SCLs were higher than those of patients without SCLs. Of patients with EDSS scores of at least 6, those with SCLs were younger than those without SCLs (P = .01). Patients with SCLs were 55% less likely to have been on continuous disease-modifying therapy since diagnosis than patients without SCLs (adjusted odds ratio, 0.45; 95% CI, 0.25-0.81; P = .008). CONCLUSIONS: Prevalence and association with disability of SCLs in patients with MS are comparable with existing literature. Patients with MS with SCLs have higher levels of disability and attain EDSS scores of at least 6 at a younger age.

The Dilemma of When to Stop Disease-Modifying Therapy in Multiple Sclerosis: A Narrative Review and Canadian Regional Reimbursement Policies.

BACKGROUND: Disease-modifying therapy (DMT) has changed the landscape of multiple sclerosis (MS) care. However, there is lack of consensus on the duration of treatment and the selection of individuals most likely to benefit from continued treatment. Current evidence, practice guidelines, health policy, and ethical considerations presented together may further inform challenging clinical decision making and future directions. The objectives of this study were to conduct a narrative review of original research and practice guideline recommendations on discontinuation of DMTs in MS; to collect information regarding Canadian regional reimbursement policies for DMT coverage in MS; and to present ethical considerations applicable to such decision making. METHODS: A literature review was conducted of the MEDLINE/PubMed, OneFile (GALE), Scopus (Elsevier), and ProQuest Biological Science Collection databases. Data regarding Canadian regional reimbursement policies for DMT coverage in MS were collected from the ministry/government websites. Ethical considerations were reviewed in the context of the identified evidence, guidelines, and policies. RESULTS: The literature lacks evidence from prospective randomized controlled trials that directly addresses the issue of discontinuation of DMTs in MS. Current practice guidelines advocate the vital role of patient choice in decision making. There are regional variations in Expanded Disability Status Scale criteria scores for continuing MS DMT coverage among Canadian provinces/territories. CONCLUSIONS: In the absence of strong evidence on discontinuation of DMTs, shared decision making and consideration of the ethical complexities could help in the decision-making process.

Current concepts in portal vein thrombosis: etiology, clinical presentation and management.

OBJECTIVE: The aim of this article is to focus on etiology, risk factors, clinical presentation and classification systems of acute and chronic PVT as well as focusing on current diagnostic and therapeutic options for the management of acute and chronic PVT. RESULTS: PVT represents a serious clinical concern in cirrhotic patients and in those with specific local or systemic risk factors. The rate and extent of thrombus formation can significantly impact patient presentation and the resulting clinical outcomes. The presentation of acute PVT can range from abdominal pain to intestinal ischemia/infarction and even death, while chronic PVT can remain clinically silent. A number of imaging modalities including US, CT and MRI can be used to confirm the diagnosis. In addition to addressing underlying risk factors, AC therapy forms a cornerstone of treatment and has demonstrated efficacy in both acute and chronic settings. Proper caution should be used when initiating AC therapy in cirrhotic patients given their underlying coagulopathic status with attention now being paid to NOACs and LMWH. For patients with bowel ischemia, extensive thrombosis, contraindications or poor response to AC, or for those with co-morbidities that preclude AC, minimally invasive endovascular techniques offer alternative treatment options. CONCLUSION: Familiarity with the etiology, clinical presentation and classification of PVT optimize early detection and incorporate effective therapeutic options, the management of these complex patients should be undertaken by a multidisciplinary team. Minimally invasive catheter-based therapies and endovascular portosystemic shunt creation demonstrated efficacy in the treatment of AC-resistant patients and for patients with extensive or complicated disease.