Citations

AbstractBackground. The long-term outcome of patients with pyogenic vertebral osteomyelitis (PVO) has not been fully assessed.Methods. We conducted a retrospective cohort study to describe the long-term outcome of PVO and to assess risk factors for treatment failure in patients evaluated at our institution between 1994 and 2002. Patients were observed until July 1, 2013.Results. Two hundred sixty patients with PVO were included in this study. Twenty-seven percent (70) of patients developed their infection after an invasive spinal procedure. Staphylococcus aureus accounted for 40% (103) of infections. Forty-nine percent (128) of patients underwent spinal surgery as part of their initial therapy. The median duration of parenteral antimicrobial therapy was 42 days (interquartile range, 38–53). The estimated 2-, 5-, and 10-year cumulative probability of treatment failure-free survival was 72%, 69%, and 69%, respectively. Seventy-five percent of patients who developed treatment failure did so within 4.7 months of diagnosis. Residual neurological defects and persistent back pain were seen in 16% and 32% of patients, respectively. In a multivariate analysis, longer duration of symptoms before diagnosis and having an infection with S. aureus were associated with increased risk of treatment failure.Conclusions. Increasing duration of symptoms and infection with S. aureus were associated with treatment failure in patients with PVO. Most treatment failures occurred early after initiation of treatment. Pyogenic vertebral osteomyelitis is associated with a high 2-year failure rate. Persistent neurological deficits and back pain are common after therapy.

Objectives To quantify the occurrence of myocardial infarction ( MI ) occurring in the early postoperative period after surgical hip fracture repair and estimate the effect on 1‐year mortality. Design A population‐based, historical cohort study of individuals who underwent surgical repair of a hip fracture that used the computerized medical record linkage system of the R ochester E pidemiology P roject. Setting Academic and community hospitals, outpatient offices, and nursing homes in O lmsted C ounty, M innesota. Participants Over the 15‐year study period (1988–2002), 1,116 elderly adults underwent surgical repair of a hip fracture. Measurements At the end of the first 7 days after hip fracture repair, participants were classified into one of three groups: clinically verified MI (cv‐ MI ), subclinical myocardial ischemia, and no myocardial ischemia. One‐year mortality was compared between these groups. Multivariate models assessed risk factors for early postoperative cv‐ MI and 1‐year mortality. Results Within the first 7 days after hip fracture repair, 116 (10.4%) participants experienced cv‐ MI and 41 (3.7%) subclinical myocardial ischemia. Overall 1‐year mortality was 22%, with no difference between those with subclinical myocardial ischemia and those with no myocardial ischemia. One‐year mortality for those with cv‐ MI (35.8%) was significantly higher than for the other two groups. Occurrence of early postoperative cv‐ MI , male sex, and history of heart failure or dementia were independently associated with greater 1‐year mortality, whereas prefracture home residence and preoperative higher hemoglobin were protective. Conclusion Rates of early postoperative, cv‐ MI after hip fracture repair exceed rates after other major orthopedic surgeries and are independently associated with greater 1‐year mortality.

Abstract The canonical Wnt signaling pathway is pathogenic in a variety of cancers. We previously identified aberrant expression of the Wnt pathway transcription factor and target gene lymphoid enhancer binding factor-1 (LEF1) in chronic lymphocytic leukemia (CLL). This suggested that the Wnt signaling pathway has a role in the biology of CLL. In this study, we performed a Wnt pathway analysis using gene expression profiling and identified aberrant regulation of Wnt pathway target genes, ligands, and signaling members in CLL cells. Furthermore, we identified aberrant protein expression of LEF-1 specifically in CLL but not in normal mature B-cell subsets or after B-cell activation. Using the T cell–specific transcription factor/LEF (TCF/LEF) dual luciferase reporter assay, we demonstrated constitutive Wnt pathway activation in CLL, although the pathway was inactive in normal peripheral B cells. Importantly, LEF-1 knockdown decreased CLL B-cell survival. We also identified LEF-1 expression in CD19+/CD5+ cells obtained from patients with monoclonal B-cell lymphocytosis, suggesting a role for LEF-1 early in CLL leukemogenesis. This study has identified the constitutive activation and prosurvival function of LEF-1 and the Wnt pathway in CLL and uncovered a possible role for these factors in the preleukemic state of monoclonal B-cell lymphocytosis.

Abstract The B cell-activating factor of the TNF family receptor (BAFF-R), encoded by the TNFRSF13C gene, is critically important for transitional B cell survival to maturity. Thus, ligation of BAFF-R by BAFF delivers a potent survival signal. Reports implicating the BAFF/BAFF-R signaling axis in the pathogenesis of autoimmune human diseases and B lineage malignancies have largely prompted studies focusing on BAFF expression; however, there is an equally critical need to better understand BAFF-R expression. Initial BAFF-R expression, although characterized in murine B cells, has not yet been reported in human B lymphopoiesis. In this study, we first demonstrate that BAFF-R expression is absent from early precursors and is acquired by bone marrow B cells newly expressing the BCR. We next focused on identifying the specific genomic region that controls BAFF-R expression in mature B cells (i.e., the TNFRSF13C promoter). To accomplish this, we used in silico tools examining interspecies genomic conservation in conjunction with reporter constructs transfected into malignant B and plasma cell lines. DNase protection assays using nuclear extracts from BAFF-R–expressing cells suggested potential regulatory sites, which allowed the generation of EMSA probes that bound NFs specific to BAFF-R–expressing cells. With a more stringent analysis of interspecies homology, these assays identified a site at which a single nucleotide substitution could distinctly impact promoter activity. Finally, chromatin immunoprecipitation assays revealed the in vivo binding of the specific transcription factor c-Rel to the most proximal genomic region, and c-Rel small interfering RNA transfections in BAFF-R–expressing lines demonstrated a coincident knockdown of both c-Rel and BAFF-R mRNA.

Purpose We tested the hypothesis that the preimplantation mechanical properties of BioCleanse‐treated bone–patellar tendon–bone (BPTB) allografts are not significantly different from those of untreated specimens. Methods For this controlled laboratory study, specimens were harvested as central third or hemi‐BPTB units from both knees of 17 cadaveric tissue donors (11 men and 6 women) aged 19 to 88 years. Donor‐matched specimens (20 per group) were randomly assigned to either BioCleanse‐treated or untreated control groups. Specimens were subjected to 25 minutes of pretensioning at 89 N and then cyclically loaded under longitudinal tension between 50 N and 250 N for 1,000 cycles at 1 Hz, followed by ramp to failure at 50 mm/min. Results No statistically significant difference was found between untreated and BioCleanse‐treated specimens in stiffness (235.3 ± 37.6 N/mm v 222.3 ± 53.4 N/mm, P = .37), cyclic creep (0.38 ± 0.42 mm v 0.40 ± 0.26 mm, P = .81), maximum force (1,685.7 ± 471.6 N v 1,807.0 ± 657.8 N, P = .47), or ultimate stress (29.0 ± 9.8 MPa v 29.0 ± 12.8 MPa, P = .98). Conclusions The preimplantation mechanical properties of BPTB allografts treated with BioCleanse are not significantly different from those of untreated controls. Clinical Relevance This laboratory study compares the biomechanical properties of chemically treated allografts, which are currently being used in anterior cruciate ligament reconstruction, with those of nontreated fresh‐frozen allografts.