Rapid high-throughput processing of tissue samples for microbiological diagnosis of periprosthetic joint infections using bead-beating homogenization.

Enrichment of periprosthetic tissue samples in blood culture bottles (BCBs) for microbiological diagnosis of periprosthetic joint infections (PJI) is more reliable than the use of an enrichment broth. Nevertheless, the extremely time-consuming homogenization of the samples for BCB processing has so far limited its use, especially in high-throughput settings. We aimed to establish a highly scalable homogenization process of tissue samples for long-term incubation in BCBs. A protocol for homogenization of tissue samples using bead beating was established and validated. In a second step, the use of the homogenate for enrichment in BCBs was compared to the use of thioglycolate broth (TB) in terms of diagnostic accuracy using clinical tissue samples from 150 patients with suspected PJI. Among 150 analyzed samples, 35 samples met the microbiological criteria for PJI. Using BCB, 32 of 35 (91.4%) PJI were detected compared to 30 of 35 (85.7%) by TB. The use of BCB had a lower secondary contamination rate (2/115; 1.7% vs 4/115; 3.5%) but the trend was not significant due to low numbers of samples (P = 0.39). The time to process a batch of 12 samples using the established homogenization method was 23 ± 5 min (n = 10 batches). We established and validated a homogenization workflow that achieves the highest sensitivity in the microbiological diagnostic of PJI. The enrichment of the tissue homogenate in BCBs showed equally good results as the use of enrichment broth and allows semi-automated high-throughput processing while demonstrating lower contamination rates in our study.

Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases.

BACKGROUND: Since metastatic spreading of solid tumor cells often leads to a fatal outcome for most cancer patients, new approaches for patient-individualized, targeted immunotherapy are urgently needed. METHODS: Here, we established cell lines from four bone metastases of different tumor entities. We assessed AdCAR NK-92-mediated cytotoxicity in vitro in standard cytotoxicity assays as well as 3D spheroid models Results: AdCAR-engineered NK-92 cells successfully demonstrated distinct and specific cytotoxic potential targeting different tumor antigens expressed on cell lines established from bone metastases of mammary, renal cell and colorectal carcinoma as well as melanomas. In that process AdCAR NK-92 cells produced a multitude of NK effector molecules as well as pro inflammatory cytokines. Furthermore, AdCAR NK-92 showed increased cytotoxicity in 3D spheroid models which can recapitulate in vivo architecture, thereby bridging the gap between in vitro and in vivo models. CONCLUSIONS: AdCAR NK-92 cells may provide an interesting and promising "off-the-shelf" cellular product for the targeted therapy of cancers metastasizing to the bone, while utilization of clinically approved, therapeutic antibodies, as exchangeable adapter molecules can facilitate quick clinical translation.

In Vitro Evaluation of CD276-CAR NK-92 Functionality, Migration and Invasion Potential in the Presence of Immune Inhibitory Factors of the Tumor Microenvironment.

BACKGROUND: Melanoma is the most lethal of all skin-related cancers with incidences continuously rising. Novel therapeutic approaches are urgently needed, especially for the treatment of metastasizing or therapy-resistant melanoma. CAR-modified immune cells have shown excellent results in treating hematological malignancies and might represent a new treatment strategy for refractory melanoma. However, solid tumors pose some obstacles for cellular immunotherapy, including the identification of tumor-specific target antigens, insufficient homing and infiltration of immune cells as well as immune cell dysfunction in the immunosuppressive tumor microenvironment (TME). METHODS: In order to investigate whether CAR NK cell-based immunotherapy can overcome the obstacles posed by the TME in melanoma, we generated CAR NK-92 cells targeting CD276 (B7-H3) which is abundantly expressed in solid tumors, including melanoma, and tested their effectivity in vitro in the presence of low pH, hypoxia and other known factors of the TME influencing anti-tumor responses. Moreover, the CRISPR/Cas9-induced disruption of the inhibitory receptor NKG2A was assessed for its potential enhancement of NK-92-mediated anti-tumor activity. RESULTS: CD276-CAR NK-92 cells induced specific cytolysis of melanoma cell lines while being able to overcome a variety of the immunosuppressive effects normally exerted by the TME. NKG2A knock-out did not further improve CAR NK-92 cell-mediated cytotoxicity. CONCLUSIONS: The strong cytotoxic effect of a CD276-specific CAR in combination with an "off-the-shelf" NK-92 cell line not being impaired by some of the most prominent negative factors of the TME make CD276-CAR NK-92 cells a promising cellular product for the treatment of melanoma and beyond.

Novel adapter CAR-T cell technology for precisely controllable multiplex cancer targeting.

Chimeric antigen receptor (CAR)-T therapy holds great promise to sustainably improve cancer treatment. However, currently, a broad applicability of CAR-T cell therapies is hampered by limited CAR-T cell versatility and tractability and the lack of exclusive target antigens to discriminate cancerous from healthy tissues. To achieve temporal and qualitative control on CAR-T function, we engineered the Adapter CAR (AdCAR) system. AdCAR-T are redirected to surface antigens via biotin-labeled adapter molecules in the context of a specific linker structure, referred to as Linker-Label-Epitope. AdCAR-T execute highly specific and controllable effector function against a multiplicity of target antigens. In mice, AdCAR-T durably eliminate aggressive lymphoma. Importantly, AdCAR-T might prevent antigen evasion by combinatorial simultaneous or sequential targeting of multiple antigens and are capable to identify and differentially lyse cancer cells by integration of adapter molecule-mediated signals based on multiplex antigen expression profiles. In consequence the AdCAR technology enables controllable, flexible, combinatorial, and selective targeting.

Establishment and Characterization of a Sclerosing Spindle Cell Rhabdomyosarcoma Cell Line with a Complex Genomic Profile.

Sclerosing spindle cell rhabdomyosarcoma (SSRMS) is a rare rhabdomyosarcomas (RMS) subtype. Especially cases bearing a myogenic differentiation 1 (MYOD1) mutation are characterized by a high recurrence and metastasis rate, often leading to a fatal outcome. SSRMS cell lines are valuable in vitro models for studying disease mechanisms and for the preclinical evaluation of new therapeutic approaches. In this study, a cell line established from a primary SSRMS tumor of a 24-year-old female after multimodal chemotherapeutic pretreatment has been characterized in detail, including immunohistochemistry, growth characteristics, cytogenetic analysis, mutation analysis, evaluation of stem cell marker expression, differentiation potential, and tumorigenicity in mice. The cell line which was designated SRH exhibited a complex genomic profile, including several translocations and deletions. Array-comparative genomic hybridization (CGH) revealed an overall predominating loss of gene loci. The mesenchymal tumor origin was underlined by the expression of mesenchymal markers and potential to undergo adipogenic and osteogenic differentiation. Despite myogenic marker expression, terminal myogenic differentiation was inhibited, which might be elicited by the MYOD1 hotspot mutation. In vivo tumorigenicity could be confirmed after subcutaneous injection into NOD/SCID/γcnull mice. Summarized, the SRH cell line is the first adult SSRMS cell line available for preclinical research on this rare RMS subtype.

Adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cells: an off-the-shelf cellular therapeutic for universal tumor targeting.

Despite the recent success of CAR T cells targeting CD19 and CD22 in hematological malignancies, the production of CAR T cells still requires an extensive manufacturing process. The well-established NK-92 cell line provides a promising alternative to produce CAR-modified effector cells in a GMP-compliant, cost-effective way. NK-92 can be redirected against a variety of surface antigens by our adapter CAR (AdCAR) system utilizing biotinylated antibodies (bAb) as adapter molecules. Selected bAb were capable of inducing significant AdCAR NK-92-mediated lysis of non-Hodgkin lymphoma (NHL) and mantle-cell lymphoma (MCL) cell lines as well as primary MCL and chronic lymphocytic leukemia (CLL) cells. AdCAR specificity was proven using a JeKo-1 CD19/CD20 knockout antigen-loss model. Moreover, through combinations of bAb, AdCAR NK-92 cells are capable of combatting tumor antigen evasion mechanisms. In conclusion, we successfully generated the AdCAR NK-92 cell line which can be manufactured as an "off-the-shelf, on-demand" product allowing universal and tunable tumor targeting.

Fluoroscopic Marker-Based Guidance System Improves Gamma Lag Screw Placement During Nailing of Intertrochanteric Fractures: A Randomized Controlled Trial.

OBJECTIVES: To determine whether a fluoroscopy-based navigation system would improve tip-apex distance (TAD) compared with the conventional technique. DESIGN: Randomized controlled trial. SETTING: Level 1 trauma center. PATIENTS: A total of 161 patients were screened for inclusion in the study. After meeting inclusion and exclusion criteria, 31 patients were randomized (n = 18 navigated vs. n = 13 control group), with the patient blinded to the result. INTERVENTION: Fluoroscopy-based navigated guidance of lag screw length and position. MAIN OUTCOME MEASURES: Average TAD and the proportion of TAD over 25 mm. RESULTS: TAD was lower in the navigated group compared with the control group (mean = 17.5 vs. 24.2 mm; P = 0.0018). No navigated cases exceeded the 25 mm TAD threshold, compared with 39% of conventional cases (P = 0.0076). Navigation resulted in fewer drilling attempts compared with the conventional technique (median = 1 vs. 4 attempts; P < 0.0001). We detected no significant differences in operation time or total number of fluoroscopic images (P > 0.05). CONCLUSIONS: Fluoroscopy-based computer navigated Gamma nailing for intertrochanteric fractures improved TAD and reduced the number of drilling attempts without increasing operation time compared with the conventional fluoroscopy-guided technique in a teaching hospital setting. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Variability of landmark acquisition affects tunnel calculation in image-free ACL navigation.

PURPOSE: The purpose of this study was to determine the inter- and intraobserver variability of intraarticular landmark identification for tunnel position calculation in image-free anterior cruciate ligament (ACL) navigation. METHODS: In a test/retest scenario, thirteen experienced ACL surgeons (>50 reconstructions year) experienced in image-free ACL navigation were asked to identify the landmarks required for image-free ACL navigation in the same cadaver knee. Landmark positions were registered using a fluoroscopic ACL navigation system. Positions were determined using validated radiological measurement methods. For variability analysis, mean positions, deviations between the test/retest positions, standard deviations (SD) and range were calculated. RESULTS: Interobserver analysis showed a mean variability (SD) for the tibial landmark positions of 3.0 mm with deviations of up to 24.3 mm (range). Mean femoral landmark variability was 2.9 mm (SD) with deviations of up to 11.3 mm (range). Intraobserver analysis showed a tibial reproducibility of 2.2 mm (SD 2.0 mm; range 10.9 mm) and a femoral of 1.9 mm (SD 1.9 mm; range 10.4 mm). CONCLUSION: The data of the presented study suggest that a considerable inter- and intraobserver variability in intraarticular landmark identification exists. Reasonable ranges were found that have to be considered as a potential risk for miscalculation of tunnel positions in image-free ACL reconstruction. CLINICAL RELEVANCE: Landmark acquisition affects tunnel calculation in image-free ACL. LEVEL OF EVIDENCE: IV.

Pathologic fracture of the distal radius in a 25-year-old patient with a large unicameral bone cyst.

BACKGROUND: Distal radius fractures (DRF) are often referred to as osteoporosis indicator fractures as their incidence increases from age 45. In the group of young adults, distal radius fractures normally result from high-energy trauma. Wrist fractures in young patients without adequate trauma thus raise suspicion of a pathologic fracture. In this report we present the case of a fractured unicameral bone cyst (UBC) at the distal radius in a young adult.To the author's best knowledge, this is the first detailed report in an UBC at the distal radius causing a pathologic DRF in an adult patient. CASE PRESENTATION: A 25-year-old otherwise healthy male presented to our Emergency Department after a simple fall on his right outstretched hand. Extended diagnostics revealed a pathologic, dorsally displaced, intra-articular distal radius fracture secondary to a unicameral bone cyst occupying almost the whole metaphysis of the distal radius. To stabilize the fracture, a combined dorsal and volar approach was used for open reduction and internal fixation. A tissue specimen for histopathological examination was gathered and the lesion was filled with an autologous bone graft harvested from the ipsilateral femur using a reamer-irrigator-aspirator (RIA) system. Following one revision surgery due to an intra-articular step-off, the patient recovered without further complications. CONCLUSIONS: Pathologic fractures in young patients caused by unicameral bone cysts require extended diagnostics and adequate treatment. A single step surgical treatment is reasonable if fracture and bone cyst are treated appropriately. Arthroscopically assisted fracture repair may be considered in intra-articular fractures or whenever co-pathologies of the carpus are suspected.

Position of polyaxial versus monoaxial screws in locked plating for proximal humeral fractures: analysis of a prospective randomized study.

BACKGROUND: Aim of the study was to compare the chosen position of polyaxial locking screws with the position of monoaxial screws in the humeral head of proximal humeral fractures treated by locked plating. METHODS: In a prospective randomized observational study, 124 consecutive patients (mean age 70.9±14.8 years) sustaining a displaced proximal humeral fracture were treated with either monoaxial or polyaxial screw-inserted locking plate fixation. The chosen positions of locking screws were identified from standardized postoperative radiographs in anteroposterior and outlet-view, with regard to a regional mapping of the humeral head. RESULTS: In monoaxial locking technique, a mean of 6 screws purchased the humeral head (95% CI 5.1-6.2), and in polyaxial locking technique, a mean of 4 screws (95% CI 3.3-4.5), respectively. Screws were placed in the regions superolateral: monoaxial 24.8%, polyaxial 20.7% (p=0.49); superomedial: monoaxial 21.9%, polyaxial 20.0% (p=0.433); inferolateral: monoaxial 32.5%, polyaxial 35.0% (p=0.354); inferomedial: monoaxial 20.8%, polyaxial 24.2% (p=0.07), superoposterior: monoaxial 45.5%, polyaxial 30.8% (p=0.57); superoanterior: monoaxial 4.4%, polyaxial 8.3% (p=0.33); inferoposterior: monoaxial 22.5%, polyaxial 29.8% (p=0.49) and inferoanterior: monoaxial 27.5%, polyaxial: 31.2% (p=0.09). CONCLUSION: The chosen screws' position in monoaxial and polyaxial locking plate fixation of displaced proximal humeral fractures do not differ significantly. However, loss of fixation is observed more frequently if the fixation did not include at least one screw within the superoposterior region of the humeral head, suggesting that a screw purchasing the superoposterior region is beneficial in locked plating of proximal humeral fractures. LEVEL OF EVIDENCE: Treatment Study, Level II.

Mesenchymal stem cells from osteoporotic patients feature impaired signal transduction but sustained osteoinduction in response to BMP-2 stimulation.

Osteoporotic fractures show reduced callus formation and delayed bone healing. Cellular sources of fracture healing are mesenchymal stem cells (MSC) that differentiate into osteoblasts by stimulation with osteoinductive cytokines, such as BMP-2. We hypothesized that impaired signal transduction and reduced osteogenic differentiation capacity in response to BMP-2 may underlie the delayed fracture healing. Therefore, MSC were isolated from femoral heads of healthy and osteoporotic patients. Grouping was carried out by bone mineral densitometry in an age-matched manner. MSC were stimulated with BMP-2. Signal transduction was assessed by western blotting of pSMAD1/5/8 and pERK1/2 as well as by quantitative RT-PCR of Runx-2, Dlx5, and Osteocalcin. Osteogenic differentiation was assessed by quantifying Alizarin Red staining. Osteoporotic MSC featured an accurate phosphorylation pattern of SMAD1/5/8 but a significantly reduced activation of ERK1/2 by BMP-2 stimulation. Furthermore, osteoporotic MSC showed significantly reduced basal expression levels of Runx-2 and Dlx5. However, Runx-2, Dlx5, and Osteocalcin expression showed adequate up-regulation due to BMP-2 stimulation. The global osteogenic differentiation in standard osteogenic differentiation media was reduced in osteoporotic MSC. Nevertheless, osteoporotic MSC were shown to feature an adequate induction of osteogenic differentiation due to BMP-2 stimulation. Taken together, we here demonstrate osteoporosis associated alterations in BMP-2 signaling but sustained specific osteogenic differentiation capacity in response to BMP-2. Therefore, BMP-2 may represent a promising therapeutic agent for the treatment of fractures in osteoporotic patients.

Mechanical torque measurement in the proximal femur correlates to failure load and bone mineral density ex vivo.

Knowledge of local bone quality is essential for surgeons to determine operation techniques. A device for intraoperative measurement of local bone quality has been developed by the AO-Research Foundation (Densi - Probe®). We used this device to experimentally measure peak breakaway torque of trabecular bone in the proximal femur and correlated this with local bone mineral density (BMD) and failure load. Bone mineral density of 160 cadaver femurs was measured by ex situ dualenergy X-ray absorptiometry. The failure load of all femurs was analyzed by side-impact analysis. Femur fractures were fixed and mechanical peak torque was measured with the DensiProbe® device. Correlation was calculated whereas correlation coefficient and significance was calculated by Fisher's Ztransformation. Moreover, linear regression analysis was carried out. The unpaired Student's t-test was used to assess the significance of differences. The Ward triangle region had the lowest BMD with 0.511 g/cm(2) (±0.17 g/cm(2)), followed by the upper neck region with 0.546 g/cm(2) (±0.16 g/cm(2)), trochanteric region with 0.685 g/cm(2) (±0.19 g/cm(2)) and the femoral neck with 0.813 g/cm(2) (±0.2 g/cm(2)). Peak torque of DensiProbe® in the femoral head was 3.48 Nm (±2.34 Nm). Load to failure was 4050.2 N (±1586.7 N). The highest correlation of peak torque measured by Densi Probe® and load to failure was found in the femoral neck (r=0.64, P<0.001). The overall correlation of mechanical peak torque with T-score was r=0.60 (P<0.001). A correlation was found between mechanical peak torque, load to failure of bone and BMD in vitro. Trabecular strength of bone and bone mineral density are different aspects of bone strength, but a correlation was found between them. Mechanical peak torque as measured may contribute additional information about bone strength, especially in the perioperative testing.

Diagnosis and treatment of acute ankle injuries: development of an evidence-based algorithm.

Acute ankle injuries are among the most common injuries in emergency departments. However, there are still no standardized examination procedures or evidence-based treatment. Therefore, the aim of this study was to systematically search the current literature, classify the evidence, and develop an algorithm for the diagnosis and treatment of acute ankle injuries. We systematically searched PubMed and the Cochrane Database for randomized controlled trials, meta-analyses, systematic reviews or, if applicable, observational studies and classified them according to their level of evidence. According to the currently available literature, the following recommendations have been formulated: i) the Ottawa Ankle/Foot Rule should be applied in order to rule out fractures; ii) physical examination is sufficient for diagnosing injuries to the lateral ligament complex; iii) classification into stable and unstable injuries is applicable and of clinical importance; iv) the squeeze-, crossed leg- and external rotation test are indicative for injuries of the syndesmosis; v) magnetic resonance imaging is recommended to verify injuries of the syndesmosis; vi) stable ankle sprains have a good prognosis while for unstable ankle sprains, conservative treatment is at least as effective as operative treatment without the related possible complications; vii) early functional treatment leads to the fastest recovery and the least rate of reinjury; viii) supervised rehabilitation reduces residual symptoms and re-injuries. Taken these recommendations into account, we present an applicable and evidence-based, step by step, decision pathway for the diagnosis and treatment of acute ankle injuries, which can be implemented in any emergency department or doctor's practice. It provides quality assurance for the patient and promotes confidence in the attending physician.

Sports activity after short-stem hip arthroplasty.

BACKGROUND: No data are available about the sports activity of patients with bone-conserving short-stem hip implants. HYPOTHESIS: Patients can return to a good level of sports activity after implantation of a short-stem hip implant. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The sports activity level of 68 patients (76 hips) after short-stem hip arthroplasty was assessed for a minimum of 2 years after implantation. In addition to the clinical examination, a detailed evaluation of the patients' sports pattern was obtained. Furthermore, the results were analyzed with regard to gender (female and male) and age (≤55 and >55 years). RESULTS: After a mean of 2.7 years, patients showed a Harris Hip Score (HHS) of 93.6, a Western Ontario and McMaster Universities Arthritis Index (WOMAC) score of 9.5, and a University of California, Los Angeles (UCLA) activity score of 7.6, with each individual participating on average in 3.5 different disciplines after surgery compared with 3.9 before surgery. High-impact activities decreased significantly postoperatively, whereas low-impact activities increased significantly. The duration of the sports activities remained stable, while the frequency actually increased. In contrast, men participated preoperatively in more sports than women (4.3 men vs 3.3 women). However, because of a pronounced decrease in high-impact activities by men, both genders participated in an equal number of sports postoperatively (3.5 men vs 3.5 women). Finally, 45% (n = 31) reported at least one activity that they missed. Most of them were disciplines with an intermediate- or high-impact level. CONCLUSION: Patients with a short-stem hip implant can return to a good level of activity postoperatively. Participation in sports almost reached similar levels as preoperatively but with a shift from high- to low-impact activities. This seems desirable from a surgeon's point of view but should also be communicated to the patient before hip replacement.

Bupivacaine, ropivacaine, and morphine: comparison of toxicity on human hamstring-derived stem/progenitor cells.

PURPOSE: Bupivacaine, ropivacaine, and morphine are commonly administered intraarticularly after anterior cruciate ligament (ACL) reconstruction. However, their effects on human tendon stem/progenitor cells (TSPC) have not been studied. Therefore, this study investigates the cytotoxicity of these analgetics on TSPC. METHODS: Cells were isolated from human hamstring grafts of 3 female (age 15, 16 and 59) and 2 male patients (age 16 and 47). Cells were incubated using 0.5% bupivacaine, 0.5/0.75% ropivacaine, and 0.025% morphine. Cell viability was assessed after 0.5, 2, and 6 h using live/dead assay. Metabolic activity and apoptosis were measured by WST- and Annexin-V-FACS-assay after 2 h. RESULTS: Cell viability remained unchanged after 0.5 h in all groups, while treatment with bupivacaine and 0.5/0.75% ropivacaine resulted in a complete cell loss after 6 h. Contrarily, morphine showed no cytotoxic effect. Cell viability and metabolism were significantly reduced after treatment with bupivacaine (22.1; 8.3%) and 0.75% ropivacaine (56.5; 23.8%), while 0.5% ropivacaine and morphine showed no significant difference compared with controls. Apoptosis was significantly induced after incubation with bupivacaine (58.1%) and 0.75% ropivacaine (26.2%), whereas 0.5% ropivacaine only led to a slight induction compared with morphine and controls. CONCLUSIONS: Clinically administered concentrations of bupivacaine (0.5%) and ropivacaine (0.75%) have a significant cytotoxic effect on human TSPC in vitro, while ropivacaine in a concentration of 0.5% has a mild but not significant effect on apoptosis and cell metabolism. In contrast, morphine does not affect cell survival, metabolism, or apoptosis. Knowing that morphine provides comparable to even prolonged pain reduction after ACL reconstruction, the presented in vitro study suggests morphine as a potentially less toxic analgetic drug for intraarticular application in clinical practice.

Diagnostic value of the Glasgow Coma Scale for traumatic brain injury in 18,002 patients with severe multiple injuries.

Although patients with severe multiple injuries may have other reasons for unconsciousness, traumatic brain injury (TBI) in these patients is frequently defined by the Glasgow Coma Scale (GCS). Nevertheless, the diagnostic value of GCS for severe TBI in the multiple-injured patient is unknown. Therefore, we investigated the diagnostic value of GCS to identify severe TBI in multiple-injured patients. The records of 18,002 severely injured adult (ISS >16) patients from the Trauma Register of the German Society for Trauma Surgery were analyzed and initial GCS and Abbreviated Injury Scale (head) (AIS(head)) were recorded. A severe TBI was defined by an AIS(head) ≥ 3. On the other hand, unconsciousness was defined by an initial GCS ≤ 8. By these criteria, 6546 patients (36.3%) were unconscious, and 8746 patients (48.6%) had severe TBI. Nine percent of all cases (n=1643) had a GCS ≤ 8 without severe TBI. Only 56.1% of patients with severe TBI (n=4903) had been unconscious. Decreasing levels of unconsciousness (as defined by GCS) showed consistent rising prevalence of severe TBI (correlation coefficient r=-0.52). Approximately 20% of all multiple-injured patients arriving in the emergency department with an initial GCS of 15 had severe TBI (AIS(head) ≥ 3). The diagnostic value of GCS ≤ 8 for severe TBI in patients with multiple injuries has low sensitivity (56.1%) but higher specificity (82.2%). Our study indicates that the GCS (as defined ≤ 8) in unconsciousness patients with multiple injuries shows only a moderate correlation with the diagnosis of severe TBI. Nevertheless, the main reason for unconsciousness in patients with multiple injuries is TBI, since only 9% of these patients had another reason for unconsciousness. However, due to the poor sensitivity of GCS, we suggest the use of the anatomical scoring system with AIS(head) ≥ 3 to define severe TBI in patients with multiple injuries.

Current Aspects of Fragility Fracture Repair.

Due to the demographic developments worldwide, fragility fractures represent an increasing problem for the public health system. The risk of developing osteoporosis increases with age and is relatively higher in women and in the Caucasian population. The stability of bone is reduced because of accentuation of the normal loss of bone mass in ageing, leading to an increased susceptibility to fracture with an increased rate of complications after surgical stabilization. Due to this, the orthopedic surgeon has to assess the quality of the bone during preoperative planning and select the implants and postoperative care accordingly to achieve the best. Over the last 10 years fixed locking implants have been introduced into clinical practice. These represent a new type of angle stable fixation devices that address the mechanical instability between bone and implant. The novel problems associated with this device are due to higher cut-out rates when the bone structure is altered and mass is reduced. The developments in joint replacement have also resulted in longer standing times and lower complication rates with immediate fullweight-bearing after implantation. However, to date, little is known about the mechanisms of fracture healing in osteoporosis or fragility fractures. One future approach may be in supporting biological fracture healing by regenerative therapies using growth hormones and/or (stem) cells. The most frequent initial clinical symptom of osteoporosis is a fracture without a relevant trauma. At this stage, the trauma surgeon should initiate diagnostic procedures, treatment of osteoporosis and tertiary prevention according to the European guidelines. Ultimately, all female patients older than 50 years and all male patients older than 60 years with fractures should be assessed and treated for bone quality. Orthogeriatric specialists or interdisciplinary orthogeriatric teams should initiate a specific surgical treatment followed by early rehabilitation in order to allow the elderly patient to return to daily living as soon as possible.