Effects of ligandrol as a selective androgen receptor modulator in a rat model for osteoporosis.

INTRODUCTION: The selective androgen receptor modulator ligandrol (LGD-4033 or VK5211) has been shown to improve muscle tissue. In the present study, the effect of ligandrol on bone tissue was investigated in ovariectomized rat model. MATERIALS AND METHODS: Three-month-old Sprague Dawley rats were either ovariectomized (OVX, n = 60) or left intact (NON-OVX, n = 15). After 9 weeks, OVX rats were divided into four groups: untreated OVX (n = 15) group and three OVX groups (each of 15 rats) treated with ligandrol orally at doses of 0.03, 0.3, or 3 mg/kg body weight. After five weeks, lumbar vertebral bodies (L), tibiae, and femora were examined using micro-computed tomographical, biomechanical, ashing, and gene expression analyses. RESULTS: In the 3-mg ligandrol group, bone structural properties were improved (trabecular number: 38 ± 8 vs. 35 ± 7 (femur), 26 ± 7 vs. 22 ± 6 (L), 12 ± 5 vs. 6 ± 3 (tibia) and serum phosphorus levels (1.81 ± 0.17 vs.1.41 ± 0.17 mmol/l), uterus (0.43 ± 0.04 vs. 0.11 ± 0.02 g), and heart (1.13 ± 0.11 vs. 1.01 ± 0.08 g) weights were increased compared to the OVX group. Biomechanical parameters were not changed. Low and medium doses did not affect bone tissue and had fewer side effects. Body weight and food intake were not affected by ligandrol; OVX led to an increase in these parameters and worsened all bone parameters. CONCLUSION: Ligandrol at high dose showed a subtle anabolic effect on structural properties without any improvement in biomechanical properties of osteoporotic bones. Considering side effects of ligandrol at this dose, its further investigation for the therapy of postmenopausal osteoporosis should be reevaluated.

[Common infectious challenges of the thoracic and lumbar spine : Spondylodiscitis and postoperative wound infection]. / Alltägliche infektiöse Herausforderungen an der Brust- und Lendenwirbelsäule : Spondylodiszitis und postoperative Wundinfektion.

Spondylodiscitis and postoperative wound infections are the most frequent infectious diseases of the thoracic and lumbar spine. Every spinal surgeon will come into contact with such patients during his or her career. Knowledge particularly of the diagnostics, conservative and surgical treatment as well as microbiological considerations of antibiotic treatment are therefore of particular importance and are explained in this article.

Gene Expression-Based Diagnosis of Infections in Critically Ill Patients-Prospective Validation of the SepsisMetaScore in a Longitudinal Severe Trauma Cohort.

OBJECTIVES: Early diagnosis of infections is pivotal in critically ill patients. Innovative gene expression-based approaches promise to deliver precise, fast, and clinically practicable diagnostic tools to bedside. This study aimed to validate the SepsisMetaScore, an 11-gene signature previously reported by our study group, in a representative longitudinal cohort of trauma patients. DESIGN: Prospective observational cohort study. SETTING: Surgical ICUs of the University Medical Center Goettingen, Germany. PATIENTS: Critically ill patients with severe traumatic injuries. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Paired box gene (PAXgene) RNA blood tubes were drawn at predefined time points over the course of disease. The performance of the SepsisMetaScore was tested using targeted polymerase chain reaction and compared with Procalcitonin using area under the receiver operating characteristics analyses. The SepsisMetaScore showed significant differences between infected and noninfected patients (n = 52). It was able to accurately discriminate infectious from noninfectious acute inflammation with an area under the receiver operating characteristics of 0.92 (95% CI, 0.85-0.99) and significantly outperformed Procalcitonin (area under the receiver operating characteristics curve = 0.53; 95% CI, 0.42-0.64) early in the course of infection (p = 0.014). CONCLUSIONS: We demonstrated the clinical utility for diagnosis of infections with higher accuracy using the SepsisMetaScore compared with Procalcitonin in a prospective cohort of severe trauma patients. Future studies should assess whether the SepsisMetaScore may substantially improve clinical practice by accurate differentiation of infections from sterile inflammation and identification of patients at risk for sepsis. Our results support further investigation of the SepsisMetaScore for the development of tailored precision treatment of critically ill patients.

Cage or Pelvic Graft-Study on Bony Fusion of the Ventral Thoracic and Lumbar Spine in Traumatic Vertebral Fractures.

Background and Objectives: Stabilization of the spine by cage implantation or autologous pelvic bone graft are surgical methods for the treatment of traumatic spine fractures. These methods serve to stably re-adjust the spine and to prevent late detrimental effects such as pain or increasing kyphosis. They both involve ventral interventions using interbody fusion to replace the intervertebral disc space between the vertebral bodies either by cages or autologous pelvic bone grafts. We examined which of these methods serves the patients better in terms of bone fusion and the long-term clinical outcome. Materials and Methods: Forty-six patients with traumatic fractures (12 cages; mean age: 54.08/34 pelvic bone grafts; mean age: 42.18) who received an anterior fusion in the thoracic or lumbar spine were included in the study. Postoperative X-ray images were evaluated, and fusion of the stabilized segment was inspected by two experienced spine surgeons. The time to discharge from hospital and gender differences were evaluated. Results: There was a significant difference of the bone fusion rate of patients with autologous pelvic bone grafts in favor of cage implantation (p = 0.0216). Also, the stationary phase of patients who received cage implantations was clearly shorter (17.50 days vs. 23.85 days; p = 0.0089). In addition, we observed a significant gender difference with respect to the bony fusion rate in favor of females treated with cage implantations (p < 0.0001). Conclusions: Cage implantations after spinal fractures result in better bony fusion rates as compared to autologous pelvic bone grafts and a shorter stay of the patients in the hospital. Thus, we conclude that cage implantations rather than autologous pelvic bone grafts should be the preferred surgical treatment for stabilizing the spine after fracture.

Effect of Selective Androgen Receptor Modulator Enobosarm on Bone Healing in a Rat Model for Aged Male Osteoporosis.

Enobosarm (ostarine, MK-2866, or GTx-024) is a non-steroidal selective androgen receptor modulator. This study evaluated the effect of various regimens of enobosarm (EN) on bone healing in an orchiectomized rat model for aged male osteoporosis and compared it to testosterone (T) treatment. Ninety eight-month-old male Sprague Dawley rats were either orchiectomized (Orx) or left intact (Non-Orx) and divided into groups (n = 15/group): (1) Non-Orx; (2) Orx; (3) Orx+T-th; (4) Orx+EN-th; (5) Orx+T-pr; and (6) Orx+EN-pr. Prophylaxis (Pr) treatments were applied immediately after Orx for up to 18 weeks. Therapy (Th) treatments were applied 12 weeks after Orx for up to 6 weeks. Bilateral tibia osteotomy with plate osteosynthesis was performed 12 weeks after Orx in all groups. EN and T were mixed with the diet; the daily dosage was 0.35 ± 0.06 and 41 ± 8 mg/kg BW, respectively. Both T treatments improved bone healing by increasing callus volume and area, bone volume and density, and cortical width; they had no effect on prostate or levator ani weight. EN-pr increased the callus area and callus density and decreased cortical density, but increased prostate weight. The effect of T-pr and T-th on bone was stronger than EN-pr. EN-th affected bone healing negatively by reducing callus density and area and delaying osteotomy bridging. Levator ani weight was increased in both EN groups. EN treatment after fracture is not advisable in aged males. EN-pr treatment as a therapy for bone healing in men could be further investigated; endocrinological side effects must be closely monitored.

The Selective Androgen Receptor Modulator Ostarine Improves Bone Healing in Ovariectomized Rats.

Non-steroidal selective androgen receptor modulators, including ostarine, have been developed as an alternative to steroidal hormones. Ostarine has shown a beneficial effect on bone in experimental studies, but no data regarding the effect of ostarine on bone healing have yet been reported. We investigated effects of ostarine on bone healing in ovariectomized rats. Sprague-Dawley rats (3 months old) were ovariectomized (Ovx, n = 46) or left intact (Non-Ovx, n = 10). After 8 weeks, an osteotomy of the tibia metaphysis was created in all rats, and the Ovx rats were divided into four groups: untreated Ovx (n = 10) and three Ovx groups (each of 12 rats) treated with ostarine at doses of 0.04, 0.4, or 4 mg/kg BW (OS-0.04, OS-0.4, and OS-4 groups). Five weeks later, bone healing was analyzed. The OS-4 dose enhanced callus formation, increased callus density, accelerated bridging time of the osteotomy, and elevated alkaline phosphatase gene expression in callus and its protein expression in serum. In the Ovx group, most of the callus parameters were diminished. All OS treatments increased the weight of the gastrocnemius muscle, but only partly enhanced uterus weight in OS-0.4 and OS-4. Serum cholesterol level was reduced, and serum phosphorus was elevated in OS-0.04 and OS-4. Ostarine appeared to have a positive effect on early bone healing in ovariectomized rats. Considering its favorable effect on non-osteotomized bone and muscle, this treatment could be further explored as a therapy for osteoporosis. However, possible metabolic side effects should first be evaluated.

The Impact of Strontium Ranelate on Metaphyseal Bone Healing in Ovariectomized Rats.

The following questions were addressed: whether therapy with strontium ranelate (SR) should be continued or interrupted if the fractures occur during SR treatment and whether SR could be applied directly after fracture to improve bone healing. Sprague-Dawley rats (3 month old) were ovariectomized (Ovx, n = 48) or left intact (n = 12). After 8 weeks, a bilateral transverse osteotomy of the tibia metaphysis was created in all rats. Ovx rats were divided into four groups: Ovx; SR applied directly after Ovx until osteotomy (prophylaxis, SR pr, 8 weeks); SR applied after osteotomy (therapy, SR th, 5 weeks); SR applied during the whole experiment (pr + th, 13 weeks). SR dosage was 625 mg/kg body weight/day, administered in the feed. Five weeks later, tibiae were analyzed by biomechanical, histological, micro-CT, and gene expression analyses. The SR pr + th treatment increased total bone mineral density (BMD), bone volume fraction, cortical BMD and volume, callus area and density, serum alkaline phosphatase, tartrate-resistant acid phosphatase mRNA, accelerated osteotomy bridging, and callus formation at weeks 2 and 3 of healing and decreased the osteoprotegerin/receptor activator of nuclear factor kB ligand mRNA ratio. SR th enlarged callus area and improved callus formation during the 5th week of healing. SR pr improved cortical BMD preserving bone after SR discontinuation (5-week rest); the bone healing was not affected. SR content in the tibia metaphysis was the highest in SR pr + th group and was not different between SR pr and SR th. SR has a positive effect on osteoporotic bone healing in rat and SR treatment can be continued after the fracture occurs or applied directly after the fracture.

Effect of Urocortin on strength and microarchitecture of osteopenic rat femur.

As yet there is no evidence of the potential antiosteoporotic effect of Urocortin-1 (UCN), a corticotropin releasing factor related peptide, in vivo. In this study, and for the first time, we investigated the effect of UCN in a rat osteopenia model. Sixty female Sprague-Dawley rats were divided into 5 groups: (1) sham-operated, (2) untreated ovariectomized (OVX) rats, (3) and (4) OVX animals treated for 5 weeks with daily subcutaneous low-dose UCN (3 µg/kg of BW) or high-dose UCN (30 µg/kg of BW) 8 weeks after ovariectomy, and (5) OVX rats treated with daily estrogen (0.2 mg/kg of BW p.o) 8 weeks after ovariectomy for 5 weeks (E). After sacrifice, the femurs were reserved for biomechanical, histomorphometric and ash testing. In the biomechanical test, the high-dose UCN rats showed significantly improved mechanical stiffness (341.6 N/mm) compared with the untreated OVX animals (275.9 N/mm). In the histomorphometric evaluation, the high-dose UCN rats demonstrated an improved trabecular microarchitecture especially and significantly at the distal femur (distal femur Tb.Ar = 41.4% and N.Nd/mm(2) = 26.8, proximal femur Tb.Ar = 71.8% and N.Nd/mm(2) = 28.7) compared with untreated OVX rats (distal femur Tb.Ar = 23.3% and N.Nd/mm(2) = 11.7, proximal femur Tb.Ar = 60.2% and N.Nd/mm(2) = 25.2). Our results show that short-term treatment with UCN seems to have a positive effect on the metaphyseal bone structure and strength of the femur in ovariectomized rats.

Standard imaging in the emergency department in geriatric patients with immobilizing pelvic pain after low-energy trauma or without trauma: X-ray vs. computed tomography.

PURPOSE: Geriatric pelvic ring injuries, evaluated solely by X-ray, are often misclassified or even missed. This can result in prolonged immobilization and persistent pelvic pain. The aim of this study was to assess the sensitivity and specificity of X-ray imaging in patients aged ≥ 70 years with immobilizing pelvic pain. METHODS: 107 geriatric patients (23 males, 84 females) with immobilizing pain after traumatic or atraumatic causes were included in this retrospective study. 91 patients had an anteroposterior (AP) X-ray of the pelvis and after that a computed tomography (CT) of the pelvis. All patients were treated in a level 1 trauma center from December 2018 to September 2020. The mean age was 83.07 ± 6.08 years. RESULTS: The overall evaluation of the diagnostic performance of AP Pelvic X-ray imaging in the study population compared to the CT pelvis ("gold standard") resulted in a sensitivity of (2.7 %) and a specificity of (94.4 %). Specific for pelvic ring fractures in the study population there was a sensitivity of (3.4 %) and a specificity of (94.4 %). CONCLUSION: The results highlights issues with the AP Pelvic X-ray as the diagnostic tool of choice in this study population, confirming the findings of previous studies on the underestimated problem of osteoporotic pelvic ring fractures in geriatric patients. This again confirms the need for a new optimized diagnostic algorithm, which takes into account the differences of the orthogeriatric patient cohort.

Where Do We Stand on Cervical Spine Immobilisation? A Questionnaire among Prehospital Staff.

Background: Cervical collars (CC) are routinely used in prehospital trauma treatment. However, over the past years, their application was discussed more critically since they increase intravenous pressure due to reduced venous drainage and the possibility of secondary cervical spine injury. Guidelines have been adjusted accordingly. The question is how efficient has this been put into practice, and how good, as well as up to date, is the knowledge of prehospital emergency medicine personnel about indications on cervical spine immobilisation? Methods: A 15-item questionnaire regarding the self-evaluation and result checking of the right indications for the use of a cervical collar in the prehospital setting was sent to paramedics and emergency doctors in Germany. Two hundred and nineteen completed surveys were statistically analysed. Results: Mean age of the participants was 30.45 ± 8.8. 72% were male. Regarding subjective safety, the appropriate indication of CC participants reached 79.8 ± 19.5 on a metric scale from 0 (no safety) to 100 (full safety). Mean right answers were as follows: Ambulance man (RS) 0.78 ± 0.84, paramedic (RA) 0.9 ± 0.74, paramedic (NFS) 1.03 ± 0.83 and emergency doctor (ED) 1.75 ± 1.06 (p = 0.013, Kruskal-Wallis Test). Participants who estimated their knowledge < 85% had 0.83 ± 0.8 right answers, and > 85% had 1.14 ± 0.9 right answers. Conclusions: Rational spine immobilisation is still necessary in severely injured patients. This study highlights the importance of continuing education using ongoing training, lectures or online learning with a questionnaire as a monitor for success to ensure the transfer of evidence-based medicine into daily practice.

Lessons learned from biomechanical studies on cephalomedullary nails for the management of intertrochanteric fractures. A scoping review.

INTRODUCTION: The increasing socioeconomic need for optimal treatment of hip fractures in combination with the high diversity of available implants has raised numerous biomechanical questions. This study aims to provide a comprehensive overview of biomechanical research on the treatment of intertrochanteric fractures using cephalomedullary devices. METHODS: Following the PRISMA-P guidelines, a systematic literature search was performed on 31.12.2022. The databases PubMed/MEDLINE and Web of Science were searched. Scientific papers published between 01.01.2000 - 31.12.2022 were included when they reported data on implant properties related to the biomechanical stability for intertrochanteric fractures. Data extraction was undertaken using a synthesis approach, gathering data on criteria of implants, sample size, fracture type, bone material, and study results. RESULTS: The initial search identified a total of 1459 research papers, out of which forty-three papers were considered for final analysis. Due to the heterogeneous methods and parameters used in the included studies, meta-analysis was not feasible. A comprehensive assessment of implant characteristics and outcome parameters was conducted through biomechanical analysis. Various factors such as proximal and distal locking, nail diameter and length, fracture model, and bone material were thoroughly evaluated. CONCLUSION: This scoping review highlights the need for standardization in biomechanical studies on intertrochanteric fractures to ensure reliable and comparable results. Strategies such as avoiding varus, maintaining a sufficient tip-apex-distance, cement augmentation, and optimizing lesser trochanteric osteosynthesis enhance construct stability. Synthetic alternatives may offer advantages over cadaveric bone. Further research and meta-analyses are required to establish standardized protocols and enhance reliability.

Do admission glucose levels independently predict coagulopathy in multiple trauma patients? A retrospective cohort analysis.

BACKGROUND: Coagulopathy is prevalent in multiple trauma patients and worsens bleeding complications, leading to higher morbidity and mortality rates. Hyperglycemia upon admission predicts hemorrhagic shock and mortality in severely injured patients. This study aimed to assess admission glucose levels as an independent prognostic factor for coagulopathy in multiply injured patients. METHODS: This retrospective cohort study observed multiple trauma patients treated at a level I trauma center between January 1, 2005, and December 31, 2020. Coagulopathy was defined as an international normalized ratio (INR) > 1.4 and/or activated thromboplastin time (APTT) > 40 s. Analysis of variance compared clinical and laboratory parameters of patients with and without coagulopathy. Receiver-operating-characteristic (ROC) and multivariate logistic regression analyses identified risk factors associated with coagulopathy. RESULTS: The study included 913 patients, of whom 188 (20%) had coagulopathy at admission. Coagulopathy patients had higher mortality than those without (26% vs. 5.0%, p < 0.001). Mean glucose level in coagulopathy patients was 10.09 mmol/L, significantly higher than 7.97 mmol/L in non-coagulopathy patients (p < 0.001). Admission glucose showed an area under the curve (AUC) of 0.64 (95% CI [0.59-0.69], p < 0.001) with an optimal cut-off point of 12.35 mmol/L. After adjusting for other factors, patients with high admission glucose had a 1.99-fold risk of developing coagulopathy (95% CI 1.07-3.60). Other laboratory parameters associated with coagulopathy included haemoglobin, bicarbonate (HCO3), and lactate levels. CONCLUSION: This study emphasizes the significance of admission blood glucose as an independent predictor of coagulopathy. Monitoring hyperglycemia can aid in identifying high-risk patients.

Reconstruction of an Extensive Segmental Radial Shaft Bone Defect by Vascularized 3D-Printed Graft Cage.

We report here a 46-year-old male patient with a 14 cm segmental bone defect of the radial shaft after third degree open infected fracture caused by a shrapnel injury. The patient underwent fixed-angle plate osteosynthesis and bone reconstruction of the radial shaft by a vascularized 3D-printed graft cage, including plastic coverage with a latissimus dorsi flap and an additional central vascular pedicle. Bony reconstruction of segmental defects still represents a major challenge in musculo-skeletal surgery. Thereby, 3D-printed scaffolds or graft cages display a new treatment option for bone restoration. As missing vascularization sets the limits for the treatment of large-volume bone defects by 3D-printed scaffolds, in the present case, we firstly describe the reconstruction of an extensive radial shaft bone defect by using a graft cage with additional vascularization.

Identification of a vibration regime favorable for bone healing and muscle in estrogen-deficient rats.

Numerous whole-body vibration (WBV) devices of various forces are available on the market, although their influence on the musculoskeletal system is not yet understood. The effect of different WBVs on bone healing and muscle function was evaluated in rats ovariectomized at 3 months of age. 2 months after ovariectomy, bilateral metaphyseal tibia osteotomy and T-plate osteosynthesis were performed. Rats were divided into groups: intact, OVX, and OVX exposed to vertical WBVs of 35, 50, 70, or 90 Hz (experiment 1) or horizontal WBVs of 30, 50, 70, or 90 Hz (experiment 2) 5 days after osteotomy (0.5 mm, 15 min/day for 30 days). The tibia and gastrocnemius and soleus muscles were collected. Vertical vibrations (>35 Hz) improved cortical and callus densities, enlarged callus area and width, suppressed the tartrate-resistant acid phosphatase gene, enhanced citrate synthase activity, accelerated osteotomy bridging (35 and 50 Hz), upregulated the osteocalcin (Oc) gene (70 Hz), and increased relative muscle weight (50 Hz). Horizontal vibrations reduced cortical width (<90 Hz) and callus density (30 Hz), enhanced alkaline phosphatase (Alp) gene expression (50 Hz), decreased the size of oxidative fibers (35 and 70 Hz), and increased capillary density (70, 90 Hz). Biomechanical data; serum Oc, Alp, and creatine kinase activities; body weight; and food intake did not change after WBVs. Vertical WBVs of 35 and 50 Hz produced more favorable results than the higher frequencies. Horizontal WBV showed no positive or negative effects. Further studies are needed to elucidate the effects of WBV on different physiological systems, and precautions must be taken when implementing WBV in the treatment of patients.

Provision of an explanation for the inefficacy of immunotherapy in sporadic inclusion body myositis: quantitative assessment of inflammation and ß-amyloid in the muscle.

OBJECTIVE: In sporadic inclusion body myositis (IBM), inflammation and accumulation of ß-amyloid-associated molecules cause muscle fiber damage. We undertook this study to determine why intravenous immunoglobulin (IVIG) and prednisone are not effective in sporadic IBM despite their effectiveness in other inflammatory myopathies. METHODS: Relevant inflammatory and degeneration- associated markers were assessed by quantitative polymerase chain reaction and immunohistochemistry in repeated muscle biopsy specimens from patients with sporadic IBM treated in a controlled study with IVIG and prednisone (n = 5) or with prednisone alone (n = 5). Functional effects were assessed in a muscle cell culture model. RESULTS: In muscle biopsy specimens, messenger RNA (mRNA) expression of the proinflammatory chemokines CXCL9, CCL3, and CCL4 and of the cytokines interferon-γ (IFNγ), transforming growth factor ß, interleukin-10 (IL-10), and IL-1ß was significantly reduced after treatment in both groups. No consistent changes were observed for tumor necrosis factor α, IL-6, inducible costimulator (ICOS), its ligand ICOSL, and perforin. Messenger RNA expression of the degeneration-associated molecule ubiquitin and the heat-shock protein αB-crystallin was also reduced, but no changes were noted for amyloid precursor protein (APP) or desmin. By immunohistochemistry, a significant down-modulation of chemokines was observed, but not of inducible nitric oxide (NO) synthase, nitrotyrosine, IL-1ß, APP, and ubiquitin; ß-amyloid was reduced in 6 of 10 patients. Pronounced staining of IgG was observed in the muscle after treatment with IVIG, indicating penetration of infused IgG into the muscle and a possible local effect. In muscle cells exposed to IFNγ plus IL-1ß, IgG and/or prednisone down-regulated mRNA expression of IL-1ß 2.5-fold. Accumulation of ß-amyloid, overexpression of αB-crystallin, and cell death were prevented. In contrast, NO-associated cell stress remained unchanged. CONCLUSION: IVIG and prednisone reduce some inflammatory and degenerative molecules in muscle of patients with sporadic IBM and in vitro, but do not sufficiently suppress myotoxic and cell stress mediators such as NO. The data provide an explanation for the resistance of sporadic IBM to immunotherapy and identify markers that may help to design novel treatment strategies.

Nitric oxide stress in sporadic inclusion body myositis muscle fibres: inhibition of inducible nitric oxide synthase prevents interleukin-1ß-induced accumulation of ß-amyloid and cell death.

Sporadic inclusion body myositis is a severely disabling myopathy. The design of effective treatment strategies is hampered by insufficient understanding of the complex disease pathology. Particularly, the nature of interrelationships between inflammatory and degenerative pathomechanisms in sporadic inclusion body myositis has remained elusive. In Alzheimer's dementia, accumulation of ß-amyloid has been shown to be associated with upregulation of nitric oxide. Using quantitative polymerase chain reaction, an overexpression of inducible nitric oxide synthase was observed in five out of ten patients with sporadic inclusion body myositis, two of eleven with dermatomyositis, three of eight with polymyositis, two of nine with muscular dystrophy and two of ten non-myopathic controls. Immunohistochemistry confirmed protein expression of inducible nitric oxide synthase and demonstrated intracellular nitration of tyrosine, an indicator for intra-fibre production of nitric oxide, in sporadic inclusion body myositis muscle samples, but much less in dermatomyositis or polymyositis, hardly in dystrophic muscle and not in non-myopathic controls. Using fluorescent double-labelling immunohistochemistry, a significant co-localization was observed in sporadic inclusion body myositis muscle between ß-amyloid, thioflavine-S and nitrotyrosine. In primary cultures of human myotubes and in myoblasts, exposure to interleukin-1ß in combination with interferon-γ induced a robust upregulation of inducible nitric oxide synthase messenger RNA. Using fluorescent detectors of reactive oxygen species and nitric oxide, dichlorofluorescein and diaminofluorescein, respectively, flow cytometry revealed that interleukin-1ß combined with interferon-γ induced intracellular production of nitric oxide, which was associated with necrotic cell death in muscle cells. Intracellular nitration of tyrosine was noted, which partly co-localized with amyloid precursor protein, but not with desmin. Pharmacological inhibition of inducible nitric oxide synthase by 1400W reduced intracellular production of nitric oxide and prevented accumulation of ß-amyloid, nitration of tyrosine as well as cell death inflicted by interleukin-1ß combined with interferon-γ. Collectively, these data suggest that, in skeletal muscle, inducible nitric oxide synthase is a central component of interactions between interleukin-1ß and ß-amyloid, two of the most relevant molecules in sporadic inclusion body myositis. The data further our understanding of the pathology of sporadic inclusion body myositis and may point to novel treatment strategies.

[Biological reconstruction of large bone defects : Masquelet technique and new procedures]. / Biologische Rekonstruktion von großen Knochendefekten : Masquelet-Technik und neue Verfahren.

Extensive diaphyseal and metaphyseal bone defects continue to pose a major challenge for orthopedic trauma surgeons. Various treatment options have been described for the biological reconstruction of these defects. The most frequently used methods are bone segment transport, the Masquelet technique and 3D printed scaffolds. As far as the Masquelet technique is concerned, in the first stage spacers, such as polymethyl methacrylate (PMMA), calcium sulfate or polypropylene are inserted into the bone defects to induce a foreign body membrane. In the second stage the bone defect surrounded by the induced membrane is filled with autologous cancellous bone. The time interval between the first and second interventions is usually 4-8 weeks whereby the induced membranes do not lose their bioactivity even with a latency period longer than 8 weeks. Three-dimensional printed scaffolds are increasingly used but large clinical studies are lacking in order to show the exact role of this procedure in the reconstruction of bone defects.

The pelvic vascular injury score (P-VIS): a prehospital instrument to detect significant vascular injury in pelvic fractures.

PURPOSE: The purpose of this study was to identify predictive factors for peri-pelvic vascular injury in patients with pelvic fractures and to incorporate these factors into a pelvic vascular injury score (P-VIS) to detect severe bleeding during the prehospital trauma management. METHODS: To identify potential predictive factors, data were taken (1) of a Level I Trauma Centre with 467 patients (ISS ≥ 16 and AISPelvis ≥ 3). Analysis including patient's charts and digital recordings, radiographical diagnostics, mechanism and pattern of injury as well as the vascular bleeding source was performed. Statistical analysis was performed descriptively and through inference statistical calculation. To further analyse the predictive factors and finally develop the score, a 10-year time period (2012-2021) of (2) the TraumaRegister DGU® (TR-DGU) was used in a second step. Relevant peri-pelvic bleeding in patients with AISPelvis ≥ 3 (N = 9227) was defined as a combination of the following entities (target group PVITR-DGU N = 2090; 22.7%): pelvic fracture with significant bleeding (> 20% of blood volume), Injury of the iliac or femoral artery or blood transfusion of ≥ 6 units (pRBC) prior to ICU admission. The multivariate analysis revealed nine items that constitute the pelvic vascular injury score (P-VIS). RESULTS: In study (1), 467 blunt pelvic trauma patients were included of which 24 (PVI) were presented with significant vascular injury (PVI, N = 24; control (C, N = 443). Patients with pelvic fractures and vascular injury showed a higher ISS, lower haemoglobin at admission and lower blood pressure. Their mortality rate was higher (PVI: 17.4%, C: 10.3%). In the defining and validating process of the score within the TR-DGU, 9227 patients met the inclusion criteria. 2090 patients showed significant peripelvic vascular injury (PVITR-DGU), the remaining 7137 formed the control group (CTR-DGU). Nine predictive parameters for peripelvic vascular injury constituted the peripelvic vascular injury score (P-VIS): age ≥ 70 years, high-energy-trauma, penetrating trauma/open pelvic injury, shock index ≥ 1, cardio-pulmonary-resuscitation (CPR), substitution of > 1 l fluid, intubation, necessity of catecholamine substitution, remaining shock (≤ 90 mmHg) under therapy. The multi-dimensional scoring system leads to an ordinal scaled rating according to the probability of the presence of a vascular injury. A score of ≥ 3 points described the peripelvic vascular injury as probable, a result of ≥ 6 points identified a most likely vascular injury and a score of 9 points identified an apparent peripelvic vascular injury. Reapplying this score to the study population a median score of 5 points (range 3-8) (PVI) and a median score of 2 points (range 0-3) (C) (p < 0.001). The OR for peripelvic vascular injury was 24.3 for the patients who scored > 3 points vs. ≤ 2 points. The TR-DGU data set verified these findings (median of 2 points in CTR-DGU vs. median of 3 points with in PVITR-DGU). CONCLUSION: The pelvic vascular injury score (P-VIS) allows an initial risk assessment for the presence of a vascular injury in patients with unstable pelvic injury. Thus, the management of these patients can be positively influenced at a very early stage, prehospital resuscitation performed safely targeted and further resources can be activated in the final treating Trauma Centre.

Retrospective In-Hospital Mortality Analysis of GeriatricPatients Treated in a Level 1 Trauma Center.

The aim of this study is to determine the critical time intervals and influencing covariates for in-hospital mortality in geriatric trauma and orthopedic patients. During a period of five years, we retrospectively review patients aged > 60 years who were hospitalized at the Department of Trauma, Orthopedic, and Plastic Surgery. The primary outcome is the mean time to death. Survival analysis is performed using an accelerated failure time model. A total of 5388 patients are included in the analysis. Two-thirds underwent surgery (n = 3497, 65%) and one-third were conservatively treated (n = 1891, 35%). The in-hospital mortality rate is 3.1% (n = 168; surgery, n = 112; conservative, n = 56). The mean time to death is 23.3 days (±18.8) after admission in the surgery group and 11.3 days (±12.5) in the conservative treatment group. The greatest accelerating effect on mortality is found in the intensive care unit (16.52, p < 0.001). We are able to identify a critical time interval for in-hospital mortality between days 11 and 23. The day of death on weekend days/holidays, hospitalization for conservative treatment, and treatment at the intensive care unit significantly increase the risk of in-hospital mortality. Early mobilization and a short hospitalization duration seem to be of major importance in fragile patients.

Validation of direct CT measurement of malrotation in femoral neck fractures: A bone model study.

BACKGROUND: While postoperative malrotation in the subtrochanteric region is a well-known problem, malrotation after osteosynthesis in proximal femoral fractures has not been extensively studied. In this context, many methods for perioperatively assessment of femoral torsion have been described, but none of them is applicable in the basicervical region of the proximal femur. As an important difference in femoral neck fractures, the discontinuous neck fails to serve as a significant "pointer" for measurements and malfunctions to be placed in relation to the condylar plane. Considering postoperative maltorsion at any location as a substantial negative effect on patients' outcome and functional expectations, precise and patient-friendly rotation measurement standards in femoral neck fractures are desired in clinical practice. Recently, a novel computed tomography (CT) based geometric technique was described named "direct measurement" with promising results covering this diagnostic disparity, but still requires validation. Thus, we aimed to validate the previously described technique using a controlled range of displacement in a femoral neck fracture Sawbone® model. METHODS AND FINDINGS: A goniometer was designed to set retro- and anteversion of the proximal femur in a reproducible manner. Prospectively, all femurs underwent a CT scan and were measured 3D for displacement. The interclass correlation between the CT measurements and the goniometer measurements was calculated and was found to be very high (1.00, 95% confidence interval: 0.99-1.00; p < 0.001). For the mean of all measurements, the Pearson's correlation was 1.00 (p < 0.001). No significant differences in the measurements of both investigators were observed, with 20° of retroversion not significant (-1.20 ± 1.71; 95% confidence interval: -2.43-0.03; p = 0.054). CONCLUSION: This CT-based 3D measurement technique may allow for perioperative malrotation assessment in basicervical femoral neck fractures and appears to be feasible in femoral neck fractures when it comes to rare cases of osteosynthesis. Further investigations are still needed to define the thresholds of malrotation provoking functional impairment after osteosynthesis in basicervical femoral neck fractures.