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Institute
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II) (161) (remove)
Sonstige beteiligte Institutionen
EU-Project number / Contract (GA) number
- 309962 (2)
Background
To identify injury patterns and mechanisms in professional men’s basketball by means of video match analysis.
Methods
In Germany, injuries are registered with the statutory accident insurance for professional athletes (VBG) by clubs or club physicians as part of occupational accident reporting. Moderate and severe injuries (absence of > 7 days) sustained during basketball competition in one of four seasons (2014–2017 and 2018–2019) in the first or second national men’s league in Germany were prospectively analyzed using a newly developed standardized observation form. Season 2017–2018 was excluded because of missing video material.
Results
Video analysis included 175 (53%) of 329 moderate and severe match injuries. Contact patterns categorized according to the different body sites yielded eight groups of typical injury patterns: one each for the head, shoulders, and ankles, two for the thighs, and three for the knees. Injuries to the head (92%), ankles (76%), shoulders (70%), knees (47%), and thighs (32%) were mainly caused by direct contact. The injury proportion of foul play was 19%. Most injuries (61%) occurred in the central zone below the basket. More injuries occurred during the second (OR 1.8, p = 0.018) and fourth quarter (OR 1.8, p = 0.022) than during the first and third quarter of the match.
Conclusion
The eight identified injury patterns differed substantially in their mechanisms. Moderate and severe match injuries to the head, shoulders, knees, and ankles were mainly caused by collision with opponents and teammates. Thus, stricter rule enforcement is unlikely to facilitate safer match play.
Background:
To prevent bone loss in hip arthroplasty, several short stem systems have been developed, including the Mayo conservative hip system. While there is a plethora of data confirming inherent advantages of these systems, only little is known about potential complications, especially when surgeons start to use these systems.
Methods:
In this study, we present a retrospective analysis of the patients’ outcome, complications and the complication management of the first 41 Mayo conservative hips performed in 37 patients. For this reason, functional scores, radiographic analyses, peri- and postoperative complications were assessed at an average follow-up of 35 months.
Results:
The overall HHS improved from 61.2 pre-operatively to 85.6 post-operatively. The German Extra Short Musculoskeletal Function Assessment Questionnaire (XSFMA-D) improved from 30.3 pre-operatively to 12.2 post-operatively. The most common complication was an intraoperative non-displaced fracture of the proximal femur observed in 5 cases (12.1%). Diabetes, higher BMI and older ages were shown to be risk factors for these intra-operative periprosthetic fractures (p < 0.01). Radiographic analysis revealed a good offset reconstruction in all cases.
Conclusion:
In our series, a high complication rate with 12.1% of non-displaced proximal femoral fractures was observed using the Mayo conservative hip. This may be attributed to the flat learning curve of the system or the inherent patient characteristics of the presented cohort."
Background
For improved outcomes in total knee arthroplasty (TKA) correct implant fitting and positioning are crucial. In order to facilitate a best possible implant fitting and positioning patient-specific systems have been developed. However, whether or not these systems allow for better implant fitting and positioning has yet to be elucidated. For this reason, the aim was to analyse the novel patient-specific cruciate retaining knee replacement system iTotal (TM) CR G2 that utilizes custom-made implants and instruments for its ability to facilitate accurate implant fitting and positioning including correction of the hip-knee-ankle angle (HKA).
Methods
We assessed radiographic results of 106 patients who were treated with the second generation of a patient-specific cruciate retaining knee arthroplasty using iTotal\(^{TM}\) CR G2 (ConforMIS Inc.) for tricompartmental knee osteoarthritis (OA) using custom-made implants and instruments. The implant fit and positioning as well as the correction of the mechanical axis (hip-knee-ankle angle, HKA) and restoration of the joint line were determined using pre- and postoperative radiographic analyses.
Results
On average, HKA was corrected from 174.4 degrees +/- 4.6 degrees preoperatively to 178.8 degrees +/- 2.2 degrees postoperatively and the coronal femoro-tibial angle was adjusted on average 4.4 degrees. The measured preoperative tibial slope was 5.3 degrees +/- 2.2 degrees (mean +/- SD) and the average postoperative tibial slope was 4.7 degrees +/- 1.1 degrees on lateral views. The joint line was well preserved with an average modified Insall-Salvati index of 1.66 +/- 0.16 pre- and 1.67 +/- 0.16 postoperatively. The overall accuracy of fit of implant components was decent with a measured medial overhang of more than 1 mm (1.33 mm +/- 0.32 mm) in 4 cases only. Further, a lateral overhang of more than 1 mm (1.8 mm +/- 0.63) (measured in the anterior-posterior radiographs) was observed in 11 cases, with none of the 106 patients showing femoral notching.
Conclusion
The patient-specific iTotal\(^{TM}\) CR G2 total knee replacement system facilitated a proper fitting and positioning of the implant components. Moreover, a good restoration of the leg axis towards neutral alignment was achieved as planned. Nonetheless, further clinical follow-up studies are necessary to validate our findings and to determine the long-term impact of using this patient- specific system.
Bei den sehr häufigen Sprunggelenksfrakturen von Typ Weber-B und –C ist oftmals nur eine limitierte Belastung für die ersten 6 postoperativen Wochen möglich, was die funktionelle Nachbehandlung erschwert. Dies führt
wahrscheinlich zu einer Steigerung der arbeitsunfähigkeitsdauer. Die aktivkontrollierte
Nachbehandlung bietet unserer Meinung nach ein standarisiertes Verfahren, das eine selbstständige, regelmäßige und sichere Handhabung erlaubt, welche man in der Rehabilitation von operativ versorgten
Sprunggelenksfrakturen nutzen könnte. Das Ziel der Studie war herauszufinden, ob der Einsatz einer Aktiv-kontrollierten Bewegungsschiene (ACM) nach operativ versorgten Sprunggelenksbrüchen des TypesDanis-
Weber-B und -C mit der Notwendigkeit einer Teilbelastung von 6 Wochen postoperativ einen Einfluss auf die Ergebnisse nach 6 und 12 Wochen hat. In der Literatur wurde keine Studie über den Einfluss einer solchen
Bewegungsschiene im Vergleich zu einer alleinigen Physiotherapie auf den Ergebnissen nach operativ versorgten Sprunggelenksbrüchen gefunden. Als
einzige Studie dieser Art haben wir herausgefunden, dass dies zu einer besseren Funktion des verletzten Sprunggelenkes und zu einer kürzeren
Arbeitsunfähigkeitsdauer führt. Dadurch kann ein sozioökonomischer Vorteil erzielt werden.
Bouldern ist eine noch relativ junge Trendsportart aus der Familie des Klettersports, die in den letzten Jahren starken Zuwachs gewonnen hat. Es gibt bisher wenig Literatur zu Verletzungen durch Bouldern generell und insbesondere zu Indoor-Bouldern. Das Ziel dieser Studie war Daten zu Verletzungshäufigkeit, -schwere und -lokalisation durch Indoor-Bouldern zu erheben sowie den Einfluss von potenziell das Verletzungsrisiko modulierenden Faktoren zu untersuchen.
Mittels eines Online-Fragebogens wurden Boulderer retrospektiv zu anthropometrischen Daten, potenziell risikomodulierendem Verhalten sowie Verletzungen in der Vergangenheit befragt. Anschließend wurde monatlich prospektiv über ein Jahr das Auftreten neuer Verletzungen erhoben. Zusätzlich wurden Patienten der Notaufnahme und Klettersprechstunde mit Verletzungen durch Indoor-Bouldern zu Diagnose, Unfallhergang sowie potenziell risikomodulierendem Verhalten befragt.
Knapp 60% aller Probanden hatten in der Vergangenheit bereits mindestens eine Verletzung erlitten, 44% eine Verletzung, die eine ärztliche Konsultation erforderte. Während der prospektiv beobachteten 12 Monate trat bei 44% der Probanden mindestens eine Verletzung durch Indoor-Bouldern auf, davon 78% im UIAA Schweregrad 1, 19% im Schweregrad 2 und 3% im Schweregrad 3. Die obere Extremität war von 63% aller Verletzungen betroffen, die untere Extremität von 23%. Verletzungen der unteren Extremität waren häufiger im UIAA Schweregrad ≥ 2 klassifiziert (p = 0,007).
Probanden, die Bouldern erst seit maximal einem Jahr betrieben, hatten ein erhöhtes Risiko für Verletzungen der unteren Extremität (p = 0,027). Keine der untersuchten protektiven Maßnahmen inklusive Spotten konnten das Verletzungsrisiko senken. Das Nutzen von Kletterschuhen mit starkem Downturn und Vorspann erhöhte das Risiko für Verletzungen im UIAA Schweregrad ≥ 2 (p = 0,003). Verletzungen der Patienten aus Notaufnahme und Klettersprechstunde waren in 5,1% im UIAA Schweregrad 1, 48,7% im Schweregrad 2 und 46,2% im Schweregrad 3. Verletzungen der unteren Extremität waren häufiger im Schweregrad 3 (p = 0,015).
Verletzungen durch Indoor Bouldern sind häufig, der Großteil erfordert jedoch keine medizinische Behandlung. Verletzungen der unteren Extremität sind gehäuft in einem höheren Schweregrad. Die untersuchten Präventivmaßnahmen senkten das Verletzungsrisiko nicht. Einsteigerkurse sollten insbesondere sicheres Abspringen und Stürzen trainieren. Das Nutzen eines weiteren Paares Kletterschuhe ohne starken Downturn und Vorspann für das Training scheint ratsam. Zukünftige Forschung sollte sich der Verletzungsprävention insbesondere durch Stürzen und Abspringen widmen.
The use of human adipose-derived mesenchymal stem cells (ASCs) for cell-based therapeutic approaches, in terms of repair and regeneration of various tissues and organs, offers an alternative therapeutic tool in the field of regenerative medicine. The ability of ASCs to differentiate along mesenchymal lineages is not the only property that makes these cells particularly attractive for therapeutic purposes. Their promising functions in promoting angiogenesis, reducing inflammation as well as in functional tissue restoration are largely related to the trophic effects of a broad panel of secreted cytokines and growth factors. However, in cell-based approaches, the cell-loaded construct often is exposed to an ischemic microenvironment characterized by severe oxidative and nutritional stress after transplantation due to the initial lack of vascular connection, resulting in reduced cell viability and altered cell behaviour. Therefore, the effective use of ASCs in regenerative medicine first requires a comprehensive characterization of the cells in terms of their viability, differentiation capacity and especially their secretory capabilities under ischemia-mimicking conditions in order to better understand their beneficial role. Accordingly, in the first part of this work, ASCs were investigated under different ischemic conditions, in which cells were exposed to both glucose and oxygen deprivation, with respect to viability and secretory function. Using mRNA gene expression analysis, significantly higher expression of selected angiogenic, anti-apoptotic and immunomodulatory factors (IL-6, VEGF, STC-1) could be demonstrated under harsh ischemic conditions. These results were reflected at the protein expression level by a significantly increased secretion of these factors. For stanniocalcin-1 (STC-1), a factor not yet described in ASCs, a particularly high expression with significant secreted amounts of the protein could be demonstrated under harsh ischemic conditions. Thus, the first part of this work, in addition to the characterization of the viability, provided first insights into the secretory response of ASCs under ischemic conditions.
The response of ASCs to glucose deficiency in combination with severe hypoxia has been little explored to date. Thus, the focus of the second part of this work was on a more detailed investigation of the secretory response of ASCs under glucose and oxygen deprivation. For a more comprehensive analysis of the secretion profile, a cytokine antibody array was performed, which allowed the detection of a broad panel of secreted angiogenic factors
(IL-8, ANG), matrix-regulating proteins (TIMP-1, TIMP-2), chemokines (MCP-1/CCL2,
IP-10/CXCL 10) and other factors under ischemic conditions. To verify these results, selected factors were examined using ELISA. The analysis revealed that the secretion of individual factors (e.g., STC-1, VEGF) was significantly upregulated by the combination of glucose and oxygen deprivation compared to oxygen deprivation alone.
In order to investigate the impact of the secretome of ischemic ASCs on cell types involved in tissue regeneration, the effect of conditioned medium of ischemia-challenged ASCs on both endothelial cells and fibroblasts was investigated in subsequent experiments. Significantly increased viability and tube formation of endothelial cells as well as activated migration of fibroblasts by the secreted factors of ischemic ASCs could be demonstrated. A direct correlation of these effects to STC-1, which was significantly upregulated under ischemic conditions and has been described as a regulator of key cellular functions, could not be verified.
The particular secretory capacity of ASCs provides a valuable tool for cell-based therapies, such as cell-assisted lipotransfer (CAL), where by enriching fat grafts with isolated ASCs, a significantly improved survival rate of the transplanted construct is achieved with less resorption of the fat tissue as well as a reduction in adverse implications, such as fibrosis and cyst formation. In order to better understand the function of ASCs in CAL, an autologous transwell-based lipograft-ASC co-culture was established in the last part of this work, in which first investigations showed a markedly increased secretion of VEGF compared to lipografts without added ASCs. As the stability rate of the fat tissue and thus the success of CAL is presumably also dependent on the preparation of the tissue before transplantation, the conventional preparation method of fat tissue for vocal fold augmentation in laryngoplasty was additionally evaluated in vitro in a pilot experiment. By analyzing the viability and tissue structure of the clinically prepared injection material, a large number of dead cells and a clearly damaged tissue structure with necrotic areas could be demonstrated. In comparison, the preparation method of the fat tissue established in this work as small tissue fragments was able to provide a clearly intact, vital, and vascularized tissue structure. This type of adipose tissue preparation represents a promising alternative for clinical vocal fold augmentation.
In conclusion, the results of this work contribute to a comprehensive characterization of ASCs under ischemic conditions, such as those prevalent at the transplantation site or in tissue regeneration. The results obtained, especially on the secretory capacity of ASCs, provide new insights into how ASCs mediate regenerative effects in an ischemic milieu and why their use for therapeutic purposes is highly attractive and promising.
Ischemia-like stress conditions stimulate trophic activities of adipose-derived stromal/stem cells
(2020)
Adipose-derived stromal/stem cells (ASCs) have been shown to exert regenerative functions, which are mainly attributed to the secretion of trophic factors. Upon transplantation, ASCs are facing an ischemic environment characterized by oxygen and nutrient deprivation. However, current knowledge on the secretion capacity of ASCs under such conditions is limited. Thus, the present study focused on the secretory function of ASCs under glucose and oxygen deprivation as major components of ischemia. After exposure to glucose/oxygen deprivation, ASCs maintained distinct viability, but the metabolic activity was greatly reduced by glucose limitation. ASCs were able to secrete a broad panel of factors under glucose/oxygen deprivation as revealed by a cytokine antibody array. Quantification of selected factors by ELISA demonstrated that glucose deprivation in combination with hypoxia led to markedly higher secretion levels of the angiogenic and anti-apoptotic factors IL-6, VEGF, and stanniocalcin-1 as compared to the hypoxic condition alone. A conditioned medium of glucose/oxygen-deprived ASCs promoted the viability and tube formation of endothelial cells, and the proliferation and migration of fibroblasts. These findings indicate that ASCs are stimulated by ischemia-like stress conditions to secrete trophic factors and would be able to exert their beneficial function in an ischemic environment.
Die Anzahl an Fahrradfahrern steigt in allen Altersgruppen. Mit zunehmender Popularität erhöht sich die Anzahl an Unfällen mit zum Teil schweren Verletzungen. Im Zuge dessen stellt sich die Frage, welchen Einfluss das Alter auf die Art und Schwere der Verletzungen, die Überlebenswahrscheinlichkeit und die Krankenhausverweildauer bei schwerverletzten Fahrradfahrern hat.
Methoden: Es wurde eine retrospektive Auswertung der Daten des TraumaRegisters DGU® der Jahre 2010-2019 durchgeführt. Alle schwerverletzten Fahrradfahrer mit einem MAIS 3+ (N=14.651) im TR-DGU wurden in diese Studie eingeschlossen und die vorliegenden Parameter ausgewertet. Es erfolgte eine Unterteilung in vier Altersgruppen (20 - 59, 60 - 69, 70 - 79 und ≥ 80 Jahre).
Ergebnisse: Verletzungen des Schädels traten mit 64,2% mit Abstand am häufigsten auf. Es zeigte sich eine deutliche Zunahme der schweren Kopfverletzungen in der Gruppe der über 60-Jährigen. Mit steigendem Alter nahm des Weiteren die Wahrscheinlichkeit einer präklinischen Intubation, die Katecholaminpflichtigkeit, die Intensiv- und Krankenhausverweildauer sowie die Sterblichkeit zu.
Schlussfolgerung: Kopfverletzungen stellen die häufigste schwere Verletzung bei Fahrradfahrern dar. Da das Helmtragen nicht erfasst wird kann auf dessen Effektivität kein Rückschluss gezogen werden. Ein höheres Alter korreliert des Weiteren mit einer höheren Sterblichkeit, stellt jedoch keinen unabhängigen Risikofaktor zum Versterben bei einem schwerverletzten Patienten dar.
Background
Postoperative pulmonary complications (PPCs) increase morbidity and mortality of surgical patients, duration of hospital stay and costs. Postoperative atelectasis of dorsal lung regions as a common PPC has been described before, but its clinical relevance is insufficiently examined. Pulmonary electrical impedance tomography (EIT) enables the bedside visualization of regional ventilation in real-time within a transversal section of the lung. Dorsal atelectasis or effusions might cause a ventral redistribution of ventilation. We hypothesized the existence of ventral redistribution in spontaneously breathing patients during their recovery from abdominal and peripheral surgery and that vital capacity is reduced if regional ventilation shifts to ventral lung regions.
Methods
This prospective observational study included 69 adult patients undergoing elective surgery with an expected intermediate or high risk for PPCs. Patients undergoing abdominal and peripheral surgery were recruited to obtain groups of equal size. Patients received general anesthesia with and without additional regional anesthesia. On the preoperative, the first and the third postoperative day, EIT was performed at rest and during spirometry (forced breathing). The center of ventilation in dorso-ventral direction (COVy) was calculated.
Results
Both groups received intraoperative low tidal volume ventilation. Postoperative ventral redistribution of ventilation (forced breathing COVy; preoperative: 16.5 (16.0–17.3); first day: 17.8 (16.9–18.2), p < 0.004; third day: 17.4 (16.2–18.2), p = 0.020) and decreased forced vital capacity in percentage of predicted values (FVC%predicted) (median: 93, 58, 64%, respectively) persisted after abdominal surgery. In addition, dorsal to ventral shift was associated with a decrease of the FVC%predicted on the third postoperative day (r = − 0.66; p < 0.001). A redistribution of pulmonary ventilation was not observed after peripheral surgery. FVC%predicted was only decreased on the first postoperative day (median FVC%predicted on the preoperative, first and third day: 85, 81 and 88%, respectively). In ten patients occurred pulmonary complications after abdominal surgery also in two patients after peripheral surgery.
Conclusions
After abdominal surgery ventral redistribution of ventilation persisted up to the third postoperative day and was associated with decreased vital capacity. The peripheral surgery group showed only minor changes in vital capacity, suggesting a role of the location of surgery for postoperative redistribution of pulmonary ventilation.
In dieser Studie wurden Daten zur minimalinvasiven dorsalen Versorgung instabiler Frakturen der thorakolumbalen Wirbelsäule in Kombination mit Kyphoplastie erhoben. Das Patientenkollektiv umfasst 64 Patienten, welche im Zeitraum von 6/2009 bis 5/2011 an 67 Frakturen versorgt wurden. Das Durchschnittsalter bei Operation betrug 71,3 ± 8,9 Jahre. Es wurden hierzu die mono- und bisegmentalen Grund-Deckplatten-Winkel präoperativ, postoperativ sowie an drei Nachuntersuchungszeitpunkten (6w, 3–6m, >9m) bestimmt. Weiterhin wurden mittels der Visuellen-Analog-Skala die Beschwerden vor dem Unfall und unmittelbar vor der Operation retrospektiv erhoben. Das funktionelle Ergebnis wurde am dritten Nachuntersuchungszeitpunkt mittels der VAS-Pain und des VAS-Wirbelsäulenscores der Arbeitsgemeinschaft „Wirbelsäule“ der DGU ermittelt. Außerdem wurde nach einer regelmäßigen Schmerzmitteleinnahme zu den Zeitpunkten „vor dem Unfall“, „direkt nach dem Unfall“ und „zurzeit“ gefragt.
Es konnten in anderen Studien schon einige Vorteile der minimalinvasiven dorsalen Stabilisierung hinsichtlich eines geringeren Blutverlustes, eines geringeren Gewebetraumas mit weniger postoperativer Schmerzen, einer besseren postoperativen Muskelfunktion, eines besseren kosmetischen Ergebnisses, schnellerer Mobilisierung sowie geringeren operativen Komplikationen gezeigt werden. Bisher gibt es aber keine Langzeitdaten, welche die funktionellen Ergebnisse und die Wiederaufrichtung oder den Korrekturverlust einer minimalinvasiven dorsalen Instrumentierung mit zeitgleicher Kyphoplastie von traumatischen Frakturen der thorakalen und lumbalen Wirbelsäule beschreiben.
Hierbei konnten zu einem offen operierten Vergleichskollektiv keine signifikanten Unterschiede bzgl. der Wiederaufrichtung (5.2 ± 5.2 Grad perkutan vs. 6.4 ± 3.3 Grad offen, GDW bisegmental ermittelt) und des Korrekturverlustes des Grund-Deckplatten-Winkels gefunden werden (5.2 ± 5.6 Grad perkutan vs. 6.1 ± 2.4 Grad offen bei 3. NU, GDW bisegmental ermittelt). Signifikante Unterschiede ergaben sich aber bei den funktionellen Ergebnissen (VAS-Wirbelsäulenscore der Arbeitsgemeinschaft „Wirbelsäule“ der DGU) zugunsten des minimalinvasiv versorgten Kollektivs zum Zeitpunkt der dritten Nachuntersuchung.
In der Plastischen Chirurgie erfordert die Rekonstruktion von ästhetisch anspruchsvollen Bereichen in vielen Fällen die Wiederherstellung von subkutanem Fettgewebe. Neben chirurgischen Rekonstruktionen könnte das Tissue Engineering von Fettgewebe einen wertvollen Beitrag leisten. Jedoch bringt es vielschichtige Herausforderungen mit sich und ist zum aktuellen Zeitpunkt nur limitiert möglich. Ein Ansatz ist die Schaffung einer Trägermatrix zur Besiedelung und Differenzierung von Stammzellen. Auf dieser Basis sollten in der vorliegenden Arbeit zwei Teilbereiche untersucht werden. In dem ersten Teilbereich erfolgten Untersuchungen verschiedener Gewinnungsmethoden von ASCs aus dem subkutanen Fettgewebe bezogen auf ihr Effizienz. Die untersuchten Liposuktionstechniken zeigten eine deutlich höhere Effizienz gegenüber der mechanischen Gewinnungsmethode bezogen auf die gewonnene Zellzahl. In den Viabilitätsuntersuchungen zeigte sich eine ähnliche Tendenz. ASCs aller drei Gewinnungsmethoden proliferierten durchaus gleich gut, jedoch zeigten die histologischen und quantitativen Adipogeneseuntersuchungen tendenziell mehr Lipidbildung bei den Liposuktionstechniken.
Das übergeordnete Ziel des zweiten Abschnittes dieser Arbeit war es eine Trägermatrix auf Hyaluronsäure-Basis mit dem vielseitig modifizierbarem Crosslinker Polyglycidol zu untersuchen, sie mit mesenchymalen Stammzellen aus dem Fettgewebe zu besiedeln und diese adipogen zu differenzieren. Des Weiteren erfolgten erste Versuche die Hydrogele mit funktionellen Gruppen zu modifizieren um eine Verbesserung der Adhäsion der Zellen im Hydrogel zu erreichen. Die unmodifizierten Hydrogele waren zu jeder Zeit stabil in ihrer Form und zeigten nach Besiedelung mit ASCs eine gleichmäßige Verteilung der Zellen im Gel. Auch ließ sich die Adipogenese histologisch visualisieren und biochemisch bestätigen. Die inkorporierten Peptide brachten eine peptidabhängige und konzentrationsabhängige Veränderung der Zellverteilung im Hydrogel. Eine Steigerung der Funktionalität der Zellen bezogen auf das Überleben und die Adipogenese konnte in diesen ersten Versuchen noch nicht gezeigt werden.
Generell zeigt sich eine Eignung der hyaluronsäurebasierten mit Polyglycidol-verlinkten Hydrogele für das Tissue Engineering von Fettgewebe. Weitere Untersuchungen bezüglich der Modifikation der Hydrogele mit adhäsiven und adipogenen funktionellen Gruppen bietet sich daher an und könnte ein fettgewebsähnliches Umgebungsmilieu hervorbringen.
Background
To cover soft tissue defects, the perforator-based propeller flap offers the option to rotate healthy tissue into complex wounds. By rotating the flap, the perforator is torqued. As a result, perfusion changes are possible.
Methods
A retrospective data analysis of patients was done, who received a propeller flap to cover soft tissue defects of the lower extremity as well as a peri- and postoperative perfusion monitoring with a laser-Doppler-spectrophotometry system. Additionally, patient-specific data were collected.
Results
Seven patients were identified. Four patients experienced early complications, two epidermolysis of the distal flap areas, three wound healing disorders, and one partial flap necrosis. Intraoperative perfusion monitoring showed a decline of blood flow after incision of the flap, especially at distal flap site. In case of complications, there were prolonged blood flow declines up to the first postoperative day.
Conclusion
Torqueing the perforator by rotating the flap can cause an impairment in inflow and outflow. If the impairment is prolonged, perfusion-associated complications are possible. The identification of a viable perforator is particularly important. In addition, a conservative postoperative mobilization is necessary to compensate for the impaired and adapting outflow.
Bei vorliegender Studie wurde eine statistische Datenanalyse auf der Basis einer retrospektiven Untersuchung durchgeführt. Die Stichprobe bestand aus 40 Patienten, welche im Zeitraum 01/2008 bis 12/2013 bei offenen Unterschenkelfrakturen mit lappenpflichtigen Weichteildefekten behandelt wurden. Den Endpunkt der statistischen Auswertung bildete die Ausheilung der Fraktur oder die Ausbildung einer Pseudarthrose. Von 40 Patienten entwickelten 35 % der Patienten (n=14) eine Pseudarthose, während es bei 65 % der Patienten (n=26) zu einer Ausheilung der Fraktur kam. Bei Pat. mit Pseudarthrose musste signifikant häufiger eine Spongiosaplastik durchgeführt werden, als bei Pat. ohne Pseudarthrose. Ein wichtiges Ergebnis der Studie bezieht sich auf den Zeitpunkt der Lappenplastik nach der definitiven Osteosynthese. Es zeigte sich, dass bei Pat. ohne Pseudarthrose die Lappenplastik tendenziell später durchgeführt wurde, als bei Patienten mit Pseudarthrose. Dieses Ergebnis widerspricht der chirurgischen Intuition, die Weichteilrekonstruktion so schnell wie möglich durchzuführen. Durch die Möglichkeit der Wundversorgung mit einer VAC-Therapie (Unterdrucktherapie) konnte jedoch eine Entschleunigung der Dringlichkeit der Weichteilrekonstruktion erreicht werden. Daher ist abzuleiten, dass die Weichteilrekonstruktion mittels Lappenplastik erst zu einem Zeitpunkt erfolgen sollte, wenn die Gesamtsituation des Patienten die günstigsten Voraussetzungen für die Heilung bietet. Neben dem Allgemeinzustand müssen auch lokale Faktoren wie Schwellungszustand der Extremität und Keimfreiheit der Wunde beachtet werden. Ein weiteres Ergebnis mit einer statistisch signifikanten Tendenz liefert die Variable „Typ der Lappenlastik“. Pat. ohne Pseudarthrose hatten fast jeweils zu einem Drittel lokale fasziokutane Lappen, gestielte Muskellappen und freie Lappen. Bei Patienten mit Pseudarthrose hingegen wurden keine gestielten Muskellappen verwenden.
Perspektive: Durch die VAC-Therapie konnte die Dringlichkeit von Weichteilrekonstruktionen vom emergency-free flap hin zu einer früh-elektiven Operation verschoben werden. Dies könnte langfristig die Sicherheit des Gewebetransfers verbessern.
Die Verletzungsprävention hat im Profisport deutlich an Bedeutung gewonnen. Die medizinische Eingangsuntersuchung könnte um einen sportartspezifischen Leistungstest erweitert werden, um relevante Leistungs- und Funktionsdefizite zu detektieren, die das Auftreten von Verletzungen begünstigen. In einer prospektiven Kohortenstudie über fünf aufeinanderfolgende Spielzeiten wurde hierzu der Kader einer Basketball-Profimannschaft im Rahmen der medizinischen Eingangsuntersuchung einem modifizierten NBA Combine Test unterzogen. Die in den durchgeführten Korrelationsanalysen ermittelten Ergebnisse zeigten tendenziell ein erhöhtes Verletzungsrisiko bei Athleten mit Defiziten in Agilität und Ausdauer. Außerdem konnten positionsspezifische Einflüsse auf das Verletzungsgeschehen festgestellt werden. Einzelne Verletzungen schienen sich jedoch der Einflussnahme der Athleten weitestgehend zu entziehen. Insgesamt ist die Durchführung eines basketballspezifischen Leistungstests als Erweiterung der medizinischen Eignungsuntersuchung sinnvoll um Funktionsdefizite aufzuzeigen und Verletzungsrisiken zu senken. Außerdem können die erhobenen Basiswerte in der Rehabilitation nach aufgetretener Verletzung zur Bestimmung des individuellen Zeitpunkt eines Return-to-Play/-Competition genutzt werden.
There is a variation of the total number of distinct bones in the human in the literature. This difference is mainly caused by the variable existence of sesamoid bones. Sesamoid bones at the first MTP are seen regularly. In contrast additional sesamoid bones at the divond to fifth MTP are rare. We report a case of additional sesamoid bones at every metatarsophalangeal joint (MTP) of both feet.
A 22-year-old female Caucasian presented with weight-dependent pain of the divond MTP of the left foot. In the radiographs of both feet additional sesamoid bones at every MTP could be seen. This case reports a very rare variation in human anatomy. A similar case has not been displayed to the academic society and therefore should be acknowledged.
Purpose. Copal\(^®\) spacem is a new PMMA bone cement for fabricating spacers. This study compares elution of gentamicin, elution of vancomycin, and compressive strength of Copal\(^®\) spacem and of Palacos\(^®\) R+G at different vancomycin loadings in the powder of the cements. We hypothesized that antibiotic elution of Copal\(^®\) spacem is superior at comparable compressive strength. Methods. Compression test specimens were fabricated using Copal\(^®\) spacem manually loaded with 0.5 g gentamicin and additionally 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (COP specimens) and using 0.5 g gentamicin premixed Palacos\(^®\) R+G manually loaded with 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (PAL specimens). These specimens were used for determination of gentamicin and vancomycin elution (in fetal calf serum, at 22°C) and for determination of compressive strength both prior and following the elution tests. Results. Cumulative gentamicin concentrations (p < 0.005) and gentamicin concentration after 28 days (p ≤ 0.043) were significantly lower for COP specimens compared to PAL specimens. Cumulative vancomycin concentrations were significantly higher (p ≤ 0.043) for COP specimens after the second day. Vancomycin concentrations after 28 days were not significantly higher for the Copal specimens loaded with 2 g and 4 g of vancomycin. Compressive strength was not significantly different between COP specimens and PAL specimens before elution tests. Compressive strength after the elution tests was significantly lower (p = 0.005) for COP specimens loaded with 2 g of vancomycin. Conclusion. We could not demonstrate consistent superior antibiotic elution from Copal\(^®\) spacem compared to Palacos\(^®\) R+G for fabricating gentamicin and vancomycin loaded spacers. The results do not favor Copal\(^®\) spacem over Palacos\(^®\) R+G for the use as a gentamicin and vancomycin biantibiotic-loaded spacer.
In dieser Studie wird die biomechanische Stabilität des anterioren subkutanen Fixateur Interne (USS II Polyaxiales- bzw. Click’X System) zur Stabilisierung der vorderen Beckenringverletzung mit der des supraacetabulären Fixateur Externe verglichen.
An 36 Beckenmodellen aus Polyurethanschaum wurden instabile Beckenringverletzungen generiert. Diese wurden zunächst posterior mit je zwei sakroiliakalen Schrauben und anterior jeweils mit einem der drei genannten Fixateure versorgt und dann im Einbeinstand für je 1000 Zyklen mit 300, 400 und 500 N be- und entlastet.
Statistisch zeigt sich zwischen den drei Gruppen kein signifikanter Unterschied für die Stabilität.
Mit geringeren Komplikationsraten und vergleichbarer Stabilität bietet der anteriore subkutane Fixateur Interne klinisch sowie biomechanisch eine Alternative zum Fixateur Externe.
Zudem besteht die Forderung nach einem für die Beckenringfixation konzipierten subkutanen Fixations-System, das unerwünschte Bewegungsfreiheiten des Titanbügels verhindert und damit Risiken für die Patienten minimiert.
Improved treatment options for the degenerative joint disease osteoarthritis (OA) are of major interest, since OA is one of the main sources of disability, pain, and socioeconomic burden worldwide [202]. According to epidemiological data, already 27 million people suffer from OA in the US [23]. Moreover, the WHO expects OA to be the fourth most common cause of disability in 2020 [203], illustrating the need for effective and long-lasting therapy options of severe cartilage defects. Despite numerous clinically available products for the treatment of cartilage defects [62], the development of more cartilage-specific materials is still at the beginning.
Hyaluronic acid (HA) is a major component of the cartilaginous extracellular matrix (ECM) and inherently creates a cell-friendly niche by providing cell attachment and migration sites. Furthermore, it is known that the functional groups of HA are well suited for chemical modification. These characteristics render HA an attractive material for hydrogel-based tissue engineering approaches. Poly(glycidol) (PG) as chemical crosslinker basically features similar chemical characteristics as the widely used poly(ethylene glycol) (PEG), but provides additional side groups at each repeating unit that can be further chemically functionalized. With the introduction of PG as multifunctional crosslinker for HA gels, a higher cross-linking density and, accordingly, a greater potential for biomimetic functionalization may be achieved. However, despite the mentioned potential benefits, PG has not been used for cartilage regeneration approaches so far.
The initial aim of the study was to set up and optimize a HA-based hydrogel for the chondrogenic differentiation of mesenchymal stromal cells (MSCs), using different amounts and variations of cross-linkers. Therefore, the hydrogel composition was optimized by the utilization of different PEG diacrylate (PEGDA) concentrations to cross-link thiol-modified HA (Glycosil, HA-SH) via Michael addition. We aimed to generate volumestable scaffolds that simultaneously enable a maximum of ECM deposition. Histological and biochemical analysis showed 0.4% PEGDA as the most suitable concentration for these requirements (Section 5.1.2).
In order to evaluate the impact of a differently designed cross-linker on MSC chondrogenesis, HA-SH was cross-linked with PEGTA (0.6%) and compared to PEGDA (0.4%) in a next step. Following this, acrylated PG (PG-Acr) as multifunctional cross-linker alternative to acrylated PEG was evaluated. It provides around five times more functional groups when utilized in PG-Acr (0.6%) HA-SH hydrogels compared to PEGTA (0.6%) HA-SH hydrogels, thus enabling higher degrees of biomimetic functionalization. Determination of cartilage-specific ECM components showed no substantial differences between both cross-linkers while the deposition of cartilaginous matrix appeared more homogeneous in HA-SH PG-Acr gels. Taken together, we were able to successfully increase the possibilities for biomimetic functionalization in the developed HA-SH hydrogel system by the introduction of PG-Acr as cross-linker without negatively affecting MSC chondrogenesis (Section 5.1.3).
The next part of this thesis focused extensively on the biomimetic functionalization of PG-Acr (0.6%) cross-linked HA-SH hydrogels. Here, either biomimetic peptides or a chondrogenic growth factor were covalently bound into the hydrogels.
Interestingly, the incorporation of a N-cadherin mimetic (HAV), a collagen type II binding (KLER), or a cell adhesion-mediating peptide (RGD) yielded no improvement of MSC chondrogenesis. For instance, the covalent binding of 2.5mM HAV changed morphology of cell nuclei and reduced GAG production while the incorporation of 1.0mM RGD impaired collagen production. These findings may be attributed to the already supportive conditions of the employed HA-based hydrogels for chondrogenic differentiation. Most of the previous studies reporting positive peptide effects on chondrogenesis have been carried out in less supportive PEG hydrogels or in significantly stiffer MeHA-based hydrogels [99, 101, 160]. Thus, the incorporation of peptides may be more important under unfavorable conditions while inert gel systems may be useful for studying single peptide effects (Section 5.2.1).
The chondrogenic factor transforming growth factor beta 1 (TGF-b1) served as an example for growth factor binding to PG-Acr. The utilization of covalently bound TGF-b1 may thereby help overcome the need for repeated administration of TGF-b1 in in vivo applications, which may be an advantage for potential clinical application. Thus, the effect of covalently incorporated TGF-b1 was compared to the effect of the same amount of TGF-b1 without covalent binding (100nM TGF-b1) on MSC chondrogenesis. It was successfully demonstrated that covalent incorporation of TGF-b1 had a significant positive effect in a dose-dependent manner. Chondrogenesis of MSCs in hydrogels with covalently bound TGF-b1 showed enhanced levels of chondrogenesis compared to hydrogels into which TGF-b1 was merely mixed, as shown by stronger staining for GAGs, total collagen, aggrecan and collagen type II. Biochemical evaluation of GAG and collagen amounts, as well as Western blot analysis confirmed the histological results. Furthermore, the positive effect of covalently bound TGF-b1 was shown by increased expression of chondrogenic marker genes COL2A1, ACAN and SOX9. In summary, covalent growth factor incorporation utilizing PG-Acr as cross-linker demonstrated significant positive effects on chondrogenic differentiation of MSCs (Section 5.2.2).
In general, PG-Acr cross-linked HA hydrogels generated by Michael addition represent a versatile hydrogel platform due to their high degree of acrylate functionality. These hydrogels may further offer the opportunity to combine several biological modifications, such as the incorporation of biomimetic peptides together with growth factors, within one cell carrier.
A proof-of-principle experiment demonstrated the suitability of pure PG gels for studying single peptide effects. Here, the hydrogels were generated by the utilization of thiol-ene-click reaction. In this setting, without the supportive background of hyaluronic acid, MSCs showed enhanced chondrogenic differentiation in response to the incorporation of 1.0mM HAV. This was demonstrated by staining for GAGs, the cartilage-specific ECM molecules aggrecan and type II collagen, and by increased GAG and total collagen amounts shown by biochemical analysis. Thus, pure PG gels exhibit the potential to study the effects and interplay of peptides and growth factors in a highly modifiable, bioinert hydrogel environment.
The last section of the thesis was carried out as part of the EU project HydroZONES that aims to develop and generate zonal constructs. The importance of zonal organization has attracted increased attention in the last years [127, 128], however, it is still underrepresented in tissue engineering approaches so far. Thus, the feasibility of zonal distribution of cells in a scaffold combining two differently composed hydrogels was investigated. A HA-SH(FMZ) containing bottom layer was generated and a pure PG top layer was subsequently cast on top of it, utilizing both times thiol-ene-click reaction. Indeed, stable, hierarchical constructs were generated that allowed encapsulated MSCs to differentiate chondrogenically in both zones as shown by staining for GAGs and collagen type II, and by quantification of GAG amount. Thus, the feasibility of differently composed zonal hydrogels utilizing PG as a main component was successfully demonstrated (Section 5.4).
With the first-time utilization and evaluation of PG-Acr as versatile multifunctional cross-linker for the preparation of Michael addition-generated HA-SH hydrogels in the context of cartilage tissue engineering, a highly modifiable HA-based hydrogel system was introduced. It may be used in future studies as an easily applicable and versatile toolbox for the generation of biomimetically functionalized hydrogels for cell-based cartilage regeneration. The introduction of reinforcement structures to enhance mechanical resistance may thereby further increase the potential of this system for clinical applications.
Additionally, it was also demonstrated that thiol-ene clickable hydrogels can be used for the generation of cell-laden, pure PG gels or for the generation of more complex, coherent zonal constructs. Furthermore, thiol-ene clickable PG hydrogels have already been further modified and successfully been used in 3D bioprinting experiments [204]. 3D bioprinting, as part of the evolving biofabrication field [205], offers the possibilities to generate complex and hierarchical structures, and to exactly position defined layers, yet at the same time alters the requirements for the utilized hydrogels [159, 206–209]. Since a robust chondrogenesis of MSCs was demonstrated in the thiol-ene clickable hydrogel systems, they may serve as a basis for the development of hydrogels as so called bioinks which may be utilized in more sophisticated biofabrication processes.
Introduction
Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein meshwork the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release.
Methods
We employ minos-mediated integration cassette (MiMIC)-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system.
Results and discussion
Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13\(^{GFSTF}\) 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13\(^{GFSTF}\), Bruchpilot, and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13\(^{GFSTF}\) subclusters that move toward the AZ center during PHP with unaltered Unc-13\(^{GFSTF}\) protein levels.
Background
Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup.
Methods
We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma.
Results
Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture.
Conclusions
This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma.