UNASSIGNED: A 51-year-old woman with an infected left humeral shaft recalcitrant nonunion presented 3 years after initial injury. This case report focuses on the staged treatment of a 17-centimeter (cm) humeral shaft nonunion with the induced membrane technique (IMT) using a unique fixation construct of dual locked plating around a humeral nail to provide long-lasting fixation and allow for bone graft consolidation.
UNASSIGNED: Large segmental bone loss of the humerus can be treated with the IMT using nail-plate fixation constructs that allow for early mobilization, increased time for bone graft consolidation before hardware failure, and less frequent follow-up.

BACKGROUND: Infected nonunion of the tibia represents a challenging complication for orthopedic surgeons and poses a major financial burden to healthcare systems. The situation is even more compounded when the nonunion involves the metaphyseal region of long bones, a rare yet demanding complication due to the poor healing potential of infected cancellous bone; this is in addition to the increased likelihood of contamination of adjacent joints. The purpose of this study was to determine the extent and level of evidence in relation to (1) available treatment options for the management of septic tibial metaphyseal nonunions; (2) success rates and bone healing following treatment application; and (3) functional results after intervention.
METHODS: We searched the MEDLINE, Embase, and CENTRAL databases for prospective and retrospective studies through to 25 January 2021. Human-only studies exploring the efficacy of various treatment options and their results in the setting of septic, quiescent, and metaphyseal (distal or proximal) tibia nonunions in the adult population were included. For infection diagnosis, we accepted definitions provided by the authors of source studies. Of note, clinical heterogeneity rendered data pooling inappropriate.
RESULTS: In terms of the species implicated in septic tibial nonunions, staphylococcus aureus was found to be the most commonly isolated microorganism. Many authors implemented the Ilizarov external fixation device with a mean duration of treatment greater than one year. Exceptional or good bone and functional results were recorded in over 80% of patients, although the literature is scarce and possible losses of the follow-up were not recorded.
CONCLUSIONS: A demanding orthopedic condition that is scarcely studied is infected metaphyseal tibial nonunion. External fixation seems promising, but further research is needed.
BACKGROUND: PROSPERO No. CRD42020205781.

BACKGROUND: Septic and aseptic nonunion require different therapeutic strategies. However, differential diagnosis is challenging, as low-grade infections and biofilm-bound bacteria often remain undetected. Therefore, the examination of biofilm on implants by sonication and the evaluation of its value for differentiating between femoral or tibial shaft septic and aseptic nonunion in comparison to tissue culture and histopathology was the focus of this study.
METHODS: Osteosynthesis material for sonication and tissue samples for long-term culture and histopathologic examination from 53 patients with aseptic nonunion, 42 with septic nonunion and 32 with regular healed fractures were obtained during surgery. Sonication fluid was concentrated by membrane filtration and colony-forming units (CFU) were quantified after aerobic and anaerobic incubation. CFU cut-off values for differentiating between septic and aseptic nonunion or regular healers were determined by receiver operating characteristic analysis. The performances of the different diagnostic methods were calculated using cross-tabulation.
RESULTS: The cut-off value for differentiating between septic and aseptic nonunion was ≥ 13.6 CFU/10 ml sonication fluid. With a sensitivity of 52% and a specificity of 93%, the diagnostic performance of membrane filtration was lower than that of tissue culture (69%, 96%) but higher than that of histopathology (14%, 87%). Considering two criteria for infection diagnosis, the sensitivity was similar for one tissue culture with the same pathogen in broth-cultured sonication fluid and two positive tissue cultures (55%). The combination of tissue culture and membrane-filtrated sonication fluid had a sensitivity of 50%, which increased up to 62% when using a lower CFU cut-off determined from regular healers. Furthermore, membrane filtration demonstrated a significantly higher polymicrobial detection rate compared to tissue culture and sonication fluid broth culture.
CONCLUSIONS: Our findings support a multimodal approach for the differential diagnosis of nonunion, with sonication demonstrating substantial usefulness.
METHODS: Level 2 Trial registration DRKS00014657 (date of registration: 2018/04/26).

Masquelet\'s induced membrane technique offers a definitive contribution to the treatment of diaphyseal osteomyelitis. To overcome its drawbacks while maintaining its principles, technical modifications have been proposed: antibiotic cement, femoral intramedullary autograft harvested by RIA (Reamer Irrigation Aspiration) and interlocking nails.
This retrospective study gathered patients with chronic osteomyelitis of the femur or tibia. The first surgical stage consisted of bone resection in the healthy zone and use of a gentamicin cement spacer to fill the bone defect. The second stage consisted of the placement of a statically locked intramedullary nail associated with a bone autograft using the RIA technique.
Among this group of 12 men with diaphyseal osteomyelitis; 9 tibial and 2 femoral, and 1 knee nonunion, the mean bone defect was 7.3cm (±6.7). The mean time between the 2 stages was 2.7months (±3) with a mean antibiotic period of 3.25weeks (±3). There was a femoral diaphyseal fracture at the donor site, and a wrong trajectory intraoperatively during the RIA. Two patients with tibial nonunion presented with nail rupture without septic recurrence. A septic recurrence was healed by removal of the nail. At a minimum follow-up of 18months, with an average of 5years, consolidation was complete without infectious recurrence. Despite the statistical weakness related to the size of the cohort, the resumption of early weight bearing (OR=-7.68 95% CI [-13.33 to -2.08] (p=0.01)) and nail dynamization seemed to have an impact on the formation of complete consolidation (OR=-0.86 95% CI [-1.39 to -0.33] (p=0.007)).
This short series, compared to the literature, demonstrated that the proposed technical modifications improved the overall management of this rare and challenging condition while maintaining the reliability of the original technique. Dynamization was also seen to be of particular interest.
IV, retrospective study.

Septic nonunion (SN) is a common bone disorder caused by the failure of fracture healing. Local inflammation in fracture sites often causes SN; however, little is known about the molecular mechanisms of SN pathology. Herein, we identified a significant upregulation of the long non-coding RNA (lncRNA) RUNX2-AS1 (Runt-related Transcription Factor 2-Antisense 1) in the biopsies of SN patients. Overexpression or knockdown of RUNX2-AS1 in vitro could inhibit or induce, respectively, the expression of RUNX2 and RUNX2-downstream target genes, including ALPL (Alkaline Phosphatase), COL1A1 (Collagen Type I Alpha 1 Chain), IBSP (Integrin Binding Sialoprotein), MMP13 (Matrix Metallopeptidases), and SPP1 (Secreted Phosphoprotein 1), which are involved in bone differentiation. Mechanically, we demonstrated that a transcription factor c-MYC could assemble a transcriptional complex with its partner Max, a histone acetyltransferase p300, and nuclear receptor coactivator 2 (NCOA2), and this complex then bound to the promoter of RUNX2-AS1 to transactivate its expression. The mRNA and protein levels of NCOA2 were dose-dependently increased by treatment with lipopolysaccharide(LPS), a well-known inflammation trigger. LPS exposure increased the enrichment of the NCOA2-p300-c-MYC/Max complex on the RUNX2-AS1 promoter to activate its expression, thereby downregulating the expression of RUNX2 and RUNX2-downstream target genes. Depletion of NCOA2 reversed the expression of RUNX2-AS1, RUNX2, and RUNX2 target genes following LPS exposure. Taken together, our results demonstrate a new signaling pathway that contributes to the pathology of SN and may aid in preventing SN progression.

BACKGROUND: Septic nonunion is one of the major complications in fracture healing. The challenge is to identify the infection as the cause of nonunion first and then to achieve healing of the infection and the bone.
OBJECTIVE: Because of the more heterogeneous appearance of an infected nonunion, the prevalence of germ detection in surgical nonunion revision is often underestimated.
METHODS: In a retrospective study between 2010 and 2017, 86 patients with radiologically confirmed femoral shaft nonunion without clinical evidence and unremarkable medical history of a florid infection as the cause of nonunion, who had undergone primary single-stage surgical nonunion revision were analyzed. At least four intraoperatively obtained samples were evaluated for microbiological diagnosis. A distinction was made between tissue samples with subsequent 48‑h short-term incubation and tissue samples with 14-day long-term cultivation. The finding \"germ detection\" was made if at least two of the samples demonstrated bacterial growth.
RESULTS: In 18 of 86 patients with a nonunion preoperatively judged to be aseptic, positive bacterial evidence was obtained after short-term incubation. After long-term cultivation, positive bacterial detection was possible in 38 of 86 patients with a femoral shaft nonunion initially classified as aseptic. Regarding potential risk factors, the two groups demonstrated no relevant differences. In 29 patients, 1 pathogen was isolated from the obtained samples, whereas in the remaining 9 patients, a mixed culture with an average of 2.9 ± 0.5 different bacteria was detected. Identification revealed mainly low-virulence bacteria, most commonly Staphylococcus epidermidis.
CONCLUSIONS: If the preoperative diagnostics including clinical, laboratory and radiological examination as well as a careful anamnesis reveal indications of a possible infectious event, the surgical nonunion revision should be performed in two stages with specimen collection before definitive nonunion revision. For microbiological diagnosis, several representative tissue samples should independently be obtained from the nonunion site and incubated for 14 days. Only in the absence of evidence of septic nonunion is a single-stage procedure suggested.
UNASSIGNED: HINTERGRUND: Die infizierte Pseudarthrose stellt eine der schwerwiegendsten Komplikationen bei der Frakturheilung dar. Die Herausforderung besteht darin, die Infektion zuerst als Ursache einer Pseudarthrose zu erkennen und dann die Heilung der Infektion und des Knochens zu erreichen.
UNASSIGNED: Aufgrund des heterogeneren Erscheinungsbildes infizierter Pseudarthrosen wird die Prävalenz eines Keimnachweises bei der operativen Pseudarthrosenrevision häufig unterschätzt.
UNASSIGNED: In einer retrospektiven Untersuchung zwischen 2010 und 2017 wurden 86 Patienten, die aufgrund einer radiologisch gesicherten Femurschaftpseudarthrose primär revidiert wurden und die ohne klinische Hinweise auf einen floriden Infekt als Ursache der Pseudarthrose waren, analysiert. Es wurden mindestens 4 intraoperativ gewonnene Proben mikrobiologisch ausgewertet. Dabei wurde zwischen Gewebeproben mit anschließender 48-stündiger Kurzzeitbebrütung und Gewebeproben mit 14-tägiger Langzeitkultivierung unterschieden. Der Befund „Keimnachweis“ wurde gestellt, wenn mindestens 2 der Proben ein Keimwachstum zeigten.
UNASSIGNED: Bei 18 der 86 präoperativ als aseptisch eingeschätzten Pseudarthrosen konnte nach Kurzzeitbebrütung ein positiver Keimnachweis erhoben werden. Nach Langzeitbebrütung war bei 38 von 86 Patienten ein positiver Keimnachweis möglich. Hinsichtlich potenzieller Risikofaktoren zeigten die beiden Gruppen keine relevanten Unterschiede. Bei 29 Patienten wurde ein einzelner Erregertyp aus den gewonnenen Proben isoliert, während bei den übrigen 9 Patienten eine Mischkultur mit durchschnittlich 2,9 ± 0,5 verschiedenen Bakterien nachgewiesen wurde. Bei der Keimidentifizierung fanden sich mit Staphylococcus epidermidis am häufigsten niedrigvirulente Bakterien.
UNASSIGNED: Ergibt die präoperative Diagnostik unter Einbeziehung der klinischen, laborchemischen und radiologischen Untersuchung sowie der Anamnese Hinweise auf ein mögliches Infektgeschehen, sollte die operative Revision zweizeitig mit Probengewinnung vor der definitiven Pseudarthrosenrevision erfolgen. Zur mikrobiologischen Diagnostik sollten mehrere repräsentative Gewebeproben unabhängig voneinander aus der Pseudarthrosenzone gewonnen und für 14 Tage bebrütet werden. Nur bei fehlenden Hinweisen auf eine infizierte Pseudarthrose wird das einzeitige Vorgehen vorgeschlagen.

Rotationplasty or Borggreve-Van Ness surgery is lower limb salvage surgery, indicated mainly in the management of femoral bone sarcoma and congenital femur malformations in children. It can also be an interesting surgery option for managing chronic osteoarticular infections, or in cases of non union when curative therapy is no longer an option, as an alternative to femoral amputation. The principle of this surgery is to remove the affected knee and to apply a rotation of 180° to the distal part of the lower limb in order to give the ankle the function of a neo-knee. With the help of an adapted prosthesis, the aim is to allow patients to resume their social and professional activities by keeping most of their lower limb, thus avoiding the known complications of amputation (ghost limb pain, proprioceptive deficit, psychological disorders). Nevertheless, this surgery is complex and exceptional, with vascular, infectious, and psychological risks - the chimeric aspect of the lower limb may cause significant ill-being for the patient. This article reports the case of a 38-year-old patient consulting for management of a complex septic distal femoral non-union following osteosarcoma considered as being in remission. The patient underwent rotationplasty surgery on his left lower limb, with very good functional results and no surgical revision to date. In light of this particular case, we propose a didactic overview of the literature data concerning this surgery, especially in adulthood.

OBJECTIVE: The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition.
METHODS: A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree.
RESULTS: Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 109/l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases.
CONCLUSIONS: The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article: Bone Joint J 2020;102-B(7):904-911.

There are very few therapeutic alternatives for patients with proximal femoral epiphyseal bone deficit combined with a fracture at another level and signs of infection. This combination can be successfully managed with a proximal femur megaspacer. This article is intended to review our variation of this technique and to show the initial results obtained from 11 cases. Of these 11 cases, there were 6 women and 5 men. The mean age was 66 years. The average number of previous surgeries was 3. Definitive prosthetic reconstructive treatment was achieved in 7 of these 11 subjects. The average time to reimplantation was 11.7 months. Fractures or nonunion healed uneventfully. Bone union and infection control were achieved in 10 of the 11 patients.