Aims. Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set. Methods. A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy. Results. A total of 3,303 records were screened, of which 99 studies were included. Most studies were case series (77/99; 78%) and assessed one method of reconstruction (68/99; 69%). A total of 511 outcomes were reported, which were grouped into 58 distinct outcomes. Overall, 143/511 of all outcomes (28%) were provided with a clear, in-text definition, and 231 outcomes (45%) had details reported of how and when they were measured. The most commonly reported outcome was ‘recurrence of osteomyelitis’ (62; 12%). The single-most patient-reported outcome measure was ‘pain’. Conclusion. This study has highlighted significant inconsistencies in the defining, reporting, and measuring of outcomes across studies investigating surgical management for chronic osteomyelitis of the lower limb in adults. Future studies should clearly report complete details of how outcomes are defined and measured, including timing. The development of a standardized core outcome set would be of significant benefit in order to allow evidence synthesis and comparison across studies. Cite this article: Bone Jt Open 2023;4(3):146–157

Aims. The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit. Methods. We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included. Results. A total of 53 patients (54 bones) with median age of 45.5 years (interquartile range 31 to 55) and mean follow-up of 29 months (12 to 59) were included. In all, ten bones were Cierny-Mader type I, 39 were type III, and five were type IV. All patients were treated with single-staged management, except for one (planned two-stage stabilization). Positive microbial cultures grew in 75%. Overall, 46 cases (85%) had resolution of COM after index procedure, and 49 (90.7%) had resolution on last follow-up. Four patients (7%) underwent second surgical procedure and six patients (11%) had complications. Conclusion. We challenge the need for wide tumour-like resection in all cases of COM. Through detailed preoperative evaluation and planning with MDT approach, adequate debridement and local delivery of high concentration of antibiotic appears to provide comparable outcomes versus radical debridement. Cite this article: Bone Jt Open 2023;4(8):643–651

Aims. Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier. Methods. A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4). Results. At final follow-up, six patients (six bones) had recurrent infection; thus 94% were infection-free. Three infections recurred in the first year, two in the second year, and one 4.5 years postoperatively. Recurrence was not significantly related to the physiological class of the patient (1/20 Class A (5%) vs 5/80 Class B (6.25%); p = 0.833), nor was it significantly related to the aetiology of the infection, the organisms which were cultured or the presence of nonunion before surgery (1/10 with nonunion (10%) vs 5/90 without nonunion (5.6%); p = 0.570). Organisms with intermediate or high-grade resistance to gentamicin were significantly more likely in polymicrobial infections (9/21; 42.8%) compared with monobacterial osteomyelitis (7/79 (8.9%); p < 0.001). However, recurrence was not significantly more frequent when a resistant organism was present (1/16 for resistant cases (6.25%) vs 5/84 in those with a microbiologically sensitive infection (5.95%); p = 0.958). Conclusion. We found that a single-stage protocol, including the use of a high-delivery local antibiotic ceramic carrier, was effective over a period of several years. The method can be used in a wide range of patients, including those with significant comorbidities and an infected nonunion. Cite this article: Bone Joint J 2022;104-B(9):1095–1100

The treatment of chronic osteomyelitis requires both appropriate surgical and antibiotic management. Prolonged intravenous antibiotic therapy followed by oral therapy is widely utilised. Despite this, the long-term recurrence rate is approximately 25%. The aim of this cohort study was to examine the effectiveness of marginal surgical resection in combination with local application of antibiotics (Collatamp G - gentamicin in a collagen fleece). Post-operatively this was followed by a short course of intravenous antibiotics, then oral antibiotics, to 6 weeks in total. A cohort of 50 patients from a 10-year period, 2000 to 2010, with chronic osteomyelitis was identified. Most were male (n= 35, 70%) and the average age is 40.9 years (SD 15.9). The mean follow-up duration was 3.2 years (SD 1.8). The average length of admission was 9.8 days (SD 11.4). 6 patients (12%) suffered recurrence of infection requiring further treatment. We used the Cierny and Mader classification to stratify the patients further. There were 24 (48%) ‘A’ hosts and 26 (52%) ‘B’ hosts. ‘A’ hosts had a shorter duration of admission (7.1 days) than ‘B’ hosts (12.3 days). There was no significant difference between recurrence rates of ‘A’ and ‘B’ hosts. The available pre-operative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels did not predict disease recurrence. Overall, the disease-free probability for this cohort was 0.80. A similar cohort treated with prolonged systemic and oral antibiotics reported by Simpson and colleagues (JBJS Br 2001) had a disease-free probability at 0.68. Local administration of gentamicin in a collagen fleece leads to improved disease-free probability when compared with prolonged systemic antibiotic treatment. We believe this is a useful component in the management of chronic osteomyelitis

Aims. Treatment of chronic osteomyelitis (COM) for young patients remains a challenge. Large bone deficiencies secondary to COM can be treated using induced membrane technique (IMT). However, it is unclear which type of bone graft is optimal. The goal of the study was to determine the clinical effectiveness of bone marrow concentrator modified allograft (BMCA) versus bone marrow aspirate mixed allograft (BMAA) for children with COM of long bones. Methods. Between January 2013 and December 2017, 26 young patients with COM were enrolled. Different bone grafts were applied to repair bone defects secondary to IMT procedure for infection eradication. Group BMCA was administered BMCA while Group BMAA was given BMAA. The results of this case-control study were retrospectively analyzed. Results. Patient infection in both groups was eradicated after IMT surgery. As for reconstruction surgery, no substantial changes in the operative period (p = 0.852), intraoperative blood loss (p = 0.573), or length of hospital stay (p = 0.362) were found between the two groups. All patients were monitored for 12 to 60 months. The median time to bone healing was 4.0 months (interquartile range (IQR) 3.0 to 5.0; range 3 to 7) and 5.0 months (IQR 4.0 to 7.0; range 3 to 10) in Groups BMCA and BMAA, respectively. The time to heal in Group BMCA versus Group BMAA was substantially lower (p = 0.024). Conclusion. IMT with BMCA or BMAA may attain healing in large bone defects secondary to COM in children. The bone healing time was significantly shorter for BMCA, indicating that this could be considered as a new strategy for bone defect after COM treatment. Cite this article: Bone Joint Res 2021;10(1):31–40

Aims. Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up. Methods. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery. Results. The median follow-up was 4.6 years (interquartile range (IQR) 3.2 to 5.4; range 1.3 to 10.5) in Group OT compared to 4.9 years (IQR 2.1 to 6.0; range 1.0 to 8.3) in Group CG. The groups had similar defect sizes following excision (both mean 10.9 cm. 3. (1 to 30)). Infection recurrence was higher in Group OT (20/179 (11.2%) vs 8/180 (4.4%), p = 0.019) than Group CG, as was early wound leakage (33/179 (18.4%) vs 18/180 (10.0%), p = 0.024) and subsequent fracture (11/179 (6.1%) vs 1.7% (3/180), p = 0.032). Group OT cases had an odds ratio 2.9-times higher of developing any one of these complications, compared to Group CG (95% confidence interval 1.74 to 4.81, p < 0.001). The mean bone-void healing in Group CG was better than in Group OT, in those with ≥ six-month radiological follow-up (73.9% vs 40.0%, p < 0.001). Conclusion. Local antibiotic carrier choice affects outcome in chronic osteomyelitis surgery. A biphasic injectable carrier with a slower dissolution time was associated with better radiological and clinical outcomes compared to a preformed calcium sulphate pellet carrier. Cite this article: Bone Joint Res 2023;12(7):412–422

Introduction. The treatment of chronic osteomyelitis involves a debridement of affected non-viable tissue and the use of antibiotics. Where surgery leaves a cavity, dead space management is practised with antibiotic impregnated cement. These depots of local antibiotics are variable in elution properties and need removal. We review the use of bioabsorbable synthetic calcium sulphate as a carrier of gentamicin and as an adjunct in treating intramedullary osteomyelitis. Methods. A retrospective review of cases treated consecutively from 2006 to 2010 was undertaken. Variables recorded included aetiology, previous interventions, diagnostic criteria, radiological features, serology and microbiology. The Cierney-Mader system was used to classify. Treatment involved removal of implants (if any), intramedullary debridement and local resection (if needed), lavage and instillation of the gentamicin carrier, supplemented with systemic antibiotics. Follow-up involved a survival analysis to time to recurrence, clinical and functional assessment (AOFAS-Ankle/IOWA knee/Oxford Hip) and general health outcome (SF36). Results. There were 31 patients (22 male, 9 female). The mean age was 47 years (20–67). Twenty-five cases were post-surgery (6 open fractures) and 6 were haematogenous in origin. The median duration of osteomyelitis was 1.6yrs. The bones affected were 42% femur, 45% tibia, 3% radius and 10% humerus. 11 cases had diffuse as well as intramedullary involvement. 9 cases underwent segment resection and bone transport. We identified Staph. Aureus in 16 and Coag. Neg. Staph. in 6 cases. The median follow-up was 1.7 years (0.5–5.6). The median scores attained were: AOFAS-78, DASH-32, IOWA-71, Oxford-32. There were two recurrences. Discussion. Dead space management of intramedullary infections is difficult. We describe a method for delivery of local antibiotics and provide early evidence to its efficacy. The treatment success to date is 93%. Conclusion. Bioabsorbable carriers of antibiotics are efficacious adjuncts to surgical treatment of intramedullary osteomyelitis

Cite this article: Bone Joint Res 2024;13(3):124–126.

Fracture related infection, in particular chronic osteomyelitis, requires complex management plans. Meta analyses and systematic reviews have not found a gold standard of treatment for this disease. In 2017 an alternative treatment protocol was undertaken in our institution; whereby staged surgery with the use of cheaply manufactured tailored antibiotic cement rods was used in the treatment of chronic osteomyelitis, secondary to traumatic long bone fractures. Short term outcomes for this protocol demonstrated a 75.7% microbiological resolution to a negative culture and a good clinical outcome of 84.2% overall was demonstrated in terms of sinus resolution, skin changes, pain and function. Our aim now was to assess the long term outcomes of this treatment strategy. A cross-sectional study of patients who had previously undergone the set treatment protocol was performed. Patient satisfaction, effects on activities of daily living, return to work and clinical improvement at 5 years following the intervention were assessed using a patient questionnaire and the validated AAOS lower limb score. The average AAOS lower limb score was 88 which was en par to other similar studies. 80% of patients had returned to some form of work. Ongoing mild pain was a persistent problem for 50% of the patients however 98% of the patients were overall satisfied with the treatment satisfaction at 5 years. Only 1 patient required further treatment. 8 patients could not be located for follow up. Chronic osteomyelitis remains a complex disease to treat. This treatment protocol demonstrates favourable microbiological, serological and clinical short term outcomes and favourable patient satisfaction and functional long term outcomes at 5 years. Our study highlights antibiotic targeted cement rods as a feasible treatment option in managing chronic osteomyelitis

Introduction. Open tibial fractures (OTF) rank first among lower limb fractures in sub-Saharan Africa and bone infection remains the main challenge. The aim of this study was to identify the factors associated with chronic bone infection after OTF in a limited-resource setting. Methods. Patients aged 18 years and older, who underwent OTF treatment in a tertiary care hospital during the period from December 2015 to December 2020 were included in this retrospective study. Patients were contacted via phone calls and invited for a final clinical and radiological evaluation. Patients who met diagnostic criteria of chronic osteomyelitis were identified. Logistic regression was used to determine the predictive factors of OTF related chronic osteomyelitis. Results. With a mean follow-up period of 29.5±16.6 months, 33 patients out of 105 (31.4%) presented with chronic osteomyelitis. We found that time to first debridement within 6 hours (OR=0.18, 95% CI: 0.05 – 0.75, p=0.018) and severity of OTF according to Gustilo-Anderson classification (OR=2.06, 95% CI:1.34 – 3.16, p=0.001) were the independent predictive factors of chronic bone infection. Neither age, gender, socio-economic level, polytrauma, HIV status, diabetes mellitus, time to definitive surgery, were associated with chronic osteomyelitis. Conclusion. The rate of chronic bone infections after OTF is still high in the sub-Saharan African context. In addition to the overall improvement in the management of open leg fractures in those settings, emphasis should be placed on very early initial debridement to reduce the burden of these infections. Keys words. open tibial fractures, chronic bone infection, predictive factors

Materials & Methods. Chronic osteomyelitis is a complex and challenging condition the successful treatment of which requires a specialist multidisciplinary approach. Prior to tertiary referral to a specialist Orthoplastic Unit, patients often receive multiple courses of antibiotics, in usually unsuccessful attempts, to eradicate infection. This often results in the development of chronic polymicrobial infection. We reviewed the intra-operative cultures of patients treated in our Orthoplastic unit over a 9-year period from 2012–2021 to determine the spectrum of polymicrobial cultures and the relationship to pre-operative cultures. Results. We reviewed the electronic care records and laboratory results of all patients referred to or directly admitted to our unit with a diagnosis of chronic osteomyelitis between 2012–2021. We checked all culture results, antibiotic sensitivities and prescription for treatment. We also checked for any recurrence of infection within 1 year. 60 patients were treated over the 9-year period. 9 upper and 51 lower limbs. The most common referral sources were from the surgical specialties of Trauma & Orthopaedics and Plastic Surgery (62%) while an equal amount came from the Emergency Department and other inpatient medical teams, each making up 15%. A small cohort (8%) developed the infection while still being followed up post fixation. Aetiology of Infection were post fracture fixation 41 (68%), spontaneous osteomyelitis 10 (17%), soft tissue infection 4 (7%). The remaining 5 patients (8%) had a combination failed arthroplasty, arthrodesis and chronic infection from ring sequestrum. 58 patients (97%) had positive cultures with 26 being polymicrobial. 12 cultures were gram negative (G-ve), 11 G+ve 12, 4 anaerobic and 1 Fungal. In 24 patients (40%) the pre-operative cultures and antibiotic sensitivities did not correspond to the intra-operative cultures and sensitivities. 55 patients (92%) required dual or triple therapy with 8% requiring further debridement and extended therapy. 2 (3%) patients had failed treatment requiring amputation. Conclusions. Chronic osteomyelitis is a complex and challenging condition the successful treatment of which requires early referral to a specialist Orthoplastic unit. Less than half of organisms cultured pre-operatively reflect the causative organisms cultured intra-operatively with 52% of these infections being polymicrobial. After initial treatment, 8% of patients will require a further combination of extended antibiotic therapy and surgery to eradicate infection

Aim. The localization of sequestrum in chronic osteomyelitis (COM) is crucial in preoperative planning. The identification of sequestrum on plain X-ray could be difficult. CT and MRI were reported to show the sequestrum. We aimed to analyze the sequestrum characteristics on 18F-FDG-PET-CT images. Methods. A prospective study included all patients diagnosed with long-bone chronic osteomyelitis. All patients had preoperative 18F-FDG-PET-CT. Images were analyzed using RadiAnt DICOM Viewer. Axial cuts were used to measure the Standard Uptake Ratio (SUV)max in the Region of Interest (ROI) in the sequestrum, the surrounding area, and the normal bone in the same cut. Surgical debridement was done as standard; samples were taken for microbiology and histopathology, and the intraoperative finding was documented. Results. Nineteen patients (17 males/2 females) were operated on in one center between October/2021 and Jan/2023 at a mean age of 32±18. There were 10 tibias, 7 femurs, one ulna, and one fibula. Ten had postoperative COM, six open fractures, and three hematogenous OM. They all showed sequestrum on PET-CT; the dead bone appeared void, surrounded by a halo of increased uptake. There was a trend of lower uptake in the sequestrum compared to the halo around. The mean SUVmax at the sequestrum was 4.18±3.16, compared to the surrounding halo, 7.08±5.81. The normal bone has a mean SUVmax of 1.61±1.42. Sequestrum was removed successfully in all cases. Conclusion. 18F-FDG-PET-CT can precisely localize the sequestrum preoperatively, it has a lower uptake than tissues around it. This would facilitate planning and improve the quality of debridement

Introduction. Various biomaterials and bone graft substitute technologies for use in osteomyelitis treatment are currently used in clinal practice. They vary in mode of action (with or without antibiotics) and clinical application (one-stage or two-stage surgery). This systematic review aims to compare the clinical evidence of different synthetic antimicrobial bone graft substitutes and antibiotic-loaded carriers in eradicating infection and clinical outcome in patients with chronic osteomyelitis. Methods. Systematic review according to PRISMA statement on publications 2002-2023. MESH terms: osteomyelitis and bone substitutes. FREE terms: chronic osteomyelitis, bone infection. A standardized data extraction form was be used to extract data from the included papers. Results. Publications with increased methodological quality and clinical evidence for biomaterials in osteomyelitis treatment were published in the last decades. High 85-95% eradication rates of osteomyelitis were observed for various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass. Level of evidence varies significantly between products. Antibiotic pharmacokinetic release profiles vary between resorbable Ca-P and/or Ca-S biomaterials. Conclusion. Given the high 85-95% eradication rates of osteomyelitis by various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass, one-stage treatment is preferred. Surgeons should be aware of variations in mechanical properties and antibiotic pharmacokinetic release profiles between Ca-P and CA-s products. Mechanical, biological and antimicrobial properties of bioactive glass are formulation dependent. Currently, only S53P4 bioactive glass has proven antimicrobial properties. Based on this systematic review antibiotic loaded fleeces should be used with caution and restraint

Aim. Magnetic resonance imaging (MRI) and 2-[. 18. F]-fluoro-2-deoxy-D-glucose (. 18. F-FDG) Positron Emission Tomography, paired with Computed Tomography (PET/CT) are two indicated advanced imaging modalities in the complicated diagnostic work-up of osteomyelitis. PET/MRI is a relatively novel hybrid modality with suggested applications in musculoskeletal infection imaging. The goal of this study was to assess the value of hybrid . 18. F-FDG PET/MRI for chronic osteomyelitis diagnosis and surgical planning. Method. Five suspected chronic osteomyelitis patients underwent a prospective . 18. F-FDG single-injection/dual-imaging protocol with hybrid PET/CT and hybrid PET/MR. Diagnosis and relevant clinical features for the surgeon planning treatment were compared. Subsequently, 36 patients with . 18. F-FDG PET/MRI scans for suspected osteomyelitis were analysed retrospectively. Sensitivity, specificity, and accuracy were determined with the clinical assessment as the ground truth. Standardized uptake values (SUV) were measured and analysed by means of receiver operating characteristics (ROC). Results. The consensus diagnosis was identical for PET/CT and PET/MRI in the prospective cases, with PET/CT missing one clinical feature. The retrospective analysis yielded a sensitivity, specificity, and accuracy of 78%, 100%, and 86% respectively. Area under the ROC curve was .736, .755, and.769 for the SUVmax, target to background ratio, and SUVmax_ratio respectively. These results are in the same range and not statistically different compared to diagnostic value for . 18. F-FDG PET/CT imaging of osteomyelitis in literature. Conclusions. Based on our qualitative comparison, reduced radiation dose, and the diagnostic value that was found, the authors propose . 18. F-FDG PET/MRI as an alternative to . 18. F-FDG PET/CT in osteomyelitis diagnosis, if available

Objectives. Our objectives were to describe the therapeutic aspects and assess the prognosis of chronic osteomyelitis in children. Materials and methods. We made a retrospective study from January 2007 to December 2016. The study concerned children from 0 to15 years, treated for chronic osteomyelitis and monitored in the pediatric surgery department of the teaching hospital Gabriel Toure, Bamako (Mali). The other types of bone infections, osteitis and bone tumors were not included in the study. In 10 years we received and treated 215 children with chronic osteomyelitis. This represented 3.56% of all the hospitalizations. The mean age was 8.8 (± 6.67) years with extremes of 28 days and 15 years. The patients were first seen by the traditional healer in 165 (76.7%) cases. The sex ratio was 1.26. The major clinical feature was local swelling associated with pain in 110 cases (51.2%). In 135 cases (62.8%) the staphylococcus aureus was found in direct examination or culture. After a year we performed a functional and morphological assessment according to the method of DIMEGLIO. Results. Surgical treatment was performed in all patients. The average delay of stay in hospital was 4.95 ± 4.57 weeks, with extremes of 2 and 12 weeks. The means follow-up was 13 months with extremes of 3 and 20 months. Good results were found in 115 patients, fair in 60 (40 in keloid knee valgus to 11 ° in 10, muscular atrophy 10), bad in 40 (shortening member in 25 non-union in 10 valgus to 18 ° in 5) According Dimeglio score. There was no significant association between the time of consultation, prior treatment received, the surgical technique and the occurrence of complications (p> 0.05). Conclusion. The management of the chronic osteomyelitis is well codified. The functional prognosis is dependent on an early care and sequels can be dramatic in children of school age. Keywords. Chronic osteomyelitis, Treatment, Prognosis, Children

Objectives. Meropenem may be an important drug in the treatment of open tibial fractures and chronic osteomyelitis. Therefore, the objective of this study was to describe meropenem pharmacokinetics in plasma, subcutaneous adipose tissue (SCT), and cancellous bone using microdialysis in a porcine model. Methods. Six female pigs were assigned to receive 1000 mg of meropenem intravenously over five minutes. Measurements of meropenem were obtained from plasma, SCT, and cancellous bone for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The meropenem concentrations were determined using ultra-high-performance liquid chromatography. Results. The penetration of meropenem into cancellous bone, expressed as the ratio of plasma to cancellous bone area under the concentration-curve from zero to the last measured value, was incomplete and delayed. The time with concentration above the minimal inhibitory concentration (T. >MIC. ), for an MIC of 0.5 μg/ml, was shorter for cancellous bone in comparison with both plasma and SCT. For MICs above 0.5 μg/ml, T. >MIC. in cancellous bone was only shorter than SCT. Considering an MIC of 4 μg/ml, no animals achieved the target of 40% T. >MIC. in plasma and cancellous bone, while less than 20% achieved it in SCT. Conclusion. The main finding of this study was short T. >MIC. in cancellous bone after intravenous administration of 1000 mg meropenem. Consequently, in order to achieve sufficient tissue concentration in the cases of open tibial fractures and chronic osteomyelitis, supplemental application of meropenem may be necessary. Cite this article: P. Hanberg, A. Lund, K. Søballe, M. Bue. Single-dose pharmacokinetics of meropenem in porcine cancellous bone determined by microdialysis: An animal study. Bone Joint Res 2019;8:342–348. DOI: 10.1302/2046-3758.87.BJR-2018-0308.R1

Aim. To describe the histopathology of the first and last debrided bone tissue in chronic osteomyelitis and answer the following research question; is the last debrided bone tissue viable and without signs of inflammation?. Method. In total, 15 patients with chronic osteomyelitis were allocated to surgical treatment using a one stage protocol including extensive debridement. Suspected infected bone tissue eradicated early in the debridement procedure was collected as a clearly infected sample (S1). Likewise, the last eradicated bone tissue was collected as a suspected non-infected sample (S2), representing the status of the bone void. In all cases, the surgeon debrided the bone until visual confirmation of healthy bleeding bone. The samples were processed for histology, i.e. decalcification and paraffin embedding, followed by cutting and staining with Haematoxylin and Eosin. Immunohistochemistry with MAC-387 antibodies towards the calprotectin of neutrophil granulocytes (NGs) was also performed and used for estimation of a neutrophil granulocyte (NG) score (0, 1, 2 or 3), by the method described for fracture related infections (1). Results. For the S1 samples the median NG score was 3 which is considered confirmatory for infection. However, following debridement the median NG score was significantly (p = 0.032) reduced to 2. Often NGs were seen as single cells, but in seven S1 samples and in one S2 sample massive NG accumulations were observed. The S1 samples showed a mix of granulation tissue, fibrosis, viable bone, and bone necrosis. The S2 samples contained viable bone tissue and occasionally (10/15) small fragments of necrotic bone or bone debris were seen. Furthermore, a large number of erythrocytes were observed in most S2 samples. Conclusions. The present study shows that the inflammatory response still existents after debridement, although the response fades from the center of infection. Therefore, sampling of debrided bone tissue for histology must be performed initially during surgery, to avoid underestimation of the inflammatory response, i.e. the NG score. The last debrided bone tissue cannot by definition be considered completely viable and caution should be made to remove blood (rinse) before intraoperative evaluation of the viability of debrided cancellous bone. Remnant necrotic bone fragments or debris could represent low-vascular hiding places for leftover bacteria. Application of local antibiotics might have a central role in clearing of these small non-viable bone pieces at the bone void interface

Aim. The liver is the major source of acute phase proteins (APPs) and serum concentrations of several APPs are widely used as markers of inflammation and infection. The aim of the present study was to explore if a local extra hepatic osseous acute phase response occurs during osteomyelitis. Method. The systemic (liver tissue and serum) and local (bone tissue) expression of several APPs during osteomyelitis was investigated with qPCR and ELISA in a porcine model of implant associated osteomyelitis (IAO) at 5, 10 and 15 days after inoculation with S. aureus or saline, respectively. Additionally, samples were also collected from normal heathy pigs and pigs with spontaneous, chronic, haematogenous osteomyelitis. Afterwards, immunohistochemistry towards different upregulated APPs was performed on the porcine osteomyelitis lesions and on bone biopsies from human patients with chronic osteomyelitis. Results. All infected porcine bone lesions (apart from Day 5 in the IAO model) were made up by necrosis, pus, and various degree of fibrotic encapsulation. A local, highly significant upregulation of Serum Amyloid A (SAA, up to 4000-fold upregulation), Complement component C3 (C3), and Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) were present in infected pigs compared to sterile controls. For the experimental IAO animals, the upregulation of C3 and ITIH4 increased over time, i.e., the highest expression was seen on day 15 after bacterial inoculation. In the liver, only C-reactive protein (CRP) and ITIH4 (not SAA or C3) were slightly upregulated in infected pigs. Serum concentrations of CRP, SAA and haptoglobin were only upregulated at day 5 in IAO infected animals. Immunohistochemically, comparable numbers of APP positive cells (leucocytes and bone cells) were found in human and porcine bone samples with chronic osteomyelitis. Conclusions. This is to our knowledge the first description of local APP up-regulation during chronic bone infection. Only small changes in the expression of APPs were found in the liver and serum samples. Thus, the presence of an osseous upregulation of APPs appears to be part of a predominantly local response that will be difficult to measure systemically. The importance of a local immune response in bone infections seems logical as the blood supply is severely impaired during osteomyelitis. There is a real need for supportive diagnostic bone infection criteria which should be based on a comprehensive understanding of the local inflammatory response. As seen from the present study, staining for SAA or C3 could potentially improve the diagnostic performance of histopathology

Aim. Chronic osteomyelitis of long bones is one of the most severe complications in orthopedics. Different options exist for treatment of this disease, however there is still no generally accepted comprehensive protocol that could potentially guide us in each particular step. There are many classifications that were designed to help us to make clinical decision, however even the most widely used Cierny-Mader classification does not count more a half of factors, assessment of which is essential for choosing the best treatment plan. This fact may be explained by the complexity of the disease process, diversity of treatment options and multistage approach to the management of these patients. Therefore, the purpose of this study was to work out a treatment protocol and clinical classification system, which will improve final outcomes in patients with chronic osteomyelitis of long bones. Method. Three orthopedic surgeons and one general surgeon who specialize on bone and joint infection independently of each other made a review of literature dedicated to the topic of chronic osteomyelitis. Each surgeon created a list of factors that are essential to assess for successful treatment of chronic osteomyelitis. After four lists were thoroughly matched and discussed, 10 most important factors were defined. Each surgeon proposed his own protocol of treatment, based on existent data and own experience. All four protocols were discussed and analyzed to come up with new the most comprehensive one. Therefore, the new protocol was created. After the list of factors and protocol were created, surgeons independently of each other defined the most important factors for every stage in the new protocol. Thus new multi-stage classification of chronic osteomyelitis (MSC-CO) was proposed. Results. We have defined the most important factors influencing on the decision making process in treatment of chronic osteomyelitis of long bones. The new comprehensive protocol and multi-stage clinical classification were developed. Conclusions. We assume, that the proposed tools may improve the results of chronic osteomyelitis treatment. However, the clinical trials should be conducted to assess the utility of new treatment protocol and MSC-CO in daily practice

Aim. Previous studies have indicated that TNF-α and lymphotoxin-α (LTA) gene polymorphisms associate with the development of several different inflammatory diseases. However, potential associations of such gene polymorphisms with the susceptibility to extremity chronic osteomyelitis remain unknown. This study aimed to investigate potential links between TNF-α gene polymorphisms (rs1800629, rs361525, rs1799964, rs1800630, rs1799724 and rs1800750) and LTA gene polymorphism (rs909253) and the risk of developing extremity chronic osteomyelitis in Chinese population. Method. A total of 233 patients with extremity chronic osteomyelitis and 200 healthy controls were genotyped for the above 7 polymorphisms of TNF-α and LTA genes using the genotyping method*. Results. Significant difference was found regarding the genotype distribution of rs909253 between patients and healthy controls (P = 0.002). The mutant allele C frequency of rs909253 in patient group was significantly higher than that in control group (P = 0.001). Significant associations were identified between rs909253 and the risk of developing chronic osteomyelitis by dominant model (P = 0.040), recessive model (P = 0.002) and homozygous model (P = 0.001). Additionally, the mutant allele T frequency in rs1799964 in patient group was significantly higher than that in control group (P = 0.035). Significant link was found between rs1799964 and susceptibility to chronic osteomyelitis by recessive model (P = 0.048). However, no significant outcomes were identified regarding other TNF-α gene polymorphisms between the two groups. Conclusions. The present study demonstrated that rs909253 and rs1799964 polymorphisms may associate with the risk of developing chronic osteomyelitis in Chinese population. *SNaPshot