Untargeted blood serum proteomics identifies novel proteins related to neurological recovery after human spinal cord injury.

BACKGROUND: The discovery of new prognostic biomarkers following spinal cord injury (SCI) is a rapidly growing field that could help uncover the underlying pathological mechanisms of SCI and aid in the development of new therapies. To date, this search has largely focused on the initial days after the lesion. However, during the subacute stage of SCI (weeks to months after the injury), there remains potential for sensorimotor recovery, and numerous secondary events develop in various organs. Additionally, the confounding effects of early interventions after the injury are less likely to interfere with the results. METHODS: In this study, we conducted an untargeted proteomics analysis to identify biomarkers of recovery in blood serum samples during the subacute phase of SCI patients, comparing those with strong recovery to those with no recovery between 30 and 120 days. We analyzed the fraction of serum that is depleted of the most abundant proteins to unmask proteins that would otherwise go undetected. Linear models were used to identify peptides and proteins related to neurological recovery and we validated changes in some of these proteins using Enzyme-linked Immunosorbent Assay (ELISA). RESULTS: Our findings reveal that differences in subacute recovery after SCI (from 30 to 120 days) are associated with an enrichment in proteins involved in inflammation, coagulation, and lipid metabolism. Technical validation using commercial ELISAs further confirms that high levels of SERPINE1 and ARHGAP35 are associated with strong neurological recovery, while high levels of CD300a and DEFA1 are associated with a lack of recovery. CONCLUSIONS: Our study identifies new candidates for biomarkers of neurological recovery and for novel therapeutic targets after SCI.

Extent of traumatic spinal cord injury is lesion level dependent and predictive of recovery: a multicenter neuroimaging study.

Assessing the extent of the intramedullary lesion after spinal cord injury (SCI) might help to improve prognostication. However, since the neurological level of injury (NLI) impacts the recovery potential of SCI patients, the question arises whether lesion size parameters and predictive models based on those parameters are affected as well. In this retrospective observational study, the extent of the intramedullary lesion between individuals who sustained cervical and thoracolumbar SCI was compared and its relation to clinical recovery was assessed. 154 patients with sub-acute SCI (89 individuals with cervical lesions and 65 individuals with thoracolumbar lesions) underwent conventional clinical magnetic resonance imaging (MRI) 1 month after injury and clinical examination at 1 and 12 months. The morphology of the focal lesion within the spinal cord was manually assessed on the midsagittal slice of T2-weighted MR images and compared between cervical and thoracolumbar SCI patients as well as between patients who improved at least one American Spinal Injury Association Impairment Scale (AIS) grade (converters) and patients without AIS grade improvement (non-converters). The predictive value of lesion parameters including lesion length, lesion width, and preserved tissue bridges for predicting AIS grade conversion was assessed using regression models (conditional inference tree analysis). Lesion length was two times longer in thoracolumbar compared to cervical SCI patients (F = 39.48, p < 0.0001), while lesion width and tissue bridges' width did not differ. When comparing AIS grade converters and non-converters, converters showed a smaller lesion length (F = 5.46, p = 0.021), a smaller lesion width (F = 13.75, p = 0.0003) and greater tissue bridges (F = 12.87, p = 0.0005). Using regression models, tissue bridges allowed more refined subgrouping of the heterogenous patient population according to individual recovery profiles between 1 month and 12 months after SCI, while lesion length added no additional information for further subgrouping. This study characterizes differences in the anteroposterior and craniocaudal lesion extent after SCI. The two times greater lesion length in thoracolumbar compared to cervical SCI might be related to differences in the anatomy, biomechanics, and perfusion between the cervical and thoracic spine. Preserved tissue bridges were less influenced by the lesion level, while closely related to the clinical impairment. These results highlight the robustness and utility of tissue bridges as a neuroimaging biomarker for predicting clinical outcome after SCI in heterogeneous patient populations and for patient stratification in clinical trials.

Prognostic value of tissue bridges in cervical spinal cord injury: a longitudinal, multicentre, retrospective cohort study.

BACKGROUND: The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal tissue bridges-injury-spared neural tissue adjacent to the lesion-for prediction of sensorimotor recovery in a large, multicentre cohort of people with SCI. METHODS: For this longitudinal study, we included patients with acute cervical SCI (vertebrae C1-C7) admitted to one of three trauma or rehabilitation centres: Murnau, Germany (March 18, 2010-March 1, 2021); Zurich, Switzerland (May 12, 2002-March 2, 2019); and Denver, CO, USA (Jan 12, 2010-Feb 16, 2017). Patients were clinically assessed at admission (baseline), at discharge (3 months), and at 12 months post SCI. Midsagittal tissue bridges were quantified from T2-weighted images assessed at 3-4 weeks post SCI. Fractional regression and unbiased recursive partitioning models, adjusted for age, sex, centre, and neurological level of injury, were used to assess associations between tissue bridge width and baseline-adjusted total motor score, pinprick score, and light touch scores at 3 months and 12 months. Patients were stratified into subgroups according to whether they showed better or worse predicted recovery. FINDINGS: The cohort included 227 patients: 93 patients from Murnau (22 [24%] female); 43 patients from Zurich (four [9%] female); and 91 patients from Denver (14 [15%] female). 136 of these participants (from Murnau and Zurich) were followed up for up to 12 months. At 3 months, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 9·3% (SD 0·9) of maximal total motor score (95% CI 7·5-11.2), 8·6% (0·8) of maximal pinprick score (7·0-10·1), and 10·9% (0·8) of maximal light touch score (9·4-12·5). At 12 months post SCI, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 10·9% (1·3) of maximal total motor score (8·4-13·4), 5·7% (1·3) of maximal pinprick score (3·3-8·2), and 6·9% (1·4) of maximal light touch score (4·1-9·7). Partitioning models identified a tissue bridge cutoff width of 2·0 mm to be indicative of higher or lower 3-month total motor, pinprick, and light touch scores, and a cutoff of 4·0 mm to be indicative of higher and lower 12-month scores. Compared with models that contained clinical predictors only, models additionally including tissue bridges had significantly improved prediction accuracy across all three centres. INTERPRETATION: Tissue bridges, measured in the first few weeks after SCI, are associated with short-term and long-term clinical improvement. Thus, tissue bridges could potentially be used to guide rehabilitation decision making and to stratify patients into more homogeneous subgroups of recovery in regenerative and neuroprotective clinical trials. FUNDING: Wings for Life, International Foundation for Research in Paraplegia, EU project Horizon 2020 (NISCI grant), and ERA-NET NEURON.

High-resolution ultrasound of the supra- and infraclavicular levels of the brachial plexus including the axillary nerve: imaging anatomy based on multiplanar reconstructions and technical guide.

PURPOSE: The diagnosis of peripheral nerve injuries remains challenging. Electromyography and nerve conduction studies do not allow precise localization of the lesion and differentiation between lesions in continuity and non-continuity in cases with complete axonotmesis. Improved ultrasound technology allows the examination of almost the entire peripheral nervous system. The complex sono-anatomy of the brachial plexus outside of the standard scanning planes makes it difficult to access this region. METHODS: On the basis of the Visible Human Project of the National Institutes of Health (NIH), multiplanar reconstructions were created with the 3D Slicer open-source software in the various planes of the ultrasound cross-sections. The ultrasound examination itself and the guidance of the ultrasound probe in relation to the patient were recorded as video files and were synchronized through the audio channel. Subsequently, image matching was performed. RESULTS: Multiplanar reconstructions facilitate visualization of anatomical regions which are challenging to access thereby enabling physicians to evaluate the course of the peripheral nerve of interest in dynamic conditions. Sonographically visible structures could be reproducibly identified in single-frame analysis. CONCLUSION: With precise knowledge of the ultrasound anatomy, the nerve structures of the brachial plexus can also be dynamically assessed almost in their entire course. An instructional video on ultrasound of the brachial plexus supplements this manuscript and has been published on Vimeo.com.

Early Stabilization Does Not Increase Complication Rates in Acetabular Fractures of the Elderly: A Retrospective Analysis from the German Pelvis Registry.

Background: The incidence of acetabular fractures in geriatric patients has increased. Although there are strong data supporting the early operative treatment of hip fractures in geriatric patients, the optimal timing for acetabular fractures remains unclear and for several reasons, delayed treatment after trauma is common. Methods: A retrospective analysis of the German Pelvis Registry between 2008 and 2017 was performed. Ultimately, 665 patients with fractures of the anterior column or anterior column and posterior hemitransverse were enrolled. Patients above and below 65 years of age with these fracture types were analyzed regarding surgery day (within 48 hours, between 2 and 4 days, after 4 days), complication rate, reduction quality, and hospital stay. Results: The complication rate of the geriatric group was twice as high as that of younger patients; however, this finding was independent of the timing of surgery. Reduction quality and hospital stay were independent of surgical timing. Conclusions: In contrast to other fracture types, such as proximal femur fractures, the timing of surgery for acetabular fractures does not have a significant impact on the patient's outcome. The optimal time for surgery cannot be determined using the current data. However, as expected, there is a significantly higher risk for postoperative complications in the geriatric population.

Advances in the Treatment of Implant-Associated Infections of the Pelvis: Eradication Rates, Recurrence of Infection, and Outcome.

INTRODUCTION: Surgical site infections after operative stabilization of pelvic and acetabular fractures are rare but serious complications. The treatment of these infections involves additional surgical procedures, high health care costs, a prolonged stay, and often a worse outcome. In this study, we focused on the impact of the different causing bacteria, negative microbiological results with wound closure, and recurrence rates of patients with implant-associated infections after pelvic surgery. MATERIAL AND METHODS: We retrospectively analyzed a study group of 43 patients with microbiologically proven surgical site infections (SSI) after surgery of the pelvic ring or the acetabulum treated in our clinic between 2009 and 2019. Epidemiological data, injury pattern, surgical approach, and microbiological data were analyzed and correlated with long-term follow-up and recurrence of infection. RESULTS: Almost two thirds of the patients presented with polymicrobial infections, with staphylococci being the most common causing agents. An average of 5.7 (±5.4) surgical procedures were performed until definitive wound closure. Negative microbiological swabs at time of wound closure were only achieved in 9 patients (21%). Long-term follow-up revealed a recurrence of infection in only seven patients (16%) with an average interval between revision surgery and recurrence of 4.7 months. There was no significant difference of recurrence rate for the groups of patients with positive/negative microbiology in the last operative revision (71% vs. 78%). A positive trend for a correlation with recurrent infection was only found for patients with a Morel-Lavallée lesion due to run-over injuries (30% vs. 5%). Identified causing bacteria did not influence the outcome and rate of recurrence. CONCLUSION: Recurrence rates after surgical revision of implant-associated infections of the pelvis and the acetabulum are low and neither the type of causing agent nor the microbiological status at the timepoint of wound closure has a significant impact on the recurrence rate.

A Predictive Model to Identify Treatment-related Risk Factors for Odontoid Fracture Nonunion Using Machine Learning.

STUDY DESIGN: Multicenter retrospective analysis of routinely collected data. OBJECTIVE: The underlying aim of this study was to identify potential treatment-related risk factors for odontoid fracture nonunion while accounting for known patient- and injury-related risk factors. SUMMARY OF BACKGROUND DATA: Type II and III odontoid fractures represent the most common cervical spine fracture in elderly patients and are associated with a relatively high nonunion rate. The management of odontoid fractures is controversial and treatment strategies range from conservative treatment to extensive surgical stabilization and fusion. METHODS: A total of 415 individuals who sustained odontoid fracture and were treated in either of four tertiary referral centers in Austria and Germany were included in the study. We included the following potential contributing factors for fracture nonunion in cross-validated extreme gradient boosted (XGBoost) and binary logistic regression models: age, gender, fracture displacement, mechanism of injury (high vs. low energy), fracture classification (Anderson II vs. III), presence of comorbidities (Charlson comorbidity index), and treatment (conservative, anterior screw fixation with one or two screws, posterior C1/C2 spondylodesis, cervico-occipital C0-C4 fusion). RESULTS: In our cohort, 187 (45%) had radiologically confirmed odontoid nonunion six months postinjury. The odds for nonunion increase significantly with age, and are lower in type III compared to type II fractures. Also, odds for nonunion are significantly lower in posterior C1/C2 spondylodesis, and C0-C4 fusion compared to conservative treatment. Importantly, odds are not statistically significantly lower in the group treated with anterior screw fixation compared to conservative treatment. The factors gender, fracture displacement, mechanism of injury, and the presence of comorbidities did not produce significant odds. CONCLUSION: Higher age, type II fractures, and conservative treatment are the main risk factors for odontoid nonunion. Anterior screw fixation did not differ significantly from conservative treatment in terms of fracture union. LEVEL OF EVIDENCE: 3.

Trajectory of Serum Levels of Glial Fibrillary Acidic Protein Within Four Weeks Post-Injury Is Related to Neurological Recovery During the Transition from Acute to Chronic Spinal Cord Injury.

The use of biomarkers in spinal cord injury (SCI) research has evolved rapidly in recent years whereby most studies focused on the acute post-injury phase. Since SCI is characterized by persisting neurological impairments, the question arises whether blood biomarkers remain altered during the subacute post-injury time. Sample collection in the subacute phase might provide a better insight in the ongoing SCI specific molecular mechanism with fewer confounding factors compared with the acute phase where, amongst other complications, individuals receive a substantial amount of medication. This study aimed to determine if the temporal dynamics of serum biomarkers of neurodegeneration differ between individuals depending on their extent of neurological recovery in the transition phase between acute and chronic SCI. We performed a secondary analysis of biomarkers in patients with SCI (n = 41) who were treated at a level I trauma center in Germany. Patients with cervical or thoracic SCI regardless of injury severity were included. Blood samples were collected in the acute phase (1-4 days post-injury), and after 30 and 120 days post-injury. Serum protein levels of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were determined for each time-point of sample collection using R-Plex Assays (Meso Scale Discovery). Linear mixed models were used to evaluate the trajectory of GFAP and NfL over time. Fixed effects of time, neurological recovery, and injury severity, along with the recovery-by-time interaction, were included in models with random slopes and intercepts. GFAP levels increase during the first days after SCI and decrease in subacute to chronic stages. Notably, the trajectory of GFAP over time is significantly associated with the extent of neurological recovery during the transition from acute to chronic SCI with a steeper decline in individuals who recovered better. Serum levels of NfL continue to rise significantly until Day 30 followed by a decrease afterwards, independent of neurological recovery. The trajectory of serum GFAP levels qualifies as a prognostic biomarker for neurological recovery, and facilitates monitoring of disease progression in the sub-acute post-injury phase.

Systemic Immune Profile Predicts the Development of Infections in Patients with Spinal Cord Injuries.

Patients with spinal cord injury (SCI) frequently develop infections that may affect quality of life, be life-threatening, and impair their neurological recovery in the acute and subacute injury phases. Therefore, identifying patients with SCI at risk for developing infections in this stage is of utmost importance. We determined the systemic levels of immune cell populations, cytokines, chemokines, and growth factors in 81 patients with traumatic SCI at 4 weeks after injury and compared them with those of 26 age-matched healthy control subjects. Patients who developed infections between 4 and 16 weeks after injury exhibited higher numbers of neutrophils and eosinophils, as well as lower numbers of lymphocytes and eotaxin-1 (CCL11) levels. Accordingly, lasso logistic regression showed that incomplete lesions (American Spinal Injury Association Impairment Scale [AIS] C and D grades), the levels of eotaxin-1, and the number of lymphocytes, basophils, and monocytes are predictive of lower odds for infections. On the other hand, the number of neutrophils and eosinophils as well as, in a lesser extent, the levels of IP-10 (CXCL10), MCP-1 (CCL2), BDNF [brain-derived neurotrophic factor], and vascular endothelial growth factor [VEGF]-A, are predictors of increased susceptibility for developing infections. Overall, our results point to systemic immune disbalance after SCI as predictors of infection in a period when infections may greatly interfere with neurological and functional recovery and suggest new pathways and players to further explore novel therapeutic strategies.

The effect of extracorporeal shock wave therapy in acute traumatic spinal cord injury on motor and sensory function within 6 months post-injury: a study protocol for a two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled clinical trial.

BACKGROUND: The pathological mechanism in acute spinal cord injury (SCI) is dual sequential: the primary mechanical lesion and the secondary injury due to a cascade of biochemical and pathological changes initiated by the primary lesion. Therapeutic approaches have focused on modulating the mechanisms of secondary injury. Despite extensive efforts in the treatment of SCI, there is yet no causal, curative treatment approach available. Extracorporeal shock wave therapy (ESWT) has been successfully implemented in clinical use. Biological responses to therapeutic shock waves include altered metabolic activity of various cell types due to direct and indirect mechanotransduction leading to improved migration, proliferation, chemotaxis, modulation of the inflammatory response, angiogenesis, and neovascularization, thus inducing rather a regeneration than repair. The aim of this clinical study is to investigate the effect of ESWT in humans within the first 48 h after an acute traumatic SCI, with the objective to intervene in the secondary injury phase in order to reduce the extent of neuronal loss. METHODS: This two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled study has been initiated in July 2020, and a total of 82 patients with acute traumatic SCI will be recruited for the first stage in 15 participating hospitals as part of a two-armed three-stage adaptive trial design. The focused ESWT (energy flux density: 0.1-0.19 mJ/mm2, frequency: 2-5 Hz) is applied once at the level of the lesion, five segments above/below, and on the plantar surface of both feet within the first 48 h after trauma. The degree of improvement in motor and sensory function after 6 months post-injury is the primary endpoint of the study. Secondary endpoints include routine blood chemistry parameters, the degree of spasticity, the ability to walk, urological function, quality of life, and the independence in everyday life. DISCUSSION: The application of ESWT activates the nervous tissue regeneration involving a multitude of various biochemical and cellular events and leads to a decreased neuronal loss. ESWT might contribute to an improvement in the treatment of acute traumatic SCI in future clinical use. TRIAL REGISTRATION: ClinicalTrials.gov NCT04474106.

Serum Levels of Glial Fibrillary Acidic Protein and Neurofilament Light Protein Are Related to the Neurological Impairment and Spinal Edema after Traumatic Spinal Cord Injury.

Neurological examination in the acute phase after spinal cord injury (SCI) is often impossible and severely confounded by pharmacological sedation or concomitant injuries. Therefore, diagnostic biomarkers that objectively characterize severity or the presence of SCI are urgently needed to facilitate clinical decision-making. This study aimed to determine if serum markers of neural origin are related to: 1) presence and severity of SCI, and 2) magnetic resonance imaging (MRI) parameters in the very acute post-injury phase. We performed a secondary analysis of serological parameters, as well as MRI findings in patients with acute SCI (n = 38). Blood samples were collected between Days 1-4 post-injury. Serum protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and neurofilament light protein (NfL) were determined. A group of 41 age- and sex-matched healthy individuals served as control group. In the group of individuals with SCI, pre-operative sagittal and axial T2-weighted and sagittal T1-weighted MRI scans were available for 21 patients. Serum markers of neural origin are different among individuals who sustained traumatic SCI depending on injury severity, and the extent of the lesion according to MRI in the acute injury phase. Unbiased Recursive Partitioning regression with Conditional Inference Trees (URP-CTREE) produced preliminary cut-off values for NfL (75.217 pg/mL) and GFAP (73.121 pg/mL), allowing a differentiation between individuals with SCI and healthy controls within the first 4 days after SCI. Serum proteins NfL and GFAP qualify as diagnostic biomarkers for the presence and severity of SCI in the acute post-injury phase, where the reliability of clinical exams is limited.

Antibody seroprevalence and rate of asymptomatic infections with SARS-CoV-2 in Austrian hospital personnel.

BACKGROUND: The aims of this study are to determine (i) SARS-CoV-2 antibody positive employees in Austrian trauma hospitals and rehabilitation facilities, (ii) number of active virus carriers (symptomatic and asymptomatic) during the study, (iii) antibody decline in seropositive subjects over a period of around 6 months, (iv) the usefulness of rapid antibody tests for outpatient screening. METHOD: A total of 3301 employees in 11 Austrian trauma hospitals and rehabilitation facilities of the Austrian Social Insurance for Occupational Risks (AUVA) participated in this open uncontrolled prospective cohort study. Rapid lateral flow tests, detecting a combination of IgM and IgM against SARS-CoV-2), two different types of CLIA (Diasorin, Roche), RT-PCR tests and serum neutralization tests (SNTs) were performed. The tests were conducted twice, with an interval of 42.4 ± 7.7 (Min = 30, Max = 64) days. Positive participants were re-tested with CLIA/SNT at a third time point after 188.0 ± 12.8 days. RESULTS: Only 27 out of 3301 participants (0.82%) had a positive antibody test at any time point during the study confirmed via neutralization test. Among positively tested participants in either test, 50.4% did not report any symptoms consistent with common manifestations of COVID-19 during the study period or within the preceding 6 weeks. In the group who tested positive during or prior to study inclusion the most common symptoms of an acute viral illness were rhinitis (21.9%), and loss of taste and olfactory sense (21.9%). Based on the neutralization test as the true condition, the rapid antibody test performed better on serum than whole blood as 84.6% instead of 65.4% could be detected correctly. Concerning both CLIA tests overall the Roche test detected 24 (sensitivity = 88.9%) and the Diasorin test 22 positive participants (sensitivity = 81.5%). In participants with a positive SNT result, a significant drop in neutralizing antibody titre from 31.8 ± 22.9 (Md = 32.0) at T1 to 26.1 ± 17.6 (Md = 21.3) at T2 to 21.4 ± 13.4 (Md = 16.0) at T3 (χ2 = 23.848, df = 2, p < 0.001) was observed (χ2 = 23.848, df = 2, p < 0.001)-with an average time of 42.4 ± 7.7 days between T1 and T2 and 146.9 ± 13.8 days between T2 and T3. CONCLUSIONS: During the study period (May 11th-August 3rd) only 0.82% were tested positive for antibodies in our study cohort. The antibody concentration decreases significantly over time with 14.8% (4 out of 27) losing detectable antibodies.

Routine Blood Chemistry Predicts Functional Recovery After Traumatic Spinal Cord Injury: A Post Hoc Analysis.

BACKGROUND: Spinal cord injury (SCI) leads to various degrees of lifelong functional deficits. Most individuals with incomplete SCI experience a certain degree of functional recovery, especially within the first-year postinjury. However, this is difficult to predict, and surrogate biomarkers are urgently needed. OBJECTIVE: We aimed to (1) determine if routine blood chemistry parameters are related to neurological recovery after SCI, (2) evaluate if such parameters could predict functional recovery, and (3) establish cutoff values that could inform clinical decision-making. METHODS: We performed a post hoc analysis of routine blood chemistry parameters in patients with traumatic SCI (n = 676). Blood samples were collected between 24 and 72 hours as well as at 1, 2, 4, 8, and 52 weeks postinjury. Linear mixed models, regression analysis, and unbiased recursive partitioning (URP) of blood chemistry data were used to relate to and predict walking recovery 1 year postinjury. RESULTS: The temporal profile of platelet counts and serum levels of albumin, alkaline phosphatase, and creatinine differentiated patients who recovered walking from those who remained wheelchair bound. The 4 blood chemistry parameters from the sample collection 8 weeks postinjury predicted functional recovery observed 1 year after incomplete SCI. Finally, URP defined a cutoff for serum albumin at 3.7 g/dL, which in combination with baseline injury severity differentiates individuals who regain ambulation from those not able to walk. Specifically, about 80% of those with albumin >3.7 g/dL recovered walking. CONCLUSIONS: Routine blood chemistry data from the postacute phase, together with baseline injury severity, predict functional outcome after incomplete SCI.

Return to Sports after Anterior Cruciate Ligament Injury: a Matched-Pair Analysis of Repair with Internal Brace and Reconstruction Using Hamstring or Quadriceps Tendons.

PURPOSE: The purpose of this study was to evaluate sports activity before anterior cruciate ligament (ACL) injury and after surgical treatment of ACL rupture comparing ACL repair with an Internal Brace to ACL reconstruction using either a hamstring (HT) or quadriceps tendon (QT) autograft. METHODS: Between 12/2015 and 10/2016, we recruited 69 patients with a mean age of 33.4 years for a matched-pair analysis. Twenty-four patients who underwent Internal Brace reconstruction were matched according to age (±â€Š5 years), gender, Tegner activity scale (±â€Š1), BMI (±â€Š1) and concomitant injuries with 25 patients who had undergone HT reconstruction and 20 patients who had undergone QT reconstruction. The minimum follow-up was 12 months. RESULTS: Overall, the return-to-sports rate was 91.3 %. There were no significant differences (p ≥ 0.05) in the number of sports disciplines and the time before return to sports within or among the groups. Overall and within the groups, the level of sports participation did not change significantly (p ≥ 0.05) postoperatively. The patients' sense of well-being was excellent after either ACL repair with an Internal Brace or ACL reconstruction with autologous HT or QT. CONCLUSION: At short-term follow-up, ACL repair using an Internal Brace enables sports activity and provides a sense of well-being similar to that of classic ACL reconstruction using hamstring or quadriceps tendon autografts in a selected patient population. LEVEL OF EVIDENCE: Level III Retrospective comparative study.

Clinical and radiological results after Internal Brace suture versus the all-inside reconstruction technique in anterior cruciate ligament tears 12 to 18 months after index surgery.

BACKGROUND: Anterior cruciate ligament (ACL) injury can lead to reduced function, meniscal lesions, and early joint degeneration. Preservation of a torn ACL using the Internal Brace technique might re-establish normal knee kinematics, avoid donor-site morbidity due to tendon harvesting, and potentially maintain proprioception of the knee. METHODS: Fifty subjects were recruited for this study between December 2015 and October 2016. Two groups of individuals who sustained a unilateral ACL rupture were included: those who underwent surgery with preservation of the injured ACL (Internal Brace technique; IB) and those who underwent ACL reconstruction using a hamstring tendon graft (all-inside technique; AI). Subjective self-administered scores were used: the German version of the IKDC Subjective Knee Form (International Knee Documentation Committee), the German version of the WOMAC (Western Ontario and McMaster Universities Arthritis Index), SF-36 (short form), the German version of the KOOS (Knee Osteoarthritis Outcome Score), and the German version of themodified Lysholm Score by Lysholm and Gillquist. Anterior tibial translation was assessed using the KT-1000 Arthrometer (KT-1000 Knee Ligament Arthrometer, MEDmetric Corp., San Diego, CA, USA). Magnetic resonance evaluation was performed in all cases. RESULTS: Twenty-three subjects (46 %) were men, and the mean age was 34.7 years. The objective IKDC scores were "normal" in 15 and 14 patients, "nearly normal" in 11 and 7 patients, and "abnormal" in 1 and 2 patients, in the IB and AI groups, respectively. KT-1000 assessment showed a sideto-side difference of more than 3 mm on maximum manual testing in 11 (44 %) and 6 subjects (28.6 %) in the IB and AI groups, respectively. In the postoperative MRI, 20 (74 %) and 22 subjects (96 %) in the IB and AI groups had an intact ACL. Anterior tibial translation was significantly higher in the IB group compared with the AI group in the manual maximum test. CONCLUSIONS: Preservation of the native ACL with the Internal Brace primary repair technique can achieve comparable results to ACL reconstruction using Hamstring autografts over a short term. Clinically relevant limitations such as a higher incidence of pathologic laxity, with patients more prone to pivot-shift phenomenon were observed during the study period.

Minimally invasive surgery for intra-articular calcaneus fractures: a 9-year, single-center, retrospective study of a standardized technique using a 2-point distractor.

BACKGROUND: A fracture of the calcaneus can be a painful and disabling injury. Treatment modalities may be conservative or operative. Surgical treatment strategies include open reduction and internal fixation (ORIF) techniques, as well as a variety of minimally invasive methods. The aim of this study was to evaluate the treatment options and post-treatment complication rates for intra-articular calcaneal fractures at the Traumacenter Linz over a 9-year period. METHODS: All patients with calcaneal fractures treated at the Traumacenter Linz between 2007 and 2015 were included in this study. The patients records were retrospectively reviewed, and the data, including demographic parameters, cause of injury, and the time between injury and operative treatment were analyzed. The number of secondary operative interventions due to soft-tissue complications, hardware removal, and the long-term arthrodesis rate were evaluated. RESULTS: A minimally invasive 2-point-distractor method was used in 85.8% (n = 182) of all operatively managed calcaneal fractures (n = 212) in our department. The majority of the operations (88.7%) were performed within 2 days after the accident. The secondary operation rate resulting from wound complications was 2.7% in the 2-point distractor group and 16.7% in the ORIF group. A secondary arthrodesis was performed in 4.7% (n = 9) of the subtalar joints in the entire study population. CONCLUSIONS: Our data supported the assumption that severe wound complications would be less likely to occur after minimally invasive treatment compared to ORIF treatment. The rate of secondary arthrodesis in the study cohort was comparable to that in the literature. LEVEL OF EVIDENCE: IV.

The Leukotriene Receptor Antagonist Montelukast Reduces Alpha-Synuclein Load and Restores Memory in an Animal Model of Dementia with Lewy Bodies.

Dementia with Lewy bodies (DLB) represents a huge medical need as it accounts for up to 30% of all dementia cases, and there is no cure available. The underyling spectrum of pathology is complex and creates a challenge for targeted molecular therapies. We here tested the hypothesis that leukotrienes are involved in the pathology of DLB and that blocking leukotrienes through Montelukast, a leukotriene receptor antagonist and approved anti-asthmatic drug, might alleviate pathology and restore cognitive functions. Expression of 5-lipoxygenase, the rate-limiting enzyme for leukotriene production, was indeed elevated in brains with DLB. Treatment of cognitively deficient human alpha-synuclein overexpressing transgenic mice with Montelukast restored memory. Montelukast treatment resulted in modulation of beclin-1 expression, a marker for autophagy, and in a reduction in the human alpha-synulcein load in the transgenic mice. Reducing the protein aggregation load in neurodegenerative diseases might be a novel model of action of Montelukast. Moreover, this work presents leukotriene signaling as a potential drug target for DLB and shows that Montelukast might be a promising drug candidate for future DLB therapy development.

Biomarkers in Traumatic Spinal Cord Injury-Technical and Clinical Considerations: A Systematic Review.

Objective. To examine (1) if serological or cerebrospinal fluid (CSF) biomarkers can be used as diagnostic and/or prognostic tools in patients with spinal cord injury (SCI) and (2) if literature provides recommendations regarding timing and source of biomarker evaluation. Data Sources. A systematic literature search to identify studies reporting on diagnostic and prognostic blood and/or CSF biomarkers in SCI was conducted in PubMed/MEDLINE, CINAHL, Science Direct, The Cochrane Library, ISI Web of Science, and PEDro. Study Selection. Clinical trials, cohort, and pilot studies on patients with traumatic SCI investigating at least one blood or CSF biomarker were included. Following systematic screening, 19 articles were included in the final analysis. PRISMA guidelines were followed to conduct this review. Data Extraction. Independent extraction of articles was completed by 2 authors using predefined inclusion criteria and study quality indicators. Data Synthesis. Nineteen studies published between 2002 and April 2019 with 1596 patients were included in the systematic review. In 14 studies, blood biomarkers were measured, 4 studies investigated CSF biomarkers, and 1 study used both blood and CSF samples. Conclusions. Serum/CSF concentrations of several biomarkers (S100b, IL-6, GFAP, NSE, tau, TNF-α, IL-8, MCP-1, pNF-H, and IP-10) following SCI are highly time dependent and related to injury severity. Future studies need to validate these markers as true biomarkers and should control for secondary complications associated with SCI. A deeper understanding of secondary pathophysiological events after SCI and their effect on biomarker dynamics may improve their clinical significance as surrogate parameters in future clinical studies.

Functional performance testing and return to sport criteria in patients after anterior cruciate ligament injury 12-18 months after index surgery: A cross-sectional observational study.

OBJECTIVES: Objective return to sport (RTS) criteria after anterior cruciate ligament (ACL) injury are lacking. Study purposes were (1) to report Limb Symmetry Index (LSI) values achieved in a test battery, (2) to detect how many subjects meet RTS criteria 12-18 months post-operative and (3) to identify whether patient-administered scores predict RTS criteria. DESIGN: Observer-blinded, cross-sectional observational study. SETTING: Traumacenter Linz, Austria. PARTICIPANTS: Eighty-eight subjects (48 females; mean (SD) age: 34.73 (10.8) years); Twenty-five had undergone ACL repair (IB), 21 ACL reconstruction (AI). Forty-two healthy subjects served as control. MAIN OUTCOME MEASURES: Participants were evaluated using a single-leg hop test battery. The variable of interest was meeting the RTS criteria by reaching defined cut-off values. Logistic regression was used to investigate the relationship between subjective scores (IKDC, WOMAC, KOOS, Lysholm) and fulfillment of RTS criteria. Additionally, subjective physical activity and anterior knee translation were assessed. RESULTS: Thirty-six percent of IB patients and 28.6% of AI patients met RTS criteria. None of the included scores produced significant odds to predict RTS. CONCLUSIONS: Subjective scores, clinical examinations and fulfillment of RTS criteria did not differ significantly between groups. Maximum anterior translation revealed a significant difference (p = 0.009) in favor of the AI group.

Reference values for fatigued versus non-fatigued limb symmetry index measured by a newly designed single-leg hop test battery in healthy subjects: a pilot study.

PURPOSE: There is sparse evidence for return to sport criteria after knee injury. Functional performance deficits, particularly in fatigued muscular condition, should be verified prior to the attempt to return to high-risk pivoting sports. The purpose of this study was to generate reference values for the limb symmetry index (LSI) of healthy subjects in fatigued and non-fatigued muscular condition in a newly designed test battery. METHODS: Forty-two healthy subjects [22 females, 20 males; mean (SD) age 30.4 (6.6) years] were evaluated using a test battery consisting of an isometric strength test, a series of five single-leg hop tests and an integrated fatigue protocol. Subjective physical activity was assessed with the Tegner Activity Scale (TAS). The cut-off values for healthy subjects were calculated considering the fifth percentile as the minimum reference value for the LSI and single-leg hop distance. RESULTS: The mean (SD) overall LSI was 98.8% (4.6). No significant gender or age specific differences in limb symmetry were observed. The comparison of the non-fatigued LSI with the overall LSI revealed no clinically relevant change due to muscular fatigue. Repeated measures ANOVA revealed a significant within effect on fatigue/non-fatigue condition (F(1,38) = 18.000; p < 0.001, η2 = 0.321) on absolute single-leg hop distance. Moreover, a significant between effect on the TAS-parameter (F(1,38) = 5.928; p = 0.020, η2 = 0.135 between: TAS ≤ 5/TAS > 5) and on gender (F(1,38) = 23.956; p < 0.001, η2 = 0.387) could be detected. CONCLUSIONS: The absolute jumping distance in the single-leg hop for distance was significantly reduced due to fatigue. No clinically relevant effect of muscular fatigue was observed on limb symmetry in our study sample. Gender and physical activity are important factors to be considered when interpreting reference values.