Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections.

OBJECTIVES: Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. METHODS: We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. RESULTS: Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. CONCLUSION: IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement.Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179-188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1.

Hyperbaric oxygen inhibits the HMGB1/RAGE signaling pathway by upregulating Mir-107 expression in human osteoarthritic chondrocytes.

OBJECTIVE: MicroRNA (miRNA)107 expression is downregulated but high mobility group box 1 (HMGB-1), Toll-like receptors (TLRs), and receptor for advanced glycation end products (RAGE) are upregulated in osteoarthritic (OA) cartilage. We investigated mir-107/HMGB-1 signaling in OA after hyperbaric oxygen (HBO) treatment. DESIGN: MiR-107 mimic was transfected and the HMGB-1 was analyzed in OA chondrocytes. MiRNA targets were identified using bioinformatics and a luciferase reporter assay. After HBO treatment, the mRNA or protein levels of HMGB-1, RAGE, TLR2, TLR4, and inducible nitric oxide (NO) synthase (iNOS) and phosphorylation of mitogen-activated protein kinase (MAPK) were evaluated. The secreted HMGB-1 and matrix metalloproteases (MMPs) levels were quantified. Finally, we detected the HMGB-1 and iNOS expression in rabbit cartilage defects. RESULTS: Overexpression of miR-107 suppressed HMGB-1 expression in OA chondrocytes. The 3'UTR of HMGB-1 mRNA contained a 'seed-matched-sequence' for miR-107. MiR-107 was induced by HBO and a marked suppression of HMGB-1 was observed simultaneously in OA chondrocytes. Knockdown of miR-107 upregulated HMGB-1 expression in hyperoxic cells. HBO downregulated the mRNA and protein expression of HMGB-1, RAGE, TLR2, TLR4, and iNOS, and the secretion of HMGB-1. HBO decreased the nuclear translocation of nuclear factor (NF)-κB, downregulated the phosphorylation of MAPK, and significantly decreased the secretion of MMPs. Morphological and immunohistochemical observation demonstrated that HBO markedly enhanced cartilage repair and the area stained positive for HMGB-1 and iNOS tended to be lower in the HBO group. CONCLUSIONS: HBO inhibits HMGB-1/RAGE signaling related pathways by upregulating miR-107 expression in human OA chondrocytes.

The concentration of antibiotic in fresh-frozen bone graft.

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at -80 degrees C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture.Also, in bioassays the bone showed inhibitory effects against bacteria.We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro.

Elevated intraosseous pressure in the intertrochanteric region is associated with poorer results in osteonecrosis of the femoral head treated by multiple drilling.

Multiple drilling is reported to be an effective treatment for osteonecrosis of the head of femur, but its effect on intra-osseous pressure has not been described. We undertook multiple drilling and recorded the intra-osseous pressure in 75 osteonecrotic hips in 60 patients with a mean age of 42 years (19 to 67). At a mean follow-up of 37.1 months (24 to 60), 42 hips (56%) had a clinically successful outcome. The procedure was effective in reducing the mean intra-osseous pressure from 57 mmHg (SD 22) to 16 mmHg (SD 9). Hips with a successful outcome had a mean pressure of 26 mmHg (SD 19). It was less effective in preventing progression of osteonecrosis in hips with considerable involvement and in those with a high intra-osseous pressure in the intertrochanteric region (mean 45 mmHg (SD 25)). This study is not able to answer whether a return of the intra-osseous pressure to normal levels is required for satisfactory healing.

Involvement of Gas7 along the ERK1/2 MAP kinase and SOX9 pathway in chondrogenesis of human marrow-derived mesenchymal stem cells.

OBJECTIVE: The growth-arrest-specific protein, Gas7, has been shown to be involved in reorganization of the cytoskeleton and for inducing changes in cell shape during cell differentiation. The goals of this study were to investigate the novel role of human Gas7 (hGas7) in chondrogenic differentiation of human mesenchymal stem cells (hMSCs) and to identify the relationship between hGas7, extracellular signal-regulated kinase (ERK1/2) and SOX9 in the chondrogenic pathway. METHODS: Bone marrow-derived hMSCs were induced to undergo chondrogenic differentiation with transforming growth factor-beta1 (TGF-beta1) in an aggregate culture system. The expression of hGas7 and SOX9 and phosphorylation of ERK1/2 at multiple time points were investigated. Chondrogenic capacity was evaluated by the size of aggregates, by glycosaminoglycan content, and by type II collagen and proteoglycan deposition after interfering with expression of hGas7, ERK1/2 or SOX9. To delineate the functional role of these genes in chondrogenesis, inhibition of individual gene's expression in hMSCs, by antisense oligonucleotides or interference RNA (siRNA), and the effect on chondrogenic differentiation were also investigated. RESULTS: Treatment of hMSCs with TGF-beta1 resulted in a transient up-regulation of hGas7b, one of the hGas7 isoforms (day 3-day 5), a transient phosphorylation of ERK1/2 (0.5-4 h) and an up-regulation of SOX9 (2 h to day 14). Transient expression of hGas7b was also detected in hMSCs by reverse transcription-polymerase chain reaction at day 2 and day 3 following TGF-beta1 treatment. Interference with hGas7b production by hGas7b-specific antisense oligonucleotide or inhibition of p-ERK with PD98059, a specific inhibitor of ERK signaling pathway, or interference with SOX9 production by SOX9 siRNA all caused adverse effects of chondrogenic differentiation of hMSCs. Meanwhile, inhibition of p-ERK or SOX9 both blocked the expression of hGas7b. However, the p-ERK and SOX9 pathway was not affected by inhibition of hGas7b. CONCLUSION: These results provide evidence that the transient expression of hGas7b, regulated by activation of ERK1/2 and SOX9 pathway, is essential for chondrogenic differentiation of hMSCs.

Effects of hyperbaric oxygen and platelet derived growth factor on medial collateral ligament fibroblasts.

PURPOSE: This study investigated hyperbaric oxygen (HBO2) and platelet-derived growth factor-BB (PDGF-BB) to determine their combined effects on fibroblasts from rabbit medial collateral ligament (MCL). METHOD: Cells were divided into four groups: (I) Control, (II) HBO2 treatment, (III) PDGF-BB treatment and (IV) HBO2 combined with PDGF-BB treatment. All hyperoxic cells were exposed to 100% O2 at 2.5 atmospheres absolute (ATA) in a hyperbaric chamber for 120 minutes per 48 hours. Measurement of cell growth was based on increase in cell number. Cell cycle modulations were analyzed by fluorescence-activated cell sorter (FACS). Quantity of Type I and Type III collagen was determined by western blotting and image analyzer. RESULTS: Treatment doses of HBO2 alone or PDGF-bb alone dependently increased cell growth. A combination of HBO2 treatment plus PDGF-bb treatment had an additive effect on cell growth in comparison with HBO2 treatment alone or PDGF-bb treatment alone. FACS analysis revealed that HBO2 alone, PDGF-bb alone and PDGF-bb plus HBO2 treatment increase the percentage of cells accumulated in S-phase. Western blotting analysis revealed that Type III collagen content was decreased significantly after HBO2 treatment alone or HBO2 plus PDGF-bb treatment but not in PDGF-bb treatment alone. In contrast, although Type I collagen content was increased after HBO2 treatment, the increase in Type I collagen (increase /original) was not statistically significant. CONCLUSION: HBO2 or HBO2 plus PDGF-bb treatment decreases the Type III collagen/Type I collagen content, which could result in mechanically stronger collagen fibrils. We propose HBO2 therapy as a potentially effective treatment for MCL healing.

Signal transduction pathways and apoptosis in bacteria infected chondrocytes.

The mechanism underlying chronic destructive arthropathy after pyogenic arthritis is not clear. This study evaluated the role of apoptosis in Staphylococcus aureus infected human articular chondrocytes and investigated the signal transduction pathways activated by bacterial infection. Chondrocytes cultured in monolayer were challenged with bacteria for 6 h and were analyzed after incubation for 2, 18, and 24 h. Chondrocytes showed morphologic and biochemical evidences of apoptosis after infection and the following incubation period. Although treatment with extensive washing and vancomycin could ameliorate the amount of apoptosis from 31% to 15% at 2 h, from 48% to 23% at 18 h, and from 58% to 33% at 24 h, the infected samples with treatment still had higher amount of apoptosis than the un-infected controls (ANOVA P < 0.001). Accompanying with the increasing amount of apoptosis, the caspase activity was upregulated in bacteria infected samples and remained high in samples with treatment (ANOVA P < 0.05). Signal transduction pathways activated by bacterial infection were assessed by co-transfection technique. After infection, the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and cyclic AMP-dependent protein kinase activities were elevated by 7.6-, 7.3-, and 3.2-fold, respectively, compared to the uninfected controls. The data support the hypothesis that human chondrocytes will undergo apoptosis after infection by a single organism. Apoptosis and activated intracellular kinase activities may be related to the pathogenesis of post-infectious destructive arthropathy.

Surgical treatment for pathological long bone fracture in patients with multiple myeloma: a retrospective analysis of 22 cases.

BACKGROUND: The purpose of this study was to retrospectively review the cases of pathologic long bone fractures caused by multiple myeloma treated in our hospital, to analyze the surgical method, complications, radiation therapy, survival time, and influence on quality of life. METHODS: In a retrospective study, 22 patients with the pathological long bone fractures due to multiple myeloma who were surgically treated between 1987 and 1997 were analyzed. All patients received open reduction and internal fixation either with plates or intra-medullary nailing. Cement augmentations were performed in the majority of cases (91%). A detailed retrospective analysis was done to correlate the surgical methods, radiation therapy, functional results, and complications post-surgically. RESULTS: The most common site of fracture was the femur. The mean postoperative survival time was around 19 months. Post-operative pain relief was satisfactory, and only two patients required narcotics. No major complications were observed. However the union rate was only 30%, which might have been due to the inhibitory effect of radiation therapy on bone healing, or insufficient osteogentic ability of the myeloma-involved bone. CONCLUSION: Satisfactory pain relief and low implant failure rate was achieved and no definite evidence of tumor dissemination was found in this study. The authors suggest that open reduction and internal fixation with cement augmentation is a favorable treatment option for those patients suitable for surgery. However, postoperative radiation therapy may be associated with a low rate of union.

Two-staged revision total hip arthroplasty due to Salmonella infection: case report.

Salmonella infection of a hip prosthesis has rarely been reported, and only a few cases have been documented. It is painful, disabling, costly, and may be associated with life-threatening sepsis even in a healthy individual. Removal of the implant is often required to eradicate the infection. Several early studies reported procedures to control the salmonella infection, but none described reconstruction of the destroyed hip joint. We present a case of salmonella sepsis 4 years after a total hip arthroplasty (THA). After prosthesis removal, radical debridement of the infected tissues, and administration of Imipenum (500 mg, 4 times daily), the systemic sepsis and hip infection were ameliorated. Four months later, a 2-stage revision THA was done for reconstruction of the hip joint. The clinical results 51 months following the THA procedure were satisfactory without an infectious reaction.

Non-tuberculous cold abscess of the psoas muscle--an unusual manifestation of colocutaneous fistula.

We report here a case of colocutaneous fistula drained from the retroperitoneal space mimicking a cold abscess of the psoas muscle. A 60-year-old diabetic woman with a 6-year history of a chronic draining sinus over her right thigh had been treated intermittently with antibiotics. At presentation, she had no systemic toxic signs nor other constitutional symptoms. The patient was inadequately managed by curettage at first under the tentative diagnosis of tuberculous cold abscess. After the correct diagnosis of colocutaneous fistula, right nephrectomy and right hemicolectomy with ileotransverse colostomy were done. The patient was well 5 years later without recurrence. This is an atypical presentation of enterocutaneous fistula in an immunodeficient patient that should be emphasized to facilitate the correct diagnosis and early treatment.

Hyperbaric oxygen therapy mitigates the adverse effect of cigarette smoking on the bone healing of tibial lengthening: an experimental study on rabbits.

OBJECT: We investigated whether -intermittent hyperbaric oxygen (HBO) therapy can mitigate the adverse effects of cigarette smoking on the bone healing of tibial lengthening by using a previously validated rabbit model. METHODS: Eighteen male rabbits were randomly divided into three groups of six animals each. Group 1 (smoking plus HBO) went through intermittent cigarette smoke inhalation and hyperbaric oxygen therapy, group 2 (control) did not go through intermittent cigarette smoke inhalation or hyperbaric oxygen therapy and group 3 (smoking) went through intermittent cigarette smoke inhalation. Each animal's right tibia was lengthened 5 mm by using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all the animals at 1 day before operation and 3, 4, 5, and 6 weeks after operation. All of the animals were killed at 6 weeks postoperatively for biomechanical testing. RESULTS: By using the preoperative BMD as an internal control, we found that the BMD of group 1 (smoking plus HBO)and group 2 (control) was superior to that of group 3 (smoking). The mean %BMD at 3, 4, 5, and 6 weeks were 58.6%, 66.6%, 73.7%, and 83.8%, respectively, in group 1, whereas the mean %BMD were 52.0%, 64.3%, 70.1%, and 76.2%, respectively, in group 2, and the mean %BMD were 46.2%, 54.0%, 64.9%, and 69.4%, respectively, in group 3 (two-tailed t test, p > 0.05, p > 0.05, p > 0.05, and p < 0.05 at 3, 4, 5, and 6 week respectively between group 1 and group 2, p < 0.01,p < 0.01,p < 0.01, and p < 0.01 at 3, 4, 5, and 6 week, respectively, between group 1 and group 3 and p < 0.05, p < 0.05, p < 0.05, and p < 0.05 at 3, 4, 5, and 6 week respectively between group 2 and group 3). By using the contralateral nonoperated tibia as an internal control, we found that the torsional strength of group 1 (smoking plus HBO) and group 2 (control) was superior to that of group 3 (smoking). The mean percentage of maximum torque was 80.9% in group 1 (smoking plus HBO) and was 78.0% in group 2 (control), whereas the mean percentage of maximum torque was 59.6 % in group 3 (smoking) (two-tailed t test, p < 0.05 between groups land 3 and between groups 2 and 3, whereas p > 0.05 between groups 1 and 2). CONCLUSION: This study suggests that smoke inhalation delays the bone healing in tibial lengthening; however, HBO mitigates the delayed healing effect of smoke inhalation and, thus, helps the smoking animal in achieving an expeditious bone healing in tibial lengthening.

Reconstruction of ankle and heel defects by a modified wide-base reverse sural flap.

BACKGROUND: Flap reconstruction around the ankle and heel is a technically demanding procedure. Some patients have contraindications for microsurgery, however, limiting the options for local tissue transfer. In this study, we describe our experience with a new flap technique for ankle and heel coverage. METHODS: We designed a modified wide-base reverse sural flap and applied it to 20 patients with lower leg trauma from 1994 to 1997. All patients sustained Gustilo type IIIb,c open fractures with soft-tissue defects around the ankle and heel. Six cases had chronic osteomyelitis. Most of our patients had contraindications for microsurgery such as old age, poor medical condition, or heavy smoker status. The average age was 69.5 years old, and the average follow-up time was 18.5 months. RESULTS: All 20 patients underwent successful modified reverse sural flap reconstruction. There were no deep infections, no soft-tissue necrosis, or pressure ulcers. The nonunion rate was 5%. The average time for flap elevation and rotation was 29.3 minutes. No blood transfusion was required. An unsightly scar was the major complaint (60%) from our patients. Seventeen cases (85%) achieved good functional outcomes. CONCLUSION: This report demonstrates that our design of this modified wide-base reverse sural flap is suitable for flap reconstruction around the ankle and heel; especially for patients who have difficulty in receiving microsurgery. The surgical procedure is simple, and the results are satisfactory.

Bone healing of tibial lengthening is delayed by cigarette smoking: study of bone mineral density and torsional strength on rabbits.

OBJECTIVE: We investigated the effect of intermittent cigarette smoke inhalation on the bone healing of tibial lengthening in rabbits. METHODS: Twelve male rabbits were divided into two groups of six animals each. The first group underwent intermittent cigarette smoke inhalation, and the second group did not undergo intermittent cigarette smoke inhalation. Each animal's right tibia was lengthened 5 mm by using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all of the animals 1 day before operation and 3, 4, 5, and 6 weeks after operation. All of the animals were killed 6 weeks postoperatively for biomechanical testing. RESULTS: By using the preoperative BMD as an internal control, we found that the BMD of the smoke-inhalation group was decreased significantly compared with the non-smoke-inhalation group. The mean %BMD at 3, 4, 5, and 6 weeks were 49.9%, 61.2%, 65.9%, and 71.0%, respectively, in the smoke-inhalation group, whereas the mean %BMD were 54.9%, 71.8%, 76.4%, and 82.0%, respectively, in the non-smoke-inhalation group (two-tailed t test, p > 0.05, p < 0.01, p < 0.01 and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). By using the contralateral nonoperated tibia as internal control, we found that torsional strength of the smoke-inhalation group was decreased significantly compared with the non-smoke-inhalation group. The mean percentage of maximal torque was 63.8% in the smoke-inhalation group, whereas the mean percentage of maximal torque was 77.1% in the non-smoke-inhalation group (two tailed t test, p < 0.01). CONCLUSION: This study suggests that cigarette smoking delays the mineralization during the bone healing process of distraction osteogenesis and, thus, decreases the mechanical strength of the regenerating bone.

Hyperbaric oxygen pretreatment attenuates hepatic reperfusion injury.

Microcirculatory derangement, energy depletion and lipid peroxidation have been related to development of ischemia-reperfusion injury in the liver. This study investigates the effects of hyperbaric oxygen (HBO) on hepatic ischemia-reperfusion injury. Adult, male Sprague-Dawley rats were used. Three groups were evaluated: 1) sham-operated control (laparotomy only, no ischemia, no HBO), n=8; 2) ischemia control (1-h ischemia, 2-h reperfusion, no HBO), n=8; and 3) HBO pretreatment (100%, oxygen, 2.5 atm absolute, 90 min) plus ischemia (1-h ischemia, 2-h reperfusion), n=8. An in vivo microscope was used to investigate hepatic microcirculation. Tissue malondialdehyde (MDA) and adenosine triphosphate (ATP) were determined. In comparison with the ischemia control group, HBO significantly improved harmful insults following ischemia-reperfusion. HBO lessened adherent leukocyte count (6.00+/-1.31 cells/200 microm vs 11.38+/-2.88 cells/200 microm), and improved flow velocity (1.72+/-0.26 mm/s vs 0.83+/-0.19 mm/s) in post-sinusoidal venules. HBO also reduced MDA (1.04+/-0.24 nmol/mg protein vs 2.24+/-0.49 micromol/g protein), and increased ATP (2.03+/-0.17 micromol/g wet wt vs 0.73+/-0.11 micromol/g wet wt) levels. This study demonstrates that HBO before ischemia may ameliorate the ischemia-reperfusion injury of the liver in the rat model.

Tuberculosis of the ankle: report of four cases.

Tuberculosis of the ankle joint is relatively uncommon, and the treatment usually includes chemotherapy, immobilization and non-weight bearing protection. It is easily confused with pyogenic arthritis, which often leads to delayed diagnosis. We reviewed the records of 4 patients with ankle tuberculosis with advanced articular lesions without evidence of pulmonary tuberculosis. They took antituberculous agents for 5 to 6 months. Two of them had positive bacterial cultures, and all four had initially received surgical management under the impression of pyogenic osteomyelitis. Two patients underwent arthrodesis and the other two synovectomy with debridement. The clinical and radiologic results were better in the patients who underwent arthrodesis. We consider surgery with open biopsy of a painful swelling ankle to be helpful in the differential diagnosis of tuberculous and pyogenic arthritis. Arthrodesis in patients with severe osteoarticular destruction of the ankle provides a better prognosis and more stable joint than other treatment methods.

Staged management of infected humeral nonunion.

Fourteen patients with infected humeral nonunion complicated by sinus discharge were treated with a staged protocol consisting of (1) radical debridement with local antibiotic beads implantation, and (2) external skeletal fixation with autologous bone grafting. In the first stage, a thorough debridement and sequestrectomy were done. Antibiotic beads were used to obliterate the bone defect, and the wound was then directly closed. In the second stage, the bead chains were replaced with autogenous cancellous bone graft. Unilateral Hoffman external skeletal fixators were applied simultaneously. The mean follow-up period was 73.6 months (range, 29 months to 9 years). The length of time to achieve bony union ranged from 3.5 to 8 months (average, 4.3 months). Hoffman pin complication was found in two cases, which were then shifted to plate internal fixation. All the infections were eradicated, and the wounds healed without further skin graft or flap coverage. All the fractures achieved bony union except for one in a patient who died. Most patients acquired satisfactory function of elbow motion after removal of external fixation and physical therapy. The method of two-stage management was effective for infected humeral nonunion. Not only was the infection eradicated and osseous union achieved, but also the limb function and joint motion were preserved.

Effect of intermittent cigarette smoke inhalation on tibial lengthening: experimental study on rabbits.

We investigated the effect of intermittent cigarette smoke inhalation on the bone healing of tibial lengthening in rabbits. Thirty-eight male rabbits were divided into two groups of 19 animals each. The first group went through intermittent cigarette smoke inhalation, and the second group did not go through intermittent cigarette smoke inhalation. Each animal's right tibia was lengthened 5 mm using an uniplanar lengthening device. Five animals of each group were killed at 4, 6, and 8 weeks postoperatively for biomechanical testing, and one animal of each group was killed at 2, 4, 6, and 8 weeks postoperatively for histologic study. Using the contralateral nonoperated tibia as an internal control, we found that torsional strength of the lengthened tibia of the smoke inhalation group was decreased significantly compared with the non-smoke inhalation group. The mean percent of maximal torque at 4, 6, and 8 weeks were 22.0, 66.3, and 78.6%, respectively, in the smoke inhalation group, whereas the mean percent of maximal torque were 48.0, 84.1, and 90.8% %, respectively, in non-smoke inhalation group (one-tailed t test, p < 0.01, p < 0.01, and p < 0.05 at 4, 6, and 8 weeks, respectively). Our histologic observations revealed that the granulation tissue resorption, bone formation, and remodeling were delayed in smoke inhalation group. The results of this study suggest that intermittent inhalation of cigarette smoke delays, but does not prevent, the bone healing in tibial lengthening.

Management of large infected tibial defects with radical debridement and staged double-rib composite free transfer.

Seven patients with tibial fractures complicated by large infected tibial defects were treated with a two-stage protocol. In the first stage, antibiotic-impregnated polymethylmethacrylate (PMMA) bead chains were used to obliterate the debrided osseous defect, and a meshed porcine skin was used for temporary wound coverage. In the second stage, the bead chains were removed, and the defects were reconstructed with a microvascularized double-rib and serratus anterior muscle composite free transfer. The interval between the first and second operations was 2 to 4 weeks. The bone defects ranged from 6 to 9 cm, and the skin defect areas ranged from 20 to 40 cm2. Wound healing and bony union was achieved in all seven cases. Minor pin track infection was seen in one patient. Stress fractures in two cases were successfully managed with patellar tendon short-leg bracing for 6 months in one case and a plate internal fixation in the other case. Within 2 years, all seven patients returned to light work without any external support, and all of their most recent radiographs showed good consolidation and hypertrophy of grafted rib bones. No occurrence of osteomyelitis was observed during an average follow-up of 37 months (out of a range of 24 to 50 months). We conclude that this treatment protocol provides rapid recovery from osteomyelitis and the double-rib graft is a useful, durable alternative for large tibial defect management.