Immunohistochemical analysis revealed the expression of bone morphogenetic proteins-4, 6, 7, and 9 in human induced membrane samples treated with the Masquelet technique

Background Induced membrane (IM) is the key component of Masquelet reconstruction surgery for the treatment of bone defects. IM is formed around the cement spacer and is known to secrete growth factors and osteoinductive factors. However, there is limited evidence available concerning the presence of osteoinductive factors in IM. This study aimed to investigate the existence of bone morphogenetic proteins (BMPs) in IM harvested from patients during the treatment of bone defects using the Masquelet technique. Methods This study involved six patients whose bone defects had been treated using the Masquelet technique. The affected sites were the femur (n = 3) and the tibia (n = 3). During the second-stage surgery, 1 cm2 pieces of IM were harvested. Histological sections of IM were immunostained with anti-BMP-4, 6, 7, and 9 antibodies. Human bone tissue served as the positive control. Results The presence of BMP-4, 6, 7, and 9 was observed in all IM samples. Further, immunolocalization of BMP-4, 6, 7, and 9 was observed in blood vessels and fibroblasts in all IM samples. Immunolocalization of BMP-4, 6, 7, and 9 was also observed in bone tissue within the IM in one sample, in which osteogenesis inside the IM was observed. Conclusions This study showed that osteoinductive factors BMP-4, 6, 7, and 9 were present in the IM harvested from patients, providing evidence indicating that the Masquelet technique effectively contributes to healing large bone defects. Therefore, it may be possible for surgeons to omit the addition of BMPs to bone grafts, given the endogenous secretion of BMPs from the IM.

The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

Purpose Microencapsulation techniques have allowed the addition of rifampicin to bone cement, but its in vivo efficacy has not been proven. The aim of our study is to determine the superiority of cement containing gentamicin and rifampicin microcapsules in the treatment of PJI versus cement exclusively containing gentamicin. Methods An S. aureus PJI was induced in 15 NZW rabbits. A week after inoculation, the first stage of replacement was carried out, and the animals were divided into two groups: group R received a spacer containing gentamicin and rifampicin microcapsules, and group C received a spacer containing gentamicin. Intra-articular release curve of rifampicin and infection and toxicity markers were monitored for four weeks post-operatively, when microbiological analysis was performed. Results The microbiological cultures showed a significantly lower growth of S. aureus in soft tissue (2.3·104 vs 0; p = 0.01) and bone (5.7·102 vs 0; p = 0.03) in the group with rifampicin microcapsules. No differences were found in systemic toxicity markers. Rifampicin release from the cement spacer showed higher concentrations than the staphylococcal MIC throughout the analysis. Conclusion The in vivo analyses demonstrated the superiority of cement containing gentamicin and rifampicin microcapsules versus the isolated use of gentamicin in the treatment of PJI in the rabbit model without serious side effects due to the systemic absorption of rifampicin. Given the increasing incidence of staphylococci-related PJI, the development of new strategies for intra-articular administration of rifampicin for its treatment has a high clinical impact.

Treatment of chronic osteomyelitis with antibiotic-impregnated polymethyl methacrylate (PMMA) – the Cierny approach: is the second stage necessary?

Background Chronic osteomyelitis is a challenge for orthopedic surgeons. Most patients with osteomyelitis receive two-stage management according to Cierny-Mader. The first stage includes radical debridement and insertion of an antibiotic-impregnated cement spacer (ACS) (beads, rods, nails, or blocks) into the bone defect. The second stage is performed 6–8 weeks later, when the spacer is removed and a cancellous autograft is placed within the bone defect. The possibility of ACS as definitive management for osteomyelitis, avoiding the second stage, is presented. Methods Sixteen patients with osteomyelitis received radical debridement and insertion of an ACS in all forms into the bone defect as a definitive management. In 8 patients, the tibia was infected, 4 had femur infection, 2 humerus, 1 fibula, and 1 ankle. The mean age at the time of the first stage of reconstruction was 49 years (range, 13–71 years). According to the Cierny-Mader classification, 1 patient was C-M IA, another was IB, 7 IIIA, 6 IIIB, and 1 was 4A. All B hosts had systemic illnesses. The mean follow-up period was 6 years (1.5–16 years). Results No patient exhibited radiographic evidence of excessive bone loss. Signs of recurrence of osteomyelitis were not noted in any of the patients, and no fractures had occurred by the last follow-up. Conclusion Our study suggests that a proportion of patients with planned retention of ACS appear to function well without requiring further surgical intervention, especially in elderly or vulnerable patients.

Masquelet technique in management of infective non-union of long bones- A prospective study

Introduction and Aim: Masquelet’s technique is a 2-staged procedure, for treatment of infected segmental bone defect. 1st stage involves radical debridement with antibiotic-induced cement spacer. During second stage, the spacer is removed and the autologous bone graft is applied into the biomembrane formed. In this study, we evaluate the Masquelet’s technique for the management of infective non-union of long bones. Materials and Methods: 15 patients with infective non-union of long bones- tibia, femur and a case of congenital pseudoarthrosis of tibia, were treated with Masquelet’s technique. They underwent 2 stages of procedures 6-8 weeks apart and was followed up for about 9 months and radiological and clinical outcomes were assessed. Results: Out of 15 patients with infective non-union, 8 patients attained union. Out of the 7 patients with failure of the technique, higher failure rates were attributed to Pseudomonas infection. Conclusion: Masquelet’s technique is a cost-effective method for treating infective segmental non-unions, not requiring special training or sophisticated instruments. This method shows good results with Gram positive infections. Although, the outcome with Pseudomonas aeruginosa infection, have not shown satisfactory results.

One-Stage Hip Revision Arthroplasty Using Megaprosthesis in Severe Bone Loss of The Proximal Femur Due to Radiological Diffuse Osteomyelitis

Managing substantial proximal and/or distal femoral bone defects is one of the biggest challenges in chronic hip periprosthetic joint infection. Most authors use two-stage arthroplasty with a temporary antibiotic-loaded cement spacer for the management of these patients. In this study, we show our experience with one-stage exchange arthroplasty in managing severe bone defects due to radiological-extensive proximal femoral osteomyelitis. Two patients were included in the study. They showed radiological-extensive proximal femoral osteomyelitis, and they were treated with one-stage exchange arthroplasty using megaprosthesis. Diffuse osteomyelitis was confirmed in both cases; in one case, the histology was compatible with osteomyelitis, and the other case had a positive culture identified in a bone sample. At a minimum of a four-year follow-up, the patients did not reveal any clinical, radiological or laboratory signs of infection. In conclusion, one-stage exchange arthroplasty and megaprosthesis is an option for the treatment of chronic hip periprosthetic joint infection associated with radiological-diffuse proximal femoral osteomyelitis.

Is the bioactivity of induced membranes time dependent?

Purpose The induced membrane technique (IMT) is a two-stage surgical procedure for reconstruction of bone defects. Bone grafting (second stage of IMT) is recommend after 4–8 weeks assuming the highest bioactivity of IMs. However, larger studies concerning the biology and maturation of IMs and a potential time dependency of the bioactivity are missing. Therefore, aim of this study was the time-dependent structural and cellular characterization of cement spacer IMs concomitantly to an analysis of membrane bioactivity. Methods IMs from 60 patients (35–82 years) were obtained at different maturation stages (1–16 weeks). IMs were studied by histology and co-culture with mesenchymal stem cells (MSC). IM lysates were analyzed by ELISA and protein microarray. Results Increasing vascularization and fibrosis were found in membranes older than 4 and 7 weeks, respectively. MSC grew out from all membranes and all membranes enhanced proliferation of cultured MSC. Osteocalcin and osteopontin (in membrane lysates or induced in MSC by membrane tissue) were found over all time points without significant differences. In contrast to alkaline phosphatase activity, increasing levels of osteoprotegerin were found in membranes. Conclusion The histological structure of IMs changes during growth and maturation, however, biologically active MSC and factors related to osteogenesis are found over all time points with minor changes. Thus, membranes older than 8 weeks exert regenerative capacities comparable to the younger ones. The postulated narrow time frame of 4–8 weeks until bone grafting can be questioned and surgeons may choose timing for the second operation more independently and based on other clinical factors.

Masquelet Technique Combined with Tissue Flap Transplantation in The Treatment of Infectious Complex Tissue Defect: A Clinical Analysis

Background: Infectious complex tissue defects have been described as injuries with composite infectious bone defects and extensive soft tissue damage, which are still austere challenges for orthopedists all around the world. The study retrospectively evaluated the Masquelet technique combined with the tissue flap transplantation for the treatment of infectious complex tissue defects and assess key factors of success in this technique.Methods: From December 2016 to December 2019, 22 patients of infectious complex tissue defects were recruited for the study. All the cases experienced a two-stages treatment. Thorough debridement, stabilization of fracture by external fixation and implantation of a cement spacer mixed with antibiotics in the first stage. Simultaneously, suitable tissue flaps were designed and transplanted for the soft tissue defect. 6-8 weeks later, after the elimination of the infection, the cement spacer was removed carefully from the induced membrane and cancellous bone was grafted into the site of bone defect. The average duration of follow-up was 21 months.Results: Infection was eliminated after the first stage intervention without recurrence. All the transplanted tissue flaps were survived. Bone union was achieved in all patients in a period of 16-31 weeks following the second stage surgery. According to the Paley fracture healing score, 17 patients showed excellent results and 5 patients displayed good results regarding bone outcomes. When considering functional outcomes, 14 patients exhibited excellent results and 8 patients displayed good results.Conclusions: This study showed evidences that Masquelet technique combined with tissue flap transplantation was an effective method to repair the infectious complex tissue defects. We also demonstrate that a complete soft-tissue envelope plays an important role in the formation of the induced membrane which promote bone union and in the anti-infection treatment.

Severe Vancomycin-Induced IgA Bullous Dermatosis Case Report

Linear IgA Bullous Dermatosis is a rare autoimmune blistering disease with an incidence of about 0.5 to 2.3 cases per million individuals per year. Although multiple reports have documented drug exposure as a precipitating factor, formal studies validating the existence of drug-induced LABD are lacking. A 49-year-old man with history of intravenous drug use presented with left hip pain of three weeks duration after sustaining a fall. On presentation he was hemodynamically stable and physical examination was notable for poor dentition, gingivitis, stigmata of IV drug use with associated cellulitis on right antecubital fossa and proximal left thigh tenderness with stiffness and limited range of movement. Laboratory diagnostics were remarkable for elevated inflammatory markers, with no evidence of leukocytosis. CT scan without contrast of the left lower extremity that demonstrated severe left hip osteoarthritis without fracture or dislocation. Blood Cultures were collected and empirically started on Vancomycin and Piperacillin/Tazobactam for right elbow cellulitis. The patient continued to experience severe pain, prompting incision and drainage of the left hip along with acetabuloplasty, removal of the femoral head, and Stage I hip replacement with placement of prophylactic prosthetic cement spacer with Vancomycin and Tobramycin. Within twenty-four hours of surgery, he developed multiple distinct maculopapular/bullous lesions of his torso and medial thigh that rapidly progressed, involving the oral mucosa, scrotum, glans, hands, and feet with associated periorbital edema. Punch biopsy was performed and due to involvement of ~20% body surface area and transferred to a tertiary center. H&E and immunostaining of the histological sample demonstrated IgA bullous disease. The patient’s bullous lesions improved two weeks after discontinuation of Vancomycin and initiation of therapy. This case demonstrates the importance of early recognition of the rare adverse effects of commonly used medications. Vancomycin is currently used more frequently given the recent rise in the prevalence of methicillin-resistant Staphylococcus aureus infection. Further studies are needed to understand the pathophysiology, genetic predisposition, and disease penetrance.

Immunohistochemical Analysis Revealed the Expression of Bone Morphogenetic Proteins-4, 6, 7, and 9 in Human Induced Membrane Samples Treated With the Masquelet Technique

BackgroundInduced membrane (IM) is the key component of Masquelet reconstruction surgery for the treatment of bone defects. It is formed around the cement spacer and is known to secrete growth factors and osteoinductive factors. However, information on the presence of osteoinductive factors in IM is not enough in the literature. The purpose of this study was to investigate the existence of bone morphogenetic proteins (BMPs) in the IM harvested from patients during the treatment of bone defects using the Masquelet technique.MethodsWe included six patients whose bone defects were treated using the Masquelet technique. The affected bone was the femur in three patients and the tibia in three patients. During the second-stage surgery, 1-cm2 pieces of IM were harvested. Histological sections of IM were immunostained with anti-BMP-4, 6, 7, and 9 antibodies. Human bone tissue served as the positive control.ResultsThe existence of BMP-4, 6, 7, and 9 was observed in all IM samples. Further, immunolocalization of BMP-4, 6, 7, and 9 was observed in blood vessels and fibroblasts of all IM samples. Immunolocalization of BMP-4, 6, 7, and 9 was also observed in bone tissue within the IM in one sample, in which osteogenesis inside the IM was observed.ConclusionsThis study revealed that osteoinductive factors BMP-4, 6, 7, and 9 were present in the IM harvested from patients. This helps explain how the Masquelet technique effectively contributes to the healing of large bone defects. It may thus be possible for surgeons to omit the addition of BMPs to bone grafts give the endogenous secretion of BMPs from the IM.Trial registrationNot applicable.