Metal ion release after hip resurfacing arthroplasty and knee arthroplasty: a retrospective study of one hundred ninety-five cases.

PURPOSE: Hip arthroplasty with metal-on-metal bearings like hip resurfacing results in the release of metallic ions. In parallel, like every metallic implant, knee arthroplasty implants undergo passive corrosion. We analyzed blood levels of cobalt and chromium ions in patients who have a hip resurfacing arthroplasty and compared them to patients who have undergone knee arthroplasty at a minimum follow-up of one year. The hypothesis was that there is no difference in the ion release between hip resurfacing and knee arthroplasty. METHODS: Sixty-three patients who underwent knee arthroplasty were compared to a cohort of 132 patients who underwent hip resurfacing. The blood levels of cobalt and chromium ions were determined preoperatively and at six and 12 months postoperatively and then compared between groups. We analyzed the relationship between ion release and the change in clinical outcome scores (Harris Hip score, Oxford Hip score, Merle D'Aubigné Postel score, Oxford Knee score, International Knee Society score), the BMI, sex, physical activity, implant size and inclination of the acetabular implant (hip resurfacing patients only). Mixed linear models were used to assess the changes in ion blood levels over time. RESULTS: The cobalt blood levels were higher in the first 6 months in the resurfacing group (0.87 ug/L vs 0.67 ug/L; p = 0.011), while it was higher in the knee arthroplasty group at 12 months (1.20 ug/L vs 1.41 ug/L; p = 0.0008). There were no significant differences in chromium levels during the follow-up period. CONCLUSION: The increase in metal ion release after knee arthroplasty is as high as after hip resurfacing at the one year follow-up. The monitoring of this parameter probably should not be recommended in case of good clinicals outcomes.

Neuroendocrine regulation of reproduction in Atlantic cod (Gadus morhua): Evidence of Eya3 as an integrator of photoperiodic cues and nutritional regulation to initiate sexual maturation.

Evidence from mammals and aves alludes to a possibly conserved seasonal photoperiod induced neuroendocrine cascade which stimulates subsequent sexual maturation however our understanding of this mechanism in teleosts is lacking. Unlike all teleosts studied to date, the Atlantic cod (Gadus morhua) is a short day breeder with the reduction in day-length from the summer solstice stimulating gametogenesis. Cod specific orthologues of eya3, tshß and dio2 were identified and their expression was monitored in the brain and pituitary of cod held under either stimulated or inhibited photoperiod conditions. While no differential expression was apparent in brain dio2 & tshß and pituitary tshß, there was significant temporal variation in expression of pituitary eya3 under the SNP treatment, with expression level elevating in association with active gametogenesis. Under the LL treatment, sexual maturation was inhibited and there was a corresponding suppression of eya3 expression. In a second study the impact of size/energetic status on the initiation of sexual maturation was investigated. In the feed restricted population maturation was significantly suppressed (5% sexually mature) compared to the ab libitum fed stock (95% sexually mature) with there being a concomitant significant suppression in pituitary eya3 expression. Overall, these results suggest that pituitary eya3 has the potential to act as an integrator of both environmental and energetic regulation of sexual maturation of cod. Being the first account of eya3 induction in a short day breeding teleost, the conserved association with stimulation of reproduction and not seasonal state indicates that the upstream drivers which initiate the pathway differ among vertebrates according to their breeding strategies, but the pathway itself and its role in the reproductive cascade appears to be conserved across the vertebrate clade.

A commercial autogenous injection vaccine protects ballan wrasse (Labrus bergylta, Ascanius) against Aeromonas salmonicida vapA type V.

Atypical Aeromonas salmonicida (aAs) and Vibrionaceae related species are bacteria routinely recovered from diseased ballan wrasse used as cleaner fish in the Atlantic salmon farming industry. Autogenous (i.e. farm specific inactivated) multivalent vaccines formulated from these microorganisms are widely used to protect farmed wrasse despite limited experimental proof that they are primary pathogens. In this study, the components of a commercial multivalent injection vaccine containing four strains of Aeromonas salmonicida and one strain of Vibrio splendidus previously isolated from ballan wrasse in Scotland, were tested for infectivity, pathogenicity and virulence via intra peritoneal injection at pre-deployment size (25-50 g) and the efficacy of the vaccine for protection against aAs assessed. Injection with 3.5 × 109, 8 × 109 1.8 × 109 and 5 × 109 cfu/fish of Vibrio splendidus, V. ichthyoenteri, Aliivibrio logeii and A. salmonicida, respectively, did not cause significant mortalities, lesions or clinical signs after a period of 14 days. IP injection with both aAs and Photobacterium indicum successfully reproduced the clinical signs and internal lesions observed during natural outbreaks of the disease. Differences in virulence (LD50 at day 8-post infection of 3.6 × 106 cfu/fish and 1.6 × 107 cfu/fish) were observed for two aAs vapA type V isolates. In addition, the LD50 for Photobacterium indicum was 2.2 × 107 cfu/fish. The autogenous vaccine was highly protective against the two aAs vapA type V isolates after 700-degree days of immunisation. The RPSFINAL values for the first isolate were 95 and 91% at 1 × 106 cfu/fish and 1 × 107 cfu/fish, respectively, and 79% at 1 × 107 cfu/fish for the second isolate tested. In addition, significantly higher anti aAs seral antibodies (IgM), were detected by ELISA in vaccinated fish in contrast with control (mock vaccinated) fish. These results suggest wrasse can be effectively immunised and protected against aAs infection by injection with oil adjuvanted vaccines prepared with inactivated homologous isolates.

Atypical Aeromonas salmonicida vapA type V and Vibrio spp. are predominant bacteria recovered from ballan wrasse Labrus bergylta in Scotland.

Healthy and/or moribund farmed and wild ballan wrasse Labrus bergylta (>0.5 to 900 g) were sampled from hatcheries (n = 2) and Atlantic salmon Salmo salar cage sites (n = 8) in Scotland between February 2016 and October 2018. Less than half of the sampled individuals (n = 43; 32.3%) had been vaccinated (autogenous polyvalent vaccine; dip and/or injection) against atypical furunculosis (type V and VI), while 20 (15.0%) fish were not vaccinated, and the rest (70 individuals, 52.7%) were of unknown vaccination status. Swab samples from skin lesions, gill, liver, spleen and kidney were inoculated onto a variety of bacteriological agar plates, and bacteriology identification and sequencing analysis was performed on significant bacterial colonies. Atypical Aeromonas salmonicida (aAs) vapA type V was the predominant bacterial species (70/215 bacterial isolates, 32.5% of bacterial samples; 43/117 positive individual fish, 36.8%) isolated in this survey followed by Vibrio species, which were the most geographically prevalent bacteria. Photobacterium indicum/profundum was also isolated from L. bergylta for the first time during this study. The collection of these bacterial isolates provides useful information for disease management. Identifying the aAs isolates involved in disease in ballan wrasse could provide vital information for improving/updating existing autogenous vaccines.

Hip survival after plain core decompression alone versus bone morphogenetic protein and/or bone marrow reinjection with core decompression for avascular osteonecrosis of the femoral head: a retrospective case control study in ninety two patients.

INTRODUCTION: Injecting bone marrow or bone morphogenetic protein 7 (BMP) during core decompression for avascular osteonecrosis (AVN) may improve survival. We hypothesized that adding a complementary technique (injection of BMP and/or non-concentrated bone marrow) to core decompression would reduce the number of patients requiring a subsequent total hip arthroplasty (THA). METHODS: We retrospectively reviewed 92 cases from 2003 to 2018 with a minimum of 2 years of follow-up and an average follow-up of 64 months (24-204). Twenty-four patients had a core decompression (CD) (26.1% (24/92)), 25 had a CD associated with reinjection of bone marrow and BMP (rhBMP7) (27.2% (25/92)), and 43 patients had a CD with bone marrow reinjection (46.7% (43/92)). RESULTS: Hip survival after CD was 66.3% (61/92) at two years and 59.8% (55/92) at 10 years. CD with bone marrow and BMP reinjection had a better hip survival at ten years (HR: 0.492 (CI95%: 0.254-0.952) p = 0.035). A volume of necrosis greater than 30% (HR = 12.97 (CI95 [3.88-43.3] (p < 0.001))) and a Kerboul angle greater than 60° (HR: 12.5 (CI95 [2.84-54.6] (p < 0.001))) were risk factors for a subsequent THA. CONCLUSIONS: CD is an interesting non-invasive technique to preserve the native hip after AVN of the femoral head. Reinjection of bone marrow and/or BMP improved CD hip survival.

Daptomycin versus Vancomycin as Post-Operative Empirical Antibiotic Treatment for Prosthetic Joint Infections: A Case-Control Study.

Purpose: To compare safety and efficacy of Vancomycin (Van) versus Daptomycin (Dap) as post-operative empirical antibiotic treatment (PEAT) in patients with periprosthetic joint infections (PJIs). Methods: Medical charts of patients treated empirically with Van or Dap in the post-operative period of total hip/knee prosthesis septic revision until the results of intra-operative culture were reviewed. Cefotaxime, cefepime or aztreonam were used in combination with Dap or Van. Results: Twenty Dap patients were matched with 20 other Van patients according to the age and type of prosthesis. The ASA score and the distribution of the pathogens was similar in the two groups especially regarding the number of methicillin-resistant staphylococci. The mean duration of the PEAT was 6.07 ± 0.85 days. A total of 17 episodes of adverse events (AE) in 10 patients (25%) were recorded during the PEAT which led to discontinue the treatment in 5 patients, all of them treated with Van (P=0.02). At the end of a mean post-treatment follow-up of 618 +/- 219 days, 36 patients remained in remission of infection; 2 patients failed in each group. Conclusions: Our observations suggest that PEAT with Van for septic revision of PJIs is associated with a higher discontinuation rate due to AE but with a similar outcome than it is with Dap.

Expression pattern of nanos, piwil, dnd, vasa and pum genes during ontogenic development in Nile tilapia Oreochromis niloticus.

Primordial germ cells (PGCs) are specified by maternally provided determinants in fish. PGCs migrate then into prospective gonadal sites during early development and give rise to germ cell lineage. PGC disrupted animals do not sexually mature which has a range of commercial as well as environmental benefits. To find potential target genes for sterilisation of Nile tilapia, relative mRNA abundance patterns and tissue distribution of four nanos, two piwil, dnd1, vasa and three pum genes were investigated during ontogenic development from unfertilised eggs to newly hatched larvae and in adult tissues, respectively. The ontogenic pattern of RNA abundance revealed that all the investigated gene transcripts are maternally deposited to varying degrees, except for nanos2 which is not expressed in eggs. The ontogenic patterns of relative RNA abundance could be grouped into three categories. The first one, including nanos3, piwil1, piwil2, dnd1 and vasa, showed abundant transcript levels during early developmental stages which are then degraded during the period of maternal to zygotic transition between blastula and gastrula stages with a reduction in expression of four to five orders of magnitude by hatching stage. Another, including pum2 and pum3, showed similar patterns to the first group, but the transcript levels are reduced by only two orders of magnitude. The third group, including nanos1a, nanos1b and pum1, was characterised by a zygotic increase. nanos2 had no detectable transcripts until hatching stage. The tissue screening of nanos1a, nanos1b, pum1, pum2 and pum3 showed that they are expressed in various tissues, implying their potential pleiotropic effects in these tissues apart from gonads. In contrast, nanos3, piwil1, piwil2, dnd1 and vasa appeared to be exclusively expressed in gonads (both ovary and testis), and nanos2 showed testis-specific expression. Based on these results nanos3, piwil1, piwil2, dnd1 and vasa were prioritised among the 11 selected genes as potential target genes for sterilisation in Nile tilapia as they have no significant zygotic expression during embryogenesis, they are expressed exclusively in gonads and maternally deposited. These features suggest a potential role of these genes in the specification and maintenance of PGCs during the ontogenic development of Nile tilapia.

Impact of dietary phosphorous in diploid and triploid Atlantic salmon (Salmo salar L.) with reference to early skeletal development in freshwater.

In order to assess the effect of dietary phosphorus (P) in reducing vertebral malformations and improving freshwater (FW) performance in triploid Atlantic salmon (Salmo salar), both triploid and diploid Atlantic salmon were fed three different dietary P inclusion levels (low: 4.9, medium: 7.7, and high: 9.7 g available P kg-1) from first feeding until smolt. Somatic and skeletal response was assessed at fry (~0.5 g), parr (~5 g) and smolt (~45 g) stages. Triploid parr initially grew faster on the high P diet, while groups fed low P resulted in a significantly higher weight at smolt. Image analysis of double stained Alcian blue and Alizarin red S fry revealed that low P fed triploid fish presented less well mineralised vertebrae, and significantly more malformed vertebrae in both parr and smolt stages following x-ray radiographic assessment. Triploid parr fed high and medium P had similar numbers of malformed vertebrae relative to their diploid counterparts but greater numbers than at smolt. Low P fed triploids had the highest prevalence of jaw and vertebral malformations as well as the highest number of deformed vertebrae in the central caudal vertebral region, which was more pronounced at parr than at smolt. Shorter vertebrae dorso-ventral lengths were observed throughout the spinal column (R1-R4) in parr fed low P and only in the caudal region (R3) at smolt. In parr, both ploidies showed reduced phosphate homeostasis protein fgf23 gene expression in vertebrae when fed low P diets, while triploids showed greater down-regulation of osteogenic factors (alp, opn and igf1r) between diets relative to diploids, suggesting possible greater active suppression of mineralisation and reduced osteogenic potential in triploids. No effects of diet or ploidy on gene expression were evident at smolt. Comparisons between development stages suggest early P supplementation in triploids is crucial for skeletal development. Ultimately, reducing vertebral deformities observed at smolt with higher P supplementation in triploids could contribute towards improving skeletal performance and welfare of the stocks in the marine phase.

Diagnostic accuracy of the alpha defensin lateral flow device (Synovasure) for periprosthetic infections in microbiologically complex situations: A study of 42 cases in a French referral centre.

BACKGROUND: Joint aspiration is currently the reference standard test for diagnosing periprosthetic joint infection (PJI) despite the high rate of false-negative results, of which a major cause is the fastidious nature of some microorganisms. A rapid diagnostic test that detects alpha defensin (Synovasure™, Zimmer, Warsaw, IN, USA) in joint fluid can provide the diagnosis of PJI within a few minutes across the full spectrum of causative organisms (including mycobacteria and yeasts). Its performance in detecting bacterial infections is unaltered by concomitant antibiotic therapy. Few studies of Synovasure™ have been conducted by groups that were involved in designing the test, which has not been validated in France. Assessments in referral centres where complex microbiological situations are common hold considerable interest. The objective of this prospective study was to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and causes of error of Synovasure™ used to diagnose periprosthetic infection in complex microbiological situations. HYPOTHESIS: The rapid diagnostic test Synovasure™ has greater than 90% NPV for detecting periprosthetic infections in complex microbiological infections. MATERIAL AND METHODS: Synovasure™ was used 42 times in 39 patients between October 2015 and October 2017 in challenging microbiological situations [discordant joint aspiration results (n=20), negative cultures with clinical or laboratory evidence of infection, (n=21), and concomitant antibiotic therapy (n=1)]. Of the 39 patients, 23 had total knee prostheses, 13 total hip prostheses, and 3 total femoral prostheses. The reference standard to which the Synovasure™ results were compared was the PJI criteria set developed by the Musculoskeletal Infection Society (MSIS). RESULTS: Synovasure™ was negative in 30 cases with negative joint fluid cultures (30/42, 71.4%). Of the 12 (28.6%) cases with positive Synovasure™ results, only 7 (7/12, 58.3%) had positive joint fluid cultures. According to the MSIS criteria 9 cases were infected, including 8 with positive and 1 with negative Synovasure™ results. Of the 33 cases that were not infected according to MSIS criteria, 29 had negative and 3 positive Synovasure™ results; the remaining case had a positive Synovasure™ result but was excluded when metallosis was found intra-operatively. NPV was 96.7%, PPV 72.7%, sensitivity 88.9%, and specificity 90.6%. DISCUSSION: The high NPV of Synovasure™ suggests a role for this test in microbiologically complex situations as a new tool for ruling in and, most importantly, ruling out infection in doubtful cases. LEVEL OF EVIDENCE: III, prospective study of diagnostic accuracy.

Opening-wedge high tibial osteotomy performed with locking plate fixation (TomoFix) and early weight-bearing but without filling the defect. A concise follow-up note of 48 cases at 10 years' follow-up.

INTRODUCTION: Use of a locking plate during medial opening high tibial osteotomy (HTO) eliminates the need to fill the defect and its associated complications. It also allows early weight-bearing. Since long-term data with this type of construct are rare, we wanted to report the outcomes of a 51-patient cohort evaluated after a mean follow-up of 10.2years. The goals were to determine (1) the HTO survival and whether the correction was maintained between 2 and 10years later, (2) the stability of the functional outcomes, (3) the complication rate related to use of locking plates. HYPOTHESIS: The correction following medial opening HTO with a Tomofix™ plate without void filling is maintained after 10years' follow-up. MATERIAL AND METHODS: Fifty-one patients ranging from 37 to 72years of age at the time of surgery between 2003 and 2005 underwent a medial opening HTO that was stabilized with a Tomofix™ locking plate (Synthes, Oberdorf, Switzerland) without void filling. Forty-eight patients were reviewed between March and September 2014; 1 patient had died and 2 were lost to follow-up. RESULTS: The mean HKA angle went from 172±3.18° (165-178°) preoperatively to 181±1.18° (176-185°) postoperatively, to 181±1.60° (176-185°) at 2years, and 180.8±2.4° (175-184°) at 10years' follow-up. This equates to a loss of correction of 0.71±1.9° (0-6°) (p=0.02) between 2 and 10years after the surgery. Five patients underwent total knee arthroplasty (TKA), thus the 10-year survival of the HTO procedure was 88% (95% CI: 81-98%). If the five TKA procedures are excluded, the mean IKS knee score went from 90±7.4 (66-98) at 2years' follow-up to 77±15.3 (43-97) at 10years (p>0.05). There were four complications in all (8%), of which three occurred within 2years (2 cases of nonunion and 1 surgical site infection) and one occurred later (infection after 118months that resolved once the hardware was removed and the patient given appropriate antibiotics). There were no complications related to the five subsequent TKA procedure and no bone grafting was required. DISCUSSION: There was a small (less than 1 degree) but statistically significant loss of correction and non-significant deterioration in the functional outcomes. Conversely, the complication rate did not increase over time, despite the lack of void filling, particularly in patients who subsequently underwent TKA. The 10-year survival was similar to other HTO procedures. This locking plate construct without void filling is reliable after 10years. LEVEL OF EVIDENCE: Level IV, prospective study without control group.

Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients.

PURPOSE: This study aimed at describing the use of oral cyclines (i.e., doxycycline and minocycline) as suppressive antibiotic therapy (SAT) in patients with periprosthetic joint infections (PJIs). METHODS: Medical charts of all patients with surgical revisions for PJIs who were given cycline-based SAT because of a high failure of various origins were reviewed. Data regarding tolerability and effectiveness of cycline-based SAT were analysed. RESULTS: Seventy-eight patients of mean age 64 ± 17 years received cycline-base SAT in the period from January 2006 to January 2014. PJIs involved the knee in 37 patients (47%), the hip in 35 (45%), the elbow in 4 (5%), and the shoulder in 2 (3%) and were qualified as early in 31 patients (39.7%). Staphylococcus spp. were the most common pathogens accounting for 72.1% of the total number of bacterial strains identified. All included patients had surgery which consisted in debridement and implant retention in 59 of them (75.6%). Doxycycline and minocycline were prescribed as SAT in 72 (92%) and 6 (8%) patients, respectively. Adverse events were reported in 14 patients (18%), leading to SAT discontinuation in 6 of them (8%). After a mean follow-up of 1020 ± 597 days, a total of 22 (28.2%) patients had failed including 3 cases (3.8%) with documented acquisition of tetracycline resistance in initial pathogen(s). CONCLUSIONS: Our results suggest that oral cyclines used as SAT in patients treated for PJI have an acceptable tolerability and effectiveness and appear to be a reasonable option in this setting.

Course of dislocated posterior hip arthroplasty: A continuous 232-patient series at a mean 10 years' follow up (range, 1-22 years).

BACKGROUND: Dislocation rates in posterior total hip arthroplasty (THA) range between 2% and 5%, but long-term course (recurrence of dislocation or revision surgery) is not known, most series having short follow-up or small populations. We therefore conducted a retrospective study on a large series, to determine long-term rates of recurrence and surgical revision and recurrence risk factors. HYPOTHESIS: Long-term follow-up of a large cohort of THA dislocations enables recurrence rate and factors to be determined. MATERIAL AND METHOD: Five hundred and nine cases of THA dislocation were admitted to our center between 1994 and 2008. A hundred and twenty seven incomplete files and 150 patients who had received their THA elsewhere were excluded, leaving 232 patients: 150 female, 82 male. Mean age at THA (163 primary, 69 revision) was 63 years (range, 15-90 years), and 65 years (range 20-90 years) at first dislocation, with a mean interval to dislocation of 25 months. Minimum follow-up was 8 years up to 2016, or 1 year taking account of deaths (111 deaths). There were 46 anterior, 185 posterior and 1 multidirectional dislocations. The following potential recurrence factors were assessed: gander, age, body-mass index (BMI), etiology, surgical history, bearing diameter and type, component fixation means, dislocation direction, and time to dislocation. RESULTS: A hundred and thirty three of the 232 patients (57%) showed at least 1 recurrence, at a mean 38 months (range, 0.5-252 months); 78 experienced a second and 32 a third recurrence. Ninety-nine (43%) had only 1 dislocation, without recurrence, but 17 of these (17%) underwent reoperation for other causes. The reoperation rate was 17/232 (7%) excluding recurrent instability, and 84/232 (36%) for instability. Fourty-eight months after the first dislocation, 84/133 cases of recurrence (63%) had been reoperated on: 16 complete replacements, 18 bearing replacements, 42 dual mobility cups, one large diameter cup, seven Lefèvre retentive cups. The rate of revision surgery for instability was high, at 84/232 (36%), and higher again in relation to recurrence (84/133: 63%). Only posterior dislocation emerged as a factor for recurrence (HR=1.774, 95% CI [1.020-3.083]), the other tested factors showing no correlation.14 of the 84 revision surgeries for instability (16.6%) were followed by recurrence, without identifiable risk factors. CONCLUSION/DISCUSSION: The recurrence rate was 57%, with posterior dislocation as the only risk factor. The rate of revision surgery for recurrence was 84/232 (36%), with 14/84 revision procedures (16.6%) followed by further recurrence. LEVEL OF EVIDENCE: IV, retrospective, without control group.

Early nutritional programming affects liver transcriptome in diploid and triploid Atlantic salmon, Salmo salar.

BACKGROUND: To ensure sustainability of aquaculture, plant-based ingredients are being used in feeds to replace marine-derived products. However, plants contain secondary metabolites which can affect food intake and nutrient utilisation of fish. The application of nutritional stimuli during early development can induce long-term changes in animal physiology. Recently, we successfully used this approach to improve the utilisation of plant-based diets in diploid and triploid Atlantic salmon. In the present study we explored the molecular mechanisms occurring in the liver of salmon when challenged with a plant-based diet in order to determine the metabolic processes affected, and the effect of ploidy. RESULTS: Microarray analysis revealed that nutritional history had a major impact on the expression of genes. Key pathways of intermediary metabolism were up-regulated, including oxidative phosphorylation, pyruvate metabolism, TCA cycle, glycolysis and fatty acid metabolism. Other differentially expressed pathways affected by diet included protein processing in endoplasmic reticulum, RNA transport, endocytosis and purine metabolism. The interaction between diet and ploidy also had an effect on the hepatic transcriptome of salmon. The biological pathways with the highest number of genes affected by this interaction were related to gene transcription and translation, and cell processes such as proliferation, differentiation, communication and membrane trafficking. CONCLUSIONS: The present study revealed that nutritional programming induced changes in a large number of metabolic processes in Atlantic salmon, which may be associated with the improved fish performance and nutrient utilisation demonstrated previously. In addition, differences between diploid and triploid salmon were found, supporting recent data that indicate nutritional requirements of triploid salmon may differ from those of their diploid counterparts.

Prospective assessment of patients' knowledge and informational needs and of surgeon-to-patient information transfer before and after knee or hip arthroplasty.

BACKGROUND: Patients are playing an increasingly large role in their own management and must therefore receive clear, complete, and comprehensible information. In the field of hip and knee arthroplasty, little is known about the level of patient knowledge and effectiveness of surgeon-to-patient information transfer. We therefore designed a prospective observational study with the objective of assessing four factors: patient knowledge during management, quality of information transfer, informational needs, and factors associated with the level of knowledge. HYPOTHESIS: The level of patient knowledge changes during the management process. PATIENTS AND METHODS: A prospective single-centre study was conducted between January 2014 and March 2015 during the outpatient visits and inpatient stays of 63 patients who underwent arthroplasty of the hip (n=36) or knee (n=27). A single observer attended all patient visits and recorded the information provided by the surgeon. Each patient completed a self-questionnaire after the outpatient visit (T1), at admission (T2), and at discharge after surgery (T3). Semi-quantitative scores were used to assess knowledge and informational needs. The effectiveness of information transfer was evaluated by comparing the information provided by the surgeon to the replies made by the patients. RESULTS: The mean overall knowledge score (on a 0-42 scale) increased from 17.22±6.33 at T1 to 19.44±6.89 at T3 (P=0.0028). In contrast, knowledge about complications was better at T1 than at T3 (2.67±1.98 vs. 2.19±1.91; P<0.05). Agreement between information given by the surgeon and replies made by patients varied across items from 23% to 100%. The mean informational needs score (on a scale from 0 to 21) ranged from 3.67 to 4.83 and was higher at T3 than at T2 (4.83±3.77 vs. 3.67±4.86; P=0.03). The proportion of patients who wanted written information was higher at T3. Most patients sought information before the outpatient visit. At each step of the management process, the main areas about which the patients wanted information were the surgical procedure, the rehabilitation programme, and the prosthesis. Several socio-demographic or management-related factors influenced the level of knowledge. Thus, older age and lower educational attainment were associated with lower knowledge scores, whereas previous lower-limb orthopaedic surgery and amount of information provided by the surgeon were associated with higher knowledge scores. Knowledge scores were not associated with being employed vs. retired, gender, replacement of a hip vs. a knee, the surgeon, or being accompanied by another person. DISCUSSION: Our study is original in that we assessed changes in patient knowledge during the management process for hip or knee arthroplasty. The level of patient knowledge was fairly low and varied considerably across individuals and time points in the management process. These data highlight the importance of providing patients with information throughout their management and particularly at discharge, when the desire for information seems greatest. LEVEL OF EVIDENCE: IV, prospective observational study with no control group.

Suppressive antibiotic therapy with oral doxycycline for Staphylococcus aureus prosthetic joint infection: a retrospective study of 39 patients.

The aim of this study was to describe the use of oral doxycycline as suppressive antibiotic therapy (SAT) in patients with Staphylococcus aureus periprosthetic (hip or knee) joint infections. The medical charts of all patients with surgical revisions for S. aureus hip or knee prosthetic joint infections (PJIs) who were given doxycycline-based SAT because of a high risk of failure of various origins were reviewed. Data regarding tolerability and effectiveness of doxycycline-based SAT were analysed. A total of 39 patients (mean age 66.1 ± 16.3 years) received doxycycline-base SAT in the period from January 2006 to January 2014. PJIs involved the hip in 23 patients (59.0%) and the knee in 16 (41.0%), and were qualified as early in 15 patients (38.5%). Methicillin-resistant S. aureus (MRSA) accounted for 22% of the total number of bacterial strains identified. All patients included in the study had surgery, which consisted of debridement and implant retention in 32 (82.1%). Adverse events likely attributable to SAT were reported in six patients (15.4%), leading to discontinuation of SAT in three (7.7%). A total of 29 patients (74.4%) remained event-free and 10 (25.6%) failed, including 8 (20.5%) relapses and 2 (5.1%) superinfections. Overall, 8 of the 10 failure cases were related to a doxycycline-susceptible pathogen. These results suggest that oral doxycycline used as SAT in patients treated for S. aureus hip or knee PJIs has an acceptable tolerability and effectiveness and appears to be a reasonable option in this setting.

Light- and clock-control of genes involved in detoxification.

Circadian regulation of hepatic detoxification seems to be amongst the key roles of the biological clock. The liver is the major site for biotransformation, and in mammals, it contains several clock-controlled transcription factors such as proline and acidic amino acid-rich basic leucine zipper proteins (PAR bZIP) and basic-helix-loop-helix Per-Arnt-Sim (bHLH-PAS) family that act as circadian regulators of detoxification genes. This investigation explored the existence of daily and circadian expression of transcription factors involved in detoxification, as well as the temporal profile of a set of their target genes in zebrafish liver. In our study, zebrafish were able to synchronize to a light-dark (LD) cycle and displayed a diurnal pattern of activity. In addition, the expression of clock genes presented daily and circadian rhythmicity in liver. Apart from hlfa, the expression of PAR bZIP transcription factors also displayed daily rhythms, which appeared to be both light-dependent and clock-controlled, as circadian rhythms free-ran under constant conditions (continuous darkness, DD). Under LD, tefb, dbpa and dbpb expression peaked at the end of the darkness period whereas tefa showed peak levels of expression at the onset of the photophase. In addition, these four genes exhibited circadian expression under DD, with higher expression levels at the end of the subjective night. The expression of the bHLH-PAS transcription factor arh2 also showed circadian rhythmicity in zebrafish liver, peaking in the middle of the subjective night and approximately 3-4 h before peak expression of the PAR bZIP genes. Regarding the detoxification genes, the major target gene of AhR, cyp1a, showed daily and circadian expression with an acrophase 2 h after ahr2. Under LD, abcb4 also showed daily rhythmicity, with an acrophase 1-2 h after that of PAR bZIP factors during the transition between darkness and light phases, when zebrafish become active. However, the expression of six detoxification genes showed circadian rhythmicity under DD, including cyp1a and abcb4 as well as gstr1, mgst3a, abcg2 and sult2_st2. In all cases, the acrophases of these genes were found during the second half of the subjective night, in phase with the PAR bZIP transcription factors. This suggested that their expression is clock-controlled, either directly by core clock genes or through transcription factors. This study presents new data demonstrating that the process of detoxification is under circadian control in fish. Results showed that time of day should be considered when designing toxicological studies or administering drugs to fish.

Can a target zone safer than Lewinnek's safe zone be defined to prevent instability of total hip arthroplasties? Case-control study of 56 dislocated THA and 93 matched controls.

BACKGROUND: Various factors contribute to instability of total hip arthroplasty (THA), with implant orientation being a major contributor. We performed a case-control study with computed tomography (CT) data to determine whether: 1) orientation contributes to THA instability and 2) a safer target zone for stability than Lewinnek's classic safe zone can be defined. MATERIAL AND METHODS: We included prospectively 363 cases of THA dislocation that occurred during the calendar 2013 year in 24 participating hospitals. Of the 128 dislocations that occurred in patients who underwent THA at these centers, 56 (24 anterior, 32 posterior) had CT scans, thus were included in the analysis. The control group was matched 4:1 based on implant type, year of implantation, age, sex, bearing types and THA indication. Of the 428 matched control THA cases, 93 had CT scans. In all, the CT scans from 149 cases (56 unstable, 93 stable) were analyzed to determine the acetabular cup's inclination and anteversion, and the femoral stem's anteversion. RESULTS: In the unstable THA group, cup inclination was 46.9°±7.4°, cup anteversion was 20.4°±10.8° and stem anteversion was 14.2°±9.9°. In the stable THA group, cup inclination was 44.9°±5.3° (P=0.057), cup anteversion was 22.1°±5.1° (P=0.009) and stem anteversion was 13.4°±4.4° (P=0.362). The optimal total anteversion (cup+stem) of 40-60° was achieved in 16.5% of unstable THA cases and 13.9% of stable THA cases, thus this parameter does not predict stability (odds ratio [OR] of 0.40, P=0.144). The cup was positioned in Lewinnek's safe zone in 44.6% of patients in the unstable group and 68.2% of those in the stable group (OR 3.74, P=0.003). A target zone defined as 40-50° inclination and 15-30° anteversion was better able to distinguish between unstable cases (23.2%) and stable cases (71.6%) resulting in an OR of 13.91 (P<0.001). DISCUSSION: Implant positioning was the only risk factor for instability found in this study. Moreover, our findings reinforce the theory put forward by other authors that Lewinnek's safe zone is not specific enough to differentiate between stable and unstable THA implantations. The target zone for acetabular cups proposed here (40-50° inclination and 15°-30° anteversion) is related to a lower risk of instability. This orientation can be used as a guide, but must be combined with other technical elements to optimize stability. By balancing stability and biomechanics, the 40-50° inclination and 15°-30° anteversion target zone redefines the optimal positioning window. LEVEL OF EVIDENCE: III case-control study.

What are the risk factors for dislocation in primary total hip arthroplasty? A multicenter case-control study of 128 unstable and 438 stable hips.

INTRODUCTION: Dislocation after total hip arthroplasty (THA) is a leading reason for surgical revision. The risk factors for dislocation are controversial, particularly those related to the patient and to the surgical procedure itself. The differences in opinion on the impact of these factors stem from the fact they are often evaluated using retrospective studies or in limited patient populations. This led us to carry out a prospective case-control study on a large population to determine: 1) the risk factors for dislocation after THA, 2) the features of these dislocations, and 3) the contribution of patient-related factors and surgery-related factors. HYPOTHESIS: Risk factors for dislocation related to the patient and procedure can be identified using a large case-control study. PATIENTS AND METHODS: A multicenter, prospective case-control study was performed between January 1 and December 31, 2013. Four patients with stable THAs were matched to each patient with a dislocated THA. This led to 566 primary THA cases being included: 128 unstable, 438 stable. The primary matching factors were sex, age, initial diagnosis, surgical approach, implantation date and type of implants (bearing size, standard or dual-mobility cup). RESULTS: The patients with unstable THAs were 67±12 [37-73]years old on average; there were 61 women (48%) and 67 men (52%). Hip osteoarthritis (OA) was the main reason for the THA procedure in 71% (91/128) of the unstable group. The dislocation was posterior in 84 cases and anterior in 44 cases. The dislocation occurred within 3 months of the primary surgery in 48 cases (38%), 3 to 12 months after in 23 cases (18%), 1 to 5years after in 20 cases (16%), 5 to 10years after in 17 cases (13%) and more than 10years later in 20 cases. The dislocation recurred within 6 months of the initial dislocation in 23 of the 128 cases (18%). The risk factors for instability were a high ASA score with an odds ratio (OR) of 1.93 (95% CI: 1.4-2.6), neurological disability (cognitive, motor or psychiatric disorders) with an OR of 3.9 (95% CI: 2.15-7.1), history of spinal disease (lumbar stenosis, spinal fusion, discectomy, scoliosis and injury sequelae) with an OR of 1.89 (95% CI: 1.0-3.6), unrepaired joint capsule (all approaches) with an OR of 4.1 (95% CI: 2.3-7.37), unrepaired joint capsule (posterior approach) with an OR of 6.0 (95% CI: 2.2-15.9), and cup inclination outside Lewinnek's safe zone (30°-50°) with OR of 2.4 (95% CI: 1.4-4.0). DISCUSSION: This large comparative study isolated important patient-related factors for dislocation that surgeons must be aware of. We also found evidence that implanting the cup in 30° to 50° inclination has a major impact on preventing dislocation. LEVEL OF EVIDENCE: Level III; case-control study.