OA pathophysiology has a vascular component consisting of venous stasis resulting in intraosseous hypertension and hypoxia. In response, osteoblasts change their cytokine expression, accelerating bone remodelling and cartilage breakdown consistent with OA. We have characterized circulatory kinetics in OA bone in animal models with dynamic contrast enhanced MRI (DCE-MRI) and ¹⁸F PET and have demonstrated venous stasis and reduced perfusion that temporally precede and spatially coincide with OA lesions. Osteoblast uptake of ¹⁸F is consistent with abnormal perfusion, bone remodelling, and severity of OA. Circulatory kinetics with DCE-MRI in humans with OA of the knee exhibit similar venous outflow obstruction. Venous stasis is associated with hypoxia in subchondral bone. As an example of the effects of hypoxia on OA osteoblasts, we have described upregulation of fibrinolytic peptides, but a deficiency in the upregulation of PAI-1, leading to the generation of plasmin by human OA osteoblasts exposed to hypoxia in vitro. Plasmin is a serine protease that has been shown to degrade cartilage in OA. Abnormal circulatory kinetics by DCE-MRI may be an imaging biomarker of OA. Pharmacologic modulation of venous stasis would have a salutary effect on the physicochemical microcirculation of subchondral osteoblasts and the pathophysiology of OA.

The pathophysiological basis of alterations in trabecular bone of patients with osteonecrosis of the femoral head (ONFH) remains unclear. ONFH has classically been considered a vascular disease with secondary changes in the subchondral bone. However, there is increasing evidence suggesting that ONFH could be a bone disease, since alterations in the functionality of bone tissue distant from the necrotic lesion have been observed. We comparatively studied the transcriptomic profile of trabecular bone obtained from the intertrochanteric region of patients with ONFH without an obvious aetiological factor, and patients with osteoarthritis (OA) undergoing total hip replacement in our Institution. To explore the biological processes that could be affected by ONFH, we compared the transcriptomic profile of trabecular bone from the intertrochanteric region and the femoral head of patients affected by this condition. Differential gene expression was studied using an Affymetrix microarray platform. Transcriptome analysis showed a differential signature in trabecular bone from the intertrochanteric region between patients with ONFH and those with OA. The gene ontology analyses of the genes overexpressed in bone tissue of patients with ONFH revealed a range of enriched biological processes related to cell adhesion and migration and angiogenesis. In contrast, most downregulated transcripts were involved in cell division. Trabecular bone in the intertrochanteric region and in the femoral head also exhibited a differential expression profile. Among the genes differentially expressed, we highlighted those related with cytokine production and immune response. This study identified a set of differently expressed genes in trabecular bone of patients with idiopathic ONFH, which might underlie the pathophysiology of this condition. Acknowledgements: This work was supported by grants PI18/00643 and PI22/00939 from ISCIII-FEDER, Ministerio de Ciencia, Innovación y Universidades (MICINN)-AES

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remain a challenge. A novel surgical technique named Tibial Cortex Transverse Transport has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In present study, we aimed to explore the wound healing effects after undergoing this novel technique via multiple ways. A novel rat model of Tibial Cortex Transverse Transport was established with a designed external fixator and effects on wound healing were investigated. All rats were randomized into 3 groups, with 12 rats per group: sham group (negative control), fixator group (positive control) and Tibial Cortex Transverse Transport group. Laser speckle perfusion imaging, vessel perfusion, histology and immunohistochemistry were used to evaluate the wound healing processes. Gross and histological examinations showed that Tibial Cortex Transverse Transport technique accelerated wound closure and enhanced the quality of the newly formed skin tissues. In Tibial Cortex Transverse Transport group, HE staining demonstrated a better epidermis and dermis recovery, while immune-histochemical staining showed that Tibial Cortex Transverse Transport technique promoted local collagen deposition. Tibial Cortex Transverse Transport technique also benefited to angiogenesis and immunomodulation. In Tibial Cortex Transverse Transport group, blood flow in the wound area was higher than that ofother groups according to laser speckle imaging with more blood vessels observed. Enhanced neovascularization was seen in the Tibial Cortex Transverse Transport group with double immune-labelling of CD31 and α-SMA. The M2 macrophages at the wound site in the Tibial Cortex Transverse Transport group was also increased. Tibial cortex transverse transport technique accelerated wound healing through enhanced angiogenesis and immunomodulation

Abstract. Objectives. Currently, the golden standard for the management of ankle fractures is open reduction and internal fixation (ORIF), a procedure which preserves joint anatomy and function. However, ORIF is associated with high risk of infection, especially in the elderly population, who tend to suffer from osteoporosis and vascular disease. Studies recommend hindfoot nailing (HFN) as a safe and efficient management alternative for this demographic. Unlike ORIF, HFN allows immediate weight-bearing, which has been linked to a lower rate of complications. This study aims to evaluate the outcomes of hindfoot nailing in ankle fractures using a case series of 43 patients. Methods. This is a retrospective study with a sample size of 43 patients, that have a mean age of 77.3 years and several medical conditions. These patients experienced ankle fractures that were treated with HFN. Data collected included injury patterns, operative complications, rate of radiological union, comorbidities and changes in mobility and housing before and after surgery. Results. Before their fracture, 62.8% of patients mobilised using a walking stick or a wheeled frame. Following surgery, 52.4% experienced decreased level of mobility. 50% of patients achieved radiological union at the time of data analysis, whereas 52.4% of patients reported a post-operative complication, most commonly soft tissue or bone infection. Conclusions. Our study has a large sample size compared to previous research. The follow-up period varies depending on patient attendance to follow-up clinical appointments. Our patient cohort exhibits significantly lower rates of radiological union, higher incidence of complications and poor post-operative functional outcomes associated with HFN. These data contradict previous studies suggesting HFN for the surgical management of ankle fractures in the elderly and frail population and demonstrate that a more thorough evaluation of HFN is needed

Distraction histogenesis (DH) techniques have been widely accepted and practiced in orthopaedics, traumatology, and craniofacial surgery over the last two decades. Using DH methods, many previously untreatable conditions have been successfully managed with outstanding clinical outcomes. The biological mechanisms underlying DH have been studied and the tension-stress principles of tissue regeneration are attributed to upregulated gene expression, enhanced cell proliferation, angiogenesis and tissue remodelling and endogenous stem cell mobilization. The new methods of enhancing bone consolidation in DH are proposed and need further clinical studies. The novel applications of DH have now been extended for the treatment of vascular diseases, cranial defect (with neuronal disorders), hip and spinal deformity corrections and soft-tissue defects in addition to various bone defects and deformities. There are more surprises and novel mechanisms yet to be discovered for these novel applications of DH

The aim of this study was to examine the effects of cement in total knee arthroplasty on markers of inflammation and endothelial dysfunction, as surrogate markers for enhanced risk of vascular disease or precipitation of acute vascular events post-operatively. A total of 36 patients were recruited, with 18 in each of the cemented and uncemented groups. Both groups were matched for age, sex and body mass index. Venous blood samples were taken pre-operatively, day 1 and day 7 post-operatively. Serum levels of interleukin 6 (IL6), tumour necrosis factor (TNF□?, e-selectin, Von willebrand factor (vWF), tissue plasminogen activator (tPA) and soluble CD40 ligand were analysed. Also, real time analysis of the expression of CD40 and CD14/CD42a aggregates on monocytes was carried out using flow cytometry. Patients were excluded from the study if there were signs of either superficial or deep infection. The only variable to demonstrate a significant difference between the two groups was the CD1442a count. There was a significant difference in the first 24 hours (p=0.00) and from day 1 to day 7 (p=0.02). Our study suggests that the use of bone cement causes a significant rise in CD1442a count which has been linked to atherothrombosis and acute coronary syndromes. These changes may explain the increased incidence of venous thrombosis and thromboembolism post-operatively. However more research required in this field to delineate the exact pathways involved

Summary. Syndesmotic malreduction or failure to restore fibular length are the leading causes for early reoperation after ankle fracture surgery. Anatomic fracture reduction and congruent ankle mortise can be achieved in the majority of cases following revision surgery. Introduction. The goal of ankle fracture surgery is to restore anatomical congruity. However, anatomic reduction is not always achieved, and residual talar displacement and postoperative malreduction predispose a patient to post-traumatic arthritis and poor functional outcomes. The present study aimed to determine the most common surgical errors resulting in early reoperation following ankle fracture surgery. Patients & Methods. We performed a chart review to determine the most common types of malreductions that led to reoperation within the first week following ankle fracture surgery. From 2002 to 2011, we identified 5123 consecutive ankle fracture operations in 5071 patients. 79 patients (1.6%) were reoperated on due to malreduction (residual fracture displacement > 2mm) detected in postoperative radiographs. These patients were compared with an equal number of age- and sex-matched control patients. Surgical errors were classified according to the anatomical site of malreduction: fibula, medial malleolus, posterior malleolus, Chaput-Tillaux fragment, and syndesmosis. Problems related to syndesmotic reduction or fixation were further divided into four categories: malreduction of the fibula in the tibiofibular incisura due to malpositioning of a syndesmotic screw, persistent tibiofibular widening (TFCS > 6 mm), positioning of a syndesmotic screw posterior to the posterior margin of the tibia, and unnecessary use of a syndesmotic screw. Results. The mean patient age was 44 years (18 to 80), and 49% were women. There were no differences between the groups regarding diabetes, tobacco use, peripheral vascular disease, or alcohol abuse. The most common indication for reoperation was syndesmotic malreduction (47 of 79 patients; 59%). Other frequent indications for reoperation were fibular shortening and malreduction of the medial malleolus. We identified four main types of errors related to syndesmotic reduction or fixation, the most common being fibular malreduction in the tibiofibular incisura. The most commonly combined errors were malreductions of the fibula and syndesmosis, which occurred together in 16 of 79 patients (20%). Fracture-dislocation (p = 0.011), fracture type (p = 0.001), posterior malleolar fracture (p = 0.005), associated medial malleolar fracture (p = 0.001), duration of index surgery (p = 0.001), and associated medial malleolar fixation other than with two parallel screws (p = 0.045) were associated with reoperation. Correction of the malreduction was achieved in 84% of reoperated cases. Conclusion. Early reoperation after ankle fracture surgery was most commonly caused by errors related to syndesmotic reduction or failure to restore fibular length. In the majority of cases, postoperative malreduction was successfully corrected in the acute setting

Objectives

We studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection.

Objectives

Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.

We have compared the energy expenditure during walking in three patients, aged between 51 and 55 years, with unilateral disarticulation of the hip when using the mechanical-controlled stance-phase control knee (Otto Bock 3R15) and the microprocessor-controlled pneumatic swing-phase control knee (Intelligent Prosthesis, IP). All had an endoskeletal hip disarticulation prosthesis with an Otto Bock 7E7 hip and a single-axis foot. The energy expenditure was measured when walking at speeds of 30, 50, and 70 m/min.

Two patients showed a decreased uptake of oxygen (energy expenditure per unit time, ml/kg/min) of between 10.3% and 39.6% when using the IP compared with the Otto Bock 3R15 at the same speeds. One did not show any significant difference in the uptake of oxygen at 30 m/min, but at 50 and 70 m/min, a decrease in uptake of between 10.5% and 11.6% was found when using the IP. The use of the IP decreased the energy expenditure of walking in these patients.