Search

Background: The single-center, open-label, four-arm, exploratory study investigates the relation of different anti-diabetics to serum levels of active TGF-ß, a known pro-fibrotic stimulus, before and after a defined test meal. Findings: We investigated sera of patients with type 2 diabetes mellitus (T2DM) treated with metformin and sulfonylurea, insulin glargine or a DPP-4 inhibitor (DPP4i). Patients' sera were analyzed before and 5 h after a defined test meal at intervals of 30 min. The sulfonylurea/metformin group exhibited the highest basal levels of active TGF-ß (31.50 ± 3.58 ng/ml). The glargine/metformin group had active TGF-ß levels (24.98 ± 1.90 ng/ml) that were comparable to those of the healthy participants (22.12 ± 2.34 ng/ml). The lowest basal levels of active TGF-ß were detected in the DPP-4i/metformin group (12.28 ± 0.84 ng/ml). Following the intake of a standardized meal, active TGF-ß levels decreased (approx. 30%) in healthy subjects as well as in the sulfonylurea/metformin group and in the glargine/ metformin group. After 5 h, the active TGF-ß levels were normalized to basal levels. Active TGF-ß levels in the DPP-4i/metformin group did not change significantly after the test meal. Overall plasma levels of insulin and proinsulin were comparable between healthy participants, and T2DM patients in the glargin/metformin group and in the DPP4i/metformin group. However, no correlation between active TGF-ß levels, glucose, insulin or pro-insulin levels was detected. Conclusions: T2DM patients often exhibit elevated levels of pro-fibrotic active TGF-ß. Our results suggest that glargine/metformin and DPP4i/metformin treatment may more effectively reduce active TGF-ß serum levels than the sulfonylurea/metformin treatment. [ABSTRACT FROM AUTHOR]

Background: Bone morphogenic proteins (BMPs) play a key role in bone formation. Consequently, it was expected that topical application of recombinant human (rh)BMP-2 and rhBMP-7 would improve the healing of complex fractures. However, up to 36% of fracture patients do not respond to this therapy. There are hints that a systemic increase in transforming growth factor β1 (TGFβ1 ) interferes with beneficial BMP effects. Therefore, in the present work we investigated the influence of rhTGFβ1 on rhBMP signaling in primary human osteoblasts, with the aim of more specifically delineating the underlying regulatory mechanisms. Methods: BMP signaling was detected by adenoviral Smad-binding-element-reporter assays. Gene expression was determined by reverse transcription polymerase chain reaction (RT-PCR) and confirmed at the protein level by western blot. Histone deacetylase (HDAC) activity was determined using a test kit. Data sets were compared by one-way analysis of variance. Results: Our findings showed that Smad1/5/8-mediated rhBMP-2 and rhBMP-7 signaling is completely blocked by rhTGFβ1. We then investigated expression levels of genes involved in BMP signaling and regulation (for example, Smad1/5/8, TGFβ receptors type I and II, noggin, sclerostin, BMP and activin receptor membrane bound inhibitor (BAMBI), v-ski sarcoma viral oncogene homolog (Ski), Ski-related novel protein N (SnoN) and Smad ubiquitination regulatory factors (Smurfs)) and confirmed the expression of regulated genes at the protein level. Smad7 and SnoN were significantly induced by rhTGFβ1 treatment while expression of Smad1, Smad6, rhTGFβ11 and activin receptorlike kinase 1 (Alk1) was reduced. Elevated SnoN expression was accompanied by increased HDAC activity. Addition of an HDAC inhibitor, namely valproic acid, fully abolished the inhibitory effect of rhTGFβ1 on rhBMP-2 and rhBMP- 7 signaling. Conclusions: rhTGFβ1 effectively blocks rhBMP signaling in osteoblasts. As possible mechanism, we postulate an induction of SnoN that increases HDAC activity and thereby reduces the expression of factors required for efficient BMP signaling. Thus, inhibition of HDAC activity may support bone healing during rhBMP therapy in patients with elevated TGFβ serum levels. [ABSTRACT FROM AUTHOR]

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing. [ABSTRACT FROM AUTHOR]

Impactions of the articular surface are relevant prognostic parameters in the treatment of acetabular fractures. Posterior marginal impactions and acetabular dome impactions may occur depending on the direction of the force vectors during trauma. Posterior marginal impactions are mainly observed in posterior fracture dislocations, while acetabular dome impactions are frequently seen in the elderly with the hip joint in extension during trauma. Femoral head impactions are also frequently associated with acetabular fractures, mainly in fracture dislocations and transverse acetabular fractures. CT scans using thin slices are mandatory in order to preoperatively identify acetabular and femoral head impactions. Intraoperatively, the reduction techniques depend on the type of marginal impaction. Posterior impactions are usually addressed via a posterior approach by applying femoral traction under direct visualization or even by performing surgical hip dislocation. Acetabular dome impactions may be reduced using the fracture lines or by creating a cortical window. Reduction is followed by filling the void with bone or bone substitutes supported by raft screws. No clear treatment recommendations for femoral head impactions are given in the literature., Competing Interests: Declarations. Conflict of interest: No author has a conflict of interest that relates to the content discussed in this manuscript. All authors have contributed to and read the paper and have given permission for their names to be included as an author. The manuscript has not already been published and will not be submitted or published simultaneously elsewhere., (© 2024. The Author(s).)

The incidence of geriatric acetabular fractures has shown a sharp increase in the last decades. The majority of patients are male, which is different to other osteoporotic fractures. The typical pathomechanism generally differs from acetabular fractures in young patients regarding both the direction and the amount of force transmission to the acetabulum via the femoral head. Geriatric fractures very frequently involve anterior structures of the acetabulum, while the posterior wall is less frequently involved. The anterior column and posterior hemitransverse (ACPHT) fracture is the most common fracture type. Superomedial dome impactions (gull sign) are a frequent feature in geriatric acetabular fractures as well. Treatment options include nonoperative treatment, internal fixation and arthoplasty. Nonoperative treatment includes rapid mobilisation and full weighbearing under analgesia and is advisable in non- or minimally displaced fractures without subluxation of the hip joint and without positive gull sign. Open reduction and internal fixation of geriatric acetabular fractures leads to good or excellent results, if anatomic reduction is achieved intraoperatively and loss of reduction does not occur postoperatively. Primary arthroplasty of geriatric acetabular fractures is a treatment option, which does not require anatomic reduction, allows for immediate postoperative full weightbearing and obviates several complications, which are associated with internal fixation. The major issue is the fixation of the acetabular cup in the fractured bone. Primary cups, reinforcement rings or a combination of arthroplasty and internal fixation may be applied depending on the acetabular fracture type., Competing Interests: Declarations Conflict of interest No author has a conflict of interest that related to the content discussed in this manuscript. All authors have contributed to and read the paper and have given permission for their names to be included as an author. The manuscript has not already been published and will not be submitted or published simultaneously elsewhere., (© 2024. The Author(s).)

Beginning in France in the 1960s, the management of acetabular fractures has increasingly evolved toward surgical treatment strategies. The basic principles established by the pioneers of acetabular surgery, Letournel and Judet - anatomical reconstruction of the joint and stable osteosynthesis - remain unchanged. Modern advancements in surgical techniques aim to reduce access-related trauma and minimize complications. The notable rise in acetabular fractures among the elderly, which predominantly affect the anterior aspects of the acetabulum, has driven the development of less invasive, soft tissue-sparing anterior approaches. This evolution began with the ilio-inguinal approach in the 1960s, progressed to the modified Stoppa approach in the 2000s and, most recently, the Pararectus approach in the 2010s. Each of these approaches upholds the fundamental principles of effective acetabular fracture care, while offering distinct advantages and disadvantages. In this review, we examine the merits and limitations of the Pararectus approach, specifically focusing on its utility in the surgical treatment of anterior column posterior hemitransverse acetabular fractures. Ultimately, the success of the individual patient's outcome is less dependent on the chosen approach and more on the surgeon's experience and expertise. Ideally, surgeons should be proficient in all these approaches to tailor the surgical strategy to the individual patient's requirements, thereby ensuring optimal outcomes., Competing Interests: Declaration Conflict of interest The authors declare that they have no conflict of interest. No funding was received for this work., (© 2024. The Author(s).)

Introduction: Open reduction and internal fixation is considered the gold standard of treatment for displaced acetabular fractures in younger patients. For elderly patients with osteoporotic bone quality, however, primary total hip arthroplasty (THA) with the advantage of immediate postoperative mobilization might be an option. The purpose of this study was to evaluate the clinical and radiological outcomes of surgical treatment of displaced osteoporotic acetabular fractures using the acetabular roof reinforcement plate (ARRP) combined with THA., Materials and Methods: Between 2009 and 2019, 84 patients were operated using the ARRP combined with THA. Inclusion criteria were displaced osteoporotic fractures of the acetabulum with or without previous hemi- or total hip arthroplasty, age above 65 years, and pre-injury ability to walk at least with use of a walking frame. Of the 84 patients, 59 could be followed up after 6 months clinically and radiographically. Forty-nine (83%) were primary fractures and 10 (17%) periprosthetic acetabular fractures., Results: The mean age was 80.5 years (range 65-98 years). The average time from injury to surgery was 8.5 days (range 1-28). Mean time of surgery was 167 min (range 100-303 min). Immediate postoperative full weight bearing (FWB) was allowed for 51 patients (86%). At the 6-month follow-up, all 59 patients except one showed bony healing and incorporation of the ARRP. One case developed a non-union of the anterior column. No disruption, breakage or loosening of the ARRP was seen. Additional CT scans performed in 18 patients confirmed bony healing. Twenty-six patients (44%) had regained their pre-injury level of mobility. Complications requiring revision surgery occurred in 8 patients. Five of them were suffering from a prosthetic head dislocation, one from infection, one from hematoma and one from a heterotopic ossification., Conclusions: The ARRP has proven to provide sufficient primary stability to allow for immediate FWB in most cases and represents a valuable option for the surgical management of displaced acetabular fractures in this challenging patient group., (© 2021. The Author(s).)

Purpose: The aim of this study was to analyze the injury patterns and clinical course of a winter sport dominated by blunt renal trauma collective., Methods: Blunt renal trauma cases (N = 106) treated in a Level 1 Trauma Center in Austria were analyzed., Results: We encountered 12.3% grade 1, 10.4% grade 2, 32.1% grade 3, 38.7% grade 4 and 6.6% grade 5 renal traumata classified according to the American Association for the Surgery of Trauma (AAST). The mechanisms of injury (MOI) did not have an influence on the frequency of HG trauma (i.e., grade 4 and 5). No concomitant injuries (CIs) were found in 57.9% of patients. The number of patients without CIs was significantly higher in the sports associated trauma group compared to other MOIs (p < 0.01). In 94.3% the primary treatment was a non-operative management (NOM) including 56.6% conservative, 34.0% endourological, and 3.8% interventional therapies. A follow-up computed tomography (FU-CT) was performed in 81.1%, 3.3 days after trauma. After FU-CT, the primary therapy was changed in 11.4% of cases (grade ≥ 3). Comparing the Hb loss between the patients with grade 3 and 4 kidney trauma with and without revision surgery, we find a significantly increased Hb loss within the first 96 h after the trauma in the group with a needed change of therapy (p < 0.0001). The overall rate of nephrectomy (primary or secondary) was 9.4%. Independent predictors of nephrectomy were HG trauma (p < 0.01), age (p < 0.05), and sex (p < 0.05). The probability of nephrectomy was lower with (winter) sports-associated trauma (p < 0.1)., Conclusions: Sports-associated blunt renal trauma is more likely to occur isolated, and has a lower risk of severe outcomes, compared to other trauma mechanisms. NOM can successfully be performed in over 90% of all trauma grades., (© 2021. The Author(s).)

The combination of glenoid destruction with cuff arthropathy remains a challenge. A 75-year old woman presented with a post-traumatic loss of the glenoid and concomitant cuff arthropathy. Using CT-data a custom-made glenoid component was created by 3D printing. 6 months after reverse shoulder arthroplasty, the patient was free of pain with acceptable ROM. An individual glenoid component created by 3D printing is a feasible therapeutic option in patients with loss of the glenoid and concomitant cuff arthropathy.

Background: Although nonunions of the proximal humerus are rare, they cause significant disability to patients. Surgical reconstruction is challenging, especially with small and excavated head fragments. A promising surgical option is open reduction and stabilization using the Humerusblock device along with tension wires. The aim of this retrospective investigation was to evaluate the clinical and radiological results of this procedure., Materials and Methods: Fifteen patients with symptomatic surgical neck nonunions were treated with open reduction and internal fixation using the Humerusblock device without bone grafting. All patients showed a loss of bone stock, leading to excavated head fragments. The mean interval from injury to the described treatment was 6.2 months (range, 3.4-10.7). At a mean follow-up of 40.5 months, the Constant-Murley score was documented, pain and patient satisfaction were evaluated using a visual analogue scale, and x-rays were taken in two planes., Results: The patients' mean age was 69.7 years (range, 52-83). The mean Constant-Murley score improved from 24 points before surgery to 62 points at follow-up, which was an average of 80.8% of the score obtained for the contralateral arm. Radiological examination confirmed bony healing in 14 patients. All but one patient felt satisfied with the results. Three patients required revision surgery because of a hematoma, and early metal removal was performed in one patient because of infection., Conclusion: Nonunions of humeral surgical neck fractures can be successfully treated by fixation using the Humerusblock device along with tension wires without the need for additional bone grafting. Especially in patients with flat, concave head fragments, this procedure remains a promising reconstructive option to arthroplasty., Level of Evidence: Level IV; Therapeutic retrospective case series., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Valgus malalignment of the distal femur may be treated with corrective osteotomy. The purpose of this study was to compare the primary stability of a lateral opening-wedge osteotomy (LOWO) using a uniplanar compared to a biplanar technique. A study was carried out to test both surgeries, with both an intact medial cortex and with a deliberate attached cut of the medial cortex simulating a fracture. The primary hypothesis was that the biplanar technique provides higher axial and torsional stiffness. It was further hypothesized that the mechanical superiority of the biplanar technique would not be affected in the case of breakage of the far medial cortex., Methods: A LOWO was performed in ten synthetic femora (#3406 left large Femur, 4th Generation, Sawbones, Malmö, Sweden) using a lateral angle stable locking plate (NCB© Distal Femur Plate, Zimmer Biomet, Warsaw, USA). A uniplanar osteotomy was performed in five femora, and a biplanar osteotomy was performed in five femora. The femora were tested for axial and torsional loads using a servo-hydraulic testing machine (Instron 8874, Instron Structural Testing GmbH, High Wycombe, UK)., Results: Axial stiffness decreased significantly (p = 0.001) in both groups (20% in the uniplanar group and 28 % in the biplanar group) by cutting the medial cortex. The type of osteotomy had no significant effect. A slightly lower but not statistically significant axial stiffness was seen in the biplanar group both for intact and broken medial cortices. Internal torsional stiffness dropped by more than 30% for the uniplanar group and almost 24% for the biplanar group when the cortex was cut (p < 0.001). No significant change concerning internal torsional stiffness was found between the two groups. External torsional stiffness decreased by 32% for the uniplanar group and 4% for the biplanar group after the cortical cut (p = 0.029). No significant change concerning external torsional stiffness was found between the groups, but the biplanar group showed a tendency towards higher values of external torsional stiffness., Conclusions: The axial and torsional stiffness of the implant-bone construct were not significantly affected by the type of osteotomy performed. Biplanar osteotomy tended to increase external torsional stiffness. In cases of fracture of the medial cortex, biplanar osteotomy significantly reduced the external rotation at the osteotomy and showed a significantly increased external torsional stiffness.

Background: Open wedge high tibial osteotomy is widespread in treating osteoarthritis of the knee. Bone healing of the gap and the necessity of bone substitutes are under discussion. Increasing movement of the osteotomy gap can improve bone healing, while excessive movement should be avoided. It was hypothesised that the use of dynamic locking screws, compared to standard locking screws, will increase interfragmental motion while construct stability persists., Methods: In 20 tibia sawbones open wedge high tibial osteotomy was performed using standard locking screws or dynamic locking screws. An incremental cyclic (2 Hz) compression to termination protocol was applied using a material testing machine (MTS MiniBionix 858). Relative motion of the osteotomy and construct stability were measured using an optical tracking system (PONTOS 5M system). Levels of significance were set to 0.05., Findings: 19 Sawbones were statistically evaluated. Interfragmental motion increased significantly with dynamic locking screws compared to standard locking screws (P < 0.001). Lateral hinge fractured after a mean of 29,489 (dynamic locking screws) vs. 48,111 (standard locking screws) load cycles at a median load level 3 (50-1120 N) in dynamic locking screws group and at a median load level 5 (50-1440 N) (P = 0.002) in standard locking screws group., Interpretation: Using dynamic locking screws in open wedge high tibial osteotomy increases interfragmental motion within the range of optimal bone healing. A decrease in construct stability has to be considered compared to standard locking screws., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Little is known about injuries in canyoning. It was the purpose of this study to determine injury rates, patterns, causes and risk factors in canyoning; and to identify targets for future injury prevention strategies., Methods: From May to October 2015, 109 participants from 17 different countries were prospectively followed via a monthly e-mail-based questionnaire., Results: During 13,690 h of canyoning, 57 injury-events occurred. The overall injury-rate was 4.2 injuries/1000 h of canyoning. The hand (23%) and lower leg and foot (25%) were most frequently involved. Most of the injuries were mild (n = 27, 49%) and limited to the soft-tissue. There were seven severe injuries (12%) with two lateral malleolar fractures, both necessitating surgery. The majority of injuries were due to material failure (44%) and significantly more injury-events were reported when the tour included rappelling (p = 0.037). Canyoning guides suffered from significantly less injuries compared to beginners and advanced canyoneers (p < 0.001)., Conclusions: The majority of canyoning injuries are mild. On the other side, roughly one-tenth suffered from severe injury. Canyoning guides are less prone to injury-events and beginners should consider performing tours with experienced guides. Notwithstanding, rappelling was the most common activity associated with an injury and the material used was deemed causative for an injury-event in almost half of all cases. Further improvement in canyoning equipment, frequent equipment service, and instructional courses to ensure adequate employment of equipment might minimize the risk of getting injured., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Smokers frequently suffer from impaired fracture healing often due to poor bone quality and stability. Cigarette smoking harms bone cells and their homeostasis by increased formation of reactive oxygen species (ROS). The aim of this study was to investigate whether Quercetin, a naturally occurring antioxidant, can protect osteoblasts from the toxic effects of smoking. Human osteoblasts exposed to cigarette smoke medium (CSM) rapidly produced ROS and their viability decreased concentration- and time-dependently. Co-, pre- and postincubation with Quercetin dose-dependently improved their viability. Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO-) 1 and superoxide-dismutase- (SOD-) 1. Inhibiting HO-1 activity abolished the protective effect of Quercetin. Our results demonstrate that CSM damages human osteoblasts by accumulation of ROS. Quercetin can diminish this damage by scavenging the radicals and by upregulating the expression of HO-1 and SOD-1. Thus, a dietary supplementation with Quercetin could improve bone matter, stability and even fracture healing in smokers.