Admission S100B fails as neuro-marker but is a good predictor for intrahospital mortality in major trauma patients.

BACKGROUND: S100 B is an extensively studied neuro-trauma marker, but its specificity and subsequently interpretation in major trauma patients might be limited, since extracerebral injuries are known to increase serum levels. Thus, we evaluated the potential role of S100B in the assessment of severe traumatic brain injury (TBI) in multiple injured patients upon emergency room (ER) admission and the first days of intensive care unit (ICU) stay. METHODS: Retrospective study employing trauma registry data derived from a level 1 trauma center. Four cohorts of patients were grouped: isolated TBI (iTBI), polytrauma patients with TBI (PT + TBI), polytrauma patients without TBI (PT-TBI) and patients without polytrauma or TBI (control). S100B-serum levels were assessed immediately after admission in the emergency room and during the subsequent ICU stay. Values were correlated with injury severity score (ISS), Glasgow Coma Score (GCS) and in-hospital mortality. RESULTS: 780 predominantly male patients (76 %) with a median age of 48 (30-63) and a median ISS of 24 (17-30) were enrolled in the study. Admission S100B correlated with ISS and TBI severity defined by the GCS (both p < 0.0001) but not with head abbreviated injury score (AIS) (p = 0.38). Compared with survivors, non-survivors had significantly higher median S100B levels in the ER (6.14 µg/L vs. 2.06 µg/L; p < 0.0001) and at ICU-day 1 (0.69 µg/L vs. 0.17 µg/L; p < 0.0001). S100B in the ER predicted mortality with an area under curve (AUC) of 0.77 (95 % CI 0,70-0,83, p < 0.0001), vs. 0.86 at ICU-day 1 (95 % CI 0,80-0,91, p < 0.0001). CONCLUSION: In conclusion, S100B is a valid biomarker for prediction of mortality in major trauma patients with a higher accuracy when assessed at the first day of ICU stay vs. immediately after ER admission. Since S100B did not correlate with pathologic TBI findings in multiple injured patients, it failed as predictive neuro-marker because extracerebral injuries demonstrated a higher influence on admission levels than neurotrauma. Although S100B levels are indicative for injury severity they should be interpreted with caution in polytrauma patients.

Pulsed Electromagnetic Fields (PEMF)-Physiological Response and Its Potential in Trauma Treatment.

Environmental biophysical interactions are recognized to play an essential part in the human biological processes associated with trauma recovery. Many studies over several decades have furthered our understanding of the effects that Pulsed Electromagnetic Fields (PEMF) have on the human body, as well as on cellular and biophysical systems. These investigations have been driven by the observed positive clinical effects of this non-invasive treatment on patients, mainly in orthopedics. Unfortunately, the diversity of the various study setups, with regard to physical parameters, molecular and cellular response, and clinical outcomes, has made it difficult to interpret and evaluate commonalities, which could, in turn, lead to finding an underlying mechanistic understanding of this treatment modality. In this review, we give a birds-eye view of the vast landscape of studies that have been published on PEMF, presenting the reader with a scaffolded summary of relevant literature starting from categorical literature reviews down to individual studies for future research studies and clinical use. We also highlight discrepancies within the many diverse study setups to find common reporting parameters that can lead to a better universal understanding of PEMF effects.

Wavelength-Dependent Effects of Photobiomodulation for Wound Care in Diabetic Wounds.

Photobiomodulation, showing positive effects on wound healing processes, has been performed mainly with lasers in the red/infrared spectrum. Light of shorter wavelengths can significantly influence biological systems. This study aimed to evaluate and compare the therapeutic effects of pulsed LED light of different wavelengths on wound healing in a diabetic (db/db) mouse excision wound model. LED therapy by Repuls was applied at either 470 nm (blue), 540 nm (green) or 635 nm (red), at 40 mW/cm2 each. Wound size and wound perfusion were assessed and correlated to wound temperature and light absorption in the tissue. Red and trend-wise green light positively stimulated wound healing, while blue light was ineffective. Light absorption was wavelength-dependent and was associated with significantly increased wound perfusion as measured by laser Doppler imaging. Shorter wavelengths ranging from green to blue significantly increased wound surface temperature, while red light, which penetrates deeper into tissue, led to a significant increase in core body temperature. In summary, wound treatment with pulsed red or green light resulted in improved wound healing in diabetic mice. Since impeded wound healing in diabetic patients poses an ever-increasing socio-economic problem, LED therapy may be an effective, easily applied and cost-efficient supportive treatment for diabetic wound therapy.

A Novel Artificial Intelligence-Based Approach for Quantitative Assessment of Angiogenesis in the Ex Ovo CAM Model.

Angiogenesis is a highly regulated process. It promotes tissue regeneration and contributes to tumor growth. Existing therapeutic concepts interfere with different steps of angiogenesis. The quantification of the vasculature is of crucial importance for research on angiogenetic effects. The chorioallantoic membrane (CAM) assay is widely used in the study of angiogenesis. Ex ovo cultured chick embryos develop an easily accessible, highly vascularised membrane on the surface. Tumor xenografts can be incubated on this membrane enabling studies on cancer angiogenesis and other major hallmarks. However, there is no commonly accepted gold standard for the quantification of the vasculature of the CAM. We compared four widely used measurement techniques to identify the most appropriate one for the quantification of the vascular network of the CAM. The comparison of the different quantification methods suggested that the CAM assay application on the IKOSA platform is the most suitable image analysis application for the vasculature of the CAM. The new CAM application on the IKOSA platform turned out to be a reliable and feasible tool for practical use in angiogenesis research. This novel image analysis software enables a deeper exploration of various aspects of angiogenesis and might support future research on new anti-angiogenic strategies for cancer treatment.

Shockwaves Increase In Vitro Resilience of Rhizopus oryzae Biofilm under Amphotericin B Treatment.

Acoustical biophysical therapies, including ultrasound, radial pressure waves, and shockwaves, have been shown to harbor both a destructive and regenerative potential depending on physical treatment parameters. Despite the clinical relevance of fungal biofilms, little work exits comparing the efficacy of these modalities on the destruction of fungal biofilms. This study evaluates the impact of acoustical low-frequency ultrasound, radial pressure waves, and shockwaves on the viability and proliferation of in vitro Rhizopus oryzae biofilm under Amphotericin B induced apoptosis. In addition, the impact of a fibrin substrate in comparison with a traditional polystyrene well-plate one is explored. We found consistent, mechanically promoted increased Amphotericin B efficacy when treating the biofilm in conjunction with low frequency ultrasound and radial pressure waves. In contrast, shockwave induced effects of mechanotransduction results in a stronger resilience of the biofilm, which was evident by a marked increase in cellular viability, and was not observed in the other types of acoustical pressure waves. Our findings suggest that fungal biofilms not only provide another model for mechanistical investigations of the regenerative properties of shockwave therapies, but warrant future investigations into the clinical viability of the therapy.

ESWT Diminishes Axonal Regeneration following Repair of the Rat Median Nerve with Muscle-In-Vein Conduits but Not after Autologous Nerve Grafting.

Investigations reporting positive effects of extracorporeal shockwave therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT after repair of the rat median nerve with either autografts (ANGs) or MVCs. In male Lewis rats, a 7 mm segment of the right median nerve was reconstructed either with an ANG or an MVC. For each reconstructive technique, one group of animals received one application of ESWT while the other rats served as controls. The animals were observed for 12 weeks, and nerve regeneration was assessed using computerized gait analysis, the grasping test, electrophysiological evaluations and histological quantification of axons, blood vessels and lymphatic vasculature. Here, we provide for the first time a comprehensive analysis of ESWT effects on nerve regeneration in a rat model of median nerve injury. Furthermore, this study is among the first reporting the quantification of lymphatic vessels following peripheral nerve injury and reconstruction in vivo. While we found no significant direct positive effects of ESWT on peripheral nerve regeneration, results following nerve repair with MVCs were significantly inferior to those after ANG repair.

A Comparative Feasibility Study for Transcranial Extracorporeal Shock Wave Therapy.

The potential beneficial regenerative and stimulatory extracorporeal shock wave therapy (ESWT) applications to the central nervous system have garnered interest in recent years. Treatment zones for these indications are acoustically shielded by bones, which heavily impact generated sound fields. We present the results of high-resolution tissue-realistic simulations, comparing the viability of different ESWT applicators in their use for transcranial applications. The performances of electrohydraulic, electromagnetic, and piezoelectric transducers for key reflector geometries are compared. Based on density information obtained from CT imaging of the head, we utilized the non-linear wave propagation toolset Matlab k-Wave to obtain spatial therapeutic sound field geometries and waveforms. In order to understand the reliability of results on the appropriate modeling of the skull, three different bone attenuation models were compared. We find that all currently clinically ESWT applicator technologies show significant retention of peak pressures and energies past the bone barrier. Electromagnetic transducers maintain a significantly higher energy flux density compared to other technologies while low focusing strength piezoelectric applicators have the weakest transmissions. Attenuation estimates provide insights into sound field degradation and energy losses, indicating that effective transcranial therapies can readily be attained with current applicators. Furthermore, the presented approach will allow for future targeted in silico development and the design of applicators and therapy plans to ultimately improve therapeutic outcomes.

Safe and Effective Treatment of Compromised Clavicle Fracture of the Medial and Lateral Third Using Focused Shockwaves.

A delay or failure to heal is the most common possible complication in clavicle fractures, especially in cases primarily treated conservatively. As the current standard therapy, surgical revision achieves good healing results, but is associated with potential surgery-related complications. Shockwave therapy as a non-invasive therapy shows similar reasonable consolidation rates in the non-union of different localizations, but avoids complications. Compromised clavicle fractures in the middle and lateral third treated with focused high-energy shockwave therapy were compared with those treated with surgical revision (ORIF). In addition, a three-dimensional computer simulation for evaluating the pressure distribution during shockwave application accompanied the clinical study. A comparable healing rate in bony consolidation was achieved in both groups. Significantly fewer complications, however, occurred in the shockwave group. The simulations showed safe application in this instance, particularly in avoiding lung tissue affection. When applied correctly, shockwaves represent a safe and promising therapy option for compromised clavicle fractures in the middle and lateral third.

Physical Considerations for In Vitro ESWT Research Design.

In vitro investigations, which comprise the bulk of research efforts geared at identifying an underlying biomechanical mechanism for extracorporeal shock wave therapy (ESWT), are commonly hampered by inadequate descriptions of the underlying therapeutic acoustical pressure waves. We demonstrate the necessity of in-situ sound pressure measurements inside the treated samples considering the significant differences associated with available applicator technologies and cell containment. A statistical analysis of pulse-to-pulse variability in an electrohydraulic applicator yields a recommendation for a minimal pulse number of n = 300 for cell pallets and suspensions to achieve reproducible treatments. Non-linear absorption behavior of sample holders and boundary effects are shown for transient peak pressures and applied energies and may serve as a guide when in-situ measurements are not available or can be used as a controllable experimental design factor. For the use in microbiological investigations of ESWT we provide actionable identification of common problems in describing physical shockwave parameters and improving experimental setups by; (1) promoting in-situ sound field measurements, (2) statistical evaluation of applicator variability, and (3) extrapolation of treatment parameters based on focal and treatment volumes.

A Low Cost Implantation Model in the Rat That Allows a Spatial Assessment of Angiogenesis.

There is continual demand for animal models that allow a quantitative assessment of angiogenic properties of biomaterials, therapies, and pharmaceuticals. In its simplest form, this is done by subcutaneous material implantation and subsequent vessel counting which usually omits spatial data. We have refined an implantation model and paired it with a computational analytic routine which outputs not only vessel count but also vessel density, distribution, and vessel penetration depth, that relies on a centric vessel as a reference point. We have successfully validated our model by characterizing the angiogenic potential of a fibrin matrix in conjunction with recombinant human vascular endothelial growth factor (rhVEGF165). The inferior epigastric vascular pedicles of rats were sheathed with silicone tubes, which were subsequently filled with 0.2 ml of fibrin and different doses of rhVEGF165, centrically embedding the vessels. Over 4 weeks, tissue samples were harvested and subsequently immunohistologically stained and computationally analyzed. The model was able to detect variations over the angiogenic potentials of growth factor spiked fibrin matrices. Adding 20 ng of rhVEGF165 resulted in a significant increase in vasculature while 200 ng of rhVEGF165 did not improve vascular growth. Vascularized tissue volume increased during the first week and vascular density increased during the second week. Total vessel count increased significantly and exhibited a peak after 2 weeks which was followed by a resorption of vasculature by week 4. In summary, a simple implantation model to study in vivo vascularization with only a minimal workload attached was enhanced to include morphologic data of the emerging vascular tree.