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Determination of the effective dose of bone marrow mononuclear cell therapy for bone healing in vivo
(2020)
Introduction: Cell-based therapy by bone marrow mononuclear cells (BMC) in a large-sized bone defect has already shown improved vascularization and new bone formation. First clinical trials are already being conducted. BMC were isolated from bone marrow aspirate and given back to patients in combination with a scaffold within some hours. However, the optimal concentration of BMC has not yet been determined for bone healing. With this study, we want to determine the optimal dosage of the BMC in the bone defect to support bone healing.
Material and methods: Scaffolds with increasing BMC concentrations were inserted into a 5 mm femoral defect, cell concentrations of 2 × 106 BMC/mL, 1 × 107 BMC/mL and 2 × 107 BMC/mL were used. Based on the initial cell number used to colonize the scaffolds, the groups are designated 1 × 106, 5 × 106 and 1 × 107 group. Bone healing was assessed biomechanically, radiologically (µCT), and histologically after 8 weeks healing time.
Results: Improved bone healing parameters were noted in the 1 × 106 and 5 × 106 BMC groups. A significantly higher BMD was observed in the 1 × 106 BMC group compared to the other groups. Histologically, a significantly increased bone growth in the defect area was observed in group 5 × 106 BMC. This finding could be supported radiologically.
Conclusion: It was shown that the effective dose of BMC for bone defect healing ranges from 2 × 106 BMC/mL to 1 × 107 BMC/mL. This concentration range seems to be the therapeutic window for BMC-supported therapy of large bone defects. However, further studies are necessary to clarify the exact BMC-dose dependent mechanisms of bone defect healing and to determine the therapeutically effective range more precisely.
Purpose: Anaemia is one of the leading causes of death among severely injured patients. It is also known to increase the risk of death and prolong the length of hospital stay in various surgical groups. The main objective of this study is to analyse the anaemia rate on admission to the emergency department and the impact of anaemia on in-hospital mortality.
Methods: Data from the TraumaRegister DGU® (TR-DGU) between 2015 and 2019 were analysed. Inclusion criteria were age ≥ 16 years and most severe Abbreviated Injury Scale (AIS) score ≥ 3. Patients were divided into three anaemia subgroups: no or mild anaemia (NA), moderate anaemia (MA) and severe anaemia (SA). Pre-hospital data, patient characteristics, treatment in the emergency room (ER), outcomes, and differences between trauma centres were analysed.
Results: Of 67,595 patients analysed, 94.9% (n = 64,153) exhibited no or mild anaemia (Hb ≥ 9 g/dl), 3.7% (n = 2478) displayed moderate anaemia (Hb 7–8 g/dl) and 1.4% (n = 964) presented with severe anaemia (Hb < 7 g/dl). Haemoglobin (Hb) values ranged from 3 to 18 g/dl with a mean Hb value of 12.7 g/dl. In surviving patients, anaemia was associated with prolonged length of stay (LOS). Multivariate logistic regression analyses revealed moderate (p < 0.001 OR 1.88 (1.66–2.13)) and severe anaemia (p < 0.001 OR 4.21 (3.46–5.12)) to be an independent predictor for mortality. Further significant predictors are ISS score per point (OR 1.0), age 70–79 (OR 4.8), age > 80 (OR 12.0), severe pre-existing conditions (ASA 3/4) (OR 2.26), severe head injury (AIS 5/6) (OR 4.8), penetrating trauma (OR 1.8), unconsciousness (OR 4.8), shock (OR 2.2) and pre-hospital intubation (OR 1.6).
Conclusion: The majority of severely injured patients are admitted without anaemia to the ER. Injury-associated moderate and severe anaemia is an independent predictor of mortality in severely injured patients.
Aims: Understanding the orientation of fracture lines and mechanisms is the essential key to sufficient surgical therapy, but there is still a lack of visualization and teaching methods in traumatology and fracture theory. 3D-printed models offer easy approach to those fractures. This paper explains the use of the teaching possibility with 3-dimensional models of transitional fractures of the ankle.
Methods and results: For generating 3D printable models, already obtained CT data were used and segmented into its different tissues, especially parts concerning the fracture. After the segmentation process, the models were produced with FFF (fused filament fabrication) printing technology. The fracture models then were used for hands-on teaching courses in AO course (Arbeitsgemeinschaft für Osteosynthesefragen) of pediatric traumatology in 2020 in Frankfurt. In the course fracture anatomy with typical fracture lines, approaches, and screw placement could be shown, discussed and practiced.
Conclusion: The study shows the use of 3D-printed teaching models and helps to understand complicated fractures, in this case, transitional fractures of the ankle. The teaching method can be adapted to numerous other use cases.
Purpose: Total elbow arthroplasty (TEA) has evolved over the last years, with satisfactory early results, mainly not only in degenerative arthritis, but also increasingly after trauma. Outcome studies in recently published papers are mainly based on the range of motion (ROM), complication rate as well as patient-reported outcome scales and questionnaires. The purpose of this study was to add a new perspective with the “Purdue Pegboard” skill tests in a homogenous set of elderly trauma patients to contribute to a more precise objective outcome measurement in this specific population.
Methods: A retrospective review was performed on a consecutive cohort of all patients with age above 60 years that received TEA after trauma. Data from follow-up examinations over a standardized time-schedule within 2 years after TEA were included. Mayo Elbow Performance Score (MEPS), “Disability of Arm, Shoulder and Hand” (DASH) Questionnaire, ROM as well as test-scores using the Pegboard test were evaluated.
Results: Mean age was 76.0 years ± 10.3. Indications for TEA were posttraumatic arthrosis in 68.8% (n = 11) and extensive fractures that could not be reconstructed surgically in 31.3% (n = 5). The mean score of MEPS was 82.81 ± 16.63 and 29.18 ± 12.01 in the DASH. ROM presented with a mean of 109.7° ± 15.4. Patients demonstrated good, but marginally reduced test scores in the Pegboard skill tests in comparison with the healthy reference population. No relevant differences between the arm with and the arm without TEA (0.3 ± 3.6; p = 0.715) were noted after 2 years.
Conclusion: In the elderly trauma patient with complex fractures of the elbow, TEA is a good alternative to joint reconstruction using various osteosynthesis techniques. TEA is able to avoid revision surgery after open reduction and internal fixation of complex fractures. In cases of failed reconstruction, it is also a viable secondary procedure in posttraumatic arthrosis. Good outcomes in functionality and dexterity can be achieved. Skill tests like the Purdue Pegboard could add a valuable perspective in assessing functional outcomes after TEA.
Introduction: The aim of this article is to show a new concept of indication and application of the MUTARS® RS Cup System in primary and revision hip arthroplasty. This integrated system is applicable for different acetabular cup replacements in patients with acetabular fractures or instable defects, as well as periprosthetic acetabular fractures. The MUTARS® RS Cup System is a cementless revision cup for insertion into the acetabulum with an integrated polyethylene cup, which fits to a regular or bipolar head. This system replaces the conventional approach for acetabular revision with a Burch-Schneider ring, in which a normal polyethylene cup is cemented. This interface with its complications is avoided with this system of a titanium revision cup with integrated polyethylene cup. Steps of preoperative planning and the intraoperative implementation will be highlighted in this article.
Material and methods: This system was applied in 49 patients with 52 MUTARS® RS Cup Implantations in 30 males, 22 females, with an average age of 76,1 years (36,9–94,4 years).
Results and discussion: The system shows a good operative feasibility, as well as a reliable handling and safe method for stable treatment of non-reconstructable acetabular fractures or acetabular incongruencies and instabilities.
Background: Hemorrhagic shock can lead to intestinal damage with subsequent hyperinflammation and multiple organ dysfunction syndrome (MODS). The intestinal fatty acid-binding protein (I-FABP) is solely expressed in the intestine and is released extracellulary after tissue damage. This study evaluates the validity of I-FABP as an early biomarker to detect hemorrhagic shock and abdominal injury.
Patients and methods: Severely injured patients with an Injury Severity Score (ISS) ≥ 16 points and an age ≥ 18 years, admitted from January 2010 to December 2016, were included. Overall, 26 patients retrospectively presented with hemorrhagic shock to the emergency room (ER): 8 patients without abdominal injury ("HS noAbd") and 18 patients with abdominal injury ("HS Abd"). Furthermore, 16 severely injured patients without hemorrhagic shock and without abdominal injury ("noHS noAbd") were retrospectively selected as controls. Plasma I-FABP levels were measured at admission to the ER and up to 3 days posttraumatic (d1-d3).
Results: Median I-FABP levels were significantly higher in the "HS Abd" group compared with the "HS noAbd" group (28,637.0 pg/ml [IQR = 6372.4-55,550.0] vs. 7292.3 pg/ml [IQR = 1282.5-11,159.5], p < 0.05). Furthermore, I-FABP levels of both hemorrhagic shock groups were significantly higher compared with the "noHS noAbd" group (844.4 pg/ml [IQR = 530.0-1432.9], p < 0.05). The time course of I-FABP levels showed a peak on the day of admission with a subsequent decline in the post-traumatic course. Furthermore, significant correlations between I-FABP levels and clinical parameters of hemorrhagic shock, such as hemoglobin, lactate value, systolic blood pressure (SBP), and shock index, were found.The optimal cut-off level of I-FABP for detection of hemorrhagic shock was 1761.9 pg/ml with a sensitivity of 85% and a specificity of 81%.
Conclusion: This study confirmed our previous observation that I-FABP might be used as a suitable early biomarker for the detection of abdominal injuries in general. In addition, I-FABP may also be a useful and a promising parameter in the diagnosis of hemorrhagic shock, because of reflecting low intestinal perfusion.
Background: Sepsis frequently occurs after major trauma and is closely associated with dysregulations in the inflammatory/complement and coagulation system. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a dual role as an anti-fibrinolytic and anti-inflammatory factor by downregulating complement anaphylatoxin C5a. The purpose of this study was to investigate the association between TAFI and C5a levels and the development of post-traumatic sepsis. Furthermore, the predictive potential of both TAFI and C5a to indicate sepsis occurrence in polytraumatized patients was assessed. Methods: Upon admission to the emergency department (ED) and daily for the subsequent ten days, circulating levels of TAFI and C5a were determined in 48 severely injured trauma patients (injury severity score (ISS) ≥ 16). Frequency matching according to the ISS in septic vs. non-septic patients was performed. Trauma and physiologic characteristics, as well as outcomes, were assessed. Statistical correlation analyses and cut-off values for predicting sepsis were calculated. Results: Fourteen patients developed sepsis, while 34 patients did not show any signs of sepsis (no sepsis). Overall injury severity, as well as demographic parameters, were comparable between both groups (ISS: 25.78 ± 2.36 no sepsis vs. 23.46 ± 2.79 sepsis). Septic patients had significantly increased C5a levels (21.62 ± 3.14 vs. 13.40 ± 1.29 ng/mL; p < 0.05) and reduced TAFI levels upon admission to the ED (40,951 ± 5637 vs. 61,865 ± 4370 ng/mL; p < 0.05) compared to the no sepsis group. Negative correlations between TAFI and C5a (p = 0.0104) and TAFI and lactate (p = 0.0423) and positive correlations between C5a and lactate (p = 0.0173), as well as C5a and the respiratory rate (p = 0.0266), were found. In addition, correlation analyses of both TAFI and C5a with the sequential (sepsis-related) organ failure assessment (SOFA) score have confirmed their potential as early sepsis biomarkers. Cut-off values for predicting sepsis were 54,857 ng/mL for TAFI with an area under the curve (AUC) of 0.7550 (p = 0.032) and 17 ng/mL for C5a with an AUC of 0.7286 (p = 0.034). Conclusion: The development of sepsis is associated with early decreased TAFI and increased C5a levels after major trauma. Both elevated C5a and decreased TAFI may serve as promising predictive factors for the development of sepsis after polytrauma.
A 79 year old female patient was admitted to our emergency department with a fracture of the right medial femoral neck six days after a fall on her right side and a cemented hemiprosthesis was implanted. Five days later, she developed a hemorrhagic shock and was diagnosed with a delayed splenic rupture and the spleen was resected. Histopathological examination showed a delayed rupture of an otherwise normal spleen without signs of an underlying pathology. The outcome was fatal: In the postoperative course she developed pneumonia, three weeks later she succumbed due to multiple organ failure.
Even careful reevaluation of the case did not provide any clues to expect an injury of the spleen according to trauma mechanism.
This case shows that delayed splenic rupture of a normal spleen may occur even after a low energy trauma. Injury of the spleen should therefore always be considered, even with an uncharacteristic anamnesis. Physical examination after trauma should therefore always include a careful clinical evaluation. The clinical threshold for a FAST examination should be low.
The coincidence of a femoral neck fracture and a splenic rupture after a low energy trauma has not been reported before.
Background and Purpose. Leukocyte migration into alveolar space plays a critical role in pulmonary inflammation resulting in lung injury. Acute ethanol (EtOH) exposure exerts anti-inflammatory effects. The clinical use of EtOH is critical due to its side effects. Here, we compared effects of EtOH and ethyl pyruvate (EtP) on neutrophil adhesion and activation of cultured alveolar epithelial cells (A549). Experimental Approach. Time course and dose-dependent release of interleukin- (IL-) 6 and IL-8 from A549 were measured after pretreatment of A549 with EtP (2.5–10 mM), sodium pyruvate (NaP, 10 mM), or EtOH (85–170 mM), and subsequent lipopolysaccharide or IL-1beta stimulation. Neutrophil adhesion to pretreated and stimulated A549 monolayers and CD54 surface expression were determined. Key Results. Treating A549 with EtOH or EtP reduced substantially the cytokine-induced release of IL-8 and IL-6. EtOH and EtP (but not NaP) reduced the adhesion of neutrophils to monolayers in a dose- and time-dependent fashion. CD54 expression on A549 decreased after EtOH or EtP treatment before IL-1beta stimulation. Conclusions and Implications. EtP reduces secretory and adhesive potential of lung epithelial cells under inflammatory conditions. These findings suggest EtP as a potential treatment alternative that mimics the anti-inflammatory effects of EtOH in early inflammatory response in lungs.
Meeting abstract : Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2012), 23.10.-26.10.2012, Berlin.
Fragestellung: Die Behandlung langstreckiger Knochendefekte ist eine große Herausforderung. Die Masquelet-Technik zur Behandlung solcher Defekte ist eine zweizeitige Operationstechnik. Zuerst erfolgt die Insertion eines PMMA (Polymethylmethacrylat)-Zementspacers in den Knochendefekt, der die Bildung einer Membran induziert. Diese Membran enthält Wachstumsfaktoren und regenerative Zellen, die möglicherweise die Knochenheilung unterstützen. Nach einigen Wochen wird der Zementspacer entfernt und der induzierte Membranschlauch mit Beckenkammspongiosa aufgefüllt. Im weiteren Verlauf kommt es zu einer kompletten Knochenheilung. Ziele dieser Untersuchung waren die Etablierung der Masquelettechnik am Rattenmodell und die Definition eines Zeitpunkts, an welchem die Membran eine ausreichende Festigkeit sowie einen signifikanten Gehalt von Vorläuferzellen aufweist.
Methodik: Nach Genehmigung der Experimente wurden die Femura von 24 männlichen SD-Ratten osteotomiert. Die Lücke (10 mm) wurde mit PMMA-Zement aufgefüllt und mittels Miniplatte stabilisiert. Parallel wurden den Versuchstieren gleich große PMMA-Spacer subcutan unter die Rückenhaut implantiert. Nach 2, 4, bzw. 6 Wochen (W) erfolgte die Entnahme der Membranen. Ein Teil der Membran wurde für (immun)histologische Untersuchungen aufbereitet (CD34, vWF, van Giesson), ein Teil für die in vitro Kultur. Auswachsende Vorläuferzellen in vitro wurden über CD34 und STRO-1-Färbung nachgewiesen. Statistik: Mediane, Kruskal-Wallis-Test, p<0,05 ist signifikant.
Ergebnisse und Schlussfolgerungen: Im zeitlichen Verlauf nahmen die Vaskularisierung (vWF-positive Fläche [%]: 2 W: 1,8; 4 W:1.6 vs 6 W: 6,4), die Dicke der Membran ([µm]: 2 W: 350 vs 4W: 517, 6 W: 592) und der Bindegewebsanteil ([µm]: 2W: 201 vs 4W: 324, 6W: 404) signifikant zu. Der Hauptanteil elastischer Fasern war auf der dem Zement zugewandten Seite, Vaskularisierung war eher auf der Weichteil zugewandten Seite zu finden. Der Anteil CD34 positiver Zellen nahm signifikant ab (2W: 5%, 4 W: 4% vs 6 W: 1%). Auswachsende STRO-1 positive Zellen konnten nur in zweiwöchigen Membranen nachgewiesen werden. Ältere Membranen wiesen einen zunehmenden Anteil seneszenter Zellen auf. Subcutan induzierte Membranen waren vergleichbar, wiesen jedoch tendentiell eine geringere Dicke und keine STRO-1 positiven Zellen auf.
Mit dieser Studie wurde erstmalig die Induktion einer Membran nach Masquelet im Rattenmodell etabliert. Es konnte nachgewiesen werden, dass der strukturelle Aufbau sowie die zellulären Komponenten zeitlichen Änderungen unterliegen und der Ort der Induktion Einfluss auf die zellulären Komponenten der Membran hat. Junge Membranen (2W) enthielten CD34 und STRO-1 positive Zellen. 4W-Membranen enthielten nur CD34 positive Zellen wiesen aber einen signifikanten Bindegewebsanteil auf, der für eine erhöhte mechanische Stabilität spricht. Ob 2 bzw. 4 Wochen alte Membranen den Knochenheilungsprozess fördern, muss in weiterführenden Studien untersucht werden.