Immunologic response in patients with polytrauma.

Purpose: It is now known that traumatic injury initiates a complex and dynamic immune response on the first day. It is believed that in patients with polytrauma, these immune responses contribute to the development of infectious complications. Therefore, understanding the immune response to trauma is critical to improving patient outcomes through the development of new therapies and improved resuscitation strategies. The purpose of this study is to examine the parameters of immunity in patients with severe polytrauma at the stages of surgical treatment (the nearest post-traumatic period and long-term periods) in the absence and presence of purulent-inflammatory complications. Methods: We retrospectively enrolled 188 patients after severely injured trauma and 210 control group at two Level-1 Trauma Centers. Peripheral blood was collected upon presentation to the hospital and at the following time points: 1, 3, 7, 14, 21, 30, 60 and 90 days, and daily during intensive care unit admission. T-lymphocytes analyses performed using a Beckman Coulter EPICS XL flow cytometer (USA) with monoclonal antibodies (Immunotech, France). Analyses of protein levels of cytokines/chemokines, immunoglobulins, and circulating immune complexes was using ELISA. Results: Under the influence of trauma, the content of T lymphocytes decreased due to the population of T-helpers. However, the number of B lymphocytes increased. The most pronounced activation of humoral immunity was observed by the 30th day of the post-traumatic period. Concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-a), interleukin-10 (IL-10) on day 1 after injury were the highest. Later, in the post-traumatic period, a gradual decrease in the initially elevated cytokines was noted. Conclusions: As we continue to extrapolate new information on immune response factors associated with polytrauma, we will be better equipped to develop new therapeutic strategies to treat this serious clinical and social problem. In addition, individually adjusted immune control is an important interactive concept in polytrauma management.

Functions of the bone morphogenetic protein signaling pathway through non-coding RNAs.

Bone morphogenetic proteins (BMPs) are proteins of the transforming growth factor-ß (TGF-ß) family, which plays an important role in the formation of skeletal and cartilage tissue and their regeneration. BMPs play a key role in the formation of new blood vessels and promote the migration, proliferation, and differentiation of mesenchymal stem cells (MSCs) into chondroblasts and osteoblasts. It is known that malfunction of BMPs signaling can cause a disease state. Epigenetic regulation of expression plays a key role in the control of many cellular processes. Important participants in this regulation are non-coding RNAs (ncRNAs), which are RNA molecules that are not translated into proteins. The best known of these are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). In addition, the results of many studies make it possible to establish an unambiguous functional relationship between these ncRNAs. Being involved in the regulation of a large number of target genes responsible for the life of the cell, miRNAs, lncRNAs, and circRNAs are essential for the normal development and functioning of the body, and the violation of their functions accompanies the development of many pathophysiological processes including oncogenesis. In the present review, we discuss different insights into the regulation of BMPs signaling pathway by miRNAs, lncRNAs and circRNAs governed.

Ilizarov bone transport combined with the Masquelet technique for bone defects of various etiologies (preliminary results).

BACKGROUND: The Ilizarov bone transport (IBT) and the Masquelet induced membrane technique (IMT) have specific merits and shortcomings, but numerous studies have shown their efficacy in the management of extensive long-bone defects of various etiologies, including congenital deficiencies. Combining their strong benefits seems a promising strategy to enhance bone regeneration and reduce the risk of refractures in the management of post-traumatic and congenital defects and nonunion that failed to respond to other treatments. AIM: To combine IBT and IMT for the management of severe tibial defects and pseudarthrosis, and present preliminary results of this technological solution. METHODS: Seven adults with post-traumatic tibial defects (subgroup A) and nine children (subgroup B) with congenital pseudarthrosis of the tibia (CPT) were treated with the combination of IMT and IBT after the failure of previous treatments. The mean number of previous surgeries was 2.0 ± 0.2 in subgroup A and 3.3 ± 0.7 in subgroup B. Step 1 included Ilizarov frame placement and spacer introduction into the defect to generate the induced membrane which remained in the interfragmental gap after spacer removal. Step 2 was an osteotomy and bone transport of the fragment through the tunnel in the induced membrane, its compression and docking for consolidation without grafting. The outcomes were retrospectively studied after a mean follow-up of 20.8 ± 2.7 mo in subgroup A and 25.3 ± 2.3 mo in subgroup B. RESULTS: The "true defect" after resection was 13.3 ± 1.7% in subgroup A and 31.0 ± 3.0% in subgroup B relative to the contralateral limb. Upon completion of treatment, defects were filled by 75.4 ± 10.6% and 34.6 ± 4.2%, respectively. Total duration of external fixation was 397 ± 9.2 and 270.1 ± 16.3 d, including spacer retention time of 42.4 ± 4.5 and 55.8 ± 6.6 d, in subgroups A and B, respectively. Bone infection was not observed. Postoperative complications were several cases of pin-tract infection and regenerate deformity in both subgroups. Ischemic regeneration was observed in two cases of subgroup B. Complications were corrected during the course of treatment. Bone union was achieved in all patients of subgroup A and in seven patients of subgroup B. One non-united CPT case was further treated with the Ilizarov compression method only and achieved union. After a follow-up period of two to three years, refractures occurred in four cases of united CPT. CONCLUSION: The combination of IMT and IBT provides good outcomes in post-traumatic tibial defects after previous treatment failure but external fixation is longer due to spacer retention. Refractures may occur in severe CPT.

International recognition of the Ilizarov bone reconstruction techniques: Current practice and research (dedicated to 100th birthday of G. A. Ilizarov).

The Ilizarov method is one of the current methods used in bone reconstruction. It originated in the middle of the past century and comprises a number of bone reconstruction techniques executed with a ring external fixator developed by Ilizarov GA. Its main merits are viable new bone formation through distraction osteogenesis, high union rates and functional use of the limb throughout the course of treatment. The study of the phenomenon of distraction osteogenesis induced by tension stress with the Ilizarov apparatus was the impetus for advancement in bone reconstruction surgery. Since then, the original method has been used along with a number of its modifications developed due to emergence of new fixation devices and techniques of their application such as hexapod external fixators and motorized intramedullary lengthening nails. They gave rise to a relatively new orthopedic subspecialty termed "limb lengthening and reconstruction surgery". Based on a comprehensive literature search, we summarized the recent clinical practice and research in bone reconstruction by the Ilizarov method with a special focus on its modification and recognition by the world orthopedic community. The international influence of the Ilizarov method was reviewed in regard to the origin country of the authors and journal's rating. The Ilizarov method and other techniques based on distraction osteogenesis have been used in many countries and on all populated continents. It proves its international significance and confirms the greatest contribution of Ilizarov GA to bone reconstruction surgery.

Role of the Ilizarov non-free bone plasty in the management of long bone defects and nonunion: Problems solved and unsolved.

BACKGROUND: Ilizarov non-free bone plasty is a method of distraction osteogenesis using the Ilizarov apparatus for external fixation which originated in Russia and was disseminated across the world. It has been used in long bone defect and nonunion management along with free vascularized grafting and induced membrane technique. However, the shortcomings and problems of these methods still remain the issues which restrict their overall use. AIM: To study the recent available literature on the role of Ilizarov non-free bone plasty in long bone defect and nonunion management, its problems and the solutions to these problems in order to achieve better treatment outcomes. METHODS: Three databases (PubMed, Scopus, and Web of Science) were searched for literature sources on distraction osteogenesis, free vascularized grafting and induced membrane technique used in long bone defect and nonunion treatment within a five-year period (2015-2019). Full-text clinical articles in the English language were selected for analysis only if they contained treatment results, complications and described large patient samples (not less than ten cases for congenital, post-tumor resection cases or rare conditions, and more than 20 cases for the rest). Case reports were excluded. RESULTS: Fifty full-text articles and reviews on distraction osteogenesis were chosen. Thirty-five clinical studies containing large series of patients treated with this method and problems with its outcome were analyzed. It was found that distraction osteogenesis techniques provide treatment for segmental bone defects and nonunion of the lower extremity in many clinical situations, especially in complex problems. The Ilizarov techniques treat the triad of problems simultaneously (bone loss, soft-tissue loss and infection). Management of tibial defects mostly utilizes the Ilizarov circular fixator. Monolateral fixators are preferable in the femur. The use of a ring fixator is recommended in patients with an infected tibial bone gap of more than 6 cm. High rates of successful treatment were reported by the authors that ranged from 77% to 100% and depended on the pathology and the type of Ilizarov technique used. Hybrid fixation and autogenous grafting are the most applicable solutions to avoid after-frame regenerate fracture or deformity and docking site nonunion. CONCLUSION: The role of Ilizarov non-free bone plasty has not lost its significance in the treatment of segmental bone defects despite the shortcomings and treatment problems encountered.

Mechanical solutions to salvage failed distraction osteogenesis in large bone defect management.

INTRODUCTION: Ilizarov bone transport for large bone defect is challenging and may end in distraction osteogenesis failure. MATERIAL AND METHODS: Ten forearm and seven tibial defect cases with failed regeneration due to ischaemia during bone transport were studied retrospectively. Mean forearm and tibial defects were 5.5 ± 0.8 and 7.6 ± 1 cm respectively, or 22.3 ± 3.6 and 20 ± 2.3% as compared with healthy segments. Most patients had numerous previous operations (2.6 ± 0.5 and 3.4 ± 0.8 per patient, respectively), extensive scars locally and post-traumatic neuropathy. There were seven infected defects. Mechanical solutions used were (1) additional osteotomy and transport of the fragment to compact the ischaemic regenerate (10 forearms, 4 tibias) and (2) compaction of the connective tissue layer in the tibial regenerate with either two 5-mm steps (two cases) or gradually (one case). RESULTS: Bone integrity was restored in all the cases. Complete compensation of the defects was achieved in 12 patients with the first technique. Two patients with 8-cm ulna defects remained with residual discrepancy. In the forearm, mean compaction was 1.7 ± 0.4 cm. It took 25.7 ± 5.4 days followed by an average fixation period of 107.1 ± 11.8 days. In the tibia, mean longitudinal compaction by distraction measured 1.7 ± 0.8 cm. The second technique ended up with an acceptable shortening of 1 cm in two cases. Four centimeters were compressed in the third case gradually. CONCLUSION: The technical solutions used for mechanical effects on the ischaemic distraction regenerate resulted in its rescue and bone union in all the cases.

The use of flexible intramedullary nails in limb lengthening.

INTRODUCTION: Lower and upper limb length discrepancy and deformity, congenital or acquired, are amongst the most common conditions in children for orthopaedic referral. Over the last twenty years, surgical techniques have evolved in an attempt to decrease Healing Index and minimise these complications. Areas covered: The flexible intramedullary nailing (FIN) is a minimally invasive intramedullary osteosynthesis. In combination with an external fixator, it is appropriated for pediatric bone lengthenings and lengthening of bones of small diameter in adults. In the study the Scopus and/or PubMed indexed publications about this combined technique were analyzed. Expert commentary: The use of titanium or stainless steel or hydroxyapatite-coated bent elastic nails is appropriate in limb lengthening for congenital and acquired limb length discrepancy. Hydroxyapatite-coated FIN should be applied for long-term reinforcement of lengthened bone in patients with metabolic bone disorders, skeletal dysplasias with compromised bone formation. Osteoinductive surface of nails is favorable for bone formation and as well as for stable position of nails without risks of migration in long-term follow-up. The FIN is an unique intramedullary fixation which respects the bone biology which is mandatory for a good bone consolidation.

Contribution of G.A. Ilizarov to bone reconstruction: historical achievements and state of the art.

Methodological solutions of Prof. G.A. Ilizarov are the core stone of the contemporary bone lengthening and reconstruction surgery. They have been acknowledged in the orthopaedic world as one of the greatest contributions to treating bone pathologies. The Ilizarov method of transosseous compression-distraction osteosynthesis has been widely used for managing bone non-union and defects, bone infection, congenital and posttraumatic limb length discrepancies, hand and foot disorders. The optimal conditions for implementing distraction and compression osteogenesis were proven by numerous experimental studies that Prof. G.A. Ilizarov organized and supervised at a large orthopaedic research institute in Kurgan. The tension stress effect on regeneration and growth of tissues was thoroughly investigated with radiographic, histological and biochemical methods. The impact of the Ilizarov method on the progress of bone lengthening and reconstruction surgery could be called revolutionary.

Ilizarov Method for Bone Lengthening and Defect Management Review of Contemporary Literature.

Since its origination in the middle of the past century, the Ilizarov method has advanced greatly and has become a viable method for bone lengthening, severe deformity correc- tion, and defect management. As the reported studies show, it remains one of the most used tools for bone reconstruction. The original method and its modifications continue to be the topic of interest for orthopaedic scientists as evidenced by the number of clinical studies on the Ilizarov method that have been published in orthopaedic journals in the period from 2000 through 2014, most of which present the out- comes of treating large series of patients using distraction osteogenesis for bone lengthening, defect management, and deformity correction. We made a review of contemporary clinical studies on the Ilizarov method used for bone length- ening and defect management.

Management of congenital pseudarthrosis of the tibia with the Ilizarov method in a paediatric population: influence of aetiological factors.

PURPOSE: Our study compared the rates of union achieved with the Ilizarov method in congenital pseudarthrosis of the tibia (CPT) associated with neurofibromatosis type 1 (NF1) or CPT of idiopathic origin in paediatric patients. METHODS: We studied the outcomes of 28 children that were treated for CPT between 2005 and 2013. Group 1 included children (n = 14, mean age = 9.7 years) with CPT associated with NF1 while group 2 were CPT cases that had radiographic confirmation of dysplastic lesions in the tibia but lacked clinical NF1 manifestations (n = 14, mean age = 8.6 years). There was no statistical difference between the groups regarding their age or number of previous operations per patient. Individual technical solutions were planned for each patient but coaptation of bone fragments and autologous local tissue grafting to achieve a greater bone thickness and contact area at the pseudarthrosis level were mainly used. Refracture-free rate after the first operation, number of re-operations per patient, and union rates in the groups were compared. RESULTS: Bone union and weight bearing were obtained in all the cases after the first operation. Refracture-free rate was 42.86 % in group 1 and 35.71% in group 2 (no statistical difference, p > 0.05). Mean number of re-operations per patient was 1.07 and 0.78 respectively (p > 0.05). Subsequent treatment for refractures with the Ilizarov techniques gained 92.86% of union in both groups at the follow-ups by completion of the study (range, 2-9 years). CONCLUSIONS: The Ilizarov method yields comparable results in the management of CPT associated with NF1 or tibial dysplasia of idiopathic origin in paediatric cases. Further research should focus on the ways to support the Ilizarov method in order to reduce the number of repetitive surgeries or eliminate them.

Reconstruction by bone transport after resection of benign tumors of tibia: A retrospective study of 38 patients.

BACKGROUND: The commonly used reconstructive options after post resection defects in bone tumors like megaprosthesis, autograft, allograft, bone graft substitutes and recycled bone have their own demerits on a long term. Bone transport that regenerates patient's own bone is a less explored option of reconstruction after resection of benign bone tumors and reports on this are limited. This technique is very much relevant in tibia where Ilizarov fixator is surgeon and patient friendly. We report our experience. MATERIALS AND METHODS: This is a retrospective series of resection and bone transport in 38 patients with benign tumor of tibia. There were 14 males and 24 females with mean age of 23.40 years (range 9-40 years). Lesion was located in proximal third tibia in 27, middle third in two and distal third in nine patients. The diagnosis was giant cell tumor in 32, chondroblastoma in three, chondromyxoid fibroma, enchondroma and desmoplasic fibroma in one patient each. The resection was intercalary in 28 and transarticular in 10 patients. Osteosynthesis was monofocal in three, bifocal in 31 and polyfocal in four cases. RESULTS: Mean followup was 7.22 years (range 1.5-15 years). Mean resection length was 10.21 cm (range 3-22 cm). The mean duration of external fixator was 308.03 days (range 89-677 days) and mean external fixator index was 36.14 days/cm (range 16.84-97.43 days/cm). Twelve patients had difficulties in the form of 11 problems and five obstacles that were successfully managed. None of the patients had local recurrence of tumor or any long term complication. Mean Musculo-skeletal Tumour Society score at final followup was 27.18 (90.60%). CONCLUSIONS: Bone transport is an excellent option after resection of benign tumors of tibia with good local control and functional outcome, despite minor difficulties that need timely management.

The Ilizarov paradigm: thirty years with the Ilizarov method, current concerns and future research.

The Ilizarov method of bone lengthening, reconstruction and osteosynthesis has developed immensely since its introduction by G.A. Ilizarov in the Soviet Union in the 1960s and in the Western countries in the early 1980s. It has become an integral part of the arsenal used by the orthopaedic community worldwide. The evolutionary development of the method and its current role has considerably improved the quality of life for millions of people around the whole world. Despite the great versatility of its possible applications for bone injuries and diseases, the Ilizarov method could not and cannot be the alternative to a range of other methods that are applied for some specific bone conditions, but rather is a method of choice. Its combination with the current methods of internal fixation or the means of internal fixation that use the biological principles that were laid down by G.A. Ilizarov have demonstrated the importance of tension stress, blood supply, functional loading, and fragment control during bone treatment. The objective of this study was to present an overview of the current state and concerns in the application of the Ilizarov method and define the prospective research trends aimed at regeneration stimulation, better control of treatment, infection barriers and patient comfort.

Ilizarov non-free bone plasty for extensive tibial defects.

PURPOSE: The purpose of this study was to present a retrospective comparative overview of the Ilizarov non-free bone plasty techniques of one-stage multilevel fragment lengthening and gradual tibilisation of the fibula used for extensive tibial defect management. METHODS: Extensive tibial defects in 83 patients were managed either by multilevel fragment lengthening (group I, n = 41, mean defect size 13.1 ± 0.9 cm) or gradual tibilisation of the fibula (group II, n = 42, mean defect size 12.5 ± 1.2 cm) using the Ilizarov apparatus. The initial findings, treatment protocols and outcomes of those patients treated within the period 1972-2011 were studied retrospectively by medical records and radiographs, and statistically assessed with Microsoft Excel and Attestat software. RESULTS: Group I had multilevel fragment lengthening over one stage that averaged 288.0 ± 14.4 days. The mean total period of gradual tibilisation of the fibula in group II was 316.0 ± 29.7 days. The patient's age in the latter group had an effect on the completeness of leg-length equalisation. CONCLUSIONS: The techniques can be used to manage extensive tibial defects as all the defects bridged, leg-length discrepancy and deformity were corrected and patients were able to load their limbs.

Long bone reconstruction using multilevel lengthening of bone defect fragments.

PURPOSE: This paper presents experimental findings to substantiate the use of multilevel bone fragment lengthening for managing extensive long bone defects caused by diverse aetiologies and shows its clinical introduction which could provide a solution for the problem of reducing the total treatment time. METHODS: Both experimental and clinical multilevel lengthening to bridge bone defect gaps was performed with the use of the Ilizarov method only. RESULTS: The experimental findings and clinical outcomes showed that multilevel defect fragment lengthening could provide sufficient bone formation and reduction of the total osteosynthesis time in one stage as compared to traditional Ilizarov bone transport. The method of multilevel regeneration enabled management of critical-size defects that measured on average 13.5 ± 0.7 cm in 78 patients. CONCLUSIONS: The experimental and clinical results proved the efficiency of the Ilizarov non-free multilevel bone plasty that can be recommended for practical use.