Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer's disease, and dementia with Lewy bodies

The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer’s disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic–ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Selective neuronal changes in prefrontal cortex of post-stroke dementia and ageing-related dementias

Introduction:Over 30% of stroke survivors develop poststroke dementia (PSD). The precise pathological sub-strates associated with PSD are unknown. Besides cog-nitive abnormalities involving memory, executivedysfunction is a key feature of dementia associated withcerebrovascular disease or vascular dementia (VaD).Three separate yet interconnecting circuits controlexecutive function: the dorsolateral Prefrontal Cortex(dlPFC), Anterior Cingulate Cortex (ACC) and theOrbitofrontal Cortex (OFC). Pyramidal neuronal projec-tions form connections between regions of these circuitsand any cellular changes may induce dysfunctionalcircuits leading to executive dysfunction in PSD.Material and methods:Pyramidal neuronal density andvolume were assessed from cortical layers III and V in10 cases from each group using 3D stereological meth-odology. Thirtylm Nissl sections from the prefrontalcortex were analysed from the CogFAST stroke survi-vors cohort aged>75 years, who developed PSD orremained stable as post-stroke non-demented (PSND).To evaluate disease mechanisms, these groups werecompared with Alzheimer’s disease (AD), vascular dis-ease (VaD), and Mixed AD and VaD dementias, andelderly controls. Results:We found decreases (P<0.05) in pyramidalneuronal volumes in layers III and V in the dementedgroups compared to control and PSND groups in dlPFC.No changes in neuronal volumes were evident in eitherOFC or ACC. However, neuronal densities were notaltered between PSD and PSND groups in any of thethree frontal regions.Conclusions:These findings suggest selective effects andreduced neuronal volumes rather than densities indlPFC are associated with dementia and executive dys-function in PSD

Selective neuronal changes in prefrontal cortex of post-stroke dementia and ageing-related dementias

Introduction:Over 30% of stroke survivors develop poststroke dementia (PSD). The precise pathological sub-strates associated with PSD are unknown. Besides cog-nitive abnormalities involving memory, executivedysfunction is a key feature of dementia associated withcerebrovascular disease or vascular dementia (VaD).Three separate yet interconnecting circuits controlexecutive function: the dorsolateral Prefrontal Cortex(dlPFC), Anterior Cingulate Cortex (ACC) and theOrbitofrontal Cortex (OFC). Pyramidal neuronal projec-tions form connections between regions of these circuitsand any cellular changes may induce dysfunctionalcircuits leading to executive dysfunction in PSD.Material and methods:Pyramidal neuronal density andvolume were assessed from cortical layers III and V in10 cases from each group using 3D stereological meth-odology. Thirtylm Nissl sections from the prefrontalcortex were analysed from the CogFAST stroke survi-vors cohort aged>75 years, who developed PSD orremained stable as post-stroke non-demented (PSND).To evaluate disease mechanisms, these groups werecompared with Alzheimer’s disease (AD), vascular dis-ease (VaD), and Mixed AD and VaD dementias, andelderly controls. Results:We found decreases (P<0.05) in pyramidalneuronal volumes in layers III and V in the dementedgroups compared to control and PSND groups in dlPFC.No changes in neuronal volumes were evident in eitherOFC or ACC. However, neuronal densities were notaltered between PSD and PSND groups in any of thethree frontal regions.Conclusions:These findings suggest selective effects andreduced neuronal volumes rather than densities indlPFC are associated with dementia and executive dys-function in PSD

Use of Telemedicine for Post-discharge Assessment of the Surgical Wound: International Cohort Study, and Systematic Review with Meta-analysis

Objective: This study aimed to determine whether remote wound reviews using telemedicine can be safely upscaled, and if standardised assessment tools are needed. Summary background data: Surgical site infection is the most common complication of surgery worldwide, and frequently occurs after hospital discharge. Evidence to support implementation of telemedicine during postoperative recovery will be an essential component of pandemic recovery. Methods: The primary outcome of this study was surgical site infection reported up to 30-days after surgery (SSI), comparing rates reported using telemedicine (telephone and/or video assessment) to those with in-person review. The first part of this study analysed primary data from an international cohort study of adult patients undergoing abdominal surgery who were discharged from hospital before 30-days after surgery. The second part combined this data with the results of a systematic review to perform a meta-analysis of all available data conducted in accordance with PRIMSA guidelines (PROSPERO:192596). Results: The cohort study included 15,358 patients from 66 countries (8069 high, 4448 middle, 1744 low income). Of these, 6907 (45.0%) were followed up using telemedicine. The SSI rate reported using telemedicine was slightly lower than with in-person follow-up (13.4% vs. 11.1%, P<0.001), which persisted after risk adjustment in a mixed-effects model (adjusted odds ratio: 0.73, 95% confidence interval 0.63-0.84, P<0.001). This association was consistent across sensitivity and subgroup analyses, including a propensity-score matched model. In nine eligible non-randomised studies identified, a pooled mean of 64% of patients underwent telemedicine follow-up. Upon meta-analysis, the SSI rate reported was lower with telemedicine (odds ratio: 0.67, 0.47-0.94) than in-person (reference) follow-up (I2=0.45, P=0.12), although there a high risk of bias in included studies. Conclusions: Use of telemedicine to assess the surgical wound post-discharge is feasible, but risks underreporting of SSI. Standardised tools for remote assessment of SSI must be evaluated and adopted as telemedicine is upscaled globally