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

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

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

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

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

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

Se Status Prediction by Food Intake as Compared to Circulating Biomarkers in a West Algerian Population

Algeria is the largest country in Africa, located close to the Mediterranean coastal area, where nutrients consumption varies widely. Local data on selenium composition of foods are not available. We postulated a close correlation between selenium status predictions from food consumption analysis with a quantitative analysis of circulating biomarkers of selenium status. Population characteristics were recorded from 158 participants and dietary selenium intake was calculated by 24-h recall. The average total plasma selenium was 92.4 ± 18.5 µg/L and the mean of selenium intake was 62.7 µg/day. The selenoprotein P concentration was 5.5 ± 2.0 mg/L and glutathione peroxidase 3 activity was 247.3 ± 41.5 U/L. A direct comparison of the dietary-derived selenium status to the circulating selenium biomarkers showed no significant interrelation. Based on absolute intakes of meat, potato and eggs, a model was deduced that outperforms the intake composition-based prediction from all food components significantly (DeLong's test, p = 0.029), yielding an area under the curve of 82%. Selenium status prediction from food intake remains a challenge. Imprecision of survey method or information on nutrient composition makes extrapolating selenium intake from food data providing incorrect insights into the nutritional status of a given population, and laboratory analyses are needed for reliable information

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

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

Selenium Deficiency Is Associated with Mortality Risk from COVID-19

SARS-CoV-2 infections underlie the current coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium (Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. The mortality risk from a severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples (n = 166) from COVID-19 patients (n = 33) were collected consecutively and analyzed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (r = 0.7758, p < 0.001), pointing to an insufficient Se availability for optimal selenoprotein expression. In comparison with reference data from a European cross-sectional analysis (EPIC, n = 1915), the patients showed a pronounced deficit in total serum Se (mean ± SD, 50.8 ± 15.7 vs. 84.4 ± 23.4 µg/L) and SELENOP (3.0 ± 1.4 vs. 4.3 ± 1.0 mg/L) concentrations. A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L, was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared with non-survivors (Se; 53.3 ± 16.2 vs. 40.8 ± 8.1 µg/L, SELENOP; 3.3 ± 1.3 vs. 2.1 ± 0.9 mg/L), recovering with time in survivors while remaining low or even declining in non-survivors. We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion of a relevant role of Se for COVID convalescence and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients

Free Zinc as a Predictive Marker for COVID-19 Mortality Risk

Free zinc is considered to be the exchangeable and biological active form of zinc in serum, and is discussed to be a suitable biomarker for alterations in body zinc homeostasis and related diseases. Given that coronavirus disease 2019 (COVID-19) is characterized by a marked decrease in total serum zinc, and clinical data indicate that zinc status impacts the susceptibility and severity of the infection, we hypothesized that free zinc in serum might be altered in response to SARS-CoV-2 infection and may reflect disease severity. To test this hypothesis, free zinc concentrations in serum samples of survivors and nonsurvivors of COVID-19 were analyzed by fluorometric microassay. Similar to the reported total serum zinc deficit measured by total reflection X-ray fluorescence, free serum zinc in COVID-19 patients was considerably lower than that in control subjects, and surviving patients displayed significantly higher levels of free zinc than those of nonsurvivors (mean ± SD; 0.4 ± 0.2 nM vs. 0.2 ± 0.1 nM; p = 0.0004). In contrast to recovering total zinc concentrations (r = 0.706, p < 0.001) or the declining copper–zinc ratio (r = −0.646; p < 0.001), free zinc concentrations remained unaltered with time in COVID-19 nonsurvivors. Free serum zinc concentrations were particularly low in male as compared to female patients (mean ± SD; 0.4 ± 0.2 nM vs. 0.2 ± 0.1 nM; p = 0.0003). This is of particular interest, as the male sex is described as a risk factor for severe COVID-19. Overall, results indicate that depressed free serum zinc levels are associated with increased risk of death in COVID-19, suggesting that free zinc may serve as a novel prognostic marker for the severity and course of COVID-19.DFG, 316442145, FOR 2558: Interaktionen von essenziellen Spurenelementen in gesunden und erkrankten älteren Menschen(TraceAge)DFG, 424957847, TRR 296: Lokale Kontrolle der Schilddrüsenhormonwirkung (LocoTact

Selenium-Binding Protein 1 (SELENBP1) as Biomarker for Adverse Clinical Outcome After Traumatic Spinal Cord Injury

Introduction: Traumatic spinal cord injury (TSCI) presents a diagnostic challenge as it may have dramatic consequences for the affected patient. Additional biomarkers are needed for improved care and personalized therapy.Objective: Serum selenium binding protein 1 (SELENBP1) has been detected in myocardial infarction, reflecting hypoxic tissue damage and recovery odds. As SELENBP1 is usually not detected in the serum of healthy subjects, we tested the hypothesis that it may become detectable in TSCI and indicate tissue damage and regeneration odds.Methods: In this prospective observational study, patients with comparable injuries were allocated to three groups; vertebral body fractures without neurological impairment (control “C”), TSCI without remission (“G0”), and TSCI with signs of remission (“G1”). Consecutive serum samples were available from different time points and analyzed for SELENBP1 by sandwich immunoassay, for trace elements by X-ray fluorescence and for cytokines by multiplex immunoassays.Results: Serum SELENBP1 was elevated at admission in relation to the degree of neurological impairment [graded as A, B, C, or D according to the American Spinal Injury Association (AISA) impairment scale (AIS)]. Patients with the most severe neurological impairment (classified as AIS A) exhibited the highest SELENBP1 concentrations (p = 0.011). During the first 3 days, SELENBP1 levels differed between G0 and G1 (p = 0.019), and dynamics of SELENBP1 correlated to monocyte chemoattractant protein 1, chemokine ligand 3 and zinc concentrations.Conclusion: Circulating SELENBP1 concentrations are related to the degree of neurological impairment in TSCI and provide remission odds information. The tight correlation of SELENBP1 with CCL2 levels provides a novel link between Se metabolism and immune cell activation, with potential relevance for neurological damage and regeneration processes, respectively

Complications and risk management in the use of the reaming-irrigator-aspirator (RIA) system: RIA is a safe and reliable method in harvesting autologous bone graft.

Autologous bone grafting (ABG) remains the gold standard for augmentation of bone defects. The RIA system has become more prevalent, but evidence regarding risk management and complications remain scarce. This study presents the risk management and complications associated with RIA in the largest single-center case series to date.All records, operative notes, lab data and radiographs of patients receiving a RIA procedure at Heidelberg´s University Hospital between 01/01/2010 and 31/12/2016 were reviewed. Multivariate logistic regression models adjusting for clinically relevant covariates were used to examine the respective relevance regarding the presence and absence of prolonged postoperative pain (PPP).A total of 341 RIA procedures on 306 patients were performed at our level-1 trauma center. The femur was the main donor site (98.53%; N = 336) whereas only in 1.47% (N = 5) the tibia was utilized. A total of 11 patients showed a relevant loss of hemoglobin requiring blood transfusion. A total of 22 patients suffered from PPP directly associated with the RIA procedure resulting in prevalence of 6.45%. The 6 major complications in our study were of diverse origin and all intraoperative complications took place in the early phase of the RIA procedure in our center (2010-2013). Our data revealed influence of sex (p = 0.0459) and age (p = 0.0596) on the criterion PPP. The favored model including sex and age resulted in an AUC of 66.2% (CI: 55.5%-76.9%).Perioperative blood loss remains a prevalent complication during RIA reaming. In addition, PPP occurs with a prevalence of 6.45%. This study showed a complication rate of 1.76%, emphasizing RIA´s overall safety and furthermore highlighting the need for vigilance in its application and prior extensive hands-on training of surgeons. Level of Evidence: II

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

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