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Thomas Ferbert, Christina Münch, Sebastian Findeisen, William Pauly, Matthias Miska, Tobias Grossner, Michael C Tanner, Gerhard Schmidmaier, Lars Helbig Clinic for Trauma and Reconstructive Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Heidelberg, D-69118, GermanyCorrespondence: Lars Helbig, Clinic for Trauma and Reconstructive Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, Heidelberg, D-69118, Germany, Tel +496221/5635371, Fax +496221/5626300, Email lars.helbig@med.uni-heidelberg.dePurpose: A central aspect of the treatment of non-unions is the filling of bone defects. The quantity of available autologous bone for this purpose is limited. Alternatively, or additionally, bone substitutes may be used. The aim of this retrospective, single-center study including 404 non-unions in 393 patients is to investigate the effect of tricalcium phosphate (TCP) on the healing of non-unions. Furthermore, the influence of gender, age, smoking status, comorbidities, type of surgical procedure, presence of infection, and length of treatment was investigated.Methods: We evaluated three groups of patients. Group 1 received TCP + BG, group 2 received BG alone and group 3 received no augmentation. Bone stability was assessed 1 and 2 years after non-union revision surgery through analysis of radiographs using the Lane Sandhu Score. Scores ≥ 3 were rated as stable Other influencing factors were collected from the electronic medical record.Results: In 224 non-unions, bone defects were filled with autologous bone and TCP (TCP+BG). In 137 non-unions, bone defects were filled with autologous bone (BG), and in 43 non-unions presenting non-relevant defects, neither autologous bone nor TCP were used (NBG). After 2 years, 72.7% of the TCP+BG patients, 90.1% of the BG patients and 84.4% of the NBG patients achieved a consolidation score ≥ 3. Advanced age, presence of comorbidities and longer treatment period had a significantly negative effect on consolidation 1 year after surgery. Longer treatment periods also showed a negative significant effect after 2 years. It is notable that larger defects, mainly treated with the combination of autologous bone and TCP, showed similar healing rates to that of smaller defects after 2 years.Conclusion: The combination of TCP and autologous bone-grafts shows good results in the reconstruction of complicated bone-defects, but patience is required since the healing period exceeds 1 year in most patients.Keywords: non-unions, bone substitute, Lane Sandhu Score, tricalcium phosphate

Study design:A retrospective study reporting specific complications of certain skin flaps for treating pressure ulcers.Objectives:To describe the rate and type of complications after pressure ulcer surgery in patients with spinal cord injury.Setting:Germany, Rheinland Pfalz.Methods:We collected data from 352 patients treated with 421 skin flaps to determine the rate and type of complications of each skin flap used.Results:In this study, we analyzed the results of 421 skin flaps in 352 patients with a total of 657 pressure ulcers from January 2006 to December 2010. Our patients had ischial, pelvic, sacral, trochanteric and lower extremity ulcers. Ischial ulcers were most common, followed by sacral and trochanteric ulcers. There were 87 complications in 421 flaps, which was an overall rate of 21%. Suture line dehiscence was the most common complication with 27 cases (31%), followed by 22 cases of infection (25.2%), 17 cases of hematoma (19.5%), 12 cases of partial necrosis (13.7%) and 9 cases of total flap necrosis (10.3%).Conclusion:Pressure ulcers in spinal cord-injured patients are very common and difficult and expensive to treat. The high rate of complications and the associated costs suggest the importance of evaluating the efficacy of treatment options. Conservative procedures have been standardized, but there still has been limited success in establishing guidelines on how to manage complications arising from flap surgery. Our extensive documentation of flap plastics will be useful managing complications after the surgical treatment of pressure ulcers in spinal cord-injured patients. [ABSTRACT FROM AUTHOR]

Study design:A pilot study measuring the levels of serum-soluble CD95 ligand (CD95L) in eight spinal cord-injured patients.Objectives:To determine the soluble concentration of CD95L in spinal cord injury (SCI) patients after trauma.Methods:We collected blood samples from eight patients with acute traumatic SCI. Soluble CD95L serum levels were determined using an enzyme-linked immunosorbent assay. American Spinal Injury Association (ASIA) was determined according to ASIA classification. The patients were monitored, and venous blood was drawn after arrival at the hospital on the 1st and 3rd day and during the 1st, 2nd, 4th, 8th and 12th weeks after trauma.Results:The average patient age was 48.1 years (18-86 years). Three patients were paraplegic (two incomplete, one complete), five were quadriplegic (one complete, four incomplete). The serum concentration of soluble CD95L (sCD95L) decreased during the 1st week (41 ng l−1) and increased after the 2nd week in all eight patients. It peaked during the 4th week (68.5 ng l−1) and reached a plateau during the 12th week (76.2 ng l−1). There are many possible explanations for not being able to detect a statistical significance, one of course being the small sample size.Conclusion:Promising results for anti-CD95L therapy have already been documented in lab studies with rodents. Anti-CD95L blocks the pro-apoptotic and proinflammatory activity of membrane-bound CD95L during the acute phase of SCI. We observed that sCD95L levels are elevated during the subacute and intermediate phases of SCI. It would be of great interest to study a larger group of patients to determine whether higher sCD95 levels are correlated with improved or impaired neurological outcome or with increasing levels of autoimmune components in peripheral blood. [ABSTRACT FROM AUTHOR]

Background: An increased or decreased critical shoulder angle (CSA) is a known risk factor for osteoarthritis, lesions, and re-ruptures in the rotator cuff. A CSA greater than 35° correlates with degenerative rotator cuff tears, while a CSA of less than 30° correlates with osteoarthritis in the glenohumeral joint. The diagnostic gold standard for its determination is X-ray or MRI., Objectives: The primary objective of this research was to assess the viability of utilizing sonography imaging as a diagnostic tool to determine the modified critical shoulder angle (mCSA). This study aimed to investigate the feasibility and effectiveness of sonographic techniques in accurately diagnosing CSA compared to MRI., Study Design and Methods: A cohort study was carried out (level of evidence 3). The CSA (MRI) and the mCSA (ultrasound) were assessed retrospectively by two independent board-certified investigators in 109 patients with shoulder pain by MRI and musculoskeletal sonography. The CSA in the MRI dataset was determined using routine protocols and then compared to the values assessed using the modified sonography-assisted method (mCSA). Both results were analyzed with linear regression to determine a possible correlation. All investigations were performed by a DEGUM (German Society for Medical Ultrasound)-certified specialist in musculoskeletal sonography., Results: A total of 112 patients were included in this study, namely 40 female patients and 72 male patients with a mean age of 54.7 years at the time of the investigation. The mean CSA in MRI was 31.5° ± 3.899, and the mCSA in sonography was 30.1° ± 4.753. The inter- and intraobserver reliability for the CSA was factual with values of 0.993 and 0.967. The inter- and intraobserver reliability for mCSA was factual as well, with values of 0.989 and 0.948. The ANOVA analysis did not reveal a significant difference between the CSA and the mCSA values, and linear regression determined the R 2 value to be 0.358 with p < 0.05., Conclusions: Diagnosing the mCSA using sonography is a safe and valid method. No statistically significant differences between the results in MRI and sonography could be seen. Although this is a retrospective, single-center study including only Caucasian mid-Europeans, and with the known limitations of ultrasound imaging, it nevertheless shows that sonography can be used as a simple, cheap, and fast technique to assess a modified CSA, which shows very good correlation with the standard CSA without losing the diagnostic quality.

Background: Managing bone defects in non-union surgery remains challenging, especially in cases of large defects exceeding 5 cm in size. Historically, amputation and compound osteosynthesis with a remaining PMMA spacer have been viable and commonly used options. The risk of non-union after fractures varies between 2% and 30% and is dependent on various factors. Autologous bone grafts from the iliac crest are still considered the gold standard but are limited in availability, prompting consideration of artificial grafts., Objectives: The aims and objectives of the study are as follows: 1. To evaluate the radiological outcome of e.g., the consolidation and thus the stability of the bone (three out of four consolidated cortices/Lane-Sandhu-score of at least 3) by using S53P4-type bioactive glass (BaG) as a substitute material for large-sized bone defects in combination with autologous bone using the RIA technique. 2. To determine noticeable data-points as a base for future studies., Methods: In our clinic, 13 patients received bioactive glass (BaG) as a substitute in non-union therapy to promote osteoconductive aspects. BaG is a synthetic material composed of sodium, silicate, calcium, and phosphate. The primary endpoint of our study was to evaluate the radiological consolidation of bone after one and two years. To assess bone stabilization, we used a modified Lane-Sandhu score, considering only radiological criteria. A bone was considered stabilized if it achieved a minimum score of 3. For full consolidation (all four cortices consolidated), a minimum score of 4 was required. Each bone defect exceeded 5 cm in length, with an average size of 6.69 ± 1.92 cm., Results: The mean follow-up period for patients without final bone consolidation was 34.25 months, with a standard deviation of 14.57 months, a median of 32.00 months and a range of 33 months. In contrast, patients with a fully consolidated non-union had an average follow-up of 20.11 ± 15.69 months and a range of 45 months. Overall, the mean time from non-union surgery to consolidation for patients who achieved final union was 14.91 ± 6.70 months. After one year, six patients (46.2%) achieved complete bone consolidation according to the Lane-Sandhu score. Three patients (23.1%) displayed evident callus formation with expected stability, while three patients (23.1%) did not develop any callus, and one patient only formed a minimal callus with no expected stability. After two years, 9 out of 13 patients (69.2%) had a score of 4. The remaining four patients (30.8%) without expected stability either did not heal within two years or required a revision during that time., Conclusions: Bioactive glass (BaG) in combination with autologous bone (RIA) appears to be a suitable filler material for treating extensive non-unions of the femur and tibia. This approach seems to show non-inferiority to treatment with Tricalcium Phosphate (TCP). To ensure the success of this treatment, it is crucial to validate the procedure through a randomized controlled trial (RCT) with a control group using TCP, which would provide higher statistical power and more reliable results.

Background: The treatment of large-sized bone defects remains a major challenge in trauma and orthopaedic surgery. Although there are many treatment options, there is still no clear guidance on surgical management, and the influence of defect size on radiological and clinical outcome remains unclear due to the small number of affected patients. The aim of the present study was to determine the influence of defect size on the outcome of atrophic and infected nonunions of the tibia or the femur based on the diamond concept in order to provide recommendations for treatment guidance., Patients and Methods: All medical records, surgical reports, laboratory data and radiological images of patients treated surgically for atrophic or infected nonunions of the lower limbs (femur or tibia) between 1 January 2010 and 31 December 2020 were examined. Patients with proximal, diaphyseal or distal nonunions of the femur or tibia who were surgically treated at our institution according to the "diamond concept" and attended our standardised follow-up program were included in a database. Surgical treatment was performed as a one- or two-step procedure, depending on the type of nonunion. Patients with a segmental bone defect ≥5 cm were matched with patients suffering a bone defect <5 cm based on five established criteria. According to our inclusion and exclusion criteria, 70 patients with a bone defect ≥5 cm were suitable for analysis. Two groups were formed by matching: the study group (bone defect ≥5 cm; n = 39) and control group (bone defect <5 cm; n = 39). The study was approved by the local ethics committee (S-262/2017)., Results: The mean defect size was 7.13 cm in the study and 2.09 cm in the control group. The chi-square test showed equal consolidation rates between the groups (SG: 53.8%; CG: 66.7%). However, the Kaplan-Meier curve and log-rank test showed a significant difference regarding the mean duration until consolidation was achieved, with an average of 15.95 months in the study and 9.24 months in the control group (α = 0.05, p = 0.001). Linear regression showed a significant increase in consolidation duration with increasing defect size (R 2 = 0.121, p = 0.021). Logistic regression modelling showed a significant negative correlation between consolidation rate and revision performance, as well as an increasing number of revisions, prior surgeries and total number of surgeries performed on the limb. Clinical outcomes showed equal full weight bearing of the lower extremity after 5.54 months in the study vs. 4.86 months in the control group ( p = 0.267)., Conclusion: Surprisingly, defect size does not seem to have a significant effect on the consolidation rate and should not be seen as a risk factor. However, for the treatment of large-sized nonunions, the follow-up period should be prolonged up to 24 months, due to the extended time until consolidation will be achieved. This period should also pass before a premature revision with new bone augmentation is performed. In addition, it should be kept in mind that as the number of previous surgeries and revisions increases, the prospects for consolidation decrease and a change in therapeutic approach may be required.

Background: Intraoperative femoral fractures (IFF) during primary total hip arthroplasty (THA) pose a major clinical challenge, and data on mid-term implant performance, functional outcome and patient satisfaction is limited., Methods: 50 patients who sustained IFFs during primary THA were retrospectively reviewed. A control group of patients who received a primary THA without complications was matched according to gender, age, body mass index and indication for THA. Both groups were followed-up for a minimum duration of 2 years. Average follow-up duration was 5.6 years (range 2-11.8 years) for the fracture group and 6 years (range 4.1-8.3 years) for the control group respectively. The following parameters were assessed and compared: stem revision, Harris Hip Score improvement, pain scale improvement, WOMAC, Tegner Score, UCLA, SF-36, forgotten joint score and patient satisfaction., Results: There were no stem revisions in the fracture group and 1 stem revision in the control group. Stem survival was 100% and 98.1% respectively ( p = 0.447). The mean improvement in Harris hip score was 35.3 and 44.8 respectively. Significantly lower Harris Hip score improvement ( p = 0.021) and patient satisfaction ( p = 0.01) were observed in the fracture group. All other acquired parameters did not show significant differences., Conclusion: Intraoperative fractures of the proximal femur are a relevant complication that does not lead to higher revision rates but might worsen the functional outcome and negatively impact patient satisfaction in mid-term follow-up even if treated appropriately.

Background: Treatment of non-union remains challenging and often necessitates augmentation of the resulting defect with an autologous bone graft (ABG). ABG is limited in quantity and its harvesting incurs an additional surgical intervention leaving the risk for associated complications and morbidities. Therefore, artificial bone graft substitutes that might replace autologous bone are needed. S53P4-type bioactive glass (BaG) is a promising material which might be used as bone graft substitute due to its osteostimulative, conductive and antimicrobial properties. In this study, we plan to examine the clinical effectiveness of BaG as a bone graft substitute in Masquelet therapy in comparison with present standard Masquelet therapy using an ABG with tricalciumphosphate to fill the bone defect., Methods/design: This randomized controlled, clinical non-inferiority trial will be carried out at the Department of Orthopedics and Traumatology at Heidelberg University. Patients who suffer from tibial or femoral non-unions with a segmental bone defect of 2-5 cm and who are receiving Masquelet treatment will be included in the study. The resulting bone defect will either be filled with autologous bone and tricalciumphosphate (control group, N = 25) or BaG (S53P4) (study group, N = 25). Subsequent to operative therapy, all patients will receive the same standardized follow-up procedures. The primary endpoint of the study is union achieved 1year after surgery., Discussion: The results from the current study will help evaluate the clinical effectiveness of this promising biomaterial in non-union therapy. In addition, this randomized trial will help to identify potential benefits and limitations regarding the use of BaG in Masquelet therapy. Data from the study will increase the knowledge about BaG as a bone graft substitute as well as identify patients possibly benefiting from Masquelet therapy using BaG and those who are more likely to fail, thereby improving the quality of non-union treatment., Trial Registration: German Clinical Trials Register (DRKS), ID: DRKS00013882 . Registered on 22 January 2018.

Neuroinflammation presumably has an important impact on the secondary phase of spinal cord injury and is regulated by pro- and anti-inflammatory cytokines. We analyzed serum levels of three different cytokines (insulin-like-growth-factor [IGF]-1, tumor growth factor [TGF]-β1, and soluble CD 95 ligand [sCD95L]), in blood samples of 23 patients admitted with acute traumatic spinal cord injury between November 2010 and July 2013 with a follow-up period of 12 weeks. Quantification was performed using Human Quantikine Immunoassays, classification of neurological impairment was performed using the American Spinal Cord Injury Impairment Scale at time of admission and after 12 weeks. After an initial drop of all three cytokine serum levels, IGF-1, TGF-β1, and sCD95L showed significantly increased serum levels during the acute and sub-acute phases. For IGF-1 and sCD95L, we could also observe significantly higher serum levels in patients without neurological improvement compared with patients who had improvement after 12 weeks. In this study, we were able to show differences in cytokine serum levels in patients with different neurological outcome. Measuring the serum level patterns of IGF-1, TGF-β1, and sCD95L might be a useful tool for prognosis in patients with neurological improvement and tracking the pathophysiology in further studies. Further, our observations might link promising therapeutic efforts in numerous animal studies and future studies in human patients.

Case: A 20-year-old patient presented with an extended composite knee defect with destruction of the medial femoral condyle, including the medial collateral ligament. Treatment included using an anterolateral thigh flap for soft-tissue reconstruction, tensor fasciae latae muscle for ligament repair, and a massive allogenic bone graft of the medial femoral condyle that was revascularized with an osteocutaneous composite free flap from the contralateral femur. At 17 months postoperatively, the outcome was evaluated with scores on several established scales and radiographic assessment., Conclusion: The combination of vascularized soft-tissue reconstruction and osseous reconstruction using allogenic bone along with surgical angiogenesis proved to be effective. Complex extremity reconstruction should be discussed with interdisciplinary specialists.

Objective: To determine serum concentrations of soluble CD95 ligand (sCD95L) in patients with traumatic spinal cord injury., Methods: Patients with traumatic spinal cord injury were recruited. Blood was collected on admission to hospital and at 4 h, 9 h, 12 h, 24 h, 3 days, 7 days, and 2, 4, 8 and 12 weeks postadmission. Serum concentrations of sCD95L were determined via immunoassay., Result: The study included 23 patients. Mean sCD95L concentrations were significantly lower at 4 h, 9 h, 12 h and 24 h than at admission, and were significantly higher at 8 and 12 weeks, compared with admission., Conclusion: The serum sCD95L concentration fell significantly during the first 24 h after traumatic spinal cord injury. Concentrations then rose, becoming significantly higher than admission levels at 8 weeks. sCD95L may represent a possible therapeutic target for traumatic spinal cord injury., (© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Rationale: The glutamatergic theory of schizophrenia proposes a dysfunction of ionotropic N-methyl-D: -aspartate receptors (NMDA-R). Several therapeutic strategies address NMDA-R function and the effects of antipsychotic agents on NMDA-R expression have been described. Within the second-generation antipsychotics, the partial dopaminergic and serotonergic agonist aripiprazole (APZ) was able to counteract the behavioral effects of NMDA-R antagonists., Objectives: This study aims to investigate the effects of APZ on NMDA-R subunit expression and binding., Methods: We treated Sprague-Dawley rats for 4 weeks or 4 months with APZ in daily oral doses of 10 and 40 mg per kilogram of body weight. Gene expression of the NMDA-R subunits NR1, NR2A, NR2B, NR2C, and NR2D, respectively, was assessed by semiquantitative radioactive in situ hybridization and in parallel receptor binding using (3)H-MK-801 receptor autoradiography., Results: Increased expression levels of NR1 (4 weeks), NR2A (4 weeks), NR2C (4 weeks and 4 months), and NR2D (4 months) were observed in several hippocampal and cortical brain regions. The parallel reduced expression of NR2B mRNAs (4 months) resulted in a relative increase of the NR2A/NR2B ratio. Marked differences between specific brain regions, the doses of APZ, and the time points of assessment became obvious. On the receptor level, increased MK-801-binding was found after 4 weeks in the 40-mg group and after 4 months in the 10-mg group., Conclusions: The effects of APZ converge in enhanced NMDA receptor expression and a shift of subunit composition towards adult-type receptors. Our results confirm the regulatory connections between dopaminergic, serotonergic, and glutamatergic neurotransmissions with relevance for cognitive and negative symptoms of schizophrenia.

Perinatal exposure to alcohol (PEA) induces general developmental and specific neuropsychiatric disturbances accompanied by disturbed synaptic plasticity. Here we studied the long-term behavioral consequences of PEA and investigated glutamate transmission-related genes in a longitudinal fashion. After delivery, female Wistar rats and their pups were exposed to ethanol until postnatal day (PD)8 in vapor chambers. At the age of 5 months, the animals were behaviorally characterized. At both PD8 and after the behavioral testing we examined the expression of the vesicular glutamate transporter 1 and excitatory amino acid transporter (EAAT)1-4, as well as the N-methyl-D-aspartate receptor subunits (NR)1 and 2A-D, and in parallel receptor binding using (3) H-dizocilpine maleate receptor autoradiography. We found highly significant reductions of body weight and length following PEA in pups at PD8. These alterations disappeared in adulthood, when no changes of motor activity and only subtle differences of anxiety-related behavior were observed. It also did not affect T-maze learning, but had a pronounced effect on hippocampus-dependent spatial learning (Morris water maze testing). This specific learning deficit was accompanied by a dysregulation in hippocampal gene expression (significant induction of vesicular glutamate transporter 1, EAAT1, EAAT3, NR2A, 2B, 2C and 2D). Most of the examined genes turned out to be dysregulated to a higher degree at the age of 5 months. We therefore conclude that perinatal ethanol toxicity alters the plasticity of neurodevelopment and the regulation of glutamatergic gene expression, which may result in specific hippocampus-dependent learning deficits in adulthood., (© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)