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During gestation, the most drastic change in oxygen supply occurs with the onset of ventilation after birth. As the too early exposure of premature infants to high arterial oxygen pressure leads to characteristic diseases, we studied the adaptation of the oxygen sensing system and its targets, the hypoxia-inducible factor- (HIF-) regulated genes (HRGs) in the developing lung. We draw a detailed picture of the oxygen sensing system by integrating information from qPCR, immunoblotting, in situ hybridization, and single-cell RNA sequencing data in ex vivo and in vivo models. HIF1α protein was completely destabilized with the onset of pulmonary ventilation, but did not coincide with expression changes in bona fide HRGs. We observed a modified composition of the HIF-PHD system from intrauterine to neonatal phases: Phd3 was significantly decreased, while Hif2a showed a strong increase and the Hif3a isoform Ipas exclusively peaked at P0. Colocalization studies point to the Hif1a-Phd1 axis as the main regulator of the HIF-PHD system in mouse lung development, complemented by the Hif3a-Phd3 axis during gestation. Hif3a isoform expression showed a stepwise adaptation during the periods of saccular and alveolar differentiation. With a strong hypoxic stimulus, lung ex vivo organ cultures displayed a functioning HIF system at every developmental stage. Approaches with systemic hypoxia or roxadustat treatment revealed only a limited in vivo response of HRGs. Understanding the interplay of the oxygen sensing system components during the transition from saccular to alveolar phases of lung development might help to counteract prematurity-associated diseases like bronchopulmonary dysplasia.
Durch die Auswirkungen des Klimawandels – besonders durch Hitze – geraten viele indigene Baumarten innerhalb der nächsten 75 Jahre voraussichtlich an den Rand ihrer Existenz. Der Stadtstandort stellt eine zusätzliche Herausforderung dar, der durch menschliche Aktivitäten negativ, aber auch positiv beeinflusst werden kann. Besonders die Wasserverfügbarkeit kann durch geeignete vegetationstechnische Maßnahmen und intelligente Profilierung von Oberflächen befördert werden. Die Vegetation wird sich verändern. Mit gebietseinheimischen Genotypen und natürlicher Migration hitzeverträglicher Arten alleine lassen sich unsere Probleme nicht lösen. Wir brauchen Bäume in der Stadt, die beschatten und verdunsten.
Lösungsansätze sind die vielfältige Anpflanzung hitzeresistenter Genotypen indigener Arten, neuer, submediterraner Arten aus Süd- und Südosteuropa (assisted migration) sowie klimatoleranter Arten anderer Kontinente. Es ist allerdings davon auszugehen, dass sich diese Arten dann bei uns auch etablieren werden. Und das ist bei der durch die Eiszeiten verarmten Gehölzflora Mitteleuropas und für lebenswerte Städte auch gut so!
Aufgrund vermuteter, negativer Folgen, welche von der Etablierung und Ausbreitung gebietsfremder Art ausgehen können, ist um die Verwendung von Zukunftsbäumen im städtischen Raum eine Diskussion entstanden. Im Rahmen einer Forschungsarbeit an der Hochschule Osnabrück wurde daher untersucht, wie die Ausbreitungstendenz einzelner Arten von Mitarbeiter*innen in Grünflächenämtern und Botanischen Garten eingeschätzt wird.
Background
A peripheral venous catheter (PVC) is the most widely used device for obtaining vascular access, allowing the administration of fluids and medication. Up to 25% of adult patients, and 50% of pediatric patients experience a first-attempt cannulation failure. In addition to patient and clinician characteristics, device features might affect the handling and success rates. The objective of the study was to compare the first-attempt cannulation success rate between PVCs with wings and a port access (Vasofix® Safety, B. Braun, abbreviated hereon in as VS) with those without (Introcan® Safety, B. Braun, abbreviated hereon in as IS) in an anesthesiological cohort.
Methods
An open label, multi-center, randomized trial was performed. First-attempt cannulation success rates were examined, along with relevant patient, clinician, and device characteristics with univariate and multivariate analyses. Information on handling and adherence to use instructions was gathered, and available catheters were assessed for damage.
Results
Two thousand three hundred four patients were included in the intention to treat analysis. First-attempt success rate was significantly higher with winged and ported catheters (VS) than with the non-winged, non-ported design (IS) (87.5% with VS vs. 78.2% with IS; PChi < .001). Operators rated the handling of VS as superior (rating of “good” or “very good: 86.1% VS vs. 20.8% IS, PChi < .001). Reinsertion of the needle into the catheter after partial withdrawal—prior or during the catheterization attempt—was associated with an increased risk of cannulation failure (7.909, CI 5.989–10.443, P < .001 and 23.023, CI 10.372–51.105, P < .001, respectively) and a twofold risk of catheter damage (OR 1.999, CI 1.347–2.967, P = .001).
Conclusions
First-attempt cannulation success of peripheral, ported, winged catheters was higher compared to non-ported, non-winged devices. The handling of the winged and ported design was better rated by the clinicians. Needle reinsertions are related to an increase in rates of catheter damage and cannulation failure.
Background: New ischaemic brain lesions on magnetic resonance imaging (MRI) are reported in up to 86% of patients after transcatheter edge-to-edge repair of the mitral valve (TEER-MV). Knowledge of the exact procedural step(s) that carry the highest risk for cerebral embolisation may help to further improve the procedure.
Aims: The aim of this study was to identify the procedural step(s) that are associated with an increased risk of cerebral embolisation during TEER-MV with the MitraClip system. Furthermore, the risk of overt stroke and silent brain ischaemia after TEER-MV was assessed.
Methods: In this prospective, pre-specified observational study, all patients underwent continuous transcranial Doppler examination during TEER-MV to detect microembolic signals (MES). MES were assigned to specific procedural steps: (1) transseptal puncture and placement of the guide, (2) advancing and adjustment of the clip in the left atrium, (3) device interaction with the MV, and (4) removal of the clip delivery system and the guide. Neurological examination using the National Institutes of Health Stroke Scale (NIHSS) and cerebral MRI were performed before and after TEER-MV.
Results: Fifty-four patients were included. The number of MES differed significantly between the procedural steps with the highest numbers observed during device interaction with the MV. Mild neurological deterioration (NIHSS ≤3) occurred in 9/54 patients. New ischaemic lesions were detected in 21/24 patients who underwent MRI. Larger infarct volume was significantly associated with neurological deterioration.
Conclusions: Cerebral embolisation is immanent to TEER-MV and predominantly occurs during device interaction with the MV. Improvements to the procedure may focus on this procedural step.
Background
To detect changes in biological processes, samples are often studied at several time points. We examined expression data measured at different developmental stages, or more broadly, historical data. Hence, the main assumption of our proposed methodology was the independence between the examined samples over time. In addition, however, the examinations were clustered at each time point by measuring littermates from relatively few mother mice at each developmental stage. As each examination was lethal, we had an independent data structure over the entire history, but a dependent data structure at a particular time point. Over the course of these historical data, we wanted to identify abrupt changes in the parameter of interest - change points.
Results
In this study, we demonstrated the application of generalized hypothesis testing using a linear mixed effects model as a possible method to detect change points. The coefficients from the linear mixed model were used in multiple contrast tests and the effect estimates were visualized with their respective simultaneous confidence intervals. The latter were used to determine the change point(s). In small simulation studies, we modelled different courses with abrupt changes and compared the influence of different contrast matrices. We found two contrasts, both capable of answering different research questions in change point detection: The Sequen contrast to detect individual change points and the McDermott contrast to find change points due to overall progression. We provide the R code for direct use with provided examples. The applicability of those tests for real experimental data was shown with in-vivo data from a preclinical study.
Conclusion
Simultaneous confidence intervals estimated by multiple contrast tests using the model fit from a linear mixed model were capable to determine change points in clustered expression data. The confidence intervals directly delivered interpretable effect estimates representing the strength of the potential change point. Hence, scientists can define biologically relevant threshold of effect strength depending on their research question. We found two rarely used contrasts best fitted for detection of a possible change point: the Sequen and McDermott contrasts.
BACKGROUND: Postoperative delirium (POD) is an acute and common complication after surgery that can increase morbidity and mortality. Few previous studies with inconsistent findings have examined the association of preoperative pain and POD. Our purpose is to investigate the association of preoperative chronic pain and POD.
METHODS: This prospective observational cohort study included 200 patients ≥ 18 years scheduled for elective surgery under general anaesthesia in a tertiary care hospital. POD was defined as meeting diagnostic criteria during the study visits (according to delirium screening tests and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), or by diagnosis of the responsible physicians. Chronic pain was defined as pain lasting six months or longer. Features of chronic pain were assessed with the German Pain Questionnaire, including the Depression Anxiety and Stress Scale-21 (DASS-21). Associations with POD were assessed using logistic regression analysis adjusting for confounding factors.
RESULTS: Thirty-nine (22%) out of 176 patients developed POD. Chronic pain was not associated with POD after adjustment for ASA physical status, duration of anesthesia and DASS-21 Anxiety score (Odds ratio [OR], 95%-Confidence Interval [CI], 2.216 [0.968;5.070], P=0.060). A subgroup analysis of chronic pain patients revealed that current pain intensity was higher in patients with POD.
CONCLUSIONS: Preoperative chronic pain was no independent predictor for POD. Current pain intensity was higher in chronic pain patients with POD. This indicates that certain features of pain might be influential. Further research is needed to examine different forms of preoperative pain and their possible influence on POD.
Hintergrund
Die Anämie hat eine hohe Prävalenz bei Patienten vor Hüftgelenkrevisionsoperation und ist mit einer erhöhten Komplikationsrate assoziiert. Die vorliegende Arbeit untersucht erstmals den Zusammenhang von Kosten, realen DRG-Erlösen und Falldeckung der präoperativen Anämie bei elektiven Hüftgelenkrevisionsoperationen.
Methoden
Für alle Patienten, die sich von 2010 bis 2017 an 2 Campi der Charité – Universitätsmedizin Berlin einer Hüftgelenkrevisionsoperation unterzogen, wurden Daten zu Patienten sowie Transfusionen, Kosten und Erlösen gesammelt. Subgruppen- und lineare Regressionsanalysen untersuchten die Falldeckung anämischer und nichtanämischer Patienten.
Ergebnisse
Von 1187 eingeschlossenen Patienten waren 354 (29,8 %) präoperativ anämisch. Insgesamt wurden 565 (47,6 %) Patienten, mit einem deutlichen Überwiegen anämischer Patienten (72,6 % vs. 37,0 %, p < 0,001), transfundiert. Kosten (12.318 € [9027;20.044 €] vs. 8948 € [7501;11.339 €], p < 0,001) und Erlöse (11.788 € [8992;16.298 €] vs. 9611 € [8332;10.719 €], p < 0,001) waren für anämische Patienten höher, die Fallkostendeckung defizitär (−1170 € [−4467;1238 €] vs. 591 € [−1441;2103 €] €, p < 0,001). Bei anämischen Patienten nahm die Falldeckung mit zunehmender Transfusionsrate ab (p ≤ 0,001). Komorbiditäten hatten keinen signifikanten ökonomischen Einfluss.
Schlussfolgerung
Die präoperative Anämie und perioperative Transfusionen bei Hüftgelenkrevisionsoperationen sind mit erhöhten Behandlungskosten und einer finanziellen Unterdeckung für Kostenträger im Gesundheitswesen verbunden. Konzepte zur Behandlung der präoperativen Anämie (z. B. Patient Blood Management) könnten mittelfristig Behandlungskosten senken.
Intensive care units (ICU) are often overflooded with alarms from monitoring devices which constitutes a hazard to both staff and patients. To date, the suggested solutions to excessive monitoring alarms have remained on a research level. We aimed to identify patient characteristics that affect the ICU alarm rate with the goal of proposing a straightforward solution that can easily be implemented in ICUs. Alarm logs from eight adult ICUs of a tertiary care university-hospital in Berlin, Germany were retrospectively collected between September 2019 and March 2021. Adult patients admitted to the ICU with at least 24 h of continuous alarm logs were included in the study. The sum of alarms per patient per day was calculated. The median was 119. A total of 26,890 observations from 3205 patients were included. 23 variables were extracted from patients' electronic health records (EHR) and a multivariable logistic regression was performed to evaluate the association of patient characteristics and alarm rates. Invasive blood pressure monitoring (adjusted odds ratio (aOR) 4.68, 95%CI 4.15–5.29, p < 0.001), invasive mechanical ventilation (aOR 1.24, 95%CI 1.16–1.32, p < 0.001), heart failure (aOR 1.26, 95%CI 1.19–1.35, p < 0.001), chronic renal failure (aOR 1.18, 95%CI 1.10–1.27, p < 0.001), hypertension (aOR 1.19, 95%CI 1.13–1.26, p < 0.001), high RASS (aOR 1.22, 95%CI 1.18–1.25, p < 0.001) and scheduled surgical admission (aOR 1.22, 95%CI 1.13–1.32, p < 0.001) were significantly associated with a high alarm rate. Our study suggests that patient-specific alarm management should be integrated in the clinical routine of ICUs. To reduce the overall alarm load, particular attention regarding alarm management should be paid to patients with invasive blood pressure monitoring, invasive mechanical ventilation, heart failure, chronic renal failure, hypertension, high RASS or scheduled surgical admission since they are more likely to have a high contribution to noise pollution, alarm fatigue and hence compromised patient safety in ICUs.