The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study.

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

Lower leg reconstruction after resection of a squamous cell carcinoma on necrobiosis lipoidica with a pedicled fibula and an extended anterolateral thigh flap-a case report.

BACKGROUND: Extensive loss of soft tissue and bone due to neoplasia, trauma, or infection in extremities often leads to amputation. CASE PRESENTATION: We present the case of a 72-year-old female patient presenting with an extended cutaneous squamous cell carcinoma of the lower leg, developed on top of necrobiosis lipoidica. After achieving the R0 resection, a 26 × 20-cm soft tissue and 15-cm tibial bone defect resulted. The contralateral leg had been lost due to the same disease 18 years before. We achieved a successful reconstruction of the leg using a pedicled fibula transplantation, an extended anterolateral thigh perforator flap, and an internal fixation with plate and screws. Two years after the original surgery, the patient is relapse-free and mobile, with adequate function of the reconstructed foot. CONCLUSIONS: Our case presented a unique combination of pedicled fibula transplantation and free extended ALT perforator flap to reconstruct an extensive defect after resection of a rare cSCC on top of NL. In selected cases, the boundaries of limb salvage can be pushed far beyond the current standards of treatment.

Microdialysis Reveals Anti-Inflammatory Effects of Sulfated Glycosaminoglycanes in the Early Phase of Bone Healing.

Although chronic inflammation inhibits bone healing, the healing process is initiated by an inflammatory phase. In a well-tuned sequence of molecular events, pro-inflammatory cytokines are secreted to orchestrate the inflammation response to injury and the recruitment of progenitor cells. These events in turn activate the secretion of anti-inflammatory signaling molecules and attract cells and mediators that antagonize the inflammation and initiate the repair phase. Sulfated glycosaminoglycanes (sGAG) are known to interact with cytokines, chemokines and growth factors and, thus, alter the availability, duration and impact of those mediators on the local molecular level. sGAG-coated polycaprolactone-co-lactide (PCL) scaffolds were inserted into critical-size femur defects in adult male Wistar rats. The femur was stabilized with a plate, and the defect was filled with either sGAG-containing PCL scaffolds or autologous bone (positive control). Wound fluid samples obtained by microdialysis were characterized regarding alterations of cytokine concentrations over the first 24 h after surgery. The analyses revealed the inhibition of the pro-inflammatory cytokines IL-1ß and MIP-2 in the sGAG-treated groups compared to the positive control. A simultaneous increase of IL-6 and TNF-α indicated advanced regenerative capacity of sGAG, suggesting their potential to improve bone healing.

The association of Health-Related Quality of Life and 1-year-survival in sarcoma patients-results of a Nationwide Observational Study (PROSa).

BACKGROUND: Sarcomas are rare cancers of high heterogeneity. Health-Related Quality of Life (HRQoL) has been shown to be a prognostic factor for survival in other cancer entities but it is unclear whether this applies to sarcoma patients. PATIENTS AND METHODS: HRQoL was prospectively assessed in adult sarcoma patients from 2017 to 2020 in 39 German recruiting sites using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Vital status was ascertained over the course of 1 year. HRQoL domains were analysed by multivariable cox-regressions including clinical and socio-economic risk factors. RESULTS: Of 1102 patients, 126 (11.4%) died during follow-up. The hazard ratio (HR) for global health was 0.73 per 10-point increase (95% confidence interval (CI) 0.64-0.85). HR for the HRQoL-summary score was 0.74 (CI 0.64-0.85) and for physical functioning 0.82 (CI 0.74-0.89). There was also evidence that fatigue (HR 1.17, CI 1.10-1.25), appetite loss (HR 1.15, CI 1.09-1.21) and pain (HR 1.14, CI 1.08-1.20) are prognostic factors for survival. CONCLUSION: Our study adds sarcoma-specific evidence to the existing data about cancer survival in general. Clinicians and care-givers should be aware of the relations between HRQoL and survival probability and include HRQoL in routine assessment.

Impact of Sulfated Hyaluronan on Bone Metabolism in Diabetic Charcot Neuroarthropathy and Degenerative Arthritis.

Bone in diabetes mellitus is characterized by an altered microarchitecture caused by abnormal metabolism of bone cells. Together with diabetic neuropathy, this is associated with serious complications including impaired bone healing culminating in complicated fractures and dislocations, especially in the lower extremities, so-called Charcot neuroarthropathy (CN). The underlying mechanisms are not yet fully understood, and treatment of CN is challenging. Several in vitro and in vivo investigations have suggested positive effects on bone regeneration by modifying biomaterials with sulfated glycosaminoglycans (sGAG). Recent findings described a beneficial effect of sGAG for bone healing in diabetic animal models compared to healthy animals. We therefore aimed at studying the effects of low- and high-sulfated hyaluronan derivatives on osteoclast markers as well as gene expression patterns of osteoclasts and osteoblasts from patients with diabetic CN compared to non-diabetic patients with arthritis at the foot and ankle. Exposure to sulfated hyaluronan (sHA) derivatives reduced the exaggerated calcium phosphate resorption as well as the expression of genes associated with bone resorption in both groups, but more pronounced in patients with CN. Moreover, sHA derivatives reduced the release of pro-inflammatory cytokines in osteoclasts of patients with CN. The effects of sHA on osteoblasts differed only marginally between patients with CN and non-diabetic patients with arthritis. These results suggest balancing effects of sHA on osteoclastic bone resorption parameters in diabetes.

Clinical decision-making on spinal cord injury-associated pneumonia: a nationwide survey in Germany.

STUDY DESIGN: Survey study. OBJECTIVES: Spinal cord injury (SCI)-associated pneumonia (SCI-AP) is associated with poor functional recovery and a major cause of death after SCI. Better tackling SCI-AP requires a common understanding on how SCI-AP is defined. This survey examines clinical algorithms relevant for diagnosis and treatment of SCI-AP. SETTING: All departments for SCI-care in Germany. METHODS: The clinical decision-making on SCI-AP and the utility of the Centers for Disease Control and Prevention (CDC) criteria for diagnosis of 'clinically defined pneumonia' were assessed by means of a standardized questionnaire including eight case vignettes of suspected SCI-AP. The diagnostic decisions based on the case information were analysed using classification and regression trees (CART). RESULTS: The majority of responding departments were aware of the CDC-criteria (88%). In the clinical vignettes, 38-81% of the departments diagnosed SCI-AP in accordance with the CDC-criteria and 7-41% diagnosed SCI-AP in deviation from the CDC-criteria. The diagnostic agreement was not associated with the availability of standard operating procedures for SCI-AP management in the departments. CART analysis identified radiological findings, fever, and worsened gas exchange as most important for the decision on SCI-AP. Frequently requested supplementary diagnostics were microbiological analyses, C-reactive protein, and procalcitonin. For empirical antibiotic therapy, the departments used (acyl-)aminopenicillins/ß-lactamase inhibitors, cephalosporins, or combinations of (acyl-)aminopenicillins/ß-lactamase inhibitors with fluoroquinolones or carbapenems. CONCLUSIONS: This survey reveals a diagnostic ambiguity regarding SCI-AP despite the awareness of CDC-criteria and established SOPs. Heterogeneous clinical practice is encouraging the development of disease-specific guidelines for diagnosis and management of SCI-AP.

Characterization of Naturally Occurring Bioactive Factor Mixtures for Bone Regeneration.

In this study, the bone-regenerative potential of bioactive factors derived from adipose tissue, platelet-rich plasma (PRP) and conditioned medium from hypoxia-treated human telomerase immortalized bone-marrow-derived mesenchymal stem cells (hTERT-MSC) was investigated in vitro with the aim to develop cost-effective and efficient bone substitutes for optimized regeneration of bone defects. Adipose tissue was harvested from human donors undergoing reconstructive surgery, and adipose tissue extract (ATE) was prepared. Platelet lysates (PL) were produced by repeated freeze-thaw cycles of PRP, and hypoxia-conditioned medium (HCM) was obtained by culturing human telomerase immortalized bone-marrow-derived mesenchymal stromal cells for 5 days with 1% O2. Besides analysis by cytokine and angiogenesis arrays, ELISA was performed. Angiogenic potential was investigated in cocultures of bone-marrow-derived (BM)-MSC and human umbilical vein endothelial cells. Multiple angiogenic proteins and cytokines were detected in all growth factor mixtures. HCM and ATE contained high amounts of angiogenin and CCL2/MCP-1, whereas PL contained high amounts of IGFBP-1. Culturing cells with HCM and ATE significantly increased specific ALP activity of BM-MSC as well as tubule length and junctions of endothelial networks, indicating osteogenic and angiogenic stimulation. To achieve a synergism between chemoattractive potential and osteogenic and angiogenic differentiation capacity, a combination of different growth factors appears promising for potential clinical applications.

Malignant tumours of the foot and ankle.

Tumours of the foot and ankle constitute about 4-5% of all musculoskeletal tumours with the majority of them being benign. Diagnosis of malignant soft tissue or bone tumours is frequently delayed because of the relatively low prevalence and uncommon presentation at the foot and ankle. Suspicious lesions or lumps should be subjected to CT, MRI and biopsy. Subfascial location, lump size more than 5 cm, increase in size, painful and recurrent tumours should raise the suspicion of malignancy and lead to patient referral to a designated tumour centre. Neoadjuvant and adjuvant systemic chemotherapy and/or radiation therapy, isolated limb perfusion (ILP) and hyperthermia for malignant tumours have to be discussed in a multidisciplinary tumour board. With the advances in local and free tissue transfer, limb-sparing techniques have increasingly replaced primary amputations thus preserving lower limb function as much as possible without compromising on the principles of oncologic resection.

Leptin-deficiency eradicates the positive effect of traumatic brain injury on bone healing: histological analyses in a combined trauma mouse model.

INTRODUCTION: The combination of traumatic brain injury (TBI) and long-bone fracture leads to increased formation of callus and mineral density in wild-type (WT) mice. However, this effect was not detected radiologically in leptin-deficient mice. Due to the complex interactions between hormonal and bone metabolism and the important role of leptin in this setting, our aim was to investigate morphologic properties and the tissue composition in the fracture callus comparing WT and leptin-deficient mice. METHODS: Female C57/Black6N mice (n=36) and leptin deficient ob/ob mice (n=36) each were assigned to two groups (fracture Fx/combined trauma Fx/TBI). Femoral osteotomy was stabilized with external fixator, TBI was induced with controlled cortical impact injury. After sacrifice of the animals, femora were harvested, cryofixated, and 7 µm slices were prepared. Staining was performed adhering to Movat's Pentachrome protocol. Histomorphometric analysis, quantifying percentage of mineralized bone area, and a semi-quantitative evaluation of bone bridging were performed. RESULTS: Leptin deficient mice showed a higher rate of non-union after osteotomy, less callus formation in the osteotomy gap, and unexpected bone and cartilage formation independent of the osteotomy region. DISCUSSION: Leptin plays an important role in fracture healing and bone formation. Without Leptin, the positive effect of TBI on fracture healing ceases. The comprehension of the underlying pathophysiological process could sign important for novel strategies in stimulation of fracture healing.

Natural Killer (NK) Cell Functionality after human Spinal Cord Injury (SCI): protocol of a prospective, longitudinal study.

BACKGROUND: Natural killer (NK) cells comprise the main components of lymphocyte-mediated nonspecific immunity. Through their effector function they play a crucial role combating bacterial and viral challenges. They are also thought to be key contributors to the systemic spinal cord injury-induced immune-deficiency syndrome (SCI-IDS). SCI-IDS increases susceptibility to infection and extends to the post-acute and chronic phases after SCI. METHODS AND DESIGN: The prospective study of NK cell function after traumatic SCI was carried out in two centers in Berlin, Germany. SCI patients and control patients with neurologically silent vertebral fracture also undergoing surgical stabilization were enrolled. Furthermore healthy controls were included to provide reference data. The NK cell function was assessed at 7 (5-9) days, 14 days (11-28) days, and 10 (8-12) weeks post-trauma. Clinical documentation included the American Spinal Injury Association (ASIA) impairment scale (AIS), neurological level of injury, infection status, concomitant injury, and medications. The primary endpoint of the study is CD107a expression by NK cells (cytotoxicity marker) 8-12 weeks following SCI. Secondary endpoints are the NK cell's TNF-α and IFN-γ production by the NK cells 8-12 weeks following SCI. DISCUSSION: The protocol of this study was developed to investigate the hypotheses whether i) SCI impairs NK cell function throughout the post-acute and sub-acute phases after SCI and ii) the degree of impairment relates to lesion height and severity. A deeper understanding of the SCI-IDS is crucial to enable strategies for prevention of infections, which are associated with poor neurological outcome and elevated mortality. TRIAL REGISTRATION: DRKS00009855 .

Quantitative in vivo fusion assessment by (18)F-fluoride PET/CT following en bloc spondylectomy.

PURPOSE: The purpose of this retrospective analyses was to evaluate the bone viability in the ventral column of the spine following large segmental defect reconstructions. Osseous integration of implants following spinal fusion procedures is an essential precondition to provide adequate mechanical strength to any applied forces and subsequently satisfying patient outcomes. Although CT scan is the non-invasive gold standard for fusion assessment, it lacks the ability to visualize bone viability and, therefore, discrepancy remains about sensitivity and specificity of CT as evaluation tool of spinal fusion. METHODS: A novel modality, (18)F Fluoride PET/CT, specifically allows quantitative in vivo evaluation of metabolic activity of the osseous integration. Bone viability following large segmental reconstructions in patients after mono- and multi-level en bloc spondylectomies (EBS) was analyzed. Spinal fusion was assessed on plain radiographs and CT scans according to the FDA fusion criteria as well as (18)F PET/CT. RESULTS: A total of eight patients underwent (18)F PET/CT were included (one 4-level-, one 3-level, two 2-level and four 1-level EBS). The average follow-up between EBS and radiographic studies was 24.8 months. On plain radiographs and CT scans, successful fusion was confirmed in all patients. However, (18)F PET/CT showed non-union in all cases. The metabolic bone activity within the cage was fourfold decreased compared to the reference vertebra, whereas the metabolic activity of the adjacent endplates was 1.6-fold increased compared to the reference vertebra. CONCLUSION: This study suggests a discrepancy between fusion rates assessed by plain radiographs and CT scan compared to (18)F PET/CT.

Positive Outcome After a Small-Caliber Gunshot Fracture of the Upper Cervical Spine without Neurovascular Damage.

BACKGROUND: Gunshot wounds to the cervical spine most frequently concur with serious injuries to the spinal cord and cervical vessels and often have a fatal outcome. CASE REPORT: We describe the case of a 35-year-old male with a complex fracture of the C2 vertebra body and a mandibular fracture after a penetration gunshot to the cervical spine. Computed tomography (CT) at admission revealed the exact extent of the fractures and the small caliber bullet lodged next to the C2 vertebra. In this rare and extremely lucky case no collateral vascular or neurological damage was detected. Eighteen months after surgical bullet removal and posterior C1-C3 fusion complete bone healing of the C2 vertebra was achieved and there were no secondary neurovascular deficits. CONCLUSIONS: Immediate surgical C1-C3 fixation resulted in an excellent outcome without secondary neurovascular deficits in this rare case of traumatic complex C2 vertebral fracture caused by a gunshot injury.

Adequate surgical treatment of periprosthetic femoral fractures following hip arthroplasty does not correlate with functional outcome and quality of life.

PURPOSE: This study aimed to analyse functional outcome and quality of life (QoL) after surgical treatment of periprosthetic femoral fractures (PPF) following total hip arthroplasty (THA). METHODS: This retrospective study assessed 67 patients from 2005 to 2012. Epidemiologic data, surgical details, comorbidities, deaths and postoperative complications were recorded. Functional assessment included Harris Hip Score (HHS) and range of motion (ROM); QoL was assessed using the Short-Form Health Survey of 36 questions (SF-36) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. RESULTS: Mean HHS was 69 ± 21 and ROM 96° ± 17°. Mean SF-36 and WOMAC scores revealed 44 ± 7.2 and 18.9 ± 19.6, respectively. The complication rate was 25.4%; 23.7% of patients died. Analysis revealed no statistical influence on final outcome as a function of fracture type or treatment strategy. Comorbidities seem to influence functional outcome. CONCLUSION: PPF following THA are accompanied by a perceptible decline of function and remarkably high complication rates. In contrast to fracture classification and treatment type, American Society of Anesthesiologists (ASA) score predicts outcome.

[Reassessment of the emergency medical service deployment indication catalogue after traffic accidents]. / Reevaluation des Notarzteinsatzindikationskataloges nach Verkehrsunfällen.

BACKGROUND: The emergency physician indication catalogue is based on outdated studies and provides limited guidance for alarm criteria following traffic accidents. Advances in vehicle safety technology and changes in available resources necessitate a re-evaluation of the indications. The aim of this retrospective registry study is to identify preclinically assessable variables for severe injuries sustained in traffic accidents. METHODS: A total of 47,145 individuals involved in accidents between 1 January 2000 and 31 December 2021 from the GIDAS database were included. Separate datasets for severe (AIS 3+) and minor injuries were evaluated. RESULTS: Ejection (PPV 80.6%), entrapment (PPV 75.6%), burning vehicles (PPV 57.1%), challenging rescue situations (PPV 56.3%), vehicle disintegration (PPV 51.6%), and amnesia (PPV 50.3%) indicated severe injuries among vehicle occupants. For vulnerable road users (motorcyclists, cyclists, pedestrians), helmet loss (PPV 61.1%), being run over/dragging (PPV 41.9%), opponent vehicle window breakage (PPV 35.8%), and subsequent collision with objects (PPV 31.1%) were also identified. The χ2-test revealed significant associations between the variables and severe injuries. Combined variables achieved PPV values above 82%. DISCUSSION: The current emergency physician indication catalogue provides limited preclinically detectable criteria and should be revised based on the objective registry data. Query models for emergency dispatchers should be tested.

Interobserver variability in preclinical assessment of collision variables following traffic accidents.

PURPOSE: Traffic accidents persist as a leading cause of death. European law mandates the integration of automatic emergency call systems (eCall). Our project focuses on an automated injury prediction device for car accidents, correlating technical and epidemiological input data, such as age, gender, seating position, impact on the passenger compartment, seatbelt usage, impact direction, EES, vehicle class, and airbag deployment. This study aims to explore interobserver variability in data collection quality in real accident scenarios. The assessment will evaluate the impact of user training and measure the time needed for data collection to inform user recommendations for the prehospital assessment. Insights from this study can aid in evaluating the ability of different professional groups to identify potential accident-independent parameters at accident scenes. This includes, among other things, relaying information to dispatchers at rescue control centers, also within the context of telemedicine approaches. METHODS: During group sessions, real accident scenarios were presented both before and after a training presentation. Participants, including laypersons, accident research staff, emergency services, hospital physicians, and emergency physicians, visually assessed injury prediction parameters within a time limit. Training involved defining and explaining parameters using accident images. The study analyzed participant demographics, prediction accuracy, and time required, comparing assessment quality between professional groups and before and after training. RESULTS: In summary, the study demonstrates that training had a significantly positive impact on the quality of assessment for technical accident parameters. The processing time decreased significantly after training. A notable training effect was observed, particularly for the parameters of rigid collision object, affected passenger compartment, energy equivalent speed (EES), and front and side airbags. It was recommended that individuals without prior knowledge should receive training on assessing EES. Overall, it was evident that technical parameters following a traffic accident can be well assessed through training, irrespective of the professional group. CONCLUSION: Significant differences in the assessment quality of technical accident parameters were observed based on technical and medical expertise. After user training, interdisciplinary differences were reconciled, and all professional groups yielded comparable results, indicating that training can enhance the assessment abilities of all participants in the rescue chain, while the time required for assessing accident parameters was significantly reduced with training.

[Treatment strategies for recurrent rectal cancer]. / Therapiestrategien beim Rektumkarzinomrezidiv.

Multimodal treatment approaches with neoadjuvant radiotherapy and chemotherapy followed by oncological and total mesorectal excision (TME) have significantly reduced the recurrence rate even in locally advanced rectal cancer. Nevertheless, up to 10% of patients develop a local relapse. Surgical R0 resection is the only chance of a cure in the treatment of locally recurrent rectal cancer (LRRC). Due to the altered anatomy and physiology of the true pelvis as a result of the pretreatment and operations as well as the localization and extent of the recurrence, the treatment decision is individualized and remains a challenge for the interdisciplinary team. Even locally advanced tumors with involvement of adjacent structures can be treated in designated centers using multimodal treatment concepts with potentially curative intent.

Improved weight bearing during gait at 6 weeks post-surgery with an angle stable locking system after distal tibial fracture.

BACKGROUND: Functional recovery after intramedullary nailing of distal tibial fractures can be monitored using ipsilateral vertical ground reaction forces (vGRF), giving insight into recovery of patients' gait symmetry. Previous work compared patient cohorts to healthy controls, but it remains unclear if these metrics can identify treatment-based differences in return to function post-surgery. RESEARCH QUESTION: Is treatment of a distal tibial fracture with intramedullary nailing with an angle stable locking system (ASLS) associated with higher ipsilateral vGRF and improved symmetry compared to conventional intramedullary nailing at an early time point? METHODS: Thirty-nine patients treated with ASLS intramedullary nailing were retrospectively compared to thirty-nine patients with conventional locking. vGRFs were collected at 1, 6, 12, 26, and 52 weeks post-surgery during standing and gait. Discrete metrics of ipsilateral vGRF (maximal force, impulse) and asymmetry were compared between treatments at each time point. Time-scale comparisons of ipsilateral vGRF and lower limb asymmetry were additionally performed for gait trials. Mann-Whitney Test or a two-way analysis of variance tested discrete comparisons; statistical non-parametric mapping tested time-scale data between treatment groups. RESULTS: During gait, ASLS-treated patients applied more load on the operated limb (17-38% stance, p = 0.015) and consequently loaded limbs more symmetrically (8-37% stance, p = 0.008) during the loading response at 6 weeks post-surgery compared to conventional IM treatment. Discrete measures of symmetry at the same time point identified treatment-based differences in maximal force (p = 0.039) and impulse (p = 0.012), with ASLS-treated patients exhibiting more symmetry. No differences were identified in gait trials at later time points nor from all standing trials. SIGNIFICANCE: During the initial loading response of gait, increased ipsilateral vGRF and improved weightbearing symmetry were identified in ASLS patients at 6 weeks post-surgery compared to conventional IM nailing. Early and objective metrics of dynamic movement are suggested to identify treatment-based differences in functional recovery.

Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this in vivo study was to analyze if posterolateral spinal fusion (PLF) could be improved by utilizing a calcium sulfate/hydroxyapatite (CaS/HA) carrier co-delivering rhBMP-2 and zoledronic acid (ZA). Six groups were allocated (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, and CaS/HA + BMP-2 + local ZA). 10-week-old male Wistar rats, were randomly assigned to undergo L4-L5 PLF with implantation of group-dependent scaffolds. At 3 and 6 weeks, the animals were euthanized for radiography, µCT, histological staining, or biomechanical testing to evaluate spinal fusion. The results demonstrated that the CaS/HA biomaterial alone or in combination with local or systemic ZA didn't support PLF. However, the delivery of rhBMP-2 significantly promoted PLF. Combining systemic ZA with BMP-2 didn't enhance spinal fusion. Notably, the co-delivery of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF, without inhibiting systemic bone turnover, and potentially reduced the dose of rhBMP-2. Together, the treatment regimen of CaS/HA biomaterial co-delivering rhBMP-2 and ZA could potentially be a safe and cost-effective off-the-shelf bioactive bone substitute to enhance spinal fusion.

Surgical and Oncologic Outcome following Sacrectomy for Primary Malignant Bone Tumors and Locally Recurrent Rectal Cancer.

INTRODUCTION: Bone sarcoma or direct pelvic carcinoma invasion of the sacrum represent indications for partial or total sacrectomy. The aim was to describe the oncosurgical management and complication profile and to analyze our own outcome results following sacrectomy. METHODS: In a retrospective analysis, 27 patients (n = 8/10/9 sarcoma/chordoma/locally recurrent rectal cancer (LRRC)) were included. There was total sacrectomy in 9 (incl. combined L5 en bloc spondylectomy in 2), partial in 10 and hemisacrectomy in 8 patients. In 12 patients, resection was navigation-assisted. For reconstruction, an omentoplasty, VRAM-flap or spinopelvic fixation was performed in 20, 10 and 13 patients, respectively. RESULTS: With a median follow-up (FU) of 15 months, the FU rate was 93%. R0-resection was seen in 81.5% (no significant difference using navigation), and 81.5% of patients suffered from one or more minor-to-moderate complications (especially wound-healing disorders/infection). The median overall survival was 70 months. Local recurrence occurred in 20%, while 44% developed metastases and five patients died of disease. CONCLUSIONS: Resection of sacral tumors is challenging and associated with a high complication profile. Interdisciplinary cooperation with visceral/vascular and plastic surgery is essential. In chordoma patients, systemic tumor control is favorable compared to LRRC and sarcomas. Navigation offers gain in intraoperative orientation, even if there currently seems to be no oncological benefit. Complete surgical resection offers long-term survival to patients undergoing sacrectomy for a variety of complex diseases.

The SCIentinel study--prospective multicenter study to define the spinal cord injury-induced immune depression syndrome (SCI-IDS)--study protocol and interim feasibility data.

BACKGROUND: Infections are the leading cause of death in the acute phase following spinal cord injury and qualify as independent risk factor for poor neurological outcome ("disease modifying factor"). The enhanced susceptibility for infections is not stringently explained by the increased risk of aspiration in tetraplegic patients, neurogenic bladder dysfunction, or by high-dose methylprednisolone treatment. Experimental and clinical pilot data suggest that spinal cord injury disrupts the balanced interplay between the central nervous system and the immune system. The primary hypothesis is that the Spinal Cord Injury-induced Immune Depression Syndrome (SCI-IDS) is 'neurogenic' including deactivation of adaptive and innate immunity with decreased HLA-DR expression on monocytes as a key surrogate parameter. Secondary hypotheses are that the Immune Depression Syndrome is i) injury level- and ii) severity-dependent, iii) triggers transient lymphopenia, and iv) causes qualitative functional leukocyte deficits, which may endure the post-acute phase after spinal cord injury. METHODS/DESIGN: SCIentinel is a prospective, international, multicenter study aiming to recruit about 118 patients with acute spinal cord injury or control patients with acute vertebral fracture without neurological deficits scheduled for spinal surgery. The assessment points are: i) <31 hours, ii) 31-55 hours, iii) 7 days, iv) 14 days, and v) 10 weeks post-trauma. Assessment includes infections, concomitant injury, medication and neurological classification using American Spinal Injury Association impairment scale (AIS) and neurological level. Laboratory analyses comprise haematological profiling, immunophenotyping, including HLA-DR expression on monocytes, cytokines and gene expression of immune modulators. We provide an administrative interim analysis of the recruitment schedule of the trial. DISCUSSION: The objectives are to characterize the dysfunction of the innate and adaptive immune system after spinal cord injury and to explore its proposed 'neurogenic' origin by analyzing its correlation with lesion height and severity. The trial protocol considers difficulties of enrolment in an acute setting, and loss to follow up. The administrative interim analysis confirmed the feasibility of the protocol. Better understanding of the SCI-IDS is crucial to reduce co-morbidities and thereby to attenuate the impact of disease modifying factors to protect neurological "outcome at risk". This putatively results in improved spinal cord injury medical care. TRIAL REGISTRATION DRKS-ID: DRKS00000122 (German Clinical Trials Registry).