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Meintrup, David ; Borgmann, Stefan ; Seidl, Karlheinz ; Stecher, Melanie ; Jakob, Carolin Ellen Marianne ; Pilgram, Lisa ; Spinner, Christoph Daniel ; Rieg, Siegbert ; Isberner, Nora ; Hower, Martin ; Vehreschild, Maria J. G. T. ; Göpel, Siri ; Hanses, Frank ; Nowak-Machen, Martina
(1) Background: The aim of our study was to identify specific risk factors for fatal outcome in critically ill COVID-19 patients. (2) Methods: Our data set consisted of 840 patients enclosed in the LEOSS registry. Using lasso regression for variable selection, a multifactorial logistic regression model was fitted to the response variable survival. Specific risk factors and their odds ratios were derived. A nomogram was developed as a graphical representation of the model. (3) Results: 14 variables were identified as independent factors contributing to the risk of death for critically ill COVID-19 patients: age (OR 1.08, CI 1.06–1.10), cardiovascular disease (OR 1.64, CI 1.06–2.55), pulmonary disease (OR 1.87, CI 1.16–3.03), baseline Statin treatment (0.54, CI 0.33–0.87), oxygen saturation (unit = 1%, OR 0.94, CI 0.92–0.96), leukocytes (unit 1000/μL, OR 1.04, CI 1.01–1.07), lymphocytes (unit 100/μL, OR 0.96, CI 0.94–0.99), platelets (unit 100,000/μL, OR 0.70, CI 0.62–0.80), procalcitonin (unit ng/mL, OR 1.11, CI 1.05–1.18), kidney failure (OR 1.68, CI 1.05–2.70), congestive heart failure (OR 2.62, CI 1.11–6.21), severe liver failure (OR 4.93, CI 1.94–12.52), and a quick SOFA score of 3 (OR 1.78, CI 1.14–2.78). The nomogram graphically displays the importance of these 14 factors for mortality. (4) Conclusions: There are risk factors that are specific to the subpopulation of critically ill COVID-19 patients.
Neering, Sarah H. ; Adyani-Fard, Sabine ; Klocke, Astrid ; Rüttermann, Stefan ; Flemmig, Thomas Frank ; Beikler, Thomas
BACKGROUND: Plasminogen deficiency is a rare autosomal recessive disease, which is associated with aggressive periodontitis and gingival enlargement. Previously described treatments of plasminogen deficiency associated periodontitis have shown limited success. This is the first case report indicating a successful therapy approach consisting of a non-surgical supra- and subgingival debridement in combination with an adjunctive systemic antibiotic therapy and a strict supportive periodontal regimen over an observation period of 4 years.
CASE PRESENTATION: The intraoral examination of a 17-year-old Turkish female with severe plasminogen deficiency revealed generalized increased pocket probing depths ranging from 6 to 9 mm, bleeding on probing over 30%, generalized tooth mobility, and gingival hyperplasia. Alveolar bone loss ranged from 30% to 50%. Clinical attachment loss corresponded to pocket probing depths. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Prevotella nigrescens and Eikenella corrodens have been detected by realtime polymerase chain reaction. Periodontal treatment consisted of full mouth disinfection and adjunctive systemic administration of amoxicillin (500 mg tid) and metronidazole (400 mg tid). A strict supportive periodontal therapy regimen every three month in terms of supra- and subgingival debridement was rendered. The reported therapy has significantly improved periodontal health and arrested disease progression. Intraoral examination at the end of the observation period 3.5 years after non-surgical periodontal therapy showed generalized decreased pocket probing depths ranging from 1 to 6 mm, bleeding on probing lower 30%, and tooth mobility class I and II. Furthermore, microbiological analysis shows the absence of Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola after therapy.
CONCLUSION: Adjunctive antibiotic treatment may alter the oral microbiome and thus, the inflammatory response of periodontal disease associated to plasminogen deficiency and diminishes the risk of pseudomembrane formation and progressive attachment loss. This case report indicates that patients with plasminogen deficiency may benefit from non-surgical periodontal treatment in combination with an adjunctive antibiotic therapy and a strict supportive periodontal therapy regimen.
A handling study to assess use of the Respimat(®) Soft Mist™ inhaler in children under 5 years old
(2015)
Kamin, Wolfgang ; Frank, Marion ; Kattenbeck, Sabine ; Moroni-Zentgraf, Petra ; Wachtel, Herbert ; Zielen, Stefan
Background: Respimat® Soft Mist™ Inhaler (SMI) is a hand-held device that generates an aerosol with a high, fine-particle fraction, enabling efficient lung deposition. The study objective was to assess inhalation success among children using Respimat SMI, and the requirement for assistance by the parent/caregiver and/or a valved holding chamber (VHC).
Methods: This open-label study enrolled patients aged <5 years with respiratory disease and history of coughing and/or recurrent wheezing. Patients inhaled from the Respimat SMI (air only; no aerosol) using a stepwise configuration: “1” (dose released by child); “2” (dose released by parent/caregiver), and “3” (Respimat SMI with VHC, facemask, and parent/caregiver help). Co-primary endpoints included the ability to perform successful inhalation as assessed by the investigators using a standardized handling questionnaire and evaluation of the reasons for success. Inhalation profile in the successful handling configuration was verified with a pneumotachograph. Patient satisfaction and preferences were investigated in a questionnaire.
Results: Of the children aged 4 to <5 years (n=27) and 3 to <4 years (n=30), 55.6% and 30.0%, respectively, achieved success without a VHC or help; with assistance, another 29.6% and 10.0%, respectively, achieved success, and the remaining children were successful with VHC. All children aged 2 to <3 years (n=20) achieved success with the Respimat SMI and VHC. Of those aged <2 years (n=22), 95.5% had successful handling of the Respimat SMI with VHC and parent/caregiver help. Inhalation flow profiles generally confirmed the outcome of the handling assessment by the investigators. Most parent/caregiver and/or child respondents were satisfied with operation, instructions for use, handling, and ease of holding the Respimat SMI with or without a VHC.
Conclusions: The Respimat SMI is suitable for children aged <5 years; however, children aged <5 years are advised to add a VHC to complement its use.
Als man 1930 die ersten Naturschutzflächen am Bielenberg eingerichtet hat, waren bereits einschneidende Entscheidungen über die Gebietsnutzung gefallen. Auf den vormals als Ödland bezeichneten Berghängen stockte auf größeren Flächen ein gut 40- jähriger Waldbestand, wobei die Kiefer, wie Säger schreibt, recht licht stand, so dass die ursprüngliche Bodenflora noch kaum verändert erschien. Die besonders artenreichen, durch Beweidung entstandenen Kalkmagerrasen waren über den Berg verteilt noch vorhanden, vor allem aber in den Randbereichen, wo sie auch heute noch in Resten zu finden sind. Rückblickend ist davon auszugehen, dass der Berg in den 1930er Jahren seine größte Vielfalt an Pflanzenarten aufwies, da sich die Landschaft in einem durch Nutzungsänderungen bedingten Wandel befand und Sukzessionsprozesse für einen großen Strukturreichtum sorgten. Dies galt vor allem auch für die stillgelegten Steinbrüche und deren Umgebung. Nach dem Krieg wurde der Bielenberg als Pflanzenparadies wiederentdeckt, was in mehreren Gutachten und Veröffentlichungen zwischen 1950 und 1958 zum Ausdruck kam. Neben bemerkenswerten Neufunden aus der Flora war aber bereits das Verschwinden wertbestimmender Arten zu beklagen. Die bedeutenden Vorkommen des Großen Windröschens erloschen, weil die Pflanzen immer wieder von der Bevölkerung ausgegraben wurden (Preywisch 1957) und der Frauenschuh "erstickte" im immer schattigeren Dickicht des Kiefernwaldes. Später verschwanden auch die Wintergrün-Arten, die ebenfalls im dichten Unterwuchs der Kiefer keine zusagenden Bedingungen mehr vorfanden. In einer Flächenbilanz für die Kalkmagerrasen kommen Scheideler & Smolis 1983 zu dem Ergebnis, dass von ehemals ca. 20 ha gerade noch 2.500 m² verblieben sind - ein schlechtes Ergebnis nach 50 Jahren Naturschutz! Erst mit der Durchführung von Landschaftspflegemaßnahmen in den 1990er Jahren und der Schenkung privater Grünlandflächen an den Naturkundlichen Verein Egge-Weser konnte der Rückgang der Lebensräume seltener Pflanzen und Tiere der Kalkmagerrasen gestoppt werden. Durch Zurücknahme des vorgedrungenen Strauch- und Baumwuchses einschließlich kleiner Fichtenaufforstungen wurden die dem Wald südlich vorgelagerten Wiesen- und Magerrasenbestände wieder merklich vergrößert.
Der Klimawandel ist heute in weiten Teilen der Fachwelt und der Öffentlichkeit als akute Bedrohung für die Lebensgrundlagen des Menschen akzeptiert. Die unterschiedlichen Klimawandel-Szenarien unterscheiden sich im Wesentlichen im Ausmaß der zu erwartenden Temperaturerhöhungen für bestimmte Regionen und den sich daraus abzuleitenden Effekten (z. B. Niederschlagssummen oder -verteilung, Häufung von Starkregen, größere Häufigkeit von Stürmen, Meeresspiegelanstieg). In Europa wurde in den letzten 100 Jahren ein Anstieg der Jahresmitteltemperatur um 0,95°C beobachtet (EEA 2004). Für Deutschland werden für die nächsten 50 Jahre eine weitere Temperaturzunahme vor allem im Winter, eine starke Zunahme der Winterniederschläge verbunden mit einer zunehmenden Hochwassergefährdung sowie ein Rückgang der Niederschläge und ein Anstieg trockenheißer Wetterlagen im Sommer bei gleichzeitiger Häufung von Starkniederschlagsereignissen prognostiziert (LEUSCHNER & SCHIPKA 2004, EEA 2004).
Frölich, Lutz ; Peters, Oliver ; Lewczuk, Piotr ; Gruber, Oliver ; Teipel, Stefan ; Gertz, Hermann-Josef ; Jahn, Holger ; Jessen, Frank ; Kurz, Alexander ; Luckhaus, Christian ; Hüll, Michael ; Pantel, Johannes ; Reischies, Friedel ; Schröder, Johannes ; Wagner, Michael ; Rienhoff, Otto ; Wolf, Stefanie ; Bauer, Chris ; Schuchhardt, Johannes ; Heuser, Isabella ; Rüther, Eckart ; Henn, Fritz ; Maier, Wolfgang ; Wiltfang, Jens ; Kornhuber, Johannes
Background: The progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD) dementia can be predicted by cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers. Since most biomarkers reveal complementary information, a combination of biomarkers may increase the predictive power. We investigated which combination of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)-sum-of-boxes, the word list delayed free recall from the Consortium to Establish a Registry of Dementia (CERAD) test battery, hippocampal volume (HCV), amyloid-beta1–42 (Aβ42), amyloid-beta1–40 (Aβ40) levels, the ratio of Aβ42/Aβ40, phosphorylated tau, and total tau (t-Tau) levels in the CSF best predicted a short-term conversion from MCI to AD dementia.
Methods: We used 115 complete datasets from MCI patients of the "Dementia Competence Network", a German multicenter cohort study with annual follow-up up to 3 years. MCI was broadly defined to include amnestic and nonamnestic syndromes. Variables known to predict progression in MCI patients were selected a priori. Nine individual predictors were compared by receiver operating characteristic (ROC) curve analysis. ROC curves of the five best two-, three-, and four-parameter combinations were analyzed for significant superiority by a bootstrapping wrapper around a support vector machine with linear kernel. The incremental value of combinations was tested for statistical significance by comparing the specificities of the different classifiers at a given sensitivity of 85%.
Results: Out of 115 subjects, 28 (24.3%) with MCI progressed to AD dementia within a mean follow-up period of 25.5 months. At baseline, MCI-AD patients were no different from stable MCI in age and gender distribution, but had lower educational attainment. All single biomarkers were significantly different between the two groups at baseline. ROC curves of the individual predictors gave areas under the curve (AUC) between 0.66 and 0.77, and all single predictors were statistically superior to Aβ40. The AUC of the two-parameter combinations ranged from 0.77 to 0.81. The three-parameter combinations ranged from AUC 0.80–0.83, and the four-parameter combination from AUC 0.81–0.82. None of the predictor combinations was significantly superior to the two best single predictors (HCV and t-Tau). When maximizing the AUC differences by fixing sensitivity at 85%, the two- to four-parameter combinations were superior to HCV alone.
Conclusion: A combination of two biomarkers of neurodegeneration (e.g., HCV and t-Tau) is not superior over the single parameters in identifying patients with MCI who are most likely to progress to AD dementia, although there is a gradual increase in the statistical measures across increasing biomarker combinations. This may have implications for clinical diagnosis and for selecting subjects for participation in clinical trials.
Svenning, Jens-Christian ; Gravel, Dominique ; Holt, Robert D. ; Schurr, Frank ; Thuiller, Wilfried ; Münkemüller, Tamara ; Schiffers, Katja H. ; Dullinger, Stefan ; Edwards, Thomas C. ; Hickler, Thomas ; Higgins, Steven Ian ; Nabel, Julia E. M. S. ; Pagel, Jörn ; Normand, Signe
Ongoing and predicted global change makes understanding and predicting species’ range shifts an urgent scientific priority. Here, we provide a synthetic perspective on the so far poorly understood effects of interspecific interactions on range expansion rates. We present theoretical foundations for how interspecific interactions may modulate range expansion rates, consider examples from empirical studies of biological invasions and natural range expansions as well as process-based simulations, and discuss how interspecific interactions can be more broadly represented in process-based, spatiotemporally explicit range forecasts. Theory tells us that interspecific interactions affect expansion rates via alteration of local population growth rates and spatial displacement rates, but also via effects on other demographic parameters. The best empirical evidence for interspecific effects on expansion rates comes from studies of biological invasions. Notably, invasion studies indicate that competitive dominance and release from specialized enemies can enhance expansion rates. Studies of natural range expansions especially point to the potential for competition from resident species to reduce expansion rates. Overall, it is clear that interspecific interactions may have important consequences for range dynamics, but also that their effects have received too little attention to robustly generalize on their importance. We then discuss how interspecific interactions effects can be more widely incorporated in dynamic modeling of range expansions. Importantly, models must describe spatiotemporal variation in both local population dynamics and dispersal. Finally, we derive the following guidelines for when it is particularly important to explicitly represent interspecific interactions in dynamic range expansion forecasts: if most interacting species show correlated spatial or temporal trends in their effects on the target species, if the number of interacting species is low, and if the abundance of one or more strongly interacting species is not closely linked to the abundance of the target species.
Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma
(2016)
Horst, Klemens ; Simon, Tim-Philipp ; Pfeifer, Roman ; Teuben, Michel Paul Johan ; Almahmoud, Khalid ; Qiao, Zhi ; Aguiar Santos, Susana ; Castelar Wembers, Carlos Emilio ; Leonhardt, Steffen ; Heussen, Nicole ; Störmann, Philipp ; Auner, Birgit ; Relja, Borna ; Marzi, Ingo ; Haug, Alexander Tobias ; Griensven, Martijn van ; Kalbitz, Miriam ; Huber-Lang, Markus ; Tolba, René H. ; Reiss, Lucy Kathleen ; Uhlig, Stefan ; Marx, Gernot ; Pape, Hans-Christoph ; Hildebrand, Frank
Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.