Proximal femoral replacement in the management of acute periprosthetic fractures of the hip: a competing risks survival analysis.

To examine the mortality and implant survivorship of proximal femoral replacement (PFR), revision total hip arthroplasty (REV) and open reduction internal fixation (ORIF) in the treatment of acute periprosthetic fractures of the proximal femur, we retrospectively reviewed 97 consecutive acute periprosthetic proximal femoral fractures from 2000 to 2010. Three groups were defined: PFR (n=21), REV (n=19), and ORIF (n=57). Outcome measures were all-cause mortality, implant failure, and reoperation. Competing Risks survival analysis of overall mortality during the mean 35-month follow-up showed no statistical difference between the three groups (P=0.65; 12 and 60 month mortality for PFR: 37%, 45%; REV: 16%, 46%; ORIF: 14%, 100%). Implant survival was worse for the PFR group (P=0.03, 12 and 60-month implant failure rate for PFR: 5%, 39%; REV: 7%, 7%; ORIF 2%, 2%). We conclude that PFR as compared with REV or ORIF may have worse medium-term implant survival, primarily due to instability and dislocation.

Primary versus secondary distal femoral arthroplasty for treatment of total knee arthroplasty periprosthetic femur fractures.

Current methods of fixing periprosthetic fractures after total knee arthroplasty (TKA) are variable, and include open reduction and internal fixation (ORIF) via plating, retrograde nailing, or revision using standard revision TKA components or a distal femoral arthroplasty (DFA). The purpose of this study is to compare patients who failed plating techniques requiring subsequent revision to DFA to patients who underwent primary DFA. Of the 13 patients (9.2%) who failed primary ORIF, causes included nonunion (53.8%), infection (30.8%), loosening (7.7%), and refracture (7.7%). There were significantly more surgical procedures for ORIF revision to DFA compared to primary DFA. Complications for patients who underwent primary reconstruction with DFAs included extensor mechanism disruption (8.3%), infection (5.6%), and dislocation (2.8%). Primary reconstruction via ORIF is beneficial for preserving bone stock, but primary DFA may be preferred in osteopenic patients, or those at high risk for nonunion.

Gammadelta T cells mitigate the organ injury and mortality of sepsis.

Sepsis is a difficult condition to treat and is associated with a high mortality rate. Sepsis is known to cause a marked depletion of lymphocytes, although the function of different lymphocyte subsets in the response to sepsis is unclear. gammadelta T cells are found largely in epithelial-rich tissues, and previous studies of gammadelta T cells in models of sepsis have yielded divergent results. In the present study, we examined the function of gammadelta T cells during sepsis in mice using cecal ligation and puncture (CLP). Mice deficient in gammadelta T cells had decreased survival times and increased tissue damage after CLP compared with wild-type mice. Furthermore, bacterial load was increased in gammadelta T cell-deficient mice, yet antibiotic treatment did not change mortality. Additionally, we found that recruitment of neutrophils and myeloid suppressor cells to the site of infection was diminished in gammadelta T cell-deficient mice. Finally, we found that circulating levels of IFN-gamma were increased, and systemic levels of IL-10 were decreased in gammadelta T cell-deficient mice after CLP compared with wild-type mice. gammadelta T cell-deficient mice also had increased intestinal permeability after CLP compared with wild-type mice. Neutralization of IFN-gamma abrogated the increase in intestinal permeability in gammadelta T cell-deficient mice. The intestines taken from gammadelta T cell-deficient mice had decreased myeloperoxidase yet had increased tissue damage as compared with wild-type mice. Collectively, our data suggest that gammadelta T cells modulate the response to sepsis and may be a potential therapeutic target.

CD4-expressing cells are early mediators of the innate immune system during sepsis.

It is well established that the immune response to sepsis is mediated by leukocytes associated with the innate immune system. However, there is an emerging view that T lymphocytes can also mediate this response. Here, we observed a significant depletion of both CD4 and CD8 T cells in human patients after blunt trauma. To determine what effect the loss of these cells may have during a subsequent infection, we obtained CD4- and CD8-deficient mice and subjected them to cecal ligation and puncture (CLP). We observed that CD4 knockout (KO) mice showed increased CLP-induced mortality compared with CD8-deficient and wild-type (WT) mice especially within the first 30 h of injury. CD4 KO mice also exhibited significantly increased IL-6 concentrations after the CLP. The CD4 KO mice had an increased concentration of bacteremia as compared with WT mice. Antibiotic treatment decreased mortality in the CD4 KO mice as compared with no changes in the wild mice after CLP. Neutrophils isolated from septic CD4 KO mice showed decreased spontaneous oxidative burst compared with neutrophils taken from septic controls. We examined the role of IFN-gamma by using mice deficient in this cytokine and found these mice to have significantly higher mortality as compared with WT mice. Finally, we detected a 2-fold increase in CD11b+ cells that exhibited intracellular IFN-gamma staining in the peritoneum of WT mice after CLP. The data suggest that CD4+ cells may facilitate the early clearance of bacteria by regulating neutrophils function possibly through an IFN-gamma-dependent mechanism.

N-linked oligosaccharides affect the enzymatic activity of CD39: diverse interactions between seven N-linked glycosylation sites.

Rat CD39, a membrane-bound ectonucleoside triphosphate diphosphohydrolase that hydrolyzes extracellular nucleoside tri- and diphosphates, has seven potential N-glycosylation sites at asparagine residues 73, 226, 291, 333, 375, 429, and 458. To determine their roles in the structure and function of CD39, we mutated these sites individually or in combination by replacing asparagine with serine or glutamine and analyzed the surface expression and the enzymatic activity of the mutants. The results indicate that rat CD39 can be glycosylated at all seven sites when expressed in COS7 cells. Glycosylation sites 73 at the N terminus, 333 in the middle, and 429 and 458 at the C terminus were principally required for cell surface appearance of enzymatically active CD39. Whereas deletion of these sites individually had modest effects on surface ATPase activity, some double deletions of these sites had major effects on both surface activity and expression. The importance of these N-glycosylation sites is recognizable in other members of the ectonucleoside triphosphate diphosphohydrolase family.

Variation of nerve to flexor hallucis brevis.

BACKGROUND: Hallopeau's nerve is a branch of the lateral plantar nerve that supplies the flexor hallucis brevis muscle while also forming an anastomosis with the medial plantar nerve. In this study, the presence of this neural anastomosis was determined through dissection of cadaveric specimens. MATERIALS AND METHODS: Twenty-six fresh-frozen adult feet (13 matched pairs) were dissected to assess the presence or absence of Hallopeau's nerve. RESULTS: Dissections revealed four out of 26 specimens had this anastomosis. CONCLUSION: This study confirms this anatomic variation. CLINICAL RELEVANCE: The clinical significance of these anastomoses remains unknown. These anastomoses are analogous to some in the hand and forearm.

The molecular landscape of extraskeletal osteosarcoma: A clinicopathological and molecular biomarker study.

Extraskeletal osteosarcoma (ESOSA) is a rare soft tissue neoplasm representing <5% of osteosarcomas and <1% of all soft-tissue sarcomas. Herein, we investigate the clinicopathological and molecular features of ESOSA and explore potential parameters that may affect outcome. Thirty-two cases were retrieved and histomorphology was reviewed. Clinical history and follow-up were obtained through electronic record review. DNA from formalin-fixed paraffin-embedded (FFPE) tissue was extracted and processed from 27 cases. Genome-wide DNA copy number (CN) alterations and allelic imbalances were analyzed by single nucleotide polymorphism array using Affymetrix OncoScan FFPE Assay. Massive high-throughput deep parallel sequencing was performed using a customized panel targeting 410 cancer genes. Log rank, Fisher's exact test and Cox proportional hazards were used for statistical analysis. In this series of 32 patients (male n = 12, female n = 20), the average age was 66 years (19-93) and median follow up was 24 months (range 6-120 months). Frequent genomic alterations included CN losses in tumour suppressor genes including CDKN2A (70%), TP53 (56%) and RB1 (49%). Mutations affecting methylation/demethylation, chromatin remodeling and WNT/SHH pathways were identified in 40%, 27%, and 27%, respectively. PIK3CA and TERT promoter variant mutations were identified in 11% of the cases. Cases harbouring simultaneous TP53 and RB1 biallelic CN losses were associated with worse overall survival and local recurrence (p = 0.04, p = 0.02, respectively). CDKN2A losses and positive margins were also associated with worse overall survival (p = 0.002; p = 0.03, respectively). Our findings suggest that age above 60, positive margin status, simultaneous biallelic TP53 and RB1 losses and CDKN2A loss are associated with a worse outcome in ESOSA. Comparison between conventional paediatric osteosarcoma and ESOSA shows that, while both share genetic similarities, there are notable dissimilarities and mechanistic differences in the molecular pathways involved in ESOSA.

Immune Responses in U.S. Military Personnel Who Received Meningococcal Conjugate Vaccine (MenACWY) Concomitantly with Other Vaccines Were Higher than in Personnel Who Received MenACWY Alone.

Immunological responses to vaccination can differ depending on whether the vaccine is given alone or with other vaccines. This study was a retrospective evaluation of the immunogenicity of a tetravalent meningococcal conjugate vaccine for serogroups A, C, W, and Y (MenACWY) administered alone (n = 41) or concomitantly with other vaccines (n = 279) to U.S. military personnel (mean age, 21.6 years) entering the military between 2006 and 2008. Concomitant vaccines included tetanus/diphtheria (Td), inactivated polio vaccine (IPV), hepatitis vaccines, and various influenza vaccines, among others; two vaccine groups excluded Tdap and IPV. Immune responses were evaluated in baseline and postvaccination sera for Neisseria meningitidis serogroups C and Y 1 to 12 months (mean, 4.96 months) following vaccination. Functional antibodies were measured by using a serum bactericidal antibody assay with rabbit complement (rSBA) and by measurement of serogroup-specific immunoglobulin G (IgG) antibodies. The percentage of vaccinees reaching threshold levels (IgG concentration in serum, ≥2 µg/ml; rSBA titer, ≥8) corresponding to an immunologic response was higher postvaccination than at baseline (P < 0.001). Administration of MenACWY along with other vaccines was associated with higher geometric means of IgG concentrations and rSBA titers than those measured 4.60 months after a single dose of MenACWY. In addition, higher percentages of vaccinees reached the immunological threshold (range of odds ratios [ORs], 1.5 to 21.7) and more of them seroconverted (OR range, 1.8 to 4.8) when MenACWY was administered with any other vaccine than when administered alone. Additional prospective randomized clinical trials are needed to confirm the observed differences among groups in the immune response to MenACWY when given concomitantly with other vaccines to U.S. military personnel.

Analysis of outcomes in extraskeletal osteosarcoma: a review of fifty-three cases.

BACKGROUND: Extraskeletal osteosarcoma is a rare soft-tissue sarcoma about which little is known. The objectives of this study were to describe the clinical features and natural history of extraskeletal osteosarcoma and to investigate factors affecting outcomes. METHODS: A retrospective review of a prospectively maintained database of patients diagnosed with soft-tissue sarcoma was conducted. Patients with pathologically confirmed extraskeletal osteosarcoma from 1982 to 2012 were identified and were included in the analysis. Medical records were reviewed for clinical features, treatment, and outcomes. RESULTS: Fifty-three patients were identified from the database: forty-two presented with localized disease, two presented with metastatic disease, and nine presented with recurrent (local and/or distant) disease. The median patient age at diagnosis was sixty-four years, with a median follow-up time of thirty-four months (range, one to 290 months) for survivors. Of the fifty-three patients who were identified, forty-one had lesions in the extremities, fifty-one had high-grade lesions, forty had lesions >5 cm, and forty-two had deep lesions. For patients presenting with localized disease, the median survival was 45.8 months with a three-year cumulative incidence of death due to disease of 39%. All patients with localized disease were managed with surgical resection of the primary tumor: nineteen with surgery only, ten with adjuvant radiation, five with adjuvant chemotherapy, and eight with both radiation and chemotherapy. Eighteen patients relapsed: two patients had local recurrences, ten patients had distant metastases, and six patients had local recurrences and distant metastases. In log-rank analysis, patients with superficial tumors and negative margins at resection had a higher three-year event-free survival. No significant association of disease-specific or event-free survival was found with the addition of radiation, chemotherapy, or both to surgery. CONCLUSIONS: For patients presenting with localized extraskeletal osteosarcoma, three-year event-free survival was higher for patients with superficial tumors and negative margins at resection. Radiation and chemotherapeutic treatment were not associated with a lower incidence of death due to disease or a longer event-free survival.