Paediatric spine injuries in the thoracic and lumbar spine-results of the German multicentre CHILDSPINE study.

BACKGROUND: Paediatric thoracolumbar spine injuries are rare, and meaningful epidemiological data are lacking. OBJECTIVES: The aim of this study was to provide epidemiological data for paediatric patients with thoracolumbar spinal trauma in Germany with a view to enhancing future decision-making in relation to the diagnostics and treatment of these patients. MATERIALS AND METHODS: A retrospective multicentre study includes patients up to 16 years of age who were suffering from thoracolumbar spine injuries who had been treated in six German spine centres between 01/2010 and 12/2016. The clinical database was analysed for patient-specific data, trauma mechanisms, level of injury, and any accompanying injuries. Diagnostic imaging and subsequent treatment were investigated. Patients were divided into three age groups for further evaluation: age group I (0-6 years), age group II (7-9 years) and age group III (10-16 years). RESULTS: A total of 153 children with 345 thoracolumbar spine injuries met the inclusion criteria. The mean age at the time of hospitalization due to the injury was 12.9 (± 3.1) years. Boys were likelier to be affected (1:1.3). In all age groups, falls and traffic accidents were the most common causes of thoracolumbar spine injuries. A total of 95 patients (62.1%) were treated conservatively, while 58 (37.9%) of the children underwent surgical treatment. Minimally invasive procedures were the most chosen procedures. Older children and adolescents were likelier to suffer from higher-grade injuries according to the AOSpine classification. The thoracolumbar junction (T11 to L2) was the most affected level along the thoracolumbar spine (n = 90). Neurological deficits were rarely seen in all age groups. Besides extremity injuries (n = 52, 30.2%), head injuries represented the most common accompanying injuries (n = 53, 30.8%). Regarding spinal injuries, most of the patients showed no evidence of complications during their hospital stay (96.7%). CONCLUSIONS: The thoracolumbar junction was more frequently affected in older children and adolescents. The majority of thoracolumbar spinal column injuries were treated conservatively. Nevertheless, 37.9% of hospitalized children had to be treated surgically, and there was an acceptable complication rate for the surgeries that were performed.

Feasibility, Usability, and Safety of ParaGym, an Intelligent Mobile Exercise App for Individuals With Paraplegia: Protocol for a Pilot Block-Randomized Controlled Trial.

BACKGROUND: Exercise is crucial for individuals with paraplegia to reduce the risk of secondary diseases and improve independence and quality of life. However, numerous barriers such as inadequate accessibility restrict their participation in exercise programs. Digital exercise apps can help overcome these barriers. Personalization is considered a crucial feature of mobile exercise apps, as people with paraplegia have individual requirements regarding exercise programs depending on their level of impairment. Despite the increasing popularity of mobile exercise apps, there are none available that target the individual needs of this cohort. The ParaGym mobile exercise app prototype was designed to automatically tailor exercise sessions to the individual needs of users with paraplegia. OBJECTIVE: This study aims to evaluate the feasibility, usability, safety, and preliminary effectiveness of the ParaGym mobile exercise app prototype. METHODS: This pilot block-randomized controlled feasibility trial will include 45 adult participants with paraplegia. Eligible participants will be block randomized to either the intervention or waitlist control group. The intervention group will perform a 6-week exercise program using the ParaGym mobile exercise app, comprising three 35-minute exercise sessions per week. The waitlist control group will continue their usual care and receive access to the app after study completion. Participants will record all exercise sessions conducted with the app as well as additional exercise sessions conducted during the study period using exercise diaries. The primary outcomes include feasibility, usability, and safety. Feasibility will be assessed through semistructured interviews, study adherence, and retention rates. Usability will be measured using the System Usability Scale. Safety will be determined by the occurrence of adverse events. Secondary outcomes include the effects of the intervention on peak exercise capacity (VO2 peak); handgrip strength; independence, which will be measured using the Spinal Cord Independence Measure III (SCIM III); and health-related quality of life, which will be measured using the Short Form-36 Health Survey (SF-36). RESULTS: Recruitment commenced in November 2022. Overall, 12 participants were enrolled at the time of submission. Data collection commenced in January 2023, with completion expected in April 2023. CONCLUSIONS: To the best of our knowledge, this is the first study to assess the feasibility, usability, and safety of an intelligent mobile exercise app for individuals with paraplegia. Thereafter, the app should be adapted according to the findings of this trial. Future trials with an updated version of the app should aim for a larger sample size, longer intervention duration, and more diverse target group. In the long term, a fully marketable version of the ParaGym app should be implemented. This would increase the access to personalized, independent, and evidence-based exercise training for this cohort and, in the future, other people who use wheelchairs. TRIAL REGISTRATION: German Clinical Trials Register DRKS00030370; https://drks.de/search/de/trial/DRKS00030370. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45652.

Pediatric cervical spine injuries-results of the German multicenter CHILDSPINE study.

OBJECTIVES: The aim of this study was to provide epidemiological data of pediatric patients suffering from cervical spinal trauma in Germany, in order to integrate these data in future decision-making processes concerning diagnosis and therapy. MATERIALS AND METHODS: Retrospective multicenter study includes all patients up to 16 years suffering from cervical spine injuries who were treated in six German spine centers between 01/2010 and 12/2016. The clinical databases were screened for specific trauma mechanism, level of injury as well as accompanying injuries. Diagnostic imaging and the chosen therapy were analyzed. Patients were divided into three age groups for further evaluation: age group I (0-6 years), age group II (7-9 years), age group III (10-16 years). RESULTS: A total of 214 children with 265 cervical spine injuries were included during the mentioned period. The mean age at the time of injury was 11.9 (± 3.9) years. In age group I, 24 (11.2%) patients were included, age group II consisted of 22 patients (10.3%), and 168 patients belonged to age group III (78.5%). Girls and boys were equally affected. In all age groups, falls and traffic accidents were the most common causes of cervical spine injuries. A total of 180 patients (84.1%) were treated conservatively, while 34 (15.9%) children underwent surgery. Distorsion/whiplash injury was the most common entity (n = 165; 68.2%). Children aged 0-9 years had significantly (p < 0.001) more frequent injuries of the upper cervical spine (C0-C2) compared to older age groups. Patients of age group III were more likely to suffer from injuries in subaxial localizations. Neurological deficits were rarely seen in all age groups. Head injuries did represent the most common accompanying injuries (39.8%, n = 92). CONCLUSIONS: The upper cervical spine was more frequently affected in young children. Older children more often suffered from subaxial pathologies. The majority of cervical spinal column injuries were treated conservatively. Nevertheless, 15% of the hospitalized children had to be treated surgically.

[Germany-wide, Web-based ParaReg Registry for Lifelong Monitoring of People with Spinal Cord Injury: Data Model, Ethico-legal Prerequisites and Technical Implementation]. / Das deutschlandweite, webbasierte ParaReg-Register zur lebenslangen Dokumentation von Querschnittgelähmten ­ Datenmodell, rechtlich-ethische Voraussetzungen und technische Implementierung.

OBJECTIVE: In Germany, treatment paths for patients with acute spinal cord injury (SCI) differ considerably depending on intrinsic, disease-specific and extrinsic factors. Which of these factors are associated with improved outcome with fewer subsequent complications and inpatient re-admissions is not clear. The German-wide, patient-centered, web-based ParaReg registry will be implemented to improve the long-term quality of patient care and the planning of treatment paths with increased cost-effectiveness. METHODS: In the 2017-18 conceptualization phase, the data model of the registry was developed in an iterative process of the ParaReg steering committee together with the extended DMGP board and patient representatives. In ParaReg, routine social and medical data as well as internationally established neurological, functional and participation scores will be documented. The assignment of a unique patient ID allows a lifelong, cross-center documentation of inpatient stays in one of the 27 SCI centers organized in the German-speaking Medical Society for SCI (DMGP). The ParaReg data protection concept and patient information/consent are based on the Open Source Registry for Rare Diseases (OSSE) which were extended by GDPR-relevant aspects. RESULTS: In the realization phase, which started in 2019, the information technology infrastructure was implemented according to the clinical ID management module of the Technology and Methods Platform for Networked Medical Research (TMF). In parallel, the legal and ethical prerequisites for registry operation under the patronage of the DMGP were created. Recommendations of the working group data protection of the TMF were integrated into ParaReg's data protection concept. Based on the feedback from the alpha test phase with documentation of the hospitalization data of 40 patients, the ergonomics of the electronic case report forms were improved in particular for data entry on mobile devices. CONCLUSION: After completion of the monocentric alpha test phase, the multicenter data acquisition was started in 5 DMGP-SCI centers. The sustainability of ParaReg is ensured by the structural and financial support of the DMGP after expiry of the funding by the German Federal Ministry of Education and Research (BMBF).

E-vapor aerosols do not compromise bone integrity relative to cigarette smoke after 6-month inhalation in an ApoE-/- mouse model.

Cigarette smoke (CS) exposure is one of the leading risk factors for human health. Nicotine-containing inhalable products, such as e-cigarettes, can effectively support tobacco harm reduction approaches. However, there are limited comparative data on the effects of the aerosols generated from electronic vapor products (e-vapor) and CS on bone. Here, we report the effects of e-vapor aerosols and CS on bone morphology, structure, and strength in a 6-month inhalation study. Eight-week-old ApoE-/- mice were exposed to aerosols from three different e-vapor formulations-CARRIER (propylene glycol and vegetable glycerol), BASE (CARRIER and nicotine), TEST (BASE and flavor)-to CS from 3R4F reference cigarettes at matched nicotine concentrations (35 µg/L) or to fresh air (Sham) (N = 10 per group). Tibiae were analyzed for bone morphology by µCT imaging, biomechanics by three-point bending, and by histological analysis. CS inhalation caused a significant decrease in cortical and total bone volume fraction and bone density relative to e-vapor aerosols. Additionally, CS exposure caused a decrease in ultimate load and stiffness. In contrast, bone structural and biomechanical parameters were not significantly affected by e-vapor aerosol or Sham exposure. At the dissection time point, there was no significant difference in body weight or tibia bone weight or length among the groups. Histological findings revealed microcracks in cortical bone areas among all exposed groups compared to Sham control. In conclusion, because of the bone-preserving effect of e-vapor aerosols relative to CS exposure, e-vapor products could potentially constitute less harmful alternatives to cigarettes in situations in which bone health is of importance.

[Diagnostics and treatment of cervical spine trauma in pediatric patients : Recommendations from the Pediatric Spinal Trauma Group]. / Diagnostik und Therapie von Verletzungen der Halswirbelsäule im Kindesalter : Empfehlungen der AG Wirbelsäulentrauma im Kindesalter.

BACKGROUND: Severe cervical spine injuries in children under the age of 17 years are rare. Recommendations or even guidelines for the diagnostics and treatment of such injuries in children are currently not available. OBJECTIVE: The aim of the study was to formulate recommendations for diagnostics and treatment of injuries of the cervical spine in pediatric patients. MATERIAL AND METHODS: First, a search of primary and secondary literature on the topic complex of diagnostics and treatment of cervical spine injuries in children was carried out. An appropriate internal literature database was defined and maintained. Second, within the framework of 9 meetings from April 2017 to December 2019 the members of the Pediatric Spinal Trauma Group of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU) systematically formulated recommendations for the diagnostics and treatment of injuries of the cervical spine in pediatric patients by a consensus process. RESULTS: Recommendation for the diagnostics and treatment for injuries of the cervical spine could be formulated for three age groups (age group I: 0-6 years; age group II: 7-9 years; age group III: 10-16 years). The diagnostic and therapeutic principles known from adult patients suffering from injuries to the cervical spine cannot be easily transferred to pediatric patients. CONCLUSION: Injuries to the pediatric spine are rare and should be treated in specialized spine centers. Pediatric patients with a stable cardiopulmonary status should undergo magnetic resonance imaging (MRI) if a spinal trauma is suspected. Classification systems and therapeutic recommendations for injuries to the cervical spine known from adult patients could also be used for adolescent patients. This is not possible for children under the age of 10 years. Only few classification systems exist for this age group. Basic principles of the treatment of spinal trauma in children is the restoration of spinal stability and correct anatomical relationships as well as the protection of all neural structures.

[Diagnostics and treatment of thoracic and lumbar spine trauma in pediatric patients : Recommendations from the Pediatric Spinal Trauma Group]. / Diagnostik und Therapie von Verletzungen der Brust- und Lendenwirbelsäule im Kindesalter : Empfehlungen der AG Wirbelsäulentrauma im Kindesalter.

BACKGROUND: Spinal injuries in pediatric patients are overall very rare. Current reference studies including large patient numbers that enable the formulation of evidence-based recommendations on diagnostics and treatment of these injuries do not exist. OBJECTIVE: The aim of the current study was to formulate recommendations on the diagnostics and treatment for injuries of the thoracic and lumbar spine in pediatric patients. MATERIAL AND METHODS: Firstly, a search for primary and secondary literature on the topic of diagnostics and treatment of spinal injuries in children was carried out. From this, a literature database was established and maintained. Secondly, within the framework of 9 meetings in the time period from April 2017 to December 2019 the members of the Pediatric Spinal Trauma Group of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU) documented recommendations on diagnostics and treatment of injuries of the thoracic and lumbar spine in pediatric patients by a consensus process. RESULTS: Recommendations on the diagnostics and treatment of injuries of the thoracic and lumbar spine could be given for 3 age groups (age group I: 0-6 years; age group II: 7-9 years; age group III: 10-16 years). Diagnostic and therapeutic principles known from adult patients suffering from injuries to the thoracic or lumbar spine cannot easily be transferred to pediatric patients. CONCLUSION: Spinal injuries in childhood are rare and should be treated in specialized spine centers. Pediatric patients with a stable cardiopulmonary status should undergo magnetic resonance imaging (MRI) if a spinal trauma is suspected. The basic principles of the treatment of spinal trauma in children is the restoration of spinal stability and correct anatomical parameters as well as the protection of all neural structures. The potential for correction and regeneration of the individual spinal sections depending on the age of the patient must be considered for deciding between operative vs. conservative treatment. Whenever operative treatment is needed, it should be performed by minimally invasive techniques as a sole instrumentation without spondylodesis. An early removal of the screw-rod-system should be performed.

[Pediatric spine trauma-Results of a German national multicenter study including 367 patients]. / Wirbelsäulenverletzungen im Kindesalter ­ Ergebnisse einer nationalen Multizenterstudie mit 367 Patienten.

BACKGROUND: In general, pediatric spinal injuries are rare. No reliable data on the epidemiology of spinal injuries in pediatric patients in Germany are available. Especially in pediatric patients, for whom the medical history, clinical examination and the performance of imaging diagnostics are difficult to obtain, all available information on a spinal injury must be taken into account. OBJECTIVE: The aim of this study was to provide epidemiological data for pediatric patients with spinal trauma in Germany in order to enhance future decision-making for the diagnostics and treatment of these patients. MATERIAL AND METHODS: Within the framework of a national multicenter study, data were retrospectively obtained from 6 German spine centers for 7 years between January 2010 and December 2016. In addition to the demographic data, the clinical databases were screened for specific trauma mechanisms, level of injury as well as accompanying injuries. Furthermore, diagnostic imaging and the treatment selected were also analyzed. RESULTS: A total of 367 children (female: male = 1:1.2) with a total of 610 spinal injuries were included in this study. The mean age was 12 years (±3.5 years). The most frequent trauma mechanisms were falls from <3 m and traffic accidents. The imaging diagnostics were only rarely carried out with the child under anesthesia. Younger children (0-9 years old) suffered more injuries to the cervical spine, whereas injuries to the thoracic and lumbar spine were more frequently found in older children (>10 years old). The children frequently showed accompanying injuries to the head and the extremities. Accompanying spinal injuries mostly occurred in adjacent regions and only rarely in other regions. Around 75% of the children were treated conservatively. CONCLUSION: The results were different from the knowledge obtained from adult patients with spinal trauma and describe the special circumstances for pediatric patients with spinal trauma. Despite certain limitations these facts may help to enhance future decision-making for the diagnostics and treatment of these patients.

Recommendations for Diagnosis and Treatment of Odontoid Fractures in Geriatric Patients. / Empfehlungen zu Diagnostik und Behandlung von Frakturen des Dens axis bei geriatrischen Patienten.

BACKGROUND: Odontoid fractures in geriatric patients represent an entity of increasing incidence with a high rate of morbidity and mortality. The optimal diagnostic and therapeutic management is being controversially discussed in the literature. METHODS: In a consensus process and based on the current literature, the members of the working groups "Osteoporotic Fractures" and "Upper Cervical Spine" of the German Society for Orthopaedics and Trauma Surgery (DGOU) defined recommendations for the diagnostics and treatment of odontoid fractures in geriatric patients. RESULTS: For the diagnosis of odontoid fractures in symptomatic patients, computed tomography represents the gold standard, along with conventional radiographs. Magnetic resonance and dynamic imaging can be used as ancillary imaging modalities. With regard to fracture classification, the systems described by Anderson/D'Alonzo and by Eysel/Roosen have proved to be of value. A treatment algorithm was developed based on these classifications. Anderson/D'Alonzo type 1, type 3, and non-displaced type 2 fractures usually can be treated non-operatively. However, a close clinical and radiological follow-up is essential. In Anderson/D'Alonzo type 2 fractures, operative treatment is associated with better fracture healing. Displaced type 2 and type 3 fractures should be stabilized operatively. Type 2 fractures with suitable fracture patterns (Eysel/Roosen 2A/B) can be stabilized anteriorly. Posterior C I/II-stabilization procedures are well established and suitable for all fracture patterns.

Hepatic Osteodystrophy-Molecular Mechanisms Proposed to Favor Its Development.

Almost all patients with chronic liver diseases (CLD) show altered bone metabolism. Depending on the etiology, this manifests in a severe osteoporosis in up to 75% of the affected patients. Due to high prevalence, the generic term hepatic osteodystrophy (HOD) evolved, describing altered bone metabolism, decreased bone mineral density, and deterioration of bone structure in patients with CLD. Once developed, HOD is difficult to treat and increases the risk of fragility fractures. Existing fractures affect the quality of life and, more importantly, long-term prognosis of these patients, which presents with increased mortality. Thus, special care is required to support the healing process. However, for early diagnosis (reduce fracture risk) and development of adequate treatment strategies (support healing of existing fractures), it is essential to understand the underlying mechanisms that link disturbed liver function with this bone phenotype. In the present review, we summarize proposed molecular mechanisms favoring the development of HOD and compromising the healing of associated fractures, including alterations in vitamin D metabolism and action, disbalances in transforming growth factor beta (TGF-ß) and bone morphogenetic protein (BMP) signaling with histone deacetylases (HDACs) as secondary regulators, as well as alterations in the receptor activator of nuclear factor kappa B ligand (RANKL)-osteoprotegerin (OPG) system mediated by sclerostin. Based on these mechanisms, we give an overview on the limitations of early diagnosis of HOD with established serum markers.

Recommendations for the Diagnostic Testing and Therapy of Atlas Fractures. / Empfehlungen zur Diagnostik und Therapie oberer Halswirbelsäulenverletzungen: Atlasfrakturen.

In a consensus process with four sessions in 2017, the working group on "the upper cervical spine" of the German Society for Orthopaedic and Trauma Surgery (DGOU) formulated "Therapeutic Recommendations for the Diagnosis and Treatment of Fractures to the Upper Cervical Spine", incorporating their own experience and current literature. The following article describes the recommendations for the atlas vertebra. About 10% of all cervical spine injuries include the axis vertebra. The diagnostic process primarily aims to detect the injury and to determine joint incongruency and integrity of the atlas ring. For classification purposes, the Gehweiler classification and the Dickman classification are suitable. The Canadian c-spine rule is recommended for clinical screening for c-spine injuries. CT is the preferred imaging modality; MRI is needed to determine the integrity of the Lig. transversum atlantis in complete atlas ring fractures. Conservative treatment is appropriate in very many atlas fractures. Surgical treatment is recommended in existing or potential joint incongruity or instability, which are frequently seen in Gehweiler IIIB or Gehweiler IV fractures. Posterior atlanto-axial stabilisation and fusion using transarticular screws or an internal fixator are regarded as a gold standard in the majority of surgical cases. Especially in young patients, the possibility of isolated atlas osteosynthesis should be checked. A possible option for Gehweiler IV fractures is halo-fixation with mild distraction for ligamentotaxis. Secondary dislocation should be checked for frequently. Involvement of the occipito-atlantal joint complex requires stabilisation of the occiput as well.

Treatment of Injuries to the Subaxial Cervical Spine: Recommendations of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU).

STUDY DESIGN: Expert consensus. OBJECTIVES: To establish treatment recommendations for subaxial cervical spine injuries based on current literature and the knowledge of the Spine Section of the German Society for Orthopaedics and Trauma. METHODS: This recommendation summarizes the knowledge of the Spine Section of the German Society for Orthopaedics and Trauma. RESULTS: Therapeutic goals are a stable, painless cervical spine and protection against secondary neurologic damage while retaining maximum possible motion and spinal profile. The AOSpine classification for subaxial cervical injuries is recommended. The Canadian C-Spine Rule is recommended to decide on the need for imaging. Computed tomography is the favoured modality. Conventional x-ray is preserved for cases lacking a "dangerous mechanism of injury." Magnetic resonance imaging is recommended in case of unexplained neurologic deficit, prior to closed reduction and to exclude disco-ligamentous injuries. Computed tomography angiography is recommended in high-grade facet joint injuries or in the presence of vertebra-basilar symptoms. A0-, A1- and A2-injuries are treated conservatively, but have to be monitored for progressive kyphosis. A3 injuries are operated in the majority of cases. A4- and B- and C-type injuries are treated surgically. Most injuries can be treated with anterior plate stabilization and interbody support; A4 fractures need vertebral body replacement. In certain cases, additive or pure posterior instrumentation is needed. Usually, lateral mass screws suffice. A navigation system is advised for pedicle screws from C3 to C6. CONCLUSIONS: These recommendations provide a framework for the treatment of subaxial cervical spine Injuries. They give advice about diagnostic measures and the therapeutic strategy.

Recommendations for Diagnosis and Treatment of Fractures of the Ring of Axis. / Empfehlungen zur Diagnostik und Therapie oberer Halswirbelsäulenverletzungen: Axisringfrakturen.

In a consensus process with four sessions in 2017, the working group "upper cervical spine" of the German Society for Orthopaedics and Trauma Surgery (DGOU) formulated "Therapeutic Recommendations for the Diagnosis and Treatment of Upper Cervical Fractures", taking their own experience and the current literature into consideration. The following article describes the recommendations for axis ring fractures (traumatic spondylolysis C2). About 19 to 49% of all cervical spine injuries include the axis vertebra. Traumatic spondylolysis of C2 may include potential discoligamentous instability C2/3. The primary aim of the diagnostic process is to detect the injury and to determine potential disco-ligamentous instability C2/3. For classification purposes, the Josten classification or the modified Effendi classification may be used. The Canadian C-spine rule is recommended for clinical screening for C-spine injuries. CT is the preferred imaging modality and an MRI is needed to determine the integrity of the discoligamentous complex C2/3. Conservative treatment is appropriate in case of stable fractures with intact C2/3 motion segment (Josten type 2 and 2). Patients should be closely monitored, in order to detect secondary dislocation as early as possible. Surgical treatment is recommended in cases of primary severe fracture dislocation or discoligamentous instability C2/3 (Josten 3 and 4) and/or secondary fracture dislocation. Anterior cervical decompression and fusion (ACDF) C2/3 is the treatment of choice. However, in case of facet joint luxation C2/3 with looked facet (Josten 4), a primary posterior approach may be necessary.

First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury.

BACKGROUND: Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. OBJECTIVE: This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. METHODS: Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). RESULTS: ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. CONCLUSIONS: ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.

[Subaxial Cervical Spine Injuries: Treatment Recommendations of the German Orthopedic and Trauma Society]. / Therapieempfehlungen zur Versorgung von Verletzungen der subaxialen Halswirbelsäule.

In a consensus process during four sessions in 2016, the working group "lower cervical spine" of the German Society for Orthopedic and Trauma Surgery (DGOU), formulated "Therapeutic Recommendations for the Lower Cervical Spine", taking into consideration the current literature. Therapeutic goals are a permanently stable, painless cervical spine and the protection against secondary neurologic damage while retaining the greatest possible amount of motion and spinal profile. Due to its ease of use and its proven good reliability, the AOSpine classification for subaxial cervical injuries should be used. The Canadian C-Spine Rule is recommended as a clinical decision rule whether to perform imaging or not. If a structural or unstable injury is suspected by patient history or clinical findings, a spiral CT scan of the cervical spine is the favoured diagnostic modality. Conventional X-ray is reserved for patients in whom there is no "dangerous mechanism of injury". MR imaging is recommended in case of unexplained neurologic deficit, prior to closed reduction and open posterior surgery and to exclude disco-ligamentous injuries. Urgency of MR imaging depends on the specific findings. CT angiography is recommended in higher-grade facet joint injuries or in the presence of vertebra-basilar symptoms. Flexion-extension imaging is recommended only as a physician-guided dynamic fluoroscopy, when an unstable lesion is still suspected. The therapeutic strategy is mainly dependent on morphologic criteria, which are described using the AOSpine classification. A0-injuries are treated conservatively. A1- and A2-injuries are treated conservatively in the majority of cases, and in single cases a gross kyphotic deformity might indicate surgical stabilisation. A3-injuries do indicate a surgical therapy in the majority of cases, but certain cases might be treated conservatively. A4-fractures as well as B- and C-type injuries are to be treated surgically. Most injuries can be treated by anterior plate stabilisation with interbody support; when a complete burst fracture is present, corpectomy and vertebral body replacement is necessary. In certain cases, an additive posterior or pure posterior instrumentation might be possible or even mandatory. In most of these cases, lateral mass screws are sufficient; when pedicle screws are applied in C3 to C6, a 3D-navigation system is recommended. Injuries in an ankylosing spine (M3-modifier) should be treated preferably from posterior with long-segment instrumentation.

Imaging Cell Viability on Non-transparent Scaffolds - Using the Example of a Novel Knitted Titanium Implant.

Intervertebral disc degeneration and disc herniation is one of the major causes of lower back pain. Depletion of extracellular matrix, culminating in nucleus pulposus (NP) extrusion leads to intervertebral disc destruction. Currently available surgical treatments reduce the pain but do not restore the mechanical functionality of the spine. In order to preserve mechanical features of the spine, total disc or nucleus replacement thus became a wide interest. However, this arthroplasty era is still in an immature state, since none of the existing products have been clinically evaluated. This study intends to test the biocompatibility of a novel nucleus implant made of knitted titanium wires. Despite all mechanical advantages, the material has its limits for conventional optical analysis as the resulting implant is non-transparent. Here we present a strategy that describes in vitro visualization, tracking and viability testing of osteochondro-progenitor cells on the scaffold. This protocol can be used to visualize the efficiency of the cleaning protocol as well as to investigate the biocompatibility of these and other non-transparent scaffolds. Furthermore, this protocol can be used to show adherence pattern of cells as well as cell viability and proliferation rates on/in the scaffold. This in vitro biocompatibility testing assay provides a propitious tool to analyze cell-material interaction in non-transparent and opaque scaffolds.

Challenges for Restoration of Lower Urinary Tract Innervation in Patients with Spinal Cord Injury: A European Single-center Retrospective Study with Long-term Follow-up.

UNLABELLED: Xiao and colleagues in China reported successful restoration of bladder control in patients with spinal cord injury (SCI) by establishing a somatic-autonomic reflex pathway through lumbar-to-sacral ventral root nerve rerouting. We evaluated long-term results in eight patients who underwent this procedure at a German university clinic between 2005 and 2007. The primary outcome was the occurrence of voiding upon stimulation of the skin, with normalization of bladder pressure when filling, as assessed with videourodynamics at each visit. Videourodynamic variables, urinary tract infections, and bladder/stool events recorded in a patient diary were stored in a prospective database and reviewed retrospectively. Intraoperative testing indicated successful nerve rerouting in all eight patients. Duration of follow-up was 71 mo (range: 56-86). No patient reached the primary goal of voluntary voiding with normalization of detrusor pressure at any point during follow-up. No improvements in videourodynamic or diary variables regarding bladder function were observed. In view of the lack of short (12-18 mo) and long-term (71 mo) success in our patients and others, the risks of any surgical procedure using general anesthesia, and potential for unmet expectations to wreak havoc on patient emotional well-being, we cannot recommend this procedure for patients with SCI. PATIENT SUMMARY: Although the hope was to improve long-term outcomes of spinal cord injury patients, intraspinal nerve rerouting did not improve or normalize bladder function. In view of the lack of success, we cannot recommend this procedure until proven in clinical studies.

Trends in epidemiology and patho-anatomical pattern of proximal humeral fractures.

PURPOSE: Proximal humeral fractures are common and frequently associated with osteoporosis. Little is known about the association between the patho-anatomical fracture pattern of proximal humeral fractures and patient characteristics. The purpose of this six year longitudinal registry analysis of proximal humeral fractures was to study overall numbers, certain predefined pathoanatomical patterns and distribution compared with specific patient characteristics. METHODS: Data of patients treated between 2006 and 2011 in a country hospital that provides care >95 % of the city's hospitalised patients with fractures was retrospectively reviewed. Data were analysed according to patient characteristics of age, gender, comorbidity, accompanying injuries and radiological analysis of pathoanatomical fracture patterns based on Neer and Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification. RESULTS: Eight hundred and fifteen proximal humeral fractures (67% women/33% men; mean age 66 years, range 19-99) were analysed. During the study period, an overall increase of 42.5% was found: according to AO classification, 46% were type A, 22% type B and 32% type C. Based on the Neer classification, 86% were displaced, and 49% were complex with more than three parts. Of complex fractures, 57% were female patients >60 years. The number of complex fractures was five times higher in women >60 years than in men of the same age group. CONCLUSIONS: An overall increase of inpatients with displaced proximal tibial fractures was documented. Interestingly, complex displaced proximal humeral fractures, especially in older women with comorbidities, accounted for the majority of cases. These results suggest that health-care planning and hospital-based therapeutic strategies should focus on this patient group.

Depression, posttraumatic stress, and risk factors following spinal cord injury.

BACKGROUND: Chronic depression and posttraumatic stress have been frequently observed in populations of accident victims with spinal cord injuries. Studies suggest that various risk factors contribute to the development and maintenance of these symptoms. PURPOSE: This study assessed psychopathology around 4 years post-discharge in a German sample of 102 participants with spinal cord injuries. METHODS: A wide range of sociodemographic, clinical, and psychological variables was investigated with regard to their association with psychopathology. RESULTS: Approximately half of the patients (46.1 %) retrospectively reported clinically relevant depressive symptoms immediately post-discharge and 12.7 % exhibited scores indicative of a present depressive disorder. In addition, 8.8 % retrospectively reported clinically relevant symptoms of posttraumatic stress disorder (PTSD) after discharge from the hospital and 2 % were currently identified with chronic PTSD symptomatology. Time since injury and negative trauma-related appraisals of the self were strongly related to current psychopathology. CONCLUSION: Depressive reactions and posttraumatic distress may commonly occur after spinal injuries but will usually improve over time. It might be useful to routinely arrange follow-up contacts post-discharge in order to timely identify patients who are at risk of developing chronic psychopathology and require intervention.

Stress-vs-time signals allow the prediction of structurally catastrophic events during fracturing of immature cartilage and predetermine the biomechanical, biochemical, and structural impairment.

OBJECTIVE: Trauma-associated cartilage fractures occur in children and adolescents with clinically significant incidence. Several studies investigated biomechanical injury by compressive forces but the injury-related stress has not been investigated extensively. In this study, we hypothesized that the biomechanical stress occurring during compressive injury predetermines the biomechanical, biochemical, and structural consequences. We specifically investigated whether the stress-vs-time signal correlated with the injurious damage and may allow prediction of cartilage matrix fracturing. METHODS: Superficial and deeper zones disks (SZDs, DZDs; immature bovine cartilage) were biomechanically characterized, injured (50% compression, 100%/s strain-rate), and re-characterized. Correlations of the quantified functional, biochemical and histological damage with biomechanical parameters were zonally investigated. RESULTS: Injured SZDs exhibited decreased dynamic stiffness (by 93.04±1.72%), unresolvable equilibrium moduli, structural damage (2.0±0.5 on a 5-point-damage-scale), and 1.78-fold increased sGAG loss. DZDs remained intact. Measured stress-vs-time-curves during injury displayed 4 distinct shapes, which correlated with histological damage (p<0.001), loss of dynamic stiffness and sGAG (p<0.05). Damage prediction in a blinded experiment using stress-vs-time grades was 100%-correct and sensitive to differentiate single/complex matrix disruptions. Correlations of the dissipated energy and maximum stress rise with the extent of biomechanical and biochemical damage reached significance when SZDs and DZDs were analyzed as zonal composites but not separately. CONCLUSIONS: The biomechanical stress that occurs during compressive injury predetermines the biomechanical, biochemical, and structural consequences and, thus, the structural and functional damage during cartilage fracturing. A novel biomechanical method based on the interpretation of compressive yielding allows the accurate prediction of the extent of structural damage.