Characteristics of a Diverse Cohort of Stroke Patients with SARS-CoV-2 and Outcome by Sex.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. To objective of this paper is to describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease and determine the role of sex on outcome. METHODS: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage or median and interquartile range. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. RESULTS: The study included 83 patients, 47% of which were Black, 28% Hispanics/Latinos, and 16% whites. Median age was 64 years. Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p = 0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared with females, males had higher mortality (38% vs. 13%; p = 0.02) and were less likely to be discharged home (12% vs. 33%; p = 0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR = 1.47, 95% CI = 1.03-2.09). CONCLUSION: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

Intravaginal instillation of prostaglandin F2α was as effective as intramuscular injection for induction of luteal regression in lactating dairy cows.

Our objectives were to test the efficacy of intravaginal (IVG) administration of PGF2α to induce corpus luteum (CL) regression, compare circulating progesterone (P4) profiles in cows receiving IVG versus intramuscular (IM) treatment with PGF2α, and evaluate reproductive outcomes. Lactating Holstein cows were synchronized using a Double-Ovsynch protocol [GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH, 7 d later PGF2α, 1 d later PGF2α, 32 h later GnRH, 16 to 20 h timed artificial insemination (TAI)] to receive TAI at 67 ± 3 d in milk. Seven days after the first GnRH treatment (time 0), cows with at least 1 visible CL ≥15 mm were blocked by parity and randomly assigned to a treatment that consisted of IM injection (IM-PGF; n = 201) or IVG instillation (IVG-PGF; n = 201) of PGF2α. Cows in IM-PGF received a single 25-mg dose of PGF2α (dinoprost tromethamine) intramuscularly. Cows in IVG-PGF received two 25-mg doses of PGF2α 12 h apart delivered through a catheter in the cranial portion of the vagina. Blood samples were collected at 0, 12, 48, and 72 h after treatment. Ovulation to the first GnRH of Double-Ovsynch was determined through transrectal ultrasonography. Only cows with P4 ≥1 ng/mL (functional CL) at time 0 (IM-PGF = 169; IVG-PGF = 179) were included in the analyses. Binary and quantitative data were analyzed by logistic regression and ANOVA with repeated measures, respectively. Results are presented as least squares means. Concentrations of P4 and the proportion of cows with a new CL at time 0 did not differ. Overall, the proportion of cows with CL regression using 1 ng of P4/mL (IM-PGF = 89.0%; IVG-PGF = 86.7%) or 0.5 ng of P4/mL (IM-PGF = 82.2%; IVG-PGF = 82.1%) as the cutoff did not differ. Concentrations of P4 were affected by treatment, time, and treatment × time interaction. Cows in IVG-PGF had greater mean P4 at 12 h than cows in IM-PGF. Mean P4 did not differ at 48 or 72 h after treatment. The proportion of cows with estrus recorded within 3 d of treatment (IM-PGF = 45.4%; IVG-PGF = 48.9%), ovulation risk after treatment (IM-PGF = 88.5%; IVG-PGF = 85.1%), and pregnancies per artificial insemination after TAI (IM-PGF = 51.5%; IVG-PGF = 57.8%) did not differ. We concluded that 2 IVG doses of 25 mg of PGF2α 12 h apart were as effective as a single 25-mg IM dose of PGF2α for inducing luteal regression in lactating dairy cattle.

Inflammation and Monocyte Recruitment due to Aging and Mechanical Stretch in Alveolar Epithelium are Inhibited by the Molecular Chaperone 4-phenylbutyrate.

INTRODUCTION: Ventilator-Induced lung injury (VILI) is a form of acute lung injury that is initiated or exacerbated by mechanical ventilation. The aging lung is also more susceptible to injury. Harmful mechanical stretch of the alveolar epithelium is a recognized mechanism of VILI, yet little is known about how mechanical stretch affects aged epithelial cells. Disruption to Endoplasmic Reticulum (ER) homeostasis results in a condition known as ER stress that leads to disruption of cellular homeostasis, apoptosis, and inflammation. ER stress is increased with aging and other pathological stimuli. We hypothesized that age and mechanical stretch increase alveolar epithelial cells' proinflammatory responses that are mediated by ER stress. Furthermore, we believed that inhibition of this upstream mechanism with 4PBA, an ER stress reducer, alleviates subsequent inflammation and monocyte recruitment. METHODS: Type II alveolar epithelial cells (ATII) were harvested from C57Bl6/J mice 2 months (young) and 20 months (old) of age. The cells were cyclically stretched at 15% change in surface area for up to 24 hours. Prior to stretch, groups were administered 4PBA or vehicle as a control. RESULTS: Mechanical stretch and age upregulated ER stress and proinflammatory MCP-1/CCL2 and MIP-1ß/CCL4 chemokine expression in ATIIs. Age-matched and mismatched monocyte recruitment by ATII conditioned media was also quantified. CONCLUSIONS: Age increases susceptibility to stretch-induced ER stress and downstream inflammatory gene expression in a primary ATII epithelial cell model. Administration of 4PBA attenuated the increased ER stress and proinflammatory responses from stretch and/or age and significantly reduced monocyte migration to ATII conditioned media.

Lung protective ventilation and hospital survival of cardiac intensive care patients.

OBJECTIVE: To detect connections between parameters of ventilation and outcomes of cardiac intensive care patients. DESIGN AND SETTING: Noninterventional study. Between 05/11 and 05/12 all patients with acute heart failure and post cardiopulmonary resuscitation were registered. Lung protective ventilation was defined as peak inspiratory pressure (PIP) < 30 mmHg and tidal volume (Vt) < = 6 ml/kg. RESULTS: In total, 129 patients were included in the study, 68.2 % male, age 67.9 ± 13.4 years, weight 71.4 ± 37.2 kg, predictive body weight 66.9 ± 8.8 kg, mortality 47.3 %. Lung protective ventilated patients at day 1: 17.3 % with a significant difference between surviving and nonsurviving patients (24.1 % vs. 9.6 %; p < 0.05). Logistic regression models showed a strong connection between PIP and survival (odds ratio 1.13; p < 0.05). Vt showed no significant influence on survival. CONCLUSION: Our data recommends a strict observance of a low PIP for cardiac intensive care patients, whereas Vt seems to be of secondary importance.

Color vision and neuroretinal function in diabetes.

PURPOSE: We investigate how type 2 diabetes (T2DM) and diabetic retinopathy (DR) affect color vision (CV) and mfERG implicit time (IT), whether CV and IT are correlated, and whether CV and IT abnormality classifications agree. METHODS: Adams desaturated D-15 color test, mfERG, and fundus photographs were examined in 37 controls, 22 T2DM patients without DR (NoRet group), and 25 T2DM patients with DR (Ret group). Color confusion score (CCS) was calculated. ITs were averaged within the central 7 hexagons (central IT; ≤4.5°) and outside this area (peripheral IT; ≥4.5°). DR was within (DRIN) or outside (DROUT) of the central 7 hexagons. Group differences, percentages of abnormalities, correlations, and agreement were determined. RESULTS: CCS was greater in the NoRet (P = 0.002) and Ret (P < 0.0001) groups than in control group. CCS was abnormal in 3, 41, and 48 % of eyes in the control, NoRet, and Ret groups, respectively. Ret group CV abnormalities were more frequent in DRIN than in DROUT subgroups (71 vs. 18 %, respectively; P < 0.0001). CCS and IT were correlated only in the Ret group, in both retinal zones (P ≤ 0.028). Only in the Ret group did CCS and peripheral IT abnormality classifications agree (72 %; P < 0.05). CONCLUSION: CV is affected in patients with T2DM, even without DR. Central DR increases the likelihood of a CV deficit compared with non-central DR. mfERG IT averaged across central or peripheral retinal locations is less frequently abnormal than CV in the absence of DR, and these two measures are correlated only when DR is present.

The practice of neurology, 2000-2010: report of the AAN Member Research Subcommittee.

OBJECTIVE: To present an analysis of American Academy of Neurology (AAN) membership demographics and practice trends over the past decade. METHODS: Data from the 2009 AAN Census and 2010 Practice Profile Form (PPF) surveys were compared to results from 2004 and 2000 surveys. The Census was sent to all AAN members, and the PPF was sent to a random sample of US practicing neurologists. RESULTS: Since 2000, AAN membership increased by 31%, and the number of US neurologist-members increased by 14%. Mean age of US neurologists increased from 48.6 to 53.3 years, and 23.9% of neurologists are women. There was a 15% increase in the proportion of neurologists relative to the US population, from 3.41 neurologists per 100,000 population in 2000 to 3.92 neurologists in 2009. In 2009, 24.1% of US neurologists were in solo practice, 27.8% were in a neurology group, and 35.6% were in multispecialty/university settings, with little change in practice arrangements over time. The top 5 practice interest areas were unchanged since 2004 as were the number of hours devoted to patient care (42.3) or total work hours per week (57.1). Little change was observed in performed procedures, except increased use of botulinum toxin and nerve blocks and a decline in lumbar punctures. Neurologists rely more on physician assistants to see follow-up and new patients independently (p < 0.001). CONCLUSION: Despite advances in neurologic diagnosis and therapy, there has been little change in practice characteristics of US neurologists.

Information processing in severe disorders of consciousness: vegetative state and minimally conscious state.

OBJECTIVE: To study the presence of electrophysiological indicators of remaining cortical functions in patients with persistent vegetative state (PVS) and minimally conscious state (MCS). Previous electrophysiological and PET data indicated that some PVS patients have partially intact cortical processing functions. However, it remains unclear whether the reported patients were representative for PVS population or just some exceptional cases. METHODS: Event-related brain responses to stimuli of different complexity levels, recorded in 98 patients with extremely severe diffuse brain injuries, 50 of which in PVS. Four main indicators of cortical functions were: (i) N1-P2 complex as an index of simple, undifferentiated cortical processing; (ii) mismatch negativity as an index of pre-attentive, probably unconscious, cortical orientation; (iii) P3 wave as an index of deep cortical analysis of physical stimuli, and (iv) brain responses to semantic stimuli. RESULTS: Cortical responses were found in all PVS patients with a background EEG activity > 4 Hz. All responses investigated, including those to semantic stimuli that indicated comprehension of meaning, occurred significantly above chance, though less frequently than in patients with severe brain injuries who were conscious. CONCLUSIONS: Cortical responses were lacking in most patients with severe EEG slowing (< 4 Hz). Follow-up data revealed that the presence of a mismatch negativity, a short disease duration, and the traumatic etiology were related to a better outcome. SIGNIFICANCE: The data show that in a subpopulation of PVS patients with preserved thalamocortical feedback connections, remaining cortical information processing is a consistent finding and may even involve semantic levels of processing.

Focal neurological deficits and West Nile virus infection.

Our experience with West Nile virus infection revealed that 54% of 28 patients had a focal neurological deficit at presentation. A meningitis or encephalitis syndrome was absent in 47% of patients with focal deficits. Details of the variety of deficits, the time to development of deficits, and the associated radiological and laboratory findings are also discussed in the present report.

Towards optimal filtering of "standard" multifocal electroretinogram (mfERG) recordings: findings in normal and diabetic subjects.

AIMS: To study the effects of two commonly used pre-amplifier filtering bandwidths on normal multifocal electroretinogram (mfERG) responses and their comparative abilities to detect retinal disease. METHODS: 103 standard mfERGs were recorded simultaneously in two channels with different pre-amplifier settings (10-100 Hz and 10-300 Hz) from one eye of each of 20 normal subjects, 17 diabetics with non-proliferative diabetic retinopathy (NPDR), and 12 diabetics without retinopathy. Signal to noise ratios (SNR) of the normal subjects' first order mfERGs were compared between channels. All subjects' amplitudes and implicit times were derived using a "template stretching" method. For comparison, implicit time was also measured using a "template sliding" method. mfERG amplitudes and implicit times were compared between the channels and among subject groups. RESULTS: Normal mean amplitudes and implicit times were similar for the two channels. However, normal 10-100 Hz recordings had significantly higher SNR and lower intersubject variability than 10-300 Hz recordings. In NPDR, the 10-100 Hz channel identified significantly more implicit time and amplitude abnormalities. In the diabetics without retinopathy, 10-100 Hz filtering identified significantly more implicit time abnormalities than 10-300 Hz filtering. For both filter settings, diabetic implicit times were more often abnormal than amplitudes. The 10-100 Hz channel was superior for both implicit time measurements. CONCLUSION: Standard mfERGs recorded from normal eyes and filtered 10-100 Hz contain less noise, higher SNR, and less intersubject variability than those filtered at 10-300 Hz. This underlies the finding that the 10-100 Hz filter setting identifies more retinal dysfunction than the 10-300 Hz setting.

[Early rehabilitation in Baden-Wurttemberg--a study of all Baden-Wurrtemberg early rehabilitation centers]. / Frührehabilitation in Baden-Württemberg--Eine Untersuchung aller Frührehabilitationseinrichtungen Baden-Württembergs.

Over a period of 12 months, all persons among the 10.4 million inhabitants of the state of Baden-Württemberg were included in the study who had suffered severe brain damage and were treated in special early rehab units, comprising 147 beds for adults and 43 for children. With 830 patients admitted, the incidence of severe brain damage was 7.98/100.000 in adults and 1.11/100.000 in children. 50 to 70 year old patients were over-represented, those older than 70 years were underrepresented due to geriatric rehab facilities for the latter. Male patients dominated, while female were somewhat younger. 54% of the patients were admitted from the hospital which had performed primary care, with an average stay of 67 days. Average early rehab duration was 53 days (arithmetic average; median 40 days, some patients required up to one year). 32.8% of the patients had suffered traumatic brain damage (ICD 851, 852, 854) and 40.9% non-traumatic brain affection (ICD 430, 431, 433-438, 310, 348), including 12.2% CVA (ICD 433-438), 8.5% subarachnoid and 12.3% intracerebral hemorrhage. Severity as indexed by the early rehab Barthel index improved from an initial average of -119 to -34 at discharge. 80% of the patients showed an overall improvement (71% of them by up to 200 points and 46% by up to 100 points).

The Smith-Kettlewell Institute (SKI) longitudinal study of vision function and its impact among the elderly: an overview.

We present an overview of a multifaceted longitudinal study of vision function and its interaction with daily activities, health, and well-being among 900 persons aged 58 to 102 years at the first visit. Standard vision measures as well as nonconventional tests designed to assess visual performance under the nonideal conditions encountered in everyday life were used. Here we summarize a few of the findings to date, with an emphasis on a direct comparison of declines in different aspects of vision function with age. The rates of declines with advancing age vary widely for the different vision functions. Also described is the reading performance of the sample and its association with some of the vision measures. Furthermore, we describe some of the associations between vision test scores and extensive longitudinal health and functioning data collected by the Buck Center for Research in Aging. Findings show that many older people with good acuity are effectively visually impaired in performing everyday tasks involving low and changing light levels, stereopsis, glare, and low contrast. We also found that vision under nonideal conditions cannot be predicted from standard acuity on an individual basis.

Reading performance in older adults with good acuity.

PURPOSE: This study evaluated factors affecting reading performance in a sample (N = 544) of older adults (mean age 72.8 years, range 58 to 102) with good high-contrast acuity (> or = 20/32). METHODS: Using the Pepper Reading Test, the relationship between reading rate and several vision measures was assessed. RESULTS: Mean corrected reading rate fell substantially over the age range tested despite the fact that these individuals all had good acuity. However, multiple regression analysis indicated that when other measures were taken into account (most notably, low-contrast vision, motor ability, and attentional field integrity), age was not a significant independent predictor of corrected reading rate. CONCLUSION: Reading is an important skill, and ways of enhancing reading performance should be explored. Good high-contrast acuity does not assure that older individuals can read satisfactorily.

Ocular contributions to age-related loss in coarse stereopsis.

PURPOSE: To determine the basis for the dramatic decline in coarse stereopsis that occurs with age. METHODS: The Frisby test was used to assess stereopsis in a large sample of randomly selected persons over the age of 58 years. A number of other vision functions were also assessed in the same persons. The data were used to address the question of whether the decline in stereopsis reflects age-related alterations in cortical stereopsis mechanisms themselves (e.g., disparity detectors) or a degradation of the signal reaching the cortex as a result of alterations in earlier visual components. Two of three vision measures were binocular and thus reflect predominantly the function of the better eye. RESULTS: We find, as many others have reported, that even very coarse stereopsis declines dramatically with age. Despite not having separately assessed each eye, we find that among those selected to have good ocular function there was no significant decline in coarse stereopsis with age. CONCLUSION: These findings suggest that the enormous decline in coarse stereopsis with age can be accounted for by alterations in early stages of vision processing.

The fast oscillation of the electrooculogram reveals sensitivity of the human outer retina/retinal pigment epithelium to glucose level.

The effect of acute blood glucose elevations on human outer retinal function was examined. Electrooculograms were recorded as the background light cycled on/off with a 2-min period, eliciting rapid changes in the corneo-retinal standing potential known as the fast-oscillation of the electrooculogram. Recordings were made while subjects fasted and after they consumed 100 g of D-glucose. In all subjects, blood glucose levels strongly affected fast oscillation amplitude, which reflects photoreceptor-driven changes in RPE cell chloride concentration. The sensitivity of RPE metabolism to glucose fluctuations may relate to changes in the blood-retinal barrier that are known to occur in diabetes (e.g. macular edema).

Perception of dynamic acoustic patterns by an individual with unilateral verbal auditory agnosia.

Previous studies have found that subjects diagnosed with verbal auditory agnosia (VAA) from bilateral brain lesions may experience difficulties at the prephonemic level of acoustic processing. In this case study, we administered a series of speech and nonspeech discrimination tests to an individual with unilateral VAA as a result of left-temporal-lobe damage. The results indicated that the subject's ability to perceive steady-state acoustic stimuli was relatively intact but his ability to perceive dynamic stimuli was drastically reduced. We conclude that this particular aspect of acoustic processing may be a major contributing factor that disables speech perception in subjects with unilateral VAA.

The relation between visual acuity and other spatial vision measures.

PURPOSE: To examine to what extent measurement of standard visual acuity allows prediction of other spatial vision measures on an individual basis when high correlations exist between visual acuity and the other measures. METHODS: A series of spatial vision functions were measured in a sample of 900 community-dwelling older observers. Regression analysis was performed, and correlation coefficients were calculated between standard high-contrast visual acuity and other spatial vision measures including contrast sensitivity, low-contrast acuity, low-contrast low-luminance acuity (SKILL card), and disability glare acuity. RESULTS: All measures were highly and significantly correlated with standard visual acuity (r = 0.68 to 0.91). Despite the high correlations, many predictions of the other spatial vision measures from the correlation with standard acuity fell considerably outside of acceptable ranges determined by repeatability. The influence of the range of values in correlations is emphasized. CONCLUSIONS: Other spatial vision measures cannot be predicted on an individual basis from visual acuity despite high and significant correlations between the measures.

Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy.

PURPOSE: To identify local retinal abnormalities in diabetic patients with and without retinopathy, by using the multifocal electroretinogram (M-ERG). METHODS: Electroretinograms were recorded at 103 discrete retinal locations in each eye of eight persons with nonproliferative diabetic retinopathy (NPDR) and eight diabetic persons without retinopathy, using VERIS (EDI, San Mateo, CA). The amplitude and implicit time of each local (first-order) retinal response were derived and compared with normal values obtained from 16 age-matched, nondiabetic subjects. Maps of local response amplitude and implicit time were compared with fundus photographs taken at the time of testing. RESULTS: In eyes with NPDR, the implicit times of responses from retinal sites manifesting clinical pathologic fundus lesions (e.g., microaneurysms and focal edema), were markedly delayed (e.g., up to 7 msec from normal). Responses from adjacent retinal sites that were more normal in clinical appearance were also delayed, but to a lesser extent (e.g., 2-5 msec). Smaller, yet significant local response delays were also found in eyes without retinopathy. By contrast, local response amplitudes bore no consistent relationship to fundus abnormalities in eyes with retinopathy, and amplitudes were typically normal in eyes without retinopathy. CONCLUSIONS: The M-ERG reveals local retinal dysfunction in diabetic eyes even before retinopathy. The magnitude of delay of local ERG implicit time reflects the degree of local clinical abnormality in eyes with retinopathy. Local response delays found in some eyes without retinopathy suggest that the M-ERG detects subclinical local retinal dysfunction in diabetes. Analysis of M-ERG implicit time, independent of amplitude, improves the sensitivity of detection of local retinal dysfunction in diabetes.

Seeing into old age: vision function beyond acuity.

PURPOSE: To provide a comprehensive description of vision function beyond acuity in older individuals. METHODS: A sample of 900 individuals between the ages of 58 and 102 years (mean age of 75.5) was binocularly tested wearing habitual correction on a battery of psychophysical tests including high and low contrast acuity, low contrast low luminance acuity, disability glare, contrast sensitivity, color vision, stereoacuity, recovery from glare, and attentional visual fields. RESULTS: High contrast acuity is reasonably well maintained on average, even into very old ages. Spatial vision measures under conditions of reduced contrast or luminance, or glare reveal significant impairment in a large portion of the aged. Many older individuals also have greatly reduced stereopsis, poor color discrimination, and severely restricted peripheral fields under conditions of divided attention. A single exponential function relating performance to age fits all spatial vision data sets. The function for individual spatial measures lies at different positions along the age scale. The derived aging function with a time constant of approximately 15 years also fits results from other recent aging studies of acuity and contrast sensitivity. CONCLUSIONS: Standard visual acuity underestimates the degree of vision function loss suffered by many older individuals under the nonoptimal viewing conditions encountered in daily life. All spatial vision functions show a similar rate of decline with age of the population, but the age at which decline begins varies among measures.