Reconstruction of the Medial Malleolus With Iliac Crest Autograft After Traumatic Loss: A Case Report.

CASE: A 19-year-old woman sustained an open ankle fracture with complete destruction of the left medial malleolus and significant soft-tissue loss. After temporizing external fixation and coverage with a rotational posterior tibial artery perforator flap, the medial malleolus was reconstructed with an autologous iliac crest bone graft and direct repair of the deltoid ligament. The patient achieved excellent improvement in functional outcomes at 21 months with adequate restoration of ankle motion. CONCLUSION: This case shows reconstruction of the medial malleolus with autologous iliac crest bone graft after traumatic loss can be a viable treatment option for young patients.

Heterotopic ossification in the knee following retrograde nailing of a femur fracture.

BACKGROUND: Heterotopic ossification (HO) is a pathologic bone formation in extra skeletal tissue and articular space. This was an objection to nailing of femur fractures across the knee; however, this has not been the case in many thousands of cases. Nonetheless, we present a patient in who placement of a retrograde nail resulted in calcification in the knee requiring excision. CASE PRESENTATION: A 42-year-old male presented to the clinic complaining of pain, popping, clicking, and mocking in the right knee, especially in the patellar region. Nine months prior he suffered an ipsilateral femur fracture that was treated with a retrograde intramedullary nail. X-ray and CT scan were used to confirm the presentation of a heterotopic bone mass in the Hoffa area of the right knee. The patient underwent an arthrotomy for excision of the bone mass. The bone mass was excised, but bone in the ACL was not removed. The patient experienced pain relief and improved range of motion following excision. CONCLUSION: Intraarticular heterotopic ossification is an infrequent event. We present a case of heterotopic ossification in the knee following retrograde nailing. The patient experienced improved symptoms and range of motion after excision of the intraarticular heterotopic bone mass.

Intramedullary nailing of concurrent ipsilateral fractures of the tibia and femur: primary synchronous nailing versus staged osteosynthesis with temporizing external fixation.

INTRODUCTION: The optimal timing to definitive osteosynthesis in the polytraumatized patient remains an unanswered question. Early total care, damage control orthopaedics, and early appropriate care have been described to manage the fractures in these patients, but there is a paucity of literature specific to ipsilateral tibial and femoral fractures. We sought the perioperative outcomes of primary simultaneous intramedullary nailing (IMN) versus temporizing external fixation (EF) of both fractures. METHODS: A chart review of all patients who sustained fractures of the ipsilateral femur and tibia that were definitively treated with (IMN) from January 2010 to December 2020 was performed. Patients who underwent initial EF and those that were primarily treated with IMNs were examined. RESULTS: IMNs and EF were the initial treatment in 23 and 16 patients, respectively. The mean (range) injury severity score (ISS) was 23.3 (33) in the EF group vs. 18.5 (34) in the IMN group, (p = 0.0686). The EF group had a higher total transfused units of packed red blood cells 7.4 vs. 2.8, the mean initial operative time was 236 vs. 282.6 (min), (p = 0.7399), a longer mean total operative time 601.78 vs. 236 (min), and longer mean length of stay 15.6 vs. 11 (days), (p < 0.5). Rates of complications were not significantly different between groups. CONCLUSION: Primary IMN is as safe as provisional EF in the adequately resuscitated patient with ipsilateral femoral and tibial fractures. This implies the fixation of both fractures into a single surgery without increasing perioperative complications, and decreasing total hospital stay in patients with sufficient preoperative resuscitation.

Does an antibiotic nail made in a lubricated tube release antibiotic?

INTRODUCTION: The treatment of long-bone osteomyelitis has long been a difficult problem. Recently, antibiotic-impregnated intramedullary rods for the treatment of infected long-bone fractures have been gaining popularity but they are quite difficult to fabricate. Recently, a new technique that utilizes mineral oil to coat the inside of a chest tube mold prior to introduction of cement has been proven to ease fabrication. We hypothesized that the use of mineral oil would alter the elution characteristics of tobramycin from the intramedullary device. METHODS: Two groups of antibiotic nails were fabricated under sterile conditions. The control group utilized a chest tube mold. The study group utilized a chest tube that was coated with mineral oil prior to cement injection. Each intramedullary nail was placed in pooled human serum and incubated under physiologic conditions. The level of tobramycin in each sample was measured at timepoints 0, 1, 6, and 24 h. RESULTS: There was no significant difference when comparing control with the experimental group at any timepoint. Antibiotic nails eluted tobramycin at a rapid rate in the first 6 h of exposure to serum, regardless of their preparation with oil or without oil. The rate of elution fell precipitously between 6 and 24 h. CONCLUSION: We believe that although this study, as with any study, cannot perfectly recreate in vivo conditions, we have clearly shown that mineral oil has no significant effect on elution of tobramycin from antibiotic nails.

Rifampin and tobramycin combination with PMMA antibiotic cement.

Rifampin is a powerful antibiotic used in the treatment of biofilm-forming bacteria with studies supporting its use in PMMA cement. However, it has not been widely accepted for its use in PMMA cement due to a perception that it is unable to solidify in a timely manner. The technique described consists of ratio of aminoglycoside and rifampin that reduces time to solidification to approximately 15-20 min.

Results of 167 consecutive cases of acetabular fractures using the Kocher-Langenbeck approach: a case series.

BACKGROUND: Acetabular fractures are quite challenging injuries for the orthopedic surgeon because of their low incidence and their deep and complex anatomy. The objective of this study was to evaluate surgeon-independent parameters that might influence radiographic outcome and early complication rates of high-energy acetabular fractures treated by open reduction and internal fixation via the Kocher-Langenbeck approach, the golden standard for posterior access. METHODS: One hundred sixty-seven consecutive patients (111 males and 56 females) with a mean age of 41.8 years and a mean follow-up period of 10 months were surgically treated by one experienced surgeon at a level I trauma center within 10 years. To quantify the radiographic outcome, the Matta, Brooker, and Epstein grades were used. Posttraumatic arthritis and avascular necrosis of the femoral head (defined as Helfet grades 3 or 4 and Ficat/Arlet stages 3 or 4, respectively) were evaluated. Furthermore, subgroup analyses according to fracture type, age, and gender were performed for each outcome measure and complication (infection, hemorrhagic shock, revision surgery, nerve damage, and need of a total hip arthroplasty). RESULTS: 65 A1, 34 A2, 51 B1, and 17 B2 fractures were identified according to the AO/ASIF classification. Of all patients, reduction was rated anatomic in 63.5%, imperfect in 22.2%, and poor in 14.4%. Degenerative changes were observed in 49.7%; 37.9% were affected by heterotopic ossification, 21.6% by posttraumatic arthritis, and 5.4% by avascular necrosis of the femoral head. Fifteen percent were diagnosed with a nerve damage, and 4.8% sustained an infection. Total hip arthroplasty was performed in 10.2%. Revision surgery due to secondary loss of reduction, seroma/hematoma, and wound infection was indicated in 6.0%. CONCLUSIONS: Fracture type, age, and gender are prognostic factors for the surgical outcome after ORIF of high-energy acetabular fractures.

Surgical Wound Classification and Surgical Site Infections in the Orthopaedic Patient.

INTRODUCTION: The Centers for Disease Control and Prevention created a surgical wound classification system (SWC: I, clean; II, clean/contaminated; III, contaminated; and IV, dirty) to preemptively identify patients at risk of surgical site infection (SSI). The validity of this system is yet to be demonstrated in orthopaedic surgery. We hypothesize a poor association between the SWC and the rate of subsequent SSI in orthopaedic trauma cases. METHODS: Nine hundred fifty-six orthopaedic cases were reviewed. Wounds were risk stratified intraoperatively using the SWC grades (I-IV). SSI was diagnosed clinically or with objective markers. The SWC was compared with SSI rates using a Fisher exact test. Significance was set at P < 0.05. RESULTS: Four hundred patients met the selection criteria. The rate of infection was not significantly different across the SWC grades (P = 0.270). There was a significantly higher risk of SSI among patients with diabetes (P = 0.028). CONCLUSIONS: The Centers for Disease Control and Prevention SWC showed poor utility in predicting and risk stratifying postoperative SSIs in orthopaedic surgical cases.

Complication Risk After Treatment of Intertrochanteric Hip Fractures in the Medicare Population.

The study evaluated the incidence of and complications associated with the use of an intramedullary nail vs open reduction and internal fixation (ORIF) with a sliding compression hip screw and plate in treating intertrochanteric fractures. The authors hypothesized that the biomechanically stronger and less invasive intramedullary nail would have superior results and fewer complications compared with ORIF. Patients followed for up to 1 year postoperatively were identified from the 5% nationwide sample of Medicare administrative claims data (1998-2007) using the corresponding International Classification of Diseases, 9th revision, Clinical Modification, codes 820.21 and 820.31. There were 9157 patients treated with intramedullary nails and 27,687 treated with compression screw and plate fixation. Intertrochanteric hip fractures treated with an intramedullary nail during this period increased from 3.3% to 63.1% compared with ORIF. Patients treated with an intramedullary nail had a higher adjusted risk of pulmonary embolism at 90 days (P=.003) and a higher risk of mortality at 1 year (P<.001) compared with those treated with ORIF. Patients who underwent intramedullary nailing during 2006 to 2007 had a lower adjusted risk of conversion to total hip replacement at 1 year (P=.037) compared with those who had ORIF. Over the decade of the study, intramedullary nail usage increased 59.8% compared with ORIF. Increased use of intramedullary nails compared with ORIF has not shown improved outcomes or decreased complications in patients with intertrochanteric hip fractures. The increased use of intramedullary nails for intertrochanteric hip fractures appears to be multifactorial, including the less invasive nature of the surgery and increased experience with the closed surgical technique.

Medial malleolus screws: out in one view and out.

Cartilage damage or mechanical blocking from screw penetration into intra-articular cartilage can reduce the chances of successful outcomes during medial malleolus fixation. There have been diverging opinions among surgeons concerning the reliability of radiographic assessment of fracture fixation and malleolus screw positioning. Therefore, this radiographic study examines the location of medial malleolus lag screws relative to the ankle mortise articular surface. In three Sawbones models, Kirschner wires were overdrilled with a 4.0-mm cannulated cortical screw simulating screws that would be intra- and extra-articular when performing open reduction and internal fixation of a medial malleolar fracture. Under fluoroscopy, images were evaluated to determine whether known intra-articular screws appeared extra-articular in any radiographic view. No image from models with known intra-articular penetration appeared extra-articular in any view or under "live" fluoroscopy. At 20° internal rotation, a screw with a known extra-articular position appeared to be within the cartilage. Intra-operative fluoroscopy is necessary to ensure proper extra-articular placement of screws. If a screw is pictured extra-articular in any radiograph, then it can be assumed that the screw is indeed out of the joint.

Antibiotic-laden PMMA bead chains for the prevention of infection in compound fractures: current state of the art.

Antibiotic-laden PMMA bead chains are a valuable method of local antibiotic treatment in the prevention of infection in open fractures. When used in this setting, they provide high concentrations of broad-spectrum antibiotics to the area of the highest risk which may not be well perfused or reached by systemic antibiotics, while also eliminating dead space. In this article, the historical and current state of antibiotic-laden bead chains is discussed. The literature provides evidence that antibiotic-laden bead chains are a useful adjuvant with systemic antibiotics in the prevention of infection in open fractures. These bead chains can be sterilely prepared in the operating room or manufactured, and they maintain their elution and antimicrobial properties for a considerable time period. The bead chains also allow a high local concentration of antibiotics without risk of systemic toxicity or fear of clinically significant growth or persistence of bacteria on the beads. Bead chains are a practical method of local antibiotic therapy when the wounds can be closed.

Use of carbon-fiber-reinforced composite implants in orthopedic surgery.

Carbon-fiber-reinforced polyetheretherketone implants offer several benefits over traditional metal implants. Their radiolucent property permits improved, artifact-free radiographic imaging. Their lower modulus of elasticity better matches that of bone. Their fatigue strength is greater than most metal implants. This article reviews the use of these implants in orthopedic surgery, including treatment of conditions involving the spine, trauma, tumor, and infection.

Poor prognosis and advanced clinicopathological features of clear cell renal cell carcinoma (ccRCC) are associated with cytoplasmic subcellular localisation of Hypoxia inducible factor-2α.

BACKGROUND: Pre-clinical studies have implicated hypoxia inducible factor (HIF)-2α as an important oncogene for clear cell renal cell carcinoma (ccRCC). Generally considered to act as a nuclear transcription factor, a recent study has also implicated HIF-2α as a protein translational initiation complex function within the cytoplasm (Uniacke et al., 2012). We hypothesised that both the absolute expression as well as the sub-cellular localisation of HIF-2α would predict clinicopathological features and cancer specific survival (CSS) in ccRCC. METHODS: A tissue microarray (TMA) study was conducted on three hundred and eight ccRCC patients. Survival differences were investigated with the log rank test and associations with CSS with uni- and multivariate Cox regression analyses. Recursive partition tree analysis was used to identify relevant cutoff values. RESULTS: High HIF-2α nuclear (N) (cutoff >32%) expression was associated with smaller tumour sizes (p=0.002) and lower Fuhrman grades (p=0.044), whereas tumours with high cytoplasmic (C) HIF-2α (>0%) more often had positive lymph nodes (p=0.004), distant metastases (p=0.021) and higher Fuhrman grades (p<0.0001). After adjustment for TNM stage, Eastern Cooperative Oncology Group performance status (ECOG PS), and Fuhrman grade, both continuous (p<0.0001) and dichotomised (p<0.0001) HIF-2α C variables remained significant predictors of CSS, while neither HIF-2α N variable was retained. CONCLUSION: Our investigation supports that HIF-2α may have a unique tumour promoter role in the cytoplasm. This preliminary finding justifies further experimental and mechanistic studies that examine the biological functions of HIF-2α when located in the cytoplasm.

Complications of operative treatment of clavicle fractures in a Level I Trauma Center.

Traditionally, the belief is that the clavicle heals readily and with nonoperative treatment. Since evidence suggests that many clavicles benefit from operative care, the aim of this study was to find the incidence of complications after operative treatment of clavicle fractures. This retrospective study includes 56 patients (41 male and 15 female) who were treated operatively for clavicle fractures between 2010 and 2012. The indications were displacement more than 20 mm, comminution, tenting of the skin, floating shoulder, and open fractures. Seventy-five percent of the fractures occurred in the midshaft and 25 % in the lateral third of the clavicle. There were no fractures of the medial third. The midshaft fractures were either plated with 3.5 mm reconstruction plates or anatomical locking plates. For internal fixation of the lateral fractures, we used acromioclavicular hook plates. The mean follow-up period was 4.6 months (range 1.0-28.0). Three patients did not participate in the follow-up. There were 12 patients with complications (21 %). Five of them required reoperations. Two patients were reoperated due to clavicle nonunions, two patients due to traumatic refracture of the plated clavicle, and one because of pain caused by the plate. Four cases developed superficial infections, and there was one patient with a deep tissue infection. None of the patients showed signs of neurovascular impairment postoperatively. None of the patients complained about decreased range of motion or loss of muscle strength postoperatively. Plating of clavicle fractures is a procedure that results in lower rates of malunion, nonunion, and functional impairment compared with nonoperative treatment. Nonetheless, one case in ten has a complicated course. Attention to technique and careful follow-up may prevent these problems.

Histone acetylation regulates intracellular pH.

Differences in global levels of histone acetylation occur in normal and cancer cells, although the reason why cells regulate these levels has been unclear. Here we demonstrate a role for histone acetylation in regulating intracellular pH (pH(i)). As pH(i) decreases, histones are globally deacetylated by histone deacetylases (HDACs), and the released acetate anions are coexported with protons out of the cell by monocarboxylate transporters (MCTs), preventing further reductions in pH(i). Conversely, global histone acetylation increases as pH(i) rises, such as when resting cells are induced to proliferate. Inhibition of HDACs or MCTs decreases acetate export and lowers pH(i), particularly compromising pH(i) maintenance in acidic environments. Global deacetylation at low pH is reflected at a genomic level by decreased abundance and extensive redistribution of acetylation throughout the genome. Thus, acetylation of chromatin functions as a rheostat to regulate pH(i) with important implications for mechanism of action and therapeutic use of HDAC inhibitors.

IGFBP-3 nuclear localization predicts human prostate cancer recurrence.

Insulin-like growth factor binding protein-3 (IGFBP-3) is a pro-apoptotic, anti-metastasic, and anti-angiogenic protein. Low serum IGFBP-3 has been associated with risk of more aggressive prostate cancer (PCa). We investigated the impact of nuclear and cytoplasmic IGFBP-3 protein expression levels in PCa by examining their in situ expression across a wide spectrum of primary tumors by immunohistochemical analysis of tissue microarrays. Immunohistochemistry was performed on PCa microarrays constructed from 226 hormone naïve patients who underwent radical prostatectomy. Both cytoplasmic and nuclear IGFBP-3 expressions were scored in a semi-quantitative fashion using an integrated measure of intensity and positivity. The distribution of IGFBP-3 protein expression was examined across the spectrum of epithelial tissues, and its association with standard clinicopathological covariates and tumor recurrence was examined. There was a broad range of IGFBP-3 staining across all histologies examined. Tumor had higher IGFBP-3 cytoplasmic and nuclear staining than benign histologies. For IGFBP-3 nuclear staining, PCa was significantly different than benign prostatic hyperplasia, normal prostate, and prostate intraepithelial neoplasia. As both a continuous and dichotomized variable, higher nuclear IGFBP-3 expression had statistically significant associations with PCa recurrence. The cytoplasmic staining had no significance in any patient subgroup. In patients with low-grade cancer, IGFBP-3 nuclear positivity was a better predictor of recurrence than baseline PSA, tumor margin status, TNM tumor stage, or presence of capsular invasion. High nuclear IGFBP-3 is amongst the strongest predictors of cancer recurrence in patients with low-grade prostate cancers and may therefore play an important role in risk stratification.

Expression of thyroid transcription factor-1 in normal endometrium is associated with risk of endometrial cancer development.

Thyroid transcription factor-1 (TTF-1) is a DNA-binding protein that is mainly expressed in thyroid and lung tissue, but has also been found in gynecologic tissue. Recent studies have suggested that TTF-1 has tumor suppressor function in lung adenocarcinoma models. In the current study, we examined whether expression of TTF-1 in benign endometrium and endometrial hyperplasia might impact on the risk of developing endometrial cancer. Formalin-fixed paraffin-embedded endometrial tissues obtained from 535 cases were used to construct an endometrial tissue microarray. One hundred fifty of 207 patients had multiple serial endometrial specimens including 46 patients who progressed to endometrial cancer. The tissue microarray included a range of histopathologies including benign endometrium (n=231), simple hyperplasia (n=105), complex hyperplasia (n=36), simple atypical hyperplasia (n=10), complex atypical hyperplasia (n=44), and endometrial carcinoma (n=109). Expression of TTF-1 by immunohistochemistry in benign endometrium and endometrial hyperplasia was correlated with progression to cancer and clinical features known to be associated with increased risk of developing endometrial cancer. Carcinoma specimens showed a significantly greater expression of TTF-1 compared with benign endometrium and non-atypical hyperplasia (P=0.0007 and P=0.05). Presence of TTF-1 expression in benign endometrium was associated with a significantly decreased risk of cancer development (P=0.003, hazards ratio=0.104, 95% CI: 0.024-0.455). TTF-1 expression in hyperplasia did not significantly correlate with progression to cancer. The data from our study show that TTF-1 expression in normal endometrium is associated with a reduced risk of endometrial cancer development. This observation suggests that TTF-1 might function as a tumor suppressor in endometrial tissue. TTF-1 expression in normal endometrium could potentially provide clinically useful information as a biomarker for the risk of endometrial cancer.

Clinical, molecular, and genetic correlates of lymphatic spread in clear cell renal cell carcinoma.

BACKGROUND: While it is well known that clear cell renal cell carcinoma (ccRCC) that presents with lymphatic spread is associated with an extremely poor prognosis, its molecular and genetic biology is poorly understood. OBJECTIVE: Define the clinicopathologic, molecular, and genetic biological characteristics of these tumors in comparison to nonmetastatic (N0M0) renal cell carcinomas. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study defined clinicopathologic features, expression of 28 molecular markers, and occurrence of chromosomal aberrations for their correlation with lymphatic spread in three cohorts of 502, 196, and 272 patients, respectively. MEASUREMENTS: Fisher exact test or the χ(2) test were used to compare categorical variables; continuous variables were compared with the Mann-Whitney U test or student t test. Cut-off values were calculated based on receiver operating characteristic curves and the Youden Index. Uni- and multivariate regression analyses were used to investigate the correlation with lymphatic spread. RESULTS AND LIMITATIONS: In clinical analyses, a predictive model consisting of smoking history (p=0.040), T stage (p<0.0001), Fuhrman grade (p<0.0001), Eastern Cooperative Oncology Group performance status (p<0.0001), and microvascular invasion (p<0.0001) was independently associated with lymphatic spread. After adjustment with these clinical variables, low carbonic anhydrase IX (CAIX) (p=0.043) and high epithelial vascular endothelial growth factor receptor 2 (p=0.033) protein expression were associated with a higher risk of lymphatic spread, and loss of chromosome 3p (p<0.0001) with a lower risk. The current study is limited by its retrospective design, small sample size, and single-center experience. CONCLUSIONS: The low rates of CAIX expression and loss of chromosome 3p suggest that lymphatic spread in ccRCC occurs independently of von Hippel-Lindau tumor suppressor inactivation.

Smoking negatively impacts renal cell carcinoma overall and cancer-specific survival.

BACKGROUND: Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC. METHODS: Eight hundred-two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow-up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status. RESULTS: Smokers presented more commonly with pulmonary comorbidities (P < .0001) and cardiac comorbidities (P = .014) and with a worse performance status (P = .031) than nonsmokers. Smoking was associated significantly with tumor multifocality (P = .022), higher pathologic tumor classification (P = .037), an increased risk of bulky lymph node metastases (P = .031), and the presence of distant metastases (P < .0001), especially lung metastases (P < .0001). Both overall survival (OS) (62.37 months vs 43.64 months; P = .001) and cancer-specific survival (CSS) (87.43 months vs 56.57 months; P = .005) were significantly worse in patients who smoked. The number of pack-years was retained as an independent predictor of CSS and OS in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers (P = .012). CONCLUSIONS: In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated.

Treatment of acute tibial shaft fractures with an expandable nailing system: a systematic review of the literature.

Locked Intramedullary Nailing is an established method of treatment for tibial shaft fractures. Locking of tibial nails is however not without its drawbacks. Locking is time consuming, and is associated with a noteworthy complication rate. The Fixion IM nailing system is an expandable nail designed to eliminate some of these drawbacks. We have performed a systematic review of the literature to determine the safety and efficacy of this system. Publications examining the use of the Fixion system were identified from the MEDLINE and the Cochrane databases. Forty-one citations were generated by the MEDLINE search. Of these, two quasi-randomised trials and eight case series satisfied our selection criteria and were reviewed. Overall the average reoperation rate for the Fixion nail was 10.2%. Shortening occurred in 3% of cases and fracture propagation was reported in 2% of cases. The Fixion cohort united at an average of 12.2 weeks and the average operative time was 54 minutes. The Fixion system eliminated complications and reoperations associated with the use of locking screws. Further studies in the form of randomised controlled trials are needed to evaluate the Fixion system against conventional locked nails.