Pursuing More Aggressive Timelines in the Surgical Treatment of Traumatic Spinal Cord Injury (TSCI): A Retrospective Cohort Study with Subgroup Analysis

Background: The optimal timing of surgical therapy for traumatic spinal cord injury (TSCI) remains unclear. The purpose of this study is to evaluate the impact of “ultra-early” (<4 h) versus “early” (4–24 h) time from injury to surgery in terms of the likelihood of neurologic recovery. Methods: The effect of surgery on neurological recovery was investigated by comparing the assessed initial and final values of the American Spinal Injury Association (ASIA) Impairment Scale (AIS). A post hoc analysis was performed to gain insight into different subgroup regeneration behaviors concerning neurological injury levels. Results: Datasets from 69 cases with traumatic spinal cord injury were analyzed. Overall, 19/46 (41.3%) patients of the “ultra-early” cohort saw neurological recovery compared to 5/23 (21.7%) patients from the “early” cohort (p = 0.112). The subgroup analysis revealed differences based on the neurological level of injury (NLI) of a patient. An optimal cutpoint for patients with a cervical lesion was estimated at 234 min. Regarding the prediction of neurological improvement, sensitivity was 90.9% with a specificity of 68.4%, resulting in an AUC (area under the curve) of 84.2%. In thoracically and lumbar injured cases, the estimate was lower, ranging from 284 (thoracic) to 245 min (lumbar) with an AUC of 51.6% and 54.3%. Conclusions: Treatment within 24 h after TSCI is associated with neurological recovery. Our hypothesis that intervention within 4 h is related to an improvement in the neurological outcome was not confirmed in our collective. In a clinical context, this suggests that after TSCI there is a time frame to get the right patient to the right hospital according to advanced trauma life support (ATLS) guidelines

Non-unions treated with bone morphogenic protein 7: introducing the quantitative measurement of human serum cytokine levels as promising tool in evaluation of adjunct non-union therapy

Background: In this study we sought to determine if application of bone morphogenic protein 7 (BMP-7) promotes physiological bone healing of non-unions and to investigate if serum cytokine analysis may serve as a promising tool in the analysis of adjunct non-union therapy. Therefore we analyzed the influence of BMP-7 application on the serum cytokine expression patterns on patients with impaired bone healing compared to patients that showed proper bone healing. Methods: Our study involved analyzing blood samples from 208 patients with long bone fractures together with patients that subsequently developed non-unions. From this large pool, 15 patients with atrophic non-union were matched to 15 patients with atrophic non-union treated with local application of BMP-7 as well as normal bone healing. Changes in the cytokine expression patterns were monitored during the 1st, 2nd, 4th, 8th, 12th and 52nd week. The patients were followed both clinically and radiologically for the entire duration of the study. Serum cytokine expression levels of transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were analyzed and compared. Results: Serum expression of TGF-β were nearly parallel in all three groups, however serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). bFGF serum concentrations increased initially in patients with proper bone healing and in those treated with BMP-7. Afterwards, values decreased; bFGF serum concentrations in the BMP-7 group were significantly higher than in the other groups (p < 0.05). PDGF serum concentration levels were nearly parallel in all groups, serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). Conclusion: Treatment with BMP-7 in patients with former non-unions led to similar cytokine expression patterns after treatment as those found in patients with proper bone healing. Our results suggest that treatment with BMP-7 promote healing of non-unions. Furthermore, quantitative measurement of serum cytokine expression is a promising tool for evaluating the effectiveness of additional non-union therapies such as adjunct application of growth factors

Challenging the Perceptions of Human Tendon Allografts: Influence of Donor Age, Sex, Height, and Tendon on Biomechanical Properties

Background: The use of allograft tendons has increased for primary and revision anterior cruciate ligament reconstruction, but allograft supply is currently limited to a narrow range of tendons and donors up to the age of 65 years. Expanding the range of donors and tendons could help offset an increasing clinical demand. Purpose: To investigate the effects of donor age, sex, height, and specific tendon on the mechanical properties of a range of human lower leg tendons. Study Design: Descriptive laboratory study. Methods: Nine tendons were retrieved from 39 fresh-frozen human cadaveric lower legs (35 donors [13 female, 22 male]; age, 49-99 years; height, 57-85 inches [145-216 cm]) including: Achilles tendon, tibialis posterior and anterior, fibularis longus and brevis, flexor and extensor hallucis longus, plantaris, and flexor digitorum longus. Tendons underwent tensile loading to failure measuring cross-sectional area (CSA), maximum load, strain at failure, ultimate tensile strength, and elastic modulus. Results from 332 tendons were analyzed using mixed-effects linear regression, accounting for donor age, sex, height, and weight. Results: Mechanical properties were significantly different among tendons and were substantially greater than the effects of donor characteristics. Significant effects of donor sex, age, and height were limited to specific tendons: Achilles tendon, tibialis posterior, and tibialis anterior. All other tendons were unaffected. The Achilles tendon was most influenced by donor variables: greater CSA in men (β = 15.45 mm2; Šidák adjusted P < .0001), decreased maximum load with each year of increased age (β = −17.20 N per year; adjusted P = .0253), and increased CSA (β = 1.92 mm2 per inch; adjusted P < .0001) and maximum load (β = 86.40 N per inch; adjusted P < .0001) with each inch of increased height. Conclusion: Mechanical properties vary significantly across different human tendons. The effects of donor age, sex, and height are relatively small, are limited to specific tendons, and affect different tendons uniquely. The findings indicate that age negatively affected only the Achilles tendon (maximum load) and challenge the exclusion of donors aged >65 years across all tendon grafts. Clinical Relevance: The findings support including a broader range of tendons for use as allografts for anterior cruciate ligament reconstruction and reviewing the current exclusion criterion of donors aged >65 years

Evaluation of the clinical effectiveness of bioactive glass (S53P4) in the treatment of non-unions of the tibia and femur: study protocol of a randomized controlled non-inferiority trial

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

Zinc Concentration Dynamics Indicate Neurological Impairment Odds after Traumatic Spinal Cord Injury

Traumatic Spinal Cord Injury (TSCI) is debilitating and often results in a loss of motor and sensory function caused by an interwoven set of pathological processes. Oxidative stress and inflammatory processes are amongst the critical factors in the secondary injury phase after TSCI. The essential trace element Zinc (Zn) plays a crucial role during this phase as part of the antioxidant defense system. The study aims to determine dynamic patterns in serum Zn concentration in patients with TSCI and test for a correlation with neurological impairment. A total of 42 patients with TSCI were enrolled in this clinical observational study. Serum samples were collected at five different points in time after injury (at admission, and after 4 h, 9 h, 12 h, 24 h, and 3 d). The analysis of the serum Zn concentrations was conducted by total reflection X-ray fluorescence (TXRF). The patients were divided into two groups-a study group S (n = 33) with neurological impairment, including patients with remission (G1, n = 18) and no remission (G0, n = 15) according to a positive AIS (American Spinal Injury Association (ASIA) Impairment Scale) conversion within 3 months after the trauma; and a control group C (n = 9), consisting of subjects with vertebral fractures without neurological impairment. The patient data and serum concentrations were examined and compared by non-parametric test methods to the neurological outcome. The median Zn concentrations in group S dropped within the first 9 h after injury (964 µg/L at admission versus 570 µg/L at 9 h, p < 0.001). This decline was stronger than in control subjects (median of 751 µg/L versus 729 µg/L, p = 0.023). A binary logistic regression analysis including the difference in serum Zn concentration from admission to 9 h after injury yielded an area under the curve (AUC) of 82.2% (CI: 64.0-100.0%) with respect to persistent neurological impairment. Early Zn concentration dynamics differed in relation to the outcome and may constitute a helpful diagnostic indicator for patients with spinal cord trauma. The fast changes in serum Zn concentrations allow an assessment of neurological impairment risk on the first day after trauma. This finding supports strategies for improving patient care by avoiding strong deficits via adjuvant nutritive measures, e.g., in unresponsive patients after trauma

Chemokine analysis as a novel diagnostic modality in the early prediction of the outcome of non-union therapy: a matched pair analysis

Background: Despite the regenerative capability of skeletal tissue fracture, non-union is common. Treatment of non-unions remains challenging, and early determination of the outcome is impossible. Chemokines play an important role in promoting the formation of new bone and remodeling existing bone. Despite their importance regarding the regulation of bone biology, the potential of chemokines as biological markers reflecting osseous regeneration is unknown. The purpose of this study was to determine (1) if serum chemokine expression levels correlate with the outcome of non-union surgery and (2) if chemokine expression analysis can be used to identify patients at risk for treatment failure. Methods: Non-union patients receiving surgical therapy in our institution between March 2012 and March 2014 were prospectively enrolled in a clinical observer study. Regular clinical and radiological follow-up was conducted for 12 months including collection of blood during the first 12 weeks. Based on the outcome, patients were declared as responders or non-responders to the therapy. To minimize biases, patients were matched (age, sex, body mass index (BMI)) and two groups of patients could be formed: responders (R, n = 10) and non-responders (NR, n = 10). Serum chemokine expression (CCL-2, CCL-3, CCL-4, CXCL-10, CCL-11, and interferon gamma (IFN-γ)) was analyzed using Luminex assays. Data was compared and correlated to the outcome. Results: CCL-3 expression in NR was significantly higher during the course of the study compared to R (p = 0.002), and the expression pattern of CCL-4 correlated with CCL-3 in both groups (NR: p &lt; 0.001 and r = 0.63). IFN-γ expression in NR was continuously higher than in R (p &lt; 0.001), and utilization of CCL-3 and IFN-γ serum expression levels 2 weeks after the treatment resulted in a predictive model that had an AUC of 0.92 (CI 0.74–1.00). Conclusion: Serum chemokine expression analysis over time is a valid and promising diagnostic tool. The chemokine expression pattern correlates with the outcome of the Masquelet therapy of lower limb non-unions. Utilization of the serum analysis of CCL-3 and IFN-γ 2 weeks after the treatment resulted in an early predictive value regarding the differentiation between patients that are likely to heal and those that are prone to high risk of treatment failure

Development and validation of an objective assessment scale for chest tube insertion under ‘direct’ and ‘indirect’ rating

Background: There is an increasing need for objective and validated educational concepts. This holds especially true for surgical procedures like chest tube insertion (CTI). Thus, we developed an instrument for objectification of learning successes: the assessment scale based on Objective Structured Assessment of Technical Skill (OSATS) for chest tube insertion, which is evaluated in this study. Primary endpoint was the evaluation of intermethod reliability (IM). Secondary endpoints are ‘indirect’ interrater reliability (IR) and construct validity of the scale (CV). Methods: Every participant (N = 59) performed a CTI on a porcine thorax. Participants received three ratings (one ‘direct’ on site, two ‘indirect’ via video rating). IM compares ‘direct’ with ‘indirect’ ratings. IR was assessed between ‘indirect’ ratings. CV was investigated by subgroup analysis based on prior experience in CTI for ‘direct’ and ‘indirect’ rating. Results: We included 59 medical students to our study. IM showed moderate conformity (‘direct’ vs. ‘indirect 1’ ICC = 0.735, 95% CI: 0.554–0.843; ‘direct’ vs. ‘indirect 2’ ICC = 0.722, 95% CI 0.533–0.835) and good conformity between ‘direct’ vs. ‘average indirect’ rating (ICC = 0.764, 95% CI: 0.6–0.86). IR showed good conformity (ICC = 0.84, 95% CI: 0.707–0.91). CV was proven between subgroups in ‘direct’ (p = 0.037) and ‘indirect’ rating (p = 0.013). Conclusion: Results for IM suggest equivalence for ‘direct’ and ‘indirect’ ratings, while both IR and CV was demonstrated in both rating methods. Thus, the assessment scale seems a reliable method for rating trainees’ performances ‘directly’ as well as ‘indirectly’. It may help to objectify and facilitate the assessment of training of chest tube insertion. - - - - - - - - - CORRECTION Published online 20.02.2019 in BMC Medical Education 19 (2019), Nr. 62; DOI: https://doi.org/10.1186/s12909-019-1491-4. Following publication of the original article, the author reported that the given name and family name of all authors were swapped. The original article has been corrected

App-based serious gaming for training of chest tube insertion: study protocol for a randomized controlled trial

Background: Chest tube insertion is a standard intervention for management of various injuries of the thorax. Quick and accurate execution facilitates efficient therapy without further complications. Here, we propose a new training concept comprised of e-learning elements as well as continuous rating using an objective structured assessment of technical skills (OSATS) tool. The study protocol is presented for a randomized trial to evaluate e-learning with app-based serious gaming for chest drain insertion. Methods: The proposed randomized trial will be carried out at the Department of Orthopedics and Traumatology at Heidelberg University in the context of regular curricular teaching for medical students (n = 90, 3rd to 6th year). The intervention group will use e-learning with the serious gaming app Touch Surgery (TM) for chest drain insertion, whereas the control group uses serious gaming for an unrelated procedure. Primary endpoint is operative performance of chest drain insertion in a porcine cadaveric model according to OSATS. Discussion: The randomized trial will help determine the value of e-learning with the serious gaming app Touch Surgery (TM) for chest drain insertion by using the OSATS score. The study will improve surgical training for trauma situations. Trial registration: Trial Registration Number, DRKS00009994. Registered on 27 May 2016