Easy and safe: A new surgical fixation -technique for acute and chronic anterior instabilities of the sternoclavicular joint: technique and results.

BACKGROUND: Instabilities of the SC joint are a rare injury, accounting for only 3% of all injuries of the shoulder-girdle. While acute posterior dislocations are an emergency and require immediate surgical intervention, anterior instabilities (first and second degree according to Allman) can mostly be treated conservatively. Chronic and highly instable acute anterior instabilities often imposes a significant limitation on the lives of affected patients. Currently, there is no established therapeutic algorithm in place. METHODS: This retrospective case series with prospective collection of data was performed at a level-I trauma centre. Patients treated surgically for anterior SC joint instabilities between January 2013 and December 2019 and with a minimum follow-up of 24 months were included. The injuries comprised of six acute anterior dislocations treated with tape-cerclage in a "figure-of-8" configuration; twelve patients with chronic anterior SC instabilities were treated with autologous tendon grafts. For one highly unstable chronic anterior instability in addition to the tendon graft synthetic suture material was applied. The clinical evaluation consisted of a physical examination and a standardized questionnaire, which included subjective and objective shoulder scores. RESULTS: Out of 24, 19 patients (79%) with an average age of 32 years ± 15 were available for follow-up. 63% of the patients were male. After a mean follow-up of 57 months, the mean age- and sex-adapted Constant-Murley Shoulder Score (CS) of acute anterior luxations amounted to 90 points ± 20, Nottingham Clavicle Score (NCS) to 81 points ± 22 and DASH Score to 11 points ± 18. Chronic anterior instabilities had a mean CS of 90 points ± 12, NCS of 83 points ± 17 and DASH Score of 4 points ± 5. The study shows a complication rate of 10%. Two patients underwent revision surgery. CONCLUSION: To conlude, monocortical SCJ fixation in a "figure-of-8" fashion presents a low risk for complication and a low revision rate and can achieve equally good functional outcome after the treatment of highly unstable acute and chronic anterior SCJ instabilities than other published techniques. Our approach presents less risk to the neurovascular structures of the mediastinum than other published techniques requiring bicortical drilling, therefore making the technique more accessible to hospitals without a cardiothoracic surgical background.

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.

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.

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 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.

Proximal humerus fracture and acromioclavicular joint dislocation.

Proximal humerus fractures and injuries to the acromioclavicular joint are among the most common traumatic diseases of the upper extremity. Fractures of the proximal humerus occur most frequently in older people and are an indicator fracture of osteoporosis. While a large proportion of only slightly displaced fractures can be treated non-operatively, more complex fractures require surgical treatment. The choice of optimal treatment and the decision between joint-preserving surgery by means of osteosynthesis or endoprosthetic treatment is often a difficult decision in which both fracture morphology factors and individual factors should be taken into account. If endoprosthetic treatment is indicated, satisfactory long-term functional and clinical results have been achieved with a reverse shoulder arthroplasty. Injuries to the acromioclavicular joint occur primarily in young, athletic individuals. The common classification according to Rockwood divides the injury into 6 degrees of severity depending on the dislocation. This classification forms the basis for the decision on non-operative or surgical treatment. The indication for surgical treatment for higher-grade injuries is the subject of controversial debate in the latest literature. In chronic injuries, an autologous tendon transplant is also performed. Whereas in the past, treatment was often carried out using a hook plate, which was associated with complications, the gold standard today is minimally invasive treatment using Endobutton systems. This review provides an overview of the two injury patterns and discusses the various treatment options.

First In Vivo Electromyographic Analysis of Mechanical Load Scenarios of the Cervicothoracic Junction During Daily Activities as a Basis for Future Postoperative Behavioral Instructions.

STUDY DESIGN: Clinical Research. OBJECTIVES: Study participants were twenty- eigth healty volunteers. BACKGROUND: Soft tissue complications after posterior cervicothoracic fusion surgery occur frequently. Postoperative myofascial dehiscence (PMD) can cause disability and pain. So far, it is unknown whether patients can affect PMD development through behavioral adjustment. Consequently, this study aimed to analyze how much mechanical stress daily activities exert on the posterior muscles and fascia at the cervicothoracic junction. MATERIALS AND METHODS: Surface electromyography was applied next to the upper thoracic spine at the trapezius muscle. All volunteers performed 22 different daily activities, such as tooth brushing, dressing, standing up, and different horizontal positions. During the exercises, the electromyographic activity was measured. For each volunteer, root mean square values were determined. All exercises were then repeated with the use of a clavicular bandage to unload the shoulder and cervicothoracic muscles. Afterwards, the rankings were statistically compared interindividually. RESULTS: Among the different tasks, significant differences in regard to the root mean square values were noted. For instance, horizontal positions caused significantly lower muscle activation compared with all other exercises (P≤ 0.001). Notably, no relevant electromyographic differences were detected between the tasks with and without a clavicular bandage. CONCLUSIONS: This in vivo electromyographic analysis of cervicothoracic muscle activity during daily activities demonstrates that myofascial strain differs among various daily activities. Data indicate that potential postoperative mobilization protocols and behavioral instructions may have the potential to reduce the biomechanical load and consequently the risk of PMD and, therefore, may reduce the risk for surgical wound-related complications, disability, and need for revision surgery.

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.

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.

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.

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.