16 research outputs found
Age-dependent favorable visual recovery despite significant retinal atrophy in pediatric MOGAD: how much retina do you really need to see well?
Neuritis òptica; Tomografia de coherència òpticaNeuritis óptica; TomografÃa de coherencia ópticaOptic neuritis; Optical coherence tomographyBackground
To investigate age-related severity, patterns of retinal structural damage, and functional visual recovery in pediatric and adult cohorts of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) optic neuritis (ON).
Methods
All MOGAD patients from the 5 participating centers were included. Patients with initial manifestation <18 years were included in the pediatric (MOGADped) cohort and patients with ≥18 years in the adult (MOGADadult) cohort. For patients with MOGAD ON, examinations at least ≥6 months after ON onset were included in the analyses. Using spectral domain optical coherence tomography (SD-OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIPL). High- and 2.5% low-contrast visual acuity (HCVA, LCVA) and visual-evoked potentials (VEP) were obtained.
Results
Twenty MOGADped (10.3±3.7 years, 30 MOGAD ON eyes) and 39 MOGADadult (34.9±11.6 years, 42 MOGAD ON eyes) patients were included. The average number of ON episodes per ON eye was similar in both groups (1.8±1.3 and 2.0±1.7). In both pediatric and adult MOGAD, ON led to pronounced neuroaxonal retinal atrophy (pRNFL: 63.1±18.7 and 64.3±22.9 μm; GCIPL: 0.42±0.09 and 0.44±0.13 mm3, respectively) and moderate delay of the VEP latencies (117.9±10.7 and 118.0±14.5 ms). In contrast, visual acuity was substantially better in children (HCVA: 51.4±9.3 vs. 35.0±20.6 raw letters, p=0.001; LCVA: 22.8±14.6 vs. 13.5±16.4, p=0.028). Complete visual recovery (HCVA-logMAR 0.0) occurred in 73.3% of MOGADped and 31% MOGADadults ON eyes, while 3.3% and 31% demonstrated moderate to severe (logMAR > 0.5) visual impairment. Independent of retinal atrophy, age at ON onset significantly correlated with visual outcome.
Conclusion
Pediatric MOGAD ON showed better visual recovery than adult MOGAD ON despite profound and almost identical neuroaxonal retinal atrophy. Age-related cortical neuroplasticity may account for the substantial discrepancy between structural changes and functional outcomes.JH is (partially) funded by the German Federal Ministry of Education and Research (Grant Numbers 01ZZ1603[A-D] and 01ZZ1804[A-H] (DIFUTURE)). Open Access funding enabled and organized by Projekt DEAL
Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode
Optical coherence tomography; Optic neuritis; Pediatric patientsTomografÃa de coherencia óptica; Neuritis óptica; Pacientes pediátricosTomografia de coherència òptica; Neuritis òptica; Pacients pedià tricsBackground
Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode.
Methods
Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls.
Results
Thirteen MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGADped compared to MSped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGADped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016).
Conclusion
First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.Open Access funding enabled and organized by Projekt DEAL. No
Single-cell mRNA transfection studies: Delivery, kinetics and statistics by numbers
AbstractIn artificial gene delivery, messenger RNA (mRNA) is an attractive alternative to plasmid DNA (pDNA) since it does not require transfer into the cell nucleus. Here we show that, unlike for pDNA transfection, the delivery statistics and dynamics of mRNA-mediated expression are generic and predictable in terms of mathematical modeling. We measured the single-cell expression time-courses and levels of enhanced green fluorescent protein (eGFP) using time-lapse microscopy and flow cytometry (FC). The single-cell analysis provides direct access to the distribution of onset times, life times and expression rates of mRNA and eGFP. We introduce a two-step stochastic delivery model that reproduces the number distribution of successfully delivered and translated mRNA molecules and thereby the dose–response relation. Our results establish a statistical framework for mRNA transfection and as such should advance the development of RNA carriers and small interfering/micro RNA-based drugs.From the Clinical EditorThis team of authors established a statistical framework for mRNA transfection by using a two-step stochastic delivery model that reproduces the number distribution of successfully delivered and translated mRNA molecules and thereby their dose-response relation. This study establishes a nice connection between theory and experimental planning and will aid the cellular delivery of mRNA molecules
Age-dependent favorable visual recovery despite significant retinal atrophy in pediatric MOGAD: how much retina do you really need to see well?
BACKGROUND To investigate age-related severity, patterns of retinal structural damage, and functional visual recovery in pediatric and adult cohorts of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) optic neuritis (ON). METHODS All MOGAD patients from the 5 participating centers were included. Patients with initial manifestation 0.5) visual impairment. Independent of retinal atrophy, age at ON onset significantly correlated with visual outcome. CONCLUSION Pediatric MOGAD ON showed better visual recovery than adult MOGAD ON despite profound and almost identical neuroaxonal retinal atrophy. Age-related cortical neuroplasticity may account for the substantial discrepancy between structural changes and functional outcomes
Akut-Inanspruchnahme von kinder- und jugendpsychiatrischer Behandlung und ihre Veränderung in einem Zeitraum von fünf Jahren (2011-2015)
Im Rahmen einer retrospektiven Querschnittsanalyse wurden stationäre Routinedaten aus vier deutschen kinder- und jugendpsychiatrischen Kliniken (=18671) über einen Zeitraum von 5 Jahren (2011- 2015) hinsichtlich der Ausprägung und Veränderung von soziodemographischen, aufnahmebezogenen und behandlungsbezogenen Merkmalen von stationärer Akut-Inanspruchnahme (=7339 Krisen) untersucht. Steigende Fallzahlen und eine signifikant verkürzte Verweildauer weisen auf einen zunehmenden Aufnahmedruck durch Akut-Inanspruchnahme im stationären Sektor der KJP hin. Affektive Störungen verdrängen in dem Zusammenhang belastungs- und direkt stressbezogenen Störungen. Adoleszente und Mädchen erweisen sich als besonders gefährdet. Zeitliche Aspekte sind bei der Anpassung von Versorgungskapazitäten zu berücksichtigen. Hierbei sollte der Fokus nicht nur auf sozial schwachen, sondern generell kinderreichen Regionen, liegen. Schulbasierte Präventions- und Beratungsprogramme sollten gefördert werden
Endocarditis following ocrelizumab in relapsing-remitting MS
Ocrelizumab is a monoclonal anti-CD20 antibody targeting B cells, which is authorized for relapsing-remitting MS (RRMS) and active primary progressive MS. Here, we report, to the best of our knowledge, the first case of infective endocarditis in a patient treated with ocrelizumab
Anatomic accuracy, physiologic characteristics, and fidelity of very low birth weight infant airway simulators
Background!#!Medical simulation training requires realistic simulators with high fidelity. This prospective multi-center study investigated anatomic precision, physiologic characteristics, and fidelity of four commercially available very low birth weight infant simulators.!##!Methods!#!We measured airway angles and distances in the simulators Premature AirwayPaul (SIMCharacters), Premature Anne (Laerdal Medical), Premie HAL S2209 (Gaumard), and Preterm Baby (Lifecast Body Simulation) using computer tomography and compared these to human cadavers of premature stillbirths. The simulators' physiologic characteristics were tested, and highly experienced experts rated their physical and functional fidelity.!##!Results!#!The airway angles corresponded to those of the reference cadavers in three simulators. The nasal inlet to glottis distance and the mouth aperture to glottis distance were only accurate in one simulator. All simulators had airway resistances up to 20 times higher and compliances up to 19 times lower than published reference values. Fifty-six highly experienced experts gave three simulators (Premature AirwayPaul: 5.1 ± 1.0, Premature Anne 4.9 ± 1.1, Preterm Baby 5.0 ± 1.0) good overall ratings and one simulator (Premie HAL S2209: 2.8 ± 1.0) an unfavorable rating.!##!Conclusion!#!The simulator physiology deviated significantly from preterm infants' reference values concerning resistance and compliance, potentially promoting a wrong ventilation technique.!##!Impact!#!Very low birth weight infant simulators showed physiological properties far deviating from corresponding patient reference values. Only ventilation with very high peak pressure achieved tidal volumes in the simulators, as aimed at in very low birth weight infants, potentially promoting a wrong ventilation technique. Compared to very low birth weight infant cadavers, most tested simulators accurately reproduced the anatomic angular relationships, but their airway dimensions were relatively too large for the represented body. The more professional experience the experts had, the lower they rated the very low birth weight infant simulators
Atrophy of optic nerve detected by transorbital sonography in patients with demyelinating diseases of the central nervous system
Transorbital sonography (TOS) has emerged as promising imaging method for the diagnosis and follow-up of acute optic neuritis (ON). Available studies report an increase in the optic nerve diameter (OND) and the optic nerve sheath diameter (ONSD) in the case of a first episode of ON in the affected eye compared to either the contralateral unaffected eye or controls. However, the utility of TOS in the case of recurrent episodes of ON has never been assessed.
In our prospective cohort study, the diagnostic utility of TOS in patients with demyelinating diseases of the central nervous system was assessed, and the association between TOS, optical coherence tomography (OCT) and visual evoked potentials was examined further.
Seventy-eight patients with a history of demyelinating disorders of the central nervous system (mean age 38.2 14.2 years; 24% with acute ON) were included. No differences in the OND (3.2 0.5 mm vs. 3.2 0.4 mm) and ONSD (5.1 0.8 mm vs. 5.1 0.7 mm) measurements were found between patients with and without acute ON. Papillary swelling was more frequent in patients with acute ON (14.2% vs. 1.5%, = 0.002). Patients with a history of previous ON were found to have lower OND ( < 0.001) and ONSD ( = 0.007) compared to patients without a history of previous ON. TOS measurements were inversely associated with disease duration and positively correlated with OCT findings. No association with visual evoked potential measurements was found.
No evidence was found for TOS-sensitive differences in the OND and ONSD of patients with demyelinating diseases, according to the presence of acute ON. The association between TOS and OCT measurements deserves further investigation