What does cognitive screening reveal about early cognitive performance following endovascular clot retrieval and intravenous thrombolysis in acute ischaemic stroke?

Background Little is known regarding cognitive outcomes following treatment with endovascular clot retrieval (ECR) and intravenous tissue plasminogen activator (t-PA). We aimed to determine if there were any differences on a measure of cognitive screening between patients treated with ECR, t-PA, and those who were managed conservatively. Methods The medical records of ischaemic stroke patients admitted to Monash Medical Centre between January 2019 and December 2019 were retrospectively reviewed. Information extracted from medical records included age, sex, National Institutes of Health Stroke Scale at presentation, location of occlusion, treatment type, medical history, and cognitive screening performance measured by the Montreal Cognitive Assessment (MoCA). Results Eighty-two patients met the inclusion criteria (mean age = 66.5 ± 13.9; 49 male, 33 female). Patients treated with ECR performed significantly better on the MoCA (n = 36, 24.1 ± 4.3) compared to those who were managed conservatively (n = 26, 20.7 ± 5.5). Performance for patients treated with t-PA (n = 20, 23.9 ± 3.5) fell between the ECR and conservative management groups, but they did not significantly differ from either. Conclusion Our retrospective chart review found that ischaemic stroke patients treated with ECR appear to perform better on cognitive screening compared to patients who are managed conservatively. We also found that patients treated with ECR and t-PA appear to have similar cognitive screening performances in the acute stages following ischaemic stroke, although this finding is likely to have been impacted by group differences in stroke characteristics and may reflect the possibility that the ECR group performed better than expected based on their stroke severity.

Cardiovascular disease and the risk of incident falls and mortality among adults aged ≥ 65 years presenting to the emergency department: a cohort study from national registry data in Denmark.

BACKGROUND: Falls cause 58% of injury-related Emergency Department (ED) attendances. Previous research has highlighted the potential role of cardiovascular risk factors for falls. This study investigated the impact of cardiovascular disease (CVD) risk on three-year incident falls, with presentation to the ED, and mortality. METHODS: A matched cohort study design was employed using national registry data from 82,292 adults (33% male) aged ≥ 65 years living in Denmark who attended the ED in 2013. We compared age and gender matched ED attendees presenting with a fall versus another reason. The cohort was followed for three-year incident falls, with presentation to the ED, and mortality. The impact of falls-related CVDs was also examined. RESULTS: Three-year incident falls was twofold higher among age and gender matched ED attendees aged ≥ 65 years presenting with a fall versus another reason at baseline. A presentation of falls with hip fracture had the highest percentage of incident falls in the 65-74 age group (22%) and the highest percentage mortality in all age groups (27-62%). CVD was not a significant factor in presenting with a fall at the ED, nor did it contribute significantly to the prediction of three-year incident falls. CVD was strongly associated with mortality risk among the ED fall group (RR = 1.81, 95% CI: 1.67-1.97) and showed interactions with both age and fall history. CONCLUSION: In this large study of adults aged ≥ 65 years attending the ED utilising data from national administrative registers in Denmark, we confirm that older adults attending the ED with a fall, including those with hip fracture, were at greatest risk for future falls. While CVD did not predict incident falls, it increased the risk of mortality in the three-year follow up with advancing age. This may be informative for the provision of care pathways for older adults attending the ED due to a fall.

Psychometric deficits in autoimmune encephalitis: A retrospective study from the Australian Autoimmune Encephalitis Consortium.

BACKGROUND AND PURPOSE: Despite the rapid increase in research examining outcomes in autoimmune encephalitis (AE) patients, there are few cohort studies examining cognitive outcomes in this population. The current study aimed to characterise psychometric outcomes in this population, and explore variables that may predict psychometric outcomes. METHODS: This retrospective observational study collected psychometric data from 59 patients across six secondary and tertiary referral centres in metropolitan hospitals in Victoria, Australia between January 2008 and July 2019. Frequency and pattern analysis were employed to define and characterize psychometric outcomes. Univariable logistic regression was performed to examine predictors of intact and pathological psychometric outcomes. RESULTS: Deficits in psychometric markers of executive dysfunction were the most common finding in this cohort, followed by deficits on tasks sensitive to memory. A total of 54.2% of patients were classified as having psychometric impairments across at least two cognitive domains. Twenty-nine patterns were observed, suggesting outcomes in AE are complex. None of the demographic data, clinical features or auxiliary examination variables were predictors of psychometric outcome. CONCLUSIONS: Cognitive outcomes in AE are complex. Further detailed and standardized cognitive testing, in combination with magnetic resonance imaging volumetrics and serum/cerebrospinal fluid biomarkers, is required to provide rigorous assessments of disease outcomes.

Is orthostatic hypotension and co-existing supine and seated hypertension associated with future falls in community-dwelling older adults? Results from The Irish Longitudinal Study on Ageing (TILDA).

Orthostatic hypotension (OH) often co-exists with hypertension. As increasing age affects baroreflex sensitivity, it loses its ability to reduce blood pressure when lying down. Therefore, supine hypertension may be an important indicator of baroreflex function. This study examines (i) the association between OH and future falls in community-dwelling older adults and (ii) if these associations persist in those with co-existing OH and baseline hypertension, measured supine and seated. Data from 1500 community-dwelling adults aged ≥65 years from The Irish Longitudinal Study on Ageing (TILDA) were used. Continuous beat-to-beat blood pressure was measured using digital photoplethysmography during an active stand procedure with OH defined as a drop in systolic blood pressure (SBP) ≥20 mmHg and/or ≥10 mm Hg in diastolic blood pressure (DBP) within 3 minutes of standing. OH at 40 seconds (OH40) was used as a marker of impaired early stabilisation and OH sustained over the second minute (sustained OH) was used to indicate a more persistent deficit, similar to traditional OH definitions. Seated and supine hypertension were defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Modified Poisson models were used to estimate relative risk of falls (recurrent, injurious, unexplained) and syncope occurring over four year follow-up. OH40 was independently associated with recurrent (RR = 1.30, 95% CI = 1.02,1.65), injurious (RR = 1.43, 95% CI = 1.13,1.79) and unexplained falls (RR = 1.55, 95% CI = 1.13,2.13). Sustained OH was associated with injurious (RR = 1.55, 95% CI = 1.18,2.05) and unexplained falls (RR = 1.63, 95% CI = 1.06,2.50). OH and co-existing hypertension was associated with all falls outcomes but effect sizes were consistently larger with seated versus supine hypertension. OH, particularly when co-existing with hypertension, was independently associated with increased risk of future falls. Stronger effect sizes were observed with seated versus supine hypertension. This supports previous findings and highlights the importance of assessing orthostatic blood pressure behaviour in older adults at risk of falls and with hypertension. Observed associations may reflect underlying comorbidities, reduced cerebral perfusion or presence of white matter hyperintensities.

Bilateral Subretinal Fluid Mimicking Subretinal Neovascularization Within 24 Hours After Selective Laser Trabeculoplasty.

PURPOSE: Selective laser trabeculoplasty (SLT), which is widely regarded as a safe procedure, is a frequently used treatment for open-angle glaucoma. Although it is presumed to be associated with an inflammatory cascade and possible postoperative inflammation, only 2 cases of SLT complicated by cystoid macular edema have been previously reported. Until now there are no previous reports of SLT causing subretinal fluid (SRF). METHODS/IMPORTANCE: Clinical examination, optical coherence tomography, and fluorescein angiography demonstrated a previously unreported clinical entity consisting of bilateral SRF, developing within 24 hours of bilateral inferior 180-degree SLT for open-angle glaucoma. RESULTS: Rapid bilateral, subjective loss of vision occurred within 24 hours post-SLT. This was associated with bilateral SRF resulting in 48 µm (OD) and 35 µm (OS) increase in macular thickness on optical coherence tomography. Fundus fluorescein angiography demonstrated profuse, well-demarcated subfoveal leakage. SRF resolved within 4 days, but eventual best corrected visual acuity was subjectively and objectively decreased. CONCLUSIONS: The sudden onset of loss of vision and the development of subfoveal SRF within 24 hours of SLT strongly suggests cause and effect. This previously unreported clinical entity of bilateral SRF within 24 hours of SLT may be secondary to an intraocular inflammatory cascade, similar to previous hypotheses regarding 3 cases of cystoid macular edema post-SLT. Given the dramatic initial loss of vision and compromised long-term visual outcome, clinicians and patients need to be informed of this new clinical entity of SLT associated with SRF and permanent retinal pigment epithelial changes.

Long-term changes in neurocognition and behavior following treatment of sleep disordered breathing in school-aged children.

STUDY OBJECTIVES: Sleep disordered breathing (SDB) in children is associated with detrimental neurocognitive and behavioral consequences. The long term impact of treatment on these outcomes is unknown. This study examined the long-term effect of treatment of SDB on neurocognition, academic ability, and behavior in a cohort of school-aged children. DESIGN: Four-year longitudinal study. Children originally diagnosed with SDB and healthy non-snoring controls underwent repeat polysomnography and age-standardized neurocognitive and behavioral assessment 4y following initial testing. SETTING: Melbourne Children's Sleep Centre, Melbourne, Australia. PARTICIPANTS: Children 12-16 years of age, originally assessed at 7-12 years, were categorized into Treated (N = 12), Untreated (N = 26), and Control (N = 18) groups. INTERVENTIONS: Adenotonsillectomy, Tonsillectomy, Nasal Steroids. Decision to treat was independent of this study. MEASUREMENTS AND RESULTS: Changes in sleep and respiratory parameters over time were assessed. A decrease in obstructive apnea hypopnea index (OAHI) from Time 1 to Time 2 was seen in 63% and 100% of the Untreated and Treated groups, respectively. The predictive relationship between change in OAHI and standardized neurocognitive, academic, and behavioral scores over time was examined. Improvements in OAHI were predictive of improvements in Performance IQ, but not Verbal IQ or academic measures. Initial group differences in behavioral assessment on the Child Behavior Checklist did not change over time. Children with SDB at baseline continued to exhibit significantly poorer behavior than Controls at follow-up, irrespective of treatment. CONCLUSIONS: After four years, improvements in SDB are concomitant with improvements in some areas of neurocognition, but not academic ability or behavior in school-aged children.

Primordium of an artificial Bruch's membrane made of nanofibers for engineering of retinal pigment epithelium cell monolayers.

Transplanted retinal pigment epithelium (RPE) cells hold promise for treatment of age-related macular degeneration (AMD) and Stargardt disease (SD), but it is conceivable that the degenerated host Bruch's membrane (BM) as a natural substrate for RPE might not optimally support transplanted cell survival with correct cellular organization. We fabricated novel ultrathin three-dimensional (3-D) nanofibrous membranes from collagen type I and poly(lactic-co-glycolic acid) (PLGA) by an advanced clinical-grade needle-free electrospinning process. The nanofibrillar 3-D networks closely mimicked the fibrillar architecture of the native inner collagenous layer of human BM. Human RPE cells grown on our nanofibrous membranes bore a striking resemblance to native human RPE. They exhibited a correctly orientated monolayer with a polygonal cell shape and abundant sheet-like microvilli on their apical surfaces. RPE cells built tight junctions and expressed RPE65 protein. Flat 2-D PLGA film and cover glass as controls delivered inferior RPE layers. Our nanofibrous membranes may imitate the natural BM to such extent that they allow for the engineering of an in vivo-like human RPE monolayer that maintains the natural biofunctional characteristics. Such ultrathin membranes may provide a promising vehicle for a functional RPE cell monolayer implantation in the subretinal space in patients with AMD or SD.

A clinically-feasible protocol for using human platelet lysate and mesenchymal stem cells in regenerative therapies.

The transplantation of human stem cells seeded on biomaterials holds promise for many clinical applications in cranio-maxillo-facial tissue engineering and regenerative medicine. However, stem cell propagation necessary to produce sufficient cell numbers currently utilizes fetal calf serum (FCS) as a growth supplement which may subsequently transmit animal pathogens. Human platelet lysate (HPL) could potentially be utilized to produce clinical-grade stem cell-loaded biomaterials as an appropriate FCS substitute that is in line with clinically-applicable practice. The goal of this study was to investigate whether HPL can be successfully used to propagate human mesenchymal stem cells (HMSCs) seeded on clinically-approved collagen materials under clinically-applicable conditions using FCS as a control. HMSCs were isolated from bone marrow and cultured in the presence of 10% FCS or 10% HPL. Characterization of HMSCs was performed by flow cytometry and through osteogenic and adipogenic differentiation assays. Proliferative capacity of HMSCs on both matrices was investigated by mitochondrial dehydrogenase assays (WST) and tissue coverage scanning electron microscopy (SEM). The isolated HMSC differentiated into osteogenic and adipogenic cells authenticating the multipotentiality of the HMSCs. WST tests and the SEM images demonstrated that HPL was generally superior to FCS in promoting growth of seeded HMSCs. For all other tests HPL supported HMSCs at least equal to FCS. In conclusion, HPL is an effective growth factor to allow expansion of clinical-grade HMSCs on clinically-approved biomaterials for maxillofacial and oral implantology applications.

Nanospiderwebs: artificial 3D extracellular matrix from nanofibers by novel clinical grade electrospinning for stem cell delivery.

Novel clinical grade electrospinning methods could provide three-dimensional (3D) nanostructured biomaterials comprising of synthetic or natural biopolymer nanofibers. Such advanced materials could potentially mimic the natural extracellular matrix (ECM) accurately and may provide superior niche-like spaces on the subcellular scale for optimal stem-cell attachment and individual cell homing in regenerative therapies. The goal of this study was to design several novel "nanofibrous extracellular matrices" (NF-ECMs) with a natural mesh-like 3D architecture through a unique needle-free multi-jet electrospinning method in highly controlled manner to comply with good manufacturing practices (GMP) for the production of advanced healthcare materials for regenerative medicine, and to test cellular behavior of human mesenchymal stem cells (HMSCs) on these. Biopolymers manufactured as 3D NF-ECM meshes under clinical grade GMP-like conditions show higher intrinsic cytobiocompatibility with superior cell integration and proliferation if compared to their 2D counterparts or a clinically-approved collagen membrane.

Working memory in children with sleep-disordered breathing: objective versus subjective measures.

BACKGROUND: Parents consistently report working memory deficits in children with sleep-disordered breathing (SDB); however, results from objective testing measures are inconsistent. This study aims to examine and compare working memory performance in children with various degrees of severity of SDB using both parent report and objective testing. METHODS: Subjects included 127 children aged 7-12 years (mean age 9.6 ± 1.6 y: 71 M/56 F). Overnight polysomnography classified subjects into four groups: control (N=34); primary snoring (PS: N=55), mild obstructive sleep apnoea (mild OSA: N=22) and moderate to severe OSA (MS OSA: N=16). The Behaviour Rating Inventory of Executive Function (BRIEF) was used as the parent reported measure of working memory. A computerised task involving immediate recognition of playing cards (CogHealth) was used as the objective measure. RESULTS: Results of the BRIEF revealed working memory deficits at all severities of SDB compared to controls. Results of CogHealth revealed no difference between SDB groups and controls; however, mild OSA performed significantly worse than PS. Comparison of the two measures revealed that parents of controls reported less deficits, and parents of PS reported more deficits, than were found on the objective measure of working memory. CONCLUSIONS: This study showed that parents of children with less severe SDB have a tendency to overestimate the level of working memory deficit in their children, possibly as a reflection of behaviour. This suggests that observation of deficits in working memory may be largely dependent on the assessment method and children with SDB may not be as impaired as previously thought.

Cognitive and academic functions are impaired in children with all severities of sleep-disordered breathing.

STUDY OBJECTIVE: The impact of the broad spectrum of SDB severity on cognition in childhood has not been well studied. This study investigated cognitive function in children with varying severities of SDB and control children with no history of SDB. METHODS: One hundred thirty-seven children (75 M) aged 7-12 were studied. Overnight polysomnography (PSG) classified children into four groups: primary snoring (PS) (n = 59), mild obstructive sleep apnea syndrome (OSAS) (n = 24), moderate/severe OSAS (n = 19), and controls (n = 35). Cognition was measured with a short battery of psychological tests including the Wechsler Abbreviated Scale of Intelligence (WASI), the Wide Range Achievement Test-3rd Edition (WRAT-3), the Rey Complex Figure Test (RCFT) and the Controlled Oral Word Association Test (COWAT). RESULTS: There was lower general intellectual ability in all children with SDB regardless of severity. Higher rates of impairment were also noted on measures of executive and academic functioning in children with SDB. CONCLUSIONS: Our findings suggest that neurocognitive deficits are common in children with SDB regardless of disease severity, highlighting that such difficulties may be present in children in the community who snore but are otherwise healthy; thus our results have important implications for the treatment of pediatric SDB.

Neurobehavioral function is impaired in children with all severities of sleep disordered breathing.

OBJECTIVE: Sleep disordered breathing (SDB) is common in children and ranges in severity from primary snoring (PS), to obstructive sleep apnea syndrome (OSAS). This study investigated everyday function (behavior, attention, executive skills) in children with varying degrees of SDB and control children with no history of SDB recruited from the community. METHODS: One hundred thirty-six children aged 7-12 were studied. Routine overnight polysomnography (PSG) classified children into 4 groups: PS (n=59), mild OSAS (n=24), moderate/severe OSAS (n=18), and controls (n=35). Behavioral function and behavioral aspects of attention and executive function were assessed using the Child Behavior Checklist (CBCL) and the Behavior Rating Inventory of Executive Function (BRIEF). RESULTS: Children with all severities of SDB had significantly higher rates of total, internalizing and externalizing behavioral problems compared to control children. Increased rates of behavioral executive dysfunction were also found across the SDB spectrum. CONCLUSION: Our findings suggest that behavioral, attention, and executive function difficulties are present in children with PS as well as OSAS. These results have implications for the treatment of milder forms of SDB, particularly PS, which is commonly viewed as benign.

Short-term intraocular tamponade with perfluorocarbon heavy liquid.

BACKGROUND: Inferior retinal detachment pathology can be difficult to manage due to inadequate tamponade with low specific gravity tamponade agents and the propensity for the development of proliferative vitreoretinopathy (PVR). We report the efficacy and adverse effects associated with the use of perfluorocarbon heavy liquid as a short-term tamponade in managing such pathologies. METHODS: Retrospective analysis of 17 eyes treated with short-term perfluoro-n-octane tamponade for complex inferior retinal pathology, including inferior detachment and PVR. Mean follow-up time was 14 months and mean tamponade duration was 7 days. RESULTS: Reattachment of the retina during the study period was achieved with a single set of operations in 13/17 (76%) eyes, with four eyes requiring a subsequent set of vitreoretinal operations. Postoperative visual acuity (VA) was equal to or better than preoperative VA in 14 (82%) of 17 eyes. Complications arising during the follow-up period included superior redetachment, atrophic macular changes, minor macular haemorrhage, cataract, elevated intraocular pressure, corneal defects, PVR, epiretinal membrane and retained perfluorocarbon heavy liquid. One case of intraocular inflammation occurred >6 months after removal of perfluoro-n-octane tamponade. CONCLUSION: Short-term perfluoro-n-octane tamponade achieved a stable reattachment rate of 76% when used to manage challenging retinal pathologies.

Tamoxifen therapy conveys increased risk of developing a macular hole.

PURPOSE: To determine etiological factors in the development of, as well as anatomic success rate and visual outcome of a large consecutive series of macular hole surgeries. METHODS: Retrospective analysis of 300 consecutive cases of macular hole surgery by a single surgeon (RDB) between 1999 and 2003. Patients' medical and surgical histories were recorded and analysed for factors involved in aetiology and visual outcome. RESULTS: There were 8 (4.12%) women, on tamoxifen in the study, two of these women had bilateral macular holes. When this study prevalence of tamoxifen therapy (4.12%) was compared to the estimated percentage of women in the same age group in the Australian population on tamoxifen (0.82%), a statistically significant difference (p value 0.0001) was found. Analysis of the number of bilateral holes in the tamoxifen group compared to the non-tamoxifen group was suggestive of an increased incidence of bilateral holes but not to a significantly significant degree. CONCLUSION: Whilst no published reports link tamoxifen and macular holes, this may be due to the low incidence of the condition. Our study demonstrates a strong link between tamoxifen use and macular holes. Patients being commenced on tamoxifen should be advised of possible ocular complications and receive prompt ophthalmic review if symptoms develop.