Contrast Sensitivity and Night Driving in Older People: Quantifying the Relationship Between Visual Acuity, Contrast Sensitivity, and Hazard Detection Distance in a Night-Time Driving Simulator

Purpose(i) To assess how well contrast sensitivity (CS) predicts night-time hazard detection distance (a key component of night driving ability), in normally sighted older drivers, relative to a conventional measure of high contrast visual acuity (VA); (ii) To evaluate whether CS can be accurately quantified within a night driving simulator.Materials and MethodsParticipants were 15 (five female) ophthalmologically healthy adults, aged 55–81 years. CS was measured in a driving simulator using Landolt Cs, presented under static or dynamic driving conditions, and with or without glare. In the dynamic driving conditions, the participant was asked to simultaneously maintain a (virtual) speed of 60 km/h on a country road. In the with glare conditions, two calibrated LED arrays, moved by cable robots, simulated the trajectories and luminance characteristics of the (low beam) headlights of an approaching car. For comparison, CS was also measured clinically (with and without glare) using a Optovist I instrument (Vistec Inc., Olching, Germany). Visual acuity (VA) thresholds were also assessed at high and low contrast using the Freiburg Visual Acuity Test (FrACT) under photopic conditions. As a measure of driving performance, median hazard detection distance (MHDD) was computed, in meters, across three kinds of simulated obstacles of varying contrast.ResultsContrast sensitivity and low contrast VA were both significantly associated with driving performance (both P < 0.01), whereas conventional high contrast acuity was not (P = 0.10). There was good correlation (P < 0.01) between CS measured in the driving simulator and a conventional clinical instrument (Optovist I). As expected, CS was shown to decrease in the presence of glare, in dynamic driving conditions, and as a function of age (all P < 0.01).ConclusionContrast sensitivity and low contrast VA predict night-time hazard detection ability in a manner that conventional high contrast VA does not. Either may therefore provide a useful metric for assessing fitness to drive at night, particularly in older individuals. CS measurements can be made within a driving simulator, and the data are in good agreement with conventional clinical methods (Optovist I)

Profiling endogenous adrenal function during veno-venous ECMO support in COVID-19 ARDS: a descriptive analysis

BackgroundProlonged critical illness is often accompanied by an impairment of adrenal function, which has been frequently related to conditions complicating patient management. The presumed connection between hypoxia and the pathogenesis of this critical- illness- related corticosteroid insufficiency (CIRCI) might play an important role in patients with severe acute respiratory distress syndrome (ARDS). Since extracorporeal membrane oxygenation (ECMO) is frequently used in ARDS, but data on CIRCI during this condition are scarce, this study reports the behaviour of adrenal function parameters during oxygenation support with veno-venous (vv)ECMO in coronavirus disease 2019 (COVID-19) ARDS.MethodsA total of 11 patients undergoing vvECMO due to COVID-19 ARDS at the Medical University of Vienna, who received no concurrent corticosteroid therapy, were retrospectively included in this study. We analysed the concentrations of cortisol, aldosterone, and angiotensin (Ang) metabolites (Ang I–IV, Ang 1–7, and Ang 1–5) in serum via liquid chromatography/tandem mass spectrometry before, after 1 day, 1 week, and 2 weeks during vvECMO support and conducted correlation analyses between cortisol and parameters of disease severity.ResultsCortisol concentrations appeared to be lowest after initiation of ECMO and progressively increased throughout the study period. Higher concentrations were related to disease severity and correlated markedly with interleukin-6, procalcitonin, pH, base excess, and albumin during the first day of ECMO. Fair correlations during the first day could be observed with calcium, duration of critical illness, and ECMO gas flow. Angiotensin metabolite concentrations were available in a subset of patients and indicated a more homogenous aldosterone response to plasma renin activity after 1 week of ECMO support.ConclusionOxygenation support through vvECMO may lead to a partial recovery of adrenal function over time. In homogenous patient collectives, this novel approach might help to further determine the importance of adrenal stress response in ECMO and the influence of oxygenation support on CIRCI

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Glycocalyx shedding in patients undergoing orthotopic liver transplantation

Hintergrund: Die endotheliale Glykokalyx spielt eine zentrale Rolle in der Aufrechterhaltung und Protektion der vaskulären Barriere. Syndecan-1 ist der wichtigste konstitutive Bestandteil dieser endothelialen Schicht. Die Zerstörung der Glykokalyx geht mit dem Verlust der endothelialen Selektionsbarriere und einer Veränderung der Permeabilität einher. Dies führt zum sogenannten Leakage-Syndrom, welches in weiterer Folge in einer vermehrten Extravasation von Molekülen resultiert, welche unter physiologischen Bedingungen die Barriere nicht überschreiten würden. Die durch ein terminales Leberversagen vermutlich herbeigeführten Umbauprozesse der endothelialen Glykokalyx, sowie deren Veränderung während der Lebertransplantation standen im Fokus der Forschungsarbeit.^ ^Der Verlust der endothelialen Integrität sollte weiters in Zusammenhang mit der Entstehung eines postoperativen Nierenversagens untersucht werden. Patienten & Methoden: Insgesamt 30 Patienten, welche einer Lebetransplantation unterzogen wurden, wurden in diese prospektive Studie eingeschlossen. Die Kontrollgruppe umfasste zehn gesunde Probanden. Arterielle Blutabnahme zur Detektion der Plasma-Syndecan-1 Konzentration mittels ELISA, fanden zu fünf verschiedenen Zeitpunkten (T) statt: der Ausgangswert (T0) wurde bei Narkoseeinleitung für die Lebertransplantation bestimmt; weitere Abnahmen erfolgten während der anhepatischen Phase (T1), während der Reperfusion (T2), am Ende der Operation (T3), sowie am 1. postoperativen Tag (T4). Das Auftreten akuten Nierenversagens (AKI) wurde entsprechend der AKIN-Kriterien klassifiziert. Ergebnisse: Plasma-Syndecan-1 Werte waren bei Patienten mit terminalem Leberversagen im Vergleich zur Kontrollgruppe signifikant höher.^ Syndecan-1 Werte stiegen während der Lebertransplantation sukzessive an und erreichten den höchsten Wert während der Reperfusion. Bei Patienten mit postoperativem AKI Grad 2 oder 3 waren die Syndecan-1 Werte während des gesamten Beobachtungszeitraums signifikant höher, als bei jenen, mit AKI GradBackground: The glycocalyx plays a fundamental role in the preservation of endothelial integrity. Shedding of the glycocalyx is induced by various factors, such as ischemia, reperfusion, inflammation, infection, trauma and surgery. Endothelial degradation causes capillary leakage, vascular and microvascular dysfunction, as well as platelet aggregation, leucocyte adhesion, coagulopathy and activation of the inflammatory cascade. Goal of the study was to detect the pre-assumed shedding of the glycocalyx in end-stage liver disease (ESLD) and a further aggravation during orthotopic liver transplantation (OLT). Additionally, the potential contribution of endothelial damage on postoperative acute kidney injury was assessed. Patients and Methods: Thirty liver transplant recipients were included in this prospective study. The control group consisted of ten healthy volunteers. Arterial blood samples for syndecan-1, the main protein of glycocalyx, were drawn at 5 different time points (T) during OLT (T0 = induction of anesthesia; T1 = anhepatic phase/clamping of inferior caval vein; T2 = reperfusion phase/after declamping; T3 = end of surgery; T4 = 24 hours after reperfusion) and determined by ELISA. Acute kidney injury was diagnosed and defined according the Acute Kidney Injury Network criteria. Results: Baseline plasma syndecan-1 was significantly higher in ESLD patients than in healthy volunteers (74.3 59.9 vs. 10.7 9.4 ng/mL). Syndecan-1 plasma concentration further increased significantly in the reperfusion phase (74.3 59.9 vs. 312.6 114.8 ng/mL). Syndecan-1 was significantly higher in patients with post-transplant AKI stage 2 or 3 during the whole study-period in comparison to AKI stagesubmitted by Judith Schiefer, Dr. med.univ.Zusammenfassung in deutscher Sprache2017, Medizinische Universität Wie

Response time and response time variability as indicators of response quality during static automated perimetry

PURPOSE: Perimetry is a both demanding and strenuous examination method that is often accompanied by signs of fatigue, leading to false responses and thus incorrect results. Therefore, it is essential to monitor the response quality. The purpose of this study was to evaluate the response time (RT) and its variability (RTV) as quality indicators during static automated perimetry. METHODS: Size III Goldmann stimuli (25.7′) were shown with the OCTOPUS 900 perimeter in four visual field locations with 13 different stimulus luminance levels (0.04–160 cd/m(2)). An increased rate of false-positive and false-negative catch trials (25% each) served to monitor the response quality simultaneously together with response time recording. Data evaluation was divided into global and individual analysis. For global analysis, the agreement indices (AI, agreement between time periods with an increased number of false responses to catch trials and time periods with pathological response to time-based values set into relation to time periods in which only one of the two criteria was considered pathological) and for individual analysis, the Spearman correlation coefficients were calculated. Ophthalmologically normal subjects with a visual acuity ≥ 0.8, and a maximum spherical/cylindrical ametropia of ± 8.00/2.50 dpt were included. RESULTS: Forty-eight subjects (18 males, 30 females, age 22–78 years) were examined. The total number of false responses to catch trials was (median/maximum): 6/82. RT and RTV were compared to the occurrence of incorrect responses to catch trials. The resulting individual Spearman correlation coefficients (median/maximum) were for RT: ρ(RT) = 0.05/0.35 and for RTV: ρ(RTV) = 0.27/0.61. The global analysis of the RTV showed agreement indices (median/maximum) of AI(RTV) = 0.14/0.47. CONCLUSIONS: According to this study, an increased portion of catch trials is suitable as a verification tool for possible response quality indicators. The RTV is a promising parameter for indicating the response quality. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00417-021-05349-z