Paul M. Huddleston

Ciprofloxacin Inhibition of Experimental Fracture-Healing*

Background: Fluoroquinolones, such as ciprofloxacin, have an adverse effect on growing cartilage and endochondral ossification in children. This study was carried out to determine whether ciprofloxacin also has an adverse effect on the healing of experimental fractures. Methods: Sixty male 300-gram Wistar rats were divided equally into three groups, which received ciprofloxacin, cefazolin, or no treatment for three weeks, beginning seven days after production of a closed, nondisplaced, bilateral femoral fracture. The serum concentrations of the ciprofloxacin and the cefazolin were 2.4 and 146 micrograms per milliliter, respectively. Radiographic, histological, and biomechanical studies were used to evaluate fracture-healing. Results: Radiographs revealed significantly more advanced healing of the control fractures compared with the fractures in the ciprofloxacin-treated group (average stage, 2.1 compared with 1.5, p = 0.01). The cefazolin-treated group was not different from the controls with respect to radiographic healing (average stage, 1.8 compared with 2.1, p = 0.18). Torsional strength-testing of fracture callus exposed to ciprofloxacin revealed a 16 percent decrease in strength compared with the controls (284 compared with 338 newton-millimeters, p = 0.04) and a 49 percent decrease in stiffness (twenty compared with thirty-nine newton-millimeters per degree, p = 0.001). The biomechanical strength in the cefazolin-treated group was not different from that of the controls. Fracture calluses in the animals treated with ciprofloxacin showed abnormalities in cartilage morphology and endochondral bone formation and a significant decrease in the number of chondrocytes compared with the controls (0.77 x 104 compared with 1.3 x 104 cells per square millimeter, p = 0.004). Conclusions: These data suggest that experimental fractures exposed to therapeutic concentrations of ciprofloxacin in serum demonstrate diminished healing during the early stages of fracture repair. The administration of ciprofloxacin during early fracture repair may compromise the clinical course of fracture-healing.

2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults

These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

C-Reactive Protein, Erythrocyte Sedimentation Rate and Orthopedic Implant Infection

Background C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been shown to be useful for diagnosis of prosthetic hip and knee infection. Little information is available on CRP and ESR in patients undergoing revision or resection of shoulder arthroplasties or spine implants. Methods/Results We analyzed preoperative CRP and ESR in 636 subjects who underwent knee (n = 297), hip (n = 221) or shoulder (n = 64) arthroplasty, or spine implant (n = 54) removal. A standardized definition of orthopedic implant-associated infection was applied. Receiver operating curve analysis was used to determine ideal cutoff values for differentiating infected from non-infected cases. ESR was significantly different in subjects with aseptic failure infection of knee (median 11 and 53.5 mm/h, respectively, p = <0.0001) and hip (median 11 and 30 mm/h, respectively, p = <0.0001) arthroplasties and spine implants (median 10 and 48.5 mm/h, respectively, p = 0.0033), but not shoulder arthroplasties (median 10 and 9 mm/h, respectively, p = 0.9883). Optimized ESR cutoffs for knee, hip and shoulder arthroplasties and spine implants were 19, 13, 26, and 45 mm/h, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 89 and 74% for knee, 82 and 60% for hip, and 32 and 93% for shoulder arthroplasties, and 57 and 90% for spine implants. CRP was significantly different in subjects with aseptic failure and infection of knee (median 4 and 51 mg/l, respectively, p<0.0001), hip (median 3 and 18 mg/l, respectively, p<0.0001), and shoulder (median 3 and 10 mg/l, respectively, p = 0.01) arthroplasties, and spine implants (median 3 and 20 mg/l, respectively, p = 0.0011). Optimized CRP cutoffs for knee, hip, and shoulder arthroplasties, and spine implants were 14.5, 10.3, 7, and 4.6 mg/l, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 79 and 88% for knee, 74 and 79% for hip, and 63 and 73% for shoulder arthroplasties, and 79 and 68% for spine implants. Conclusion CRP and ESR have poor sensitivity for the diagnosis of shoulder implant infection. A CRP of 4.6 mg/l had a sensitivity of 79 and a specificity of 68% to detect infection of spine implants.

LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis

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.

A Biofilm Approach to Detect Bacteria on Removed Spinal Implants

Study Design. This is a prospective study comparing the diagnosis of spinal implant infection by conventional peri-implant tissue culture with a technique which uses a combination of vortexing and bath sonication to dislodge bacteria growing as a biofilm on the surface of retrieved spinal implants. Objective. We hypothesized that the biofilm-sampling technique would be more sensitive than peri-implant tissue culture. Summary of Background Data. Culture of peri-implant tissue is inaccurate for the diagnosis of orthopedic device-related infection; cultures taken from the implant may be more sensitive. We have developed a technique which uses vortexing-bath sonication to sample bacterial biofilms on the surface of retrieved hip and knee implants, and shown that it is more sensitive than peri-prosthetic tissue culture for the microbiologic diagnosis of prosthetic knee, hip, and shoulder infection. Methods. We compared peri-implant tissue culture to the vortexing-bath sonication technique which samples bacterial biofilm on the surface of retrieved spinal implants, for the diagnosis of spinal implant infection. In addition, we compared detection of Staphylococcus and Propionibacterium acnes by rapid cycle real-time polymerase chain reaction with culture of sonicate fluid. Results. A total of 112 subjects were studied; 22 had spinal implant infection. The sensitivities of peri-implant tissue and sonicate fluid culture were 73% and 91% (P = 0.046), and the specificities were 93% and 97%, respectively. P. acnes and coagulase-negative staphylococci were the most frequent microorganisms detected among subjects with spinal implant infection, with P. acnes detected in 56 and 45%, and coagulase-negative staphylococci detected in 31 and 40% of peri-implant tissue and sonicate fluid cultures, respectively. Compared with the culture of sonicate fluid, polymerase chain reaction was 100 and 67% sensitive for the detection of culture-positive Staphylococcus and P. acnes spinal implant infection, respectively. Conclusion. Implant sonication followed by culture is more sensitive than peri-implant tissue culture for the microbiologic diagnosis of spinal implant infection.

Body mass index and risk of adverse cardiac events in elderly patients with hip fracture: a population-based study.

OBJECTIVES: To determine whether obesity affects cardiac complications after hip fracture repair.

Trends in the epidemiology of osteomyelitis: a population-based study, 1969 to 2009.

BACKGROUND The epidemiology of osteomyelitis in the United States is largely unknown. The purpose of this study was to determine long-term secular trends in the incidence of osteomyelitis in a population-based setting. METHODS The study population comprised 760 incident cases of osteomyelitis first diagnosed between January 1, 1969, and December 31, 2009, among residents of Olmsted County, Minnesota. The complete medical records for each potential subject were reviewed to confirm the osteomyelitis diagnosis and to extract details on anatomical sites, infecting organisms, etiological risk factors, and outcomes. RESULTS The overall age and sex-adjusted annual incidence of osteomyelitis was 21.8 cases per 100,000 person-years. The annual incidence was higher for men than for women and increased with age (p < 0.001). Rates increased with the calendar year (p < 0.001) from 11.4 cases per 100,000 person-years in the period from 1969 to 1979 to 24.4 per 100,000 person-years in the period from 2000 to 2009. The incidence remained relatively stable among children and young adults but almost tripled among individuals older than sixty years; this was partly driven by a significant increase in diabetes-related osteomyelitis from 2.3 cases per 100,000 person-years in the period from 1969 to 1979 to 7.6 cases per 100,000 person-years in the period from 2000 to 2009 (p < 0.001). Forty-four percent of cases involved Staphylococcus aureus infections. CONCLUSIONS The reasons for the increase in osteomyelitis between 1969 and 2009 are unclear but could comprise a variety of factors, including changes in diagnosing patterns or increases in the prevalence of risk factors (e.g., diabetes) in this population.

Risk factors for surgical site infection after posterior cervical spine surgery: an analysis of 5,441 patients from the ACS NSQIP 2005–2012

BACKGROUND CONTEXT The incidence of surgical site infection (SSI) following posterior cervical surgery has been reported as high as 18% in the literature. Few large studies have specifically examined posterior cervical procedures. PURPOSE The study aims to examine the incidence, timing, and risk factors for SSI following posterior cervical surgery. DESIGN This is a retrospective cohort study of prospectively collected data in a national surgical outcomes database. PATIENT SAMPLE The sample includes patients who underwent posterior cervical spine surgery between 2005 and 2012 identified in the American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) Participant Use Data File. OUTCOME MEASURES The 30-day rate of postoperative SSI, timing of diagnosis, and associated risk factors were determined. METHODS The ACS NSQIP was used to identify 5,441 patients who underwent posterior cervical spine surgery by Current Procedural Terminology codes from 2005 to 2012. Thirty-day readmission data were obtained for 2011-2012. The incidence and timing of SSI were determined. Multivariable logistic regression analysis was then performed to identify significant risk factors. RESULTS Of the 5,441 patients identified as having undergone posterior cervical surgery, 3,724 had a posterior cervical decompression, 1,310 had a posterior cervical fusion, and 407 underwent cervical laminoplasty. Surgical site infection within 30 days was identified in 160 patients (2.94%), with 80 of those cases being superficial SSI. There was no significant difference in SSI rate among the three procedure groups. The average time for diagnosis of SSI was over 2 weeks. In 2011-2012, 36.9% of patients with SSI were readmitted within 30 days. Several significant predictors of SSI were identified in univariate analysis, including body mass index (BMI) >35, chronic steroid use, albumin <3, hematocrit <33, platelets <100, higher American Society of Anesthesiologists class, longer operative time, and longer hospital admission. Independent risk factors, including BMI >35 (odds ratio [OR]=1.78, p=.003), chronic steroid use (OR=1.73, p=.049), and operative time >197 minutes (OR=2.08, p=.005), were identified in multivariable analysis. CONCLUSIONS Optimization of preoperative nutritional status, serum blood cell counts, and operative efficiency may lead to a reduction in SSI rates. Obese patients and patients on chronic steroid therapy should be counseled on elevated SSI risk.

Impact of body mass on hospital resource use in total hip arthroplasty.

OBJECTIVE To determine the impact of BMI on post-operative outcomes and resource utilization following elective total hip arthroplasty (THA). DESIGN A retrospective cohort analysis on all primary elective THA patients between 1996 and 2004. Primary outcomes investigated using regression analyses included length of stay (LOS) and costs (US dollars). SETTING Mayo Clinic Rochester, a tertiary care centre. SUBJECTS Patients were stratified by pre-operative BMI as normal (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), obese (30.0-34.9 kg/m(2)) and morbidly obese (> or =35.0 kg/m(2)). Of 5642 patients, 1362 (24.1 %) patients had a normal BMI, 2146 (38.0 %) were overweight, 1342 (23.8 %) were obese and 792 (14.0 %) were morbidly obese. RESULTS Adjusted LOS was similar among normal (4.99 d), overweight (5.00 d), obese (5.02 d) and morbidly obese (5.17 d) patients (P = 0.20). Adjusted overall episode costs were no different (P = 0.23) between the groups of normal (

Body Mass Index and the Impact on Hospital Resource Use in Patients Undergoing Total Knee Arthroplasty

17,211), overweight (