Prolonged suppressive antibiotic therapy is successful in the management of prosthetic joint infection.

INTRODUCTION: Prosthetic joint infection (PJI) remains one of the major challenges facing orthopaedic surgeons. There is a paucity of evidence on non-operative management of PJI. We present the results of prolonged antibiotic suppression therapy (PSAT) in PJI from a single centre. METHODS: A retrospective study was performed. Twenty-six patients were included. Two patients were excluded due to the lack of follow-up data. Failure was defined as admission for sepsis from the joint or amputation. RESULTS: Average age was 72 years (range 35-93). Mean Charlson co-morbidity index was 4.3. Mean follow-up was 3.2 years (range 1.3-5.7). Staphylococcal species were isolated in 11 cases (44%) (MRSA 1, MSSA 5, Staph. epidermidis 4 and Staph Pasteuri 1). Other bacteria included E. Coli (2), Streptococci spp. (3), Propionebacterium acnes (1) and Pseudomonas aeruginosa (1). Four cases were polymicrobial infection (16%), and no organisms were identified in two cases (8%). Candida albicans was identified in one case. All cases of bacterial infection were treated with prolonged oral doxycycline or amoxicillin. Twenty patients (80%) received 6 weeks of intravenous antibiotics prior to commencing prolonged oral antibiotics. Two patients experienced persistent symptoms and required amputation (both TKA). Two patients experienced sepsis but were treated successfully with IV antibiotics alone. The success rate of PSAT was 84% (21/25) successful at an average 3.2-year follow-up. DISCUSSION AND CONCLUSION: Prolonged suppressive antibiotic therapy is a viable option for the management of PJI with a low incidence of complications.

Kinematic TKA using navigation: Surgical technique and initial results.

BACKGROUND: Kinematic alignment for total knee arthroplasty (TKA) may be one way of improving outcomes. Previous studies have either used patient-specific instrumentation, which adds cost, or standard instrumentation, which provides no intraoperative feedback on resection alignment. HYPOTHESIS: To determine if computer navigation could reproduce native patient anatomy and simplify ligament balance during TKA whilst giving satisfactory improvements in functional scores at early follow-up. MATERIALS AND METHODS: Computer navigation was used for kinematic distal femoral and proximal tibial cuts in 100 consecutive and unselected TKAs. Resections were modified only if measured angles fell outside a pre-defined safe range of combined coronal orientation within±3 degrees of neutral and/or independent femoral or tibial cuts within±5 degrees. Pre- and postoperative measurements of the hip-knee-ankle (HKA) angle, the lateral distal femoral angle (LDFA) and the medial proximal tibial angle (MPTA) were taken using long-leg standing radiographs. Clinical evaluation was with the WOMAC and KOOS scales. RESULTS: Mean follow-up was 2.4 years (range 1.0-3.7, SD 0.8). The mean pre-op LDFA was 2.1 degrees valgus (9.2 valgus to 3.7 varus, SD 2.5) and 1.8 degrees valgus post-op (5.7 valgus to 4.2 varus, SD 2.0) (P=0.41). The mean pre-op MPTA was 3.0 degrees varus (10.6 valgus to 10.2 varus, SD 3.2) and 2.4 degrees varus post-op (4.0 valgus to 6.8 varus, SD 2.2) (P=0.03). The mean WOMAC score improved from 49.4 (29-85, SD 12.8) to 24.7 (0-73, SD 16.5) (P<0.001) and the mean KOOS score from 37.1 (7.2-77.2, SD 13.0) to 65.1 (26.8-100, SD 16) (P<0.001). Five knees (5%) required additional ligament release, four with valgus OA and one with varus OA. Two knees (2%) required lateral retinacular release for patellar tracking. DISCUSSION: Computer navigation for kinematic TKA provides the operating surgeon with full control and feedback at each step, whilst also allowing partial correction of more extreme anatomy that might be unsuitable for recreation during TKA. This technique helps to preserve ligament isometry and produces satisfactory improvements in functional scores. LEVEL OF EVIDENCE: IV (retrospective case series review).

The ongoing relevance of acetabular fracture classification.

The most widely used classification system for acetabular fractures was developed by Judet, Judet and Letournel over 50 years ago primarily to aid surgical planning. As population demographics and injury mechanisms have altered over time, the fracture patterns also appear to be changing. We conducted a retrospective review of the imaging of 100 patients with a mean age of 54.9 years (19 to 94) and a male to female ratio of 69:31 seen between 2010 and 2013 with acetabular fractures in order to determine whether the current spectrum of injury patterns can be reliably classified using the original system. Three consultant pelvic and acetabular surgeons and one senior fellow analysed anonymous imaging. Inter-observer agreement for the classification of fractures that fitted into defined categories was substantial, (κ = 0.65, 95% confidence interval (CI) 0.51 to 0.76) with improvement to near perfect on inclusion of CT imaging (κ = 0.80, 95% CI 0.69 to 0.91). However, a high proportion of injuries (46%) were felt to be unclassifiable by more than one surgeon; there was moderate agreement on which these were (κ = 0.42 95% CI 0.31 to 0.54). Further review of the unclassifiable fractures in this cohort of 100 patients showed that they tended to occur in an older population (mean age 59.1 years; 22 to 94 vs 47.2 years; 19 to 94; p = 0.003) and within this group, there was a recurring pattern of anterior column and quadrilateral plate involvement, with or without an incomplete posterior element injury.

A randomised trial of all-polyethylene and metal-backed tibial components in unicompartmental arthroplasty of the knee.

This randomised trial evaluated the outcome of a single design of unicompartmental arthroplasty of the knee (UKA) with either a cemented all-polyethylene or a metal-backed modular tibial component. A total of 63 knees in 45 patients (17 male, 28 female) were included, 27 in the all-polyethylene group and 36 in the metal-backed group. The mean age was 57.9 years (39.6 to 76.9). At a mean follow-up of 6.4 years (5 to 9.9), 11 all-polyethylene components (41%) were revised (at a mean of 5.8 years; 1.4 to 8.0) post-operatively and two metal-backed components were revised (at one and five years). One revision in both groups was for unexplained pain, one in the metal-backed group was for progression of osteoarthritis. The others in the all-polyethylene group were for aseptic loosening. The survivorship at seven years calculated by the Kaplan-Meier method for the all-polyethylene group was 56.5% (95% CI 31.9 to 75.2, number at risk 7) and for the metal-backed group was 93.8% (95% CI 77.3 to 98.4, number at risk 16) This difference was statistically significant (p < 0.001). At the most recent follow-up, significantly better mean Western Ontario and McMaster Universities Arthritis Index Scores were found in the all-polyethylene group (13.4 vs 23.0, p = 0.03) but there was no difference in the mean Knee injury and Osteoarthritis Outcome scores (68.8; 41.4 to 99.0 vs 62.6; 24.0 to 100.0), p = 0.36). There were no significant differences for range of movement (p = 0.36) or satisfaction (p = 0.23). This randomised study demonstrates that all-polyethylene components in this design of fixed bearing UKA had unsatisfactory results with significantly higher rates of failure before ten years compared with the metal-back components.

Biological microdosimetry based on radiation cytotoxicity data.

Researchers in the field of radiation microdosimetry have attempted to explain the relative biological effectiveness (RBE) of different ionising photon radiation sources on the basis of the singly stochastic, microdose metric lineal energy y, which only addresses physical stochasticity related to energy (ε) deposition via single events in the critical targets (cell nuclei assumed here). Biological stochasticity related to variable nuclei geometries and cell orientations (relative to the incoming radiation) is usually not addressed. Here a doubly stochastic microdose metric, the single-event hit size q (=ε/T), is introduced which allows the track length T to be stochastic. The new metric is used in a plausible model of metabolic-activity-based in vitro cytotoxicity of low-dose ionising photon radiation. The cytotoxicity model has parameters E{q} (average single-event hit size with q assumed to be exponentially distributed) and E{α}, which is the average value of the cellular response parameter α. E{α} is referred to as the biological signature and it is independent of q. Only E{q} is needed for determination of RBE. The model is used to obtain biological-microdosimetry-based q spectra for 320-kV X-rays and (137)Cs gamma rays and the related RBE for cytotoxicity. The spectra are similar to published lineal energy y spectra for 200-kV X-rays and (60)Co gamma rays for 1-µm biological targets.

Medium-term outcomes of pyrocarbon arthroplasty of the proximal interphalangeal joint.

We evaluated the outcome of pyrocarbon arthroplasty for proximal interphalangeal joint osteoarthritis in 18 arthroplasties carried out by a single surgeon using the Ascension prosthesis (Ascension Orthopedics Inc., Austin, Texas) in 15 patients after a mean of 6.2 years. Significant and maintained improvements in pain scores at rest and on active movements were achieved for surviving implants, and the range of motion was comparable with preoperative measurements. The radiographs, which were evaluated for evidence of ongoing migration and potential failure, were of concern in 10 out of 18 joints. Two patients required implant removal.

Aerobiology and inhalation exposure to biological select agents and toxins.

Aerosol is the most likely route of dissemination of biological select agents and toxins in a bioterrorist attack, regardless of the natural route of exposure to the agent. The use of animal models for testing preventative and therapeutic countermeasures requires knowledge of the pathogenesis of disease after inhalation exposure. Factors that relate to outcome after respiratory exposure include the inherent infectivity and virulence and/or toxicity of the agent in the host under investigation, in addition to characteristics of the aerosol particle and host that affect the delivered dose of, and host response to, the inhaled material. This introductory article discusses the emerging science of aerobiology and the unique features of respiratory tract anatomy, physiology, and immunology that are relevant to the pathogenesis of aerosolized biothreat agents.

Expression and function of CCAAT/enhancer binding proteinbeta (C/EBPbeta) LAP and LIP isoforms in mouse mammary gland, tumors and cultured mammary epithelial cells.

CCAAT/Enhancer binding proteins (C/EBPs) play important roles in the regulation of cell growth and differentiation. This study investigated the expression and function of C/EBPbeta isoforms in the mouse mammary gland, mammary tumors, and a nontransformed mouse mammary epithelial cell line (HC11). C/EBPbeta mRNA levels are 2-5-fold higher in mouse mammary tumors derived from MMTV/c-neu transgenic mice compared with lactating and involuting mouse mammary gland. The "full-length" 38 kd C/EBPbeta LAP ("Liver-enriched Activator Protein") isoform is the predominant C/EBPbeta protein isoform in mammary tumor whole cell lysates, however, the truncated 20 kd C/EBPbeta LIP ("Liver-enriched Inhibitory Protein") isoform is also present at detectable levels (mean LAP:LIP ratio 5.3:1). The mammary tumor C/EBPbeta LAP:LIP ratio decreases 70% (from 5.3:1 to 1.6:1) when lysate preparation is switched from a rapid whole cell lysis protocol to a multistep nuclear/cytoplasmic fractionation protocol. In contrast to mammary tumors, only the C/EBPbeta LAP isoform is detectable in the mammary gland whole cell and nuclear lysates; the truncated "LIP" isoform is undetectable regardless of isolation protocol. Ectopic over expression of C/EBPbeta LIP or C/EBPbeta LAP did not alter HC11 growth rates. However, C/EBPbeta LIP over expressing HC11 cells (LAP:LIP ratio of approximately 1:1) exhibited a consistent 2-4 h delay in G(0)/S phase transition. C/EBPbeta LIP overexpressing HC11 cells did not express beta-casein mRNA (mammary epithelial cell differentiation marker) in response to lactogenic hormones. This defect in beta-casein expression was not corrected by carrying out the differentiation protocol in the presence of an artificial extracellular matrix. These results demonstrate that the "full-length" C/EBPbeta LAP isoform is the predominant C/EBPbeta protein isoform expressed in mouse mammary gland in vivo and mouse mammary epithelial cell cultures in vitro. C/EBPbeta LIP detected in mammary tumor lysates may result from in vivo production or ex vivo isolation-induced proteolysis of C/EBPbeta LAP. Ectopic overexpression of C/EBPbeta LIP (LAP:LIP ratio of approximately 1:1) inhibits mammary epithelial cell differentiation (beta-casein expression).

Patients' perceptions and responses to procedural pain: results from Thunder Project II.

BACKGROUND: Little is known about the painfulness of procedures commonly performed in acute and critical care settings. OBJECTIVE: To describe pain associated with turning, wound drain removal, tracheal suctioning, femoral catheter removal, placement of a central venous catheter, and nonburn wound dressing change and frequency of use of analgesics during procedures. METHODS: A comparative, descriptive design was used. Numeric rating scales were used to measure pain intensity and procedural distress; word lists, to measure pain quality. RESULTS: Data were obtained from 6201 patients: 176 younger than 18 years and 5957 adults. Mean pain intensity scores for turning and tracheal suctioning were 2.80 and 3.00, respectively (scale, 0-5), for 4- to 7-year-olds and 52.0 and 28.1 (scale, 0-100) for 8- to 12-year-olds. For adolescents, mean pain intensity scores for wound dressing change, turning, tracheal suctioning, and wound drain removal were 5 to 7 (scale, 0-10); mean procedural distress scores were 4.83 to 6.00 (scale, 0-10). In adults, mean pain intensity scores for all procedures were 2.65 to 4.93 (scale, 0-10); mean procedural distress scores were 1.89 to 3.47 (scale, 0-10). The most painful and distressing procedures were turning for adults and wound care for adolescents. Procedural pain was often described as sharp, stinging, stabbing, shooting, and awful. Less than 20% of patients received opiates before procedures. CONCLUSIONS: Procedural pain varies considerably and is procedure specific. Because procedures are performed so often, more individualized attention to preparation for and control of procedural pain is warranted.

Pain experiences of traumatically injured patients in a critical care setting.

BACKGROUND: Little is known about the acute pain experiences of traumatically injured critically ill patients. OBJECTIVES: To describe pain experiences of traumatically injured adults during the first 72 hours of hospitalization. METHODS: Thirty multiply injured adults at a level I trauma center participated in the study. Pain was measured by using the McGill Pain Questionnaire and a visual analog scale. Subjects completed pain measures while at rest in a supine recumbent position and after a turn onto the side. RESULTS: The typical subject was 37 years old, had 4 major blunt trauma injuries, and had received the equivalent of 55.9 mg of morphine during the 24 hours before data collection. Mean at-rest scores were 26.5 on the pain-rating index, 2 on the present pain intensity index, and 34.6 on the visual analog scale. Immediately after the turn, mean scores on the visual analog scale increased from 25 to 48.1 (P = .002). Other pain scores after the turn did not differ significantly from at-rest values. Subjects who turned had lower scores on the visual analog scale at rest (P = .02) and less anxiety (P = .02) than did those who refused to turn. Ninety-six percent reported pain in the injured areas, and 36% reported pain related to biomedical devices. No relationship was found among reported pain and demographic, treatment, or clinical variables. CONCLUSIONS: Additional research is needed on pain at rest and during commonly performed procedures and on improved methods for pain relief in traumatically injured critically ill patients.

Translating research into practice. Implications of the Thunder Project II.

The Thunder Project II study described procedural pain in a variety of acute and critical care settings. The procedures studied were turning, tracheal suctioning, wound drain removal, nonburn wound dressing change, femoral sheath removal, and central venous catheter insertion. Turning had the highest mean pain intensity, whereas femoral sheath removal and central venous catheter insertion had the least pain intensity in adults. Nonwound dressing change had the highest pain intensity for teenagers. Pain occurred in procedures that are often repeated several times a day as well as in those that may be single events. There is a wide range of pain responses to any of these procedures; as a result, standardized and thoughtful pain, and distress assessments are warranted. Planning of care, including the use of preemptive analgesic interventions, needs to be individualized. Future studies are needed to describe patient responses to other commonly performed nursing procedures and to identify effective interventions for reducing procedural pain and distress.

Signal transducer and activator of transcription 3 activates CCAAT enhancer-binding protein delta gene transcription in G0 growth-arrested mouse mammary epithelial cells and in involuting mouse mammary gland.

The CCAAT enhancer-binding protein (C/EBP) family of transcription factors is implicated in the regulation of cell proliferation and differentiation in a variety of tissues. C/EBPdelta is involved in regulating G(0) growth arrest and apoptosis of mouse mammary epithelial cells. This study shows that activation of signal transducer and activator of transcription 3 (Stat3), but not activation of Stat1 or Stat5, occurs concurrently with G(0) growth arrest of HC11 mouse mammary epithelial cells, but not NIH 3T3 fibroblasts. Promoter analysis demonstrates that the C/EBPdelta promoter fragment involved in transcriptional activation during G(0) growth arrest contains a Stat3 binding site and that mutation of this site eliminates the G(0) growth arrest inducibility of the C/EBPdelta promoter. Overexpression of Stat3 increases C/EBPdelta promoter activity during G(0) growth arrest of HC11 cells, whereas dominant negative Stat3 decreases C/EBPdelta promoter activity under the same conditions. Neither Stat3 overexpression nor dominant negative Stat3 expression influences C/EBPdelta promoter activity in growing HC11 cells or G(0) growth-arrested NIH3T3 cells, demonstrating that the effect is specific to G(0) growth arrest of mammary epithelial cells. Band shift assays and antibody interference assays demonstrate specific binding of Stat3 to the acute phase response element in the C/EBPdelta promoter in G(0) growth-arrested HC11 cell extracts and 24 h involuting mouse mammary gland extracts. These data indicate that Stat3 activates C/EBPdelta transcription in G(0) growth-arrested mouse mammary epithelial cells and binds to the C/EBPdelta promoter during involution. An autocrine mechanism of Stat3 activation is proposed.

Transcriptional regulation of C/EBPdelta in G(0) growth-arrested mouse mammary epithelial cells.

Little is known about the control of cell cycle exit/G(0) entry, or the regulation of genes that are expressed during G(0). In this report we used primer extension analysis to demonstrate the high level of C/EBPdelta mRNA expression in G(0) growth-arrested HC11 mouse mammary epithelial cells and to identify the C/EBPdelta transcription start site. The C/EBPdelta gene transcription rate and promoter activity are both highly induced in G(0) growth-arrested HC11 cells. The C/EBPdelta gene promoter also exhibits G(0)-specific autoregulation. In contrast, the C/EBPdelta promoter activity decreases in G(0) growth-arrested NIH 3T3 cells. These data indicate that C/EBPdelta is among a relatively small number of genes actively transcribed during G(0) growth arrest. C/EBPdelta may regulate the expression of genes implicated in the initiation or maintenance of mammary epithelial cell G(0) growth arrest.

Thoracic and abdominal blastomycosis in a horse.

A 5-year-old Quarter Horse mare was examined because of lethargy, fever, and weight loss of 1 month's duration. Thoracic auscultation revealed decreased lung sounds cranioventrally. Thoracic ultrasonography revealed bilateral anechoic areas with hyperechoic strands, consistent with pleural effusion and fibrin tags. A large amount of free fluid was evident during abdominal ultrasonography. Abnormalities included anemia, hyperproteinemia, hyperglobulinemia, hyperfibrinogenemia, and hypoalbuminemia. Thoracic radiography revealed alveolar infiltrates in the cranial and caudoventral lung fields. A cavitary mass, consistent with an abscess, could be seen caudodorsal to the crura of the diaphragm. Ultrasonographic evaluation of this area revealed a hypoechoic mass with septations. Bilateral thoracocentesis was performed. Bacterial culture of the pleural fluid did not yield growth, but Blastomyces dermatitidis was isolated from pleural fluid, abdominal fluid, and an aspirate of the abscess. The mare was euthanatized, and a diagnosis of thoracic and abdominal blastomycosis was confirmed at necropsy.

CCAAT/enhancer-binding protein delta regulates mammary epithelial cell G0 growth arrest and apoptosis.

CCAAT/enhancer-binding proteins (C/EBPs) are a highly conserved family of DNA-binding proteins that regulate cell-specific growth, differentiation, and apoptosis. Here, we show that induction of C/EBPdelta gene expression during G0 growth arrest is a general property of mammary-derived cell lines. C/EBPdelta is not induced during G0 growth arrest in 3T3 or IEC18 cells. C/EBPdelta induction is G0-specific in mouse mammary epithelial cells; C/EBPdelta gene expression is not induced by growth arrest in the G1, S, or G2 phase of the cell cycle. C/EBPdelta antisense-expressing cells (AS1 cells) maintain elevated cyclin D1 and phosphorylated retinoblastoma protein levels and exhibit delayed G0 growth arrest and apoptosis in response to serum and growth factor withdrawal. Conversely, C/EBPdelta-overexpressing cells exhibited a rapid decline in cyclin D1 and phosphorylated retinoblastoma protein levels, a rapid increase in the cyclin-dependent kinase inhibitor p27, and accelerated G0 growth arrest and apoptosis in response to serum and growth factor withdrawal. When C/EBPdelta levels were rescued in AS1 cells by transfection with a C/EBPdelta "sense" construct, normal G0 growth arrest and apoptosis were restored. These results demonstrate that C/EBPdelta plays a key role in the regulation of G0 growth arrest and apoptosis in mammary epithelial cells.