Zyxin is important for the stability and function of podocytes, especially during mechanical stretch.

Podocyte detachment due to mechanical stress is a common issue in hypertension-induced kidney disease. This study highlights the role of zyxin for podocyte stability and function. We have found that zyxin is significantly up-regulated in podocytes after mechanical stretch and relocalizes from focal adhesions to actin filaments. In zyxin knockout podocytes, we found that the loss of zyxin reduced the expression of vinculin and VASP as well as the expression of matrix proteins, such as fibronectin. This suggests that zyxin is a central player in the translation of mechanical forces in podocytes. In vivo, zyxin is highly up-regulated in patients suffering from diabetic nephropathy and in hypertensive DOCA-salt treated mice. Furthermore, zyxin loss in mice resulted in proteinuria and effacement of podocyte foot processes that was measured by super resolution microscopy. This highlights the essential role of zyxin for podocyte maintenance in vitro and in vivo, especially under mechanical stretch.

Zebrafish as a model for podocyte research.

Podocytes, specialized postmitotic cells, are central players in various kidney-related diseases. Zebrafish have become a valuable model system for studying podocyte biology because they are genetically easy to manipulate, transparent, and their glomerular structure is similar to that of mammals. This review provides an overview of the knowledge of podocyte biology in zebrafish larvae, with particular focus on their essential contribution to understanding the mechanisms that underlie kidney diseases as well as supporting drug development. In addition, special attention is given to advances in live-imaging techniques allowing the observation of dynamic processes, including podocyte motility, podocyte process behavior, and glomerulus maturation. The review further addresses the functional aspects of podocytes in zebrafish larvae. This includes topics such as glomerular filtration, ultrastructural analyses, and evaluation of podocyte response to nephrotoxic insults. Studies presented in this context have provided important insights into the maintenance and resistance of the glomerular filtration barrier in zebrafish larvae and explored the potential transferability of these findings to mammals such as mice, rats, and most importantly, humans. The recent ability to identify potential therapeutic targets represents a promising new way to identify drugs that could effectively treat podocyte-associated glomerulopathies in humans. In summary, this review gives an overview about the importance of zebrafish as a model for podocyte-related disease and targeted drug development. It also highlights the key role of advanced imaging techniques in transparent zebrafish larvae, improving our understanding of glomerular diseases and the significant potential for translation of these findings to humans.

Evaluation of the efficacy of cystinosin supplementation through CTNS mRNA delivery in experimental models for cystinosis.

Messenger RNA (mRNA) therapies are emerging in different disease areas, but have not yet reached the kidney field. Our aim was to study the feasibility to treat the genetic defect in cystinosis using synthetic mRNA in cell models and ctns-/- zebrafish embryos. Cystinosis is a prototype lysosomal storage disorder caused by mutations in the CTNS gene, encoding the lysosomal cystine-H+ symporter cystinosin, and leading to cystine accumulation in all cells of the body. The kidneys are the first and the most severely affected organs, presenting glomerular and proximal tubular dysfunction, progressing to end-stage kidney failure. The current therapeutic standard cysteamine, reduces cystine levels, but has many side effects and does not restore kidney function. Here, we show that synthetic mRNA can restore lysosomal cystinosin expression following lipofection into CTNS-/- kidney cells and injection into ctns-/- zebrafish. A single CTNS mRNA administration decreases cellular cystine accumulation for up to 14 days in vitro. In the ctns-/- zebrafish, CTNS mRNA therapy improves proximal tubular reabsorption, reduces proteinuria, and restores brush border expression of the multi-ligand receptor megalin. Therefore, this proof-of-principle study takes the first steps in establishing an mRNA-based therapy to restore cystinosin expression, resulting in cystine reduction in vitro and in the ctns-/- larvae, and restoration of the zebrafish pronephros function.

A Novel High-Content Screening Assay Identified Belinostat as Protective in a FSGS-Like Zebrafish Model.

BACKGROUND: FSGS affects the complex three-dimensional morphology of podocytes, resulting in loss of filtration barrier function and the development of sclerotic lesions. Therapies to treat FSGS are limited, and podocyte-specific drugs are unavailable. To address the need for treatments to delay or stop FSGS progression, researchers are exploring the repurposing of drugs that have been approved by the US Food and Drug Administration (FDA) for other purposes. METHODS: To identify drugs with potential to treat FSGS, we used a specific zebrafish screening strain to combine a high-content screening (HCS) approach with an in vivo model. This zebrafish screening strain expresses nitroreductase and the red fluorescent protein mCherry exclusively in podocytes (providing an indicator for podocyte depletion), as well as a circulating 78 kDa vitamin D-binding enhanced green fluorescent protein fusion protein (as a readout for proteinuria). To produce FSGS-like lesions in the zebrafish, we added 80 µ M metronidazole into the fish water. We used a specific screening microscope in conjunction with advanced image analysis methods to screen a library of 138 drugs and compounds (including some FDA-approved drugs) for podocyte-protective effects. Promising candidates were validated to be suitable for translational studies. RESULTS: After establishing this novel in vivo HCS assay, we identified seven drugs or compounds that were protective in our FSGS-like model. Validation experiments confirmed that the FDA-approved drug belinostat was protective against larval FSGS. Similar pan-histone deacetylase inhibitors also showed potential to reproduce this effect. CONCLUSIONS: Using an FSGS-like zebrafish model, we developed a novel in vivo HCS assay that identified belinostat and related pan-histone deacetylase inhibitors as potential candidates for treating FSGS.

[How and why to monitor apprehension after anterior cruciate ligament surgery]. / Évaluation de l'appréhension avant la reprise de sport suite à la chirurgie du ligament croisé antérieur - Comment la monitorer et pourquoi ?

Numerous studies highlight the psychological aspect being the most frequent factors limiting the resumption of sport, following an anterior cruciate ligament reconstruction surgery, even before strength, the capacity of performing high impact pivoting movements, endurance, or joint stability. Scores that quantify apprehension, have been developed as clinical tool to monitor psychological readiness and in some cases to delay the moment for return to sport. Unfortunately, there are no established cut-off values for these scores to predict when and if return to sport at the same level as pre-traumatically can be resumed. The psychological aspect of return to sport remains individual, and influenced by age, type, and level of physical activity.

De nombreuses études mettent en avant l'aspect psychologique comme étant l'un des principaux facteurs limitant la reprise de sport après reconstruction du ligament croisé antérieur, même avant le manque de force, les sauts et mouvements en pivot à haute intensité, l'endurance ou la stabilité mécanique du genou. Des scores, permettant de quantifier le degré d'appréhension, ont été élaborés afin de suivre la confiance ressentie du patient lors de mouvements liés au sport et de retarder la reprise sportive si nécessaire. Malheureusement, pour l'instant, aucun consensus n'est établi dans la littérature autour d'une valeur seuil de ces différents scores pour la reprise de sport. L'interprétation de ces scores reste pour l'instant une évaluation individualisée, influencée par l'âge, le type et le niveau du sport pratiqué par le patient.

[Approach to the athlete with low back pain]. / Prise en charge de la lombalgie chez l'athlète.

Low back pain is a common symptom in athletes, hindering their activity. The etiology is tightly linked to the type of sport, often a consequence of repetitive movements, high pressures and strain being applied to the spine and adjacent muscular and ligamentous structures and a high degree of activity. The diagnosis is the key and causes are usually not severe. However, some red flags may indicate a more serious origin. Treatment is mostly conservative and based on functional therapies with the goal of a rapid and secure return to sports. As such, sedentary lifestyle should be avoided.

La lombalgie est un symptôme courant chez les athlètes pouvant entraver leur pratique sportive. L'étiologie est intimement liée au type d'activité pratiquée, souvent secondaire aux mouvements répétitifs, aux forces appliquées sur les structures musculosquelettiques et au degré d'activité. Le diagnostic clinique reste essentiel pour la prise en charge et les causes sont le plus souvent peu sévères. Des drapeaux rouges peuvent néanmoins alerter la présence d'une atteinte grave nécessitant une prise en charge urgente. L'imagerie immédiate étant indiquée uniquement en leur présence. Le traitement est dans la majeure partie des cas conservateur et basé sur les thérapies fonctionnelles dans l'objectif d'un retour sécuritaire au sport de prédilection dès que possible. La sédentarité, quant à elle, est à proscrire.

Comparative analysis of ChAdOx1 nCoV-19 and Ad26.COV2.S SARS-CoV-2 vector vaccines.

Vector-based SARS-CoV-2 vaccines have been associated with vaccine- induced thrombosis with thrombocytopenia syndrome (VITT/TTS), but the causative factors are still unresolved. We comprehensively analyzed the ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Johnson and Johnson) vaccines. ChAdOx1 nCoV-19 contains significant amounts of host cell protein impurities, including functionally active proteasomes, and adenoviral proteins. A much smaller amount of impurities was found in Ad26.COV2.S. Platelet factor 4 formed complexes with ChAdOx1 nCoV-19 constituents, but not with purified virions from ChAdOx1 nCoV-19 or with Ad26.COV2.S. Vascular hyperpermeability was induced by ChAdOx nCoV-19 but not by Ad26.COV2.S. These differences in impurities together with EDTAinduced capillary leakage might contribute to the higher incidence rate of VITT associated with ChAdOx1 nCoV-19 compared to Ad26.COV2.S.

Adriamycin does not damage podocytes of zebrafish larvae.

Podocytes are highly specialized epithelial cells that are essential for an intact glomerular filtration barrier in the kidney. Several glomerular diseases like focal segmental glomerulosclerosis (FSGS) are initially due to podocyte injury and loss. Since causative treatments for FSGS are not available until today, drug screening is of great relevance. In order to test a high number of drugs, FSGS needs to be reliably induced in a suitable animal model. The zebrafish larva is an ideal model for kidney research due to the vast amount of offsprings, the rapid development of a simple kidney and a remarkable homology to the mammalian glomerulus. Zebrafish larvae possess a size-selective glomerular filtration barrier at 4 days post fertilization including podocytes with interdigitating foot processes that are connected by a slit membrane. Adriamycin is an anthracycline which is often used in mice and rats to induce a FSGS-like phenotype. In this study, we aimed to induce a similar phenotype to zebrafish larvae by adding adriamycin to the tank water in different concentrations. Surprisingly, zebrafish larvae did not develop glomerular injury and displayed an intact filtration barrier after treatment with adriamycin. This was shown by (immuno-) histology, our filtration assay, in vivo imaging by 2-photon microcopy, RT-(q)PCR as well as transmission electron microscopy. To summarize, adriamycin is unable to induce a podocyte-related damage in zebrafish larvae and therefore major effort must be made to establish FSGS in zebrafish larvae to identify effective drugs by screenings.

Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis.

Focal and segmental glomerulosclerosis (FSGS) is a histological pattern frequently found in patients with nephrotic syndrome that often progress to end-stage kidney disease. The initial step in development of this histologically defined entity is injury and ultimately depletion of podocytes, highly arborized interdigitating cells on the glomerular capillaries with important function for the glomerular filtration barrier. Since there are still no causal therapeutic options, animal models are needed to develop new treatment strategies. Here, we present an FSGS-like model in zebrafish larvae, an eligible vertebrate model for kidney research. In a transgenic zebrafish strain, podocytes were depleted, and the glomerular response was investigated by histological and morphometrical analysis combined with immunofluorescence staining and ultrastructural analysis by transmission electron microscopy. By intravenous injection of fluorescent high-molecular weight dextran, we confirmed leakage of the size selective filtration barrier. Additionally, we observed severe podocyte foot process effacement of remaining podocytes, activation of proximal tubule-like parietal epithelial cells identified by ultrastructural cytomorphology, and expression of proximal tubule markers. These activated cells deposited extracellular matrix on the glomerular tuft which are all hallmarks of FSGS. Our findings indicate that glomerular response to podocyte depletion in larval zebrafish resembles human FSGS in several important characteristics. Therefore, this model will help to investigate the disease development and the effects of potential drugs in a living organism.

[Diagnosis of athlete's elbow injuries]. / Diagnostic des lésions du coude de l'athlète.

The elbow joint is highly congruent and subject to less stress than other joints. This contributes to a rather low incidence of pathologies in the general population. However, in athletes who perform repeated movements with supraphysiological forces, diverse pathologies may appear. The objective of this article is to develop an anatomopathological approach to elbow pain in order to identify its origin. A rapid and precise diagnosis allows initiating an adequate treatment and minimizing time of sporting activity arrest.

L'articulation du coude est soumise à des contraintes mécaniques moindres que d'autres articulations et présente une importante congruence. Ces éléments contribuent à la faible incidence des pathologies qui l'affectent dans l'ensemble de la population. Toutefois, chez le sportif qui effectue des mouvements répétés et avec des forces supraphysiologiques, de multiples lésions peuvent survenir. L'objectif de cet article est de développer une démarche anatomopathologique pour le diagnostic des douleurs de coude. Un diagnostic rapide et précis permet la mise en place d'un traitement adéquat ainsi que de minimiser le temps d'arrêt de l'activité sportive.

Fibronectin is up-regulated in podocytes by mechanical stress.

Hypertension is one of the central causes of kidney damage. In the past it was shown that glomerular hypertension leads to morphologic changes of podocytes and effacement and is responsible for detachment of these postmitotic cells. Because we have shown that podocytes are mechanosensitive and respond to mechanical stress by reorganization of the actin cytoskeleton in vitro, we look for mechanotransducers in podocytes. In this study, we demonstrate that the extracellular matrix protein fibronectin (Fn1) might be a potential candidate. The present study shows that Fn1 is essential for the attachment of podocytes during mechanical stress. By real-time quantitative PCR as well as by liquid chromatography-mass spectrometry, we found a significant up-regulation of Fn1 caused by mechanical stretch (3 d, 0.5 Hz, and 5% extension). To study the role of Fn1 in cultured podocytes under mechanical stress, Fn1 was knocked down (Fn1 KD) by a specific small interfering RNA. Additionally, we established a Fn1 knockout (KO) podocyte cell line (Fn1 KO) by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). During mechanical stress, a significant loss of podocytes (>80%) was observed in Fn1 KD as well as Fn1 KO podocytes compared with control cells. Furthermore, Fn1 KO podocytes showed a significant down-regulation of the focal adhesion proteins talin, vinculin, and paxillin and a reduced cell spreading, indicating an important role of Fn1 in adhesion. Analyses of kidney sections from patients with diabetic nephropathy have shown a significant up-regulation of FN1 in contrast to control biopsies. In summary, we show that Fn1 plays an important role in the adaptation of podocytes to mechanical stress.-Kliewe, F., Kaling, S., Lötzsch, H., Artelt, N., Schindler, M., Rogge, H., Schröder, S., Scharf, C., Amann, K., Daniel, C., Lindenmeyer, M. T., Cohen, C. D., Endlich, K., Endlich, N. Fibronectin is up-regulated in podocytes by mechanical stress.

[Neck pain: which physical therapies are recommended ?] / Douleurs cervicales : quelles recommandations pour les thérapies physiques ?

Different physical therapies for cervicalgia are described, as well as their efficacy, adverse effects, degree of evidence and recommendations. Several guidelines recommend active exercise, patient education and various treatments described here. According to the strict criteria of evidence-based medicine, active exercise, dry needling and probably laser therapy are effective as well as acupuncture. The use of a collar-neck brace is not recommended as first intention and should be limited in duration. Despite their clinical benefit and the inclusion of many therapies in several high-level scientific guidelines, the level of evidence of the recommendations could be enhanced by new research.

Les cervicalgies sont fréquentes. Plusieurs guides de bonne pratique recommandent les exercices actifs, l'éducation des patients et des thérapies physiques dans leur prise en charge. Nous décrivons ici l'efficacité, les effets indésirables et le degré d'évidence de certaines d'entre elles. Selon les critères stricts de la médecine basée sur l'évidence, les exercices actifs, la ponction à l'aiguille à sec et probablement la thérapie au laser sont efficaces. L'acupuncture l'est également. L'utilisation d'un collier-minerve n'est pas recommandée en première intention et doit être limitée en durée. Malgré leur bénéfice clinique et l'inclusion de nombreuses thérapies dans les recommandations de bonne pratique de bon niveau scientifique, le degré d'évidence des recommandations justifierait de nouvelles recherches.

Running performance in a timed city run and body composition: A cross-sectional study in more than 3000 runners.

OBJECTIVE: The importance of body composition for running performance is unclear in the general population. The aim of this study was to evaluate whether body composition influences running speed and whether it is a better predictor of running speed than body mass index (BMI). METHODS: The study included 1353 women (38.2 ± 12.1 y of age) and 1771 men (39.6 ± 12.1 y of age) who underwent, for the first time, a measurement of body composition by bioelectrical impedance analysis between 1999 and 2016, before a timed run occurring annually in Geneva. The running distances and times were converted to average speed (km/h). Body composition was expressed as sex-specific quartiles, where quartile 1 (lowest values) was the reference quartile. The relationships between speed and BMI or body composition were analyzed by multivariate linear regressions. RESULTS: Multivariate regressions showed that the higher the fat mass index (FMI) quartile, the lower the running speed in women and men (all P < 0.001). In men, a fat-free mass index (FFMI) in quartile 4 (>20 kg/m2) was associated with a poor running performance (r = -0.50, P < 0.001), whereas in women, an FFMI in quartile 2 or 3 (15-16.4 kg/m2) was associated with a higher running speed (r = 0.23, P = 0.04; r = 0.28, P = 0.01, respectively). Body composition predicted speed better than BMI in women (R2 = 26.8% versus 14.4%) and men (R2 = 29.8% versus 25.4%). CONCLUSIONS: Running speed is negatively associated with BMI and FMI in both sexes. Body composition is a better predictor of running performance than BMI.

Unique approach to sensorimotor training with a new device combining air cushion with stochastic translations-A prospective randomized controlled clinical trial.

Sensorimotor training with a wide variety of available devices represents an important component in rehabilitation and prevention of different sports injuries and chronic diseases. The purpose of this study was to evaluate the effects of a sensorimotor training with a newly developed device, which consists of an instable platform moving on an air cushion, providing dynamic balance training by tilting and unanticipated stochastic translations on postural control. Seventy-two healthy young subjects were included in this prospective, randomized, controlled, and observer-blinded study. Balance was objectively assessed by posturography and Functional Reach Test (FRT). Additionally we evaluated the subjective rating of balance. After randomization the sensorimotor training group performed a training program on the new device over a 5-6 week study period. After this time improvement in objective and subjective measurements as a result of training became evident. A significant difference in challenging posturographic parameters (Sensory Organization Test 5: training group 5.32±5.25 vs. control group 1.78±5.05, p=0.006 and Head Shake Sensory Organization Test 5: training group 11.94±8.97 vs. control group 5.41±10.17, p=0.01) as well as a significant difference in the FRT (training group 3.34±3.35cm vs. control group 0.01±2.97cm, p=0.0001) was found. Subjective assessment revealed a significant improvement in the participants' rating of balance and alteration of balance. Subjects showed a high satisfaction with the new training device. Our findings suggest that the newly developed device could be a promising option for sensorimotor training to improve postural control.

Is there a significant seasonality in the occurrence of osteoarticular infections?

Clinical experience suggests fluctuation in the occurrence of osteoarticular infections. We performed a single-centre study during 2004-2012, dividing each year into the four seasons according to the Gregorian calendar. A total of 455 episodes of osteoarticular infections were retrieved. There were 91 prosthetic joint infections (45 of haematogenous origin) and 159 cases of septic arthritis. The median period between early symptoms and diagnosis of infection was 27 days. The overall number of infections per season, cumulated over the 8-year study period, was 119 in spring, 129 in summer, 95 in fall, and 112 in winter, which did not reflect any significant seasonal fluctuation. None of the different subgroups of infections, namely arthroplasties (p for trend = 0.755), haematogenous arthroplasty infections (p = 0.493), gram-negative episodes or arthritis (p = 0.290), showed any season-related fluctuation. We conclude that osteoarticular infections, including haematogenous prosthetic joint infections, do not show any significant seasonality.

Increased risk of joint failure in hip prostheses infected with Staphylococcus aureus treated with debridement, antibiotics and implant retention compared to Streptococcus.

PURPOSE: The debridement, antibiotic and implant retention (DAIR) procedure is an option for patients with prosthetic hip joint infections for whom arthroplasty removal is problematic. Unfortunately, some of the guidelines proposed for deciding on DAIR management of arthroplasty infections fail to take into consideration the role of the infecting pathogen. While Staphylococcus aureus and streptococci are major contributors to infected hip arthroplasties, their respective contributions to treatment success or failure rates with the DAIR procedure have not been thoroughly analysed from a microbiological perspective. METHODS: This retrospective study included all patients who were hospitalised in Geneva University Hospitals between 1996 and 2012 and were initially treated with DAIR for prosthetic hip joint monomicrobial infection due to S. aureus or Streptococcus spp. The outcome of DAIR treatment was evaluated after a minimal follow-up of two years. A literature search was also performed to retrieve data from additional DAIR-treated cases in other institutions. RESULTS: In our institution, 38 DAIR-treated patients with hip arthroplasty monomicrobial infections underwent at least one surgical debridement (median two, range one to five), exchange of mobile parts and concomitant targeted antibiotic therapy for several weeks or months. A literature search identified outcome data in other institutions from 52 additional DAIR-treated cases according to our study criteria. After merging our own data with those retrieved from other reports, we found a failure rate of 21 % instead of 24 % for S. aureus-infected, DAIR-treated patients, but no failure in 14 streptococcal-infected patients. In the pooled data, the failure rate linked with S. aureus infections was significantly higher than that with Streptococcus ssp. (19/90 vs 0/14 episodes; Fisher's exact test, P = 0.07). CONCLUSIONS: DAIR-treated patients with prosthetic hip joint infections due to S. aureus tended to have worse outcomes than those infected with Streptococcus spp. The specific influence of the infecting pathogen should be considered in future guidelines and recommendations.

[Inter-hospital CHUV-HUG medical consensus of back pain management. Its application in care pathways within CHUV of Lausanne]. / Consensus interdisciplinaire CHUV-HUG sur la prise en charge des douleurs du dos. Son application lausannoise dans la filière du dos.

Back pain is a considerable economical burden in industrialised countries. Its management varies widely across countries, including Switzerland. Thus, the University Hospital and University of Lausanne (CHUV) recently improved intern processes of back pain care. In an already existing collaborative context, the two university hospitals in French-speaking Switzerland (CHUV, University Hospital of Geneva), felt the need of a medical consensus, based on a common concept. This inter-hospital consensus produced three decisional algorithms that bear on recent concepts of back pain found in literature. Eventually, a fast track was created at CHUV, to which extern physicians will have an organised and rapid access. This fast track aims to reduce chronic back pain conditions and provides specialised education for general practitioners-in-training.

Epidemiology of adverse events and Clostridium difficile-associated diarrhea during long-term antibiotic therapy for osteoarticular infections.

OBJECTIVE: Osteoarticular infections require several weeks of antibiotic therapy, but little is known about the epidemiology of adverse events (AE) including symptomatic Clostridium difficile-associated diarrhea during treatment in these patients. METHODS: Cohort study (1996-2011) at a tertiary hospital non-endemic for clostridial ribotype O27. Patients with previous C. difficile episodes and metronidazole treatment were excluded. RESULTS: A total of 393 episodes were identified. Median age of patients was 69 years; 122 were immune-suppressed. All patients received antibiotic treatment for a median of 8 weeks, including 2 weeks intravenously (range, 0-9 weeks). Oral rifampin (600 mg/d) was used in combination in 167 (42%) episodes. A relatively small number of episodes (115/393; 29%) were complicated by AE (diarrhea, nausea, cholestasis, gastric intolerance to rifampin, rash, and mycosis), of which 41 (36%) led to treatment modification. AE occurred mainly after a median of 21 days. Fourteen patients (14/393; 3.6%) developed symptomatic C. difficile diarrhea. By multivariate Cox regression analysis, total duration of antibiotic therapy, and intravenous administration were significantly associated with AE (all p < 0.01). Regarding symptomatic C. difficile infection, rifampin (hazard ratio 0.21; 95% CI, 0.05-0.97) protected from diarrhea, but not gender or age. Hospital stay was significantly longer among patients with AE than patients without (median 78 vs. 42 d; p < 0.01). CONCLUSIONS: AE were frequent and were observed in 29% of patients treated for osteoarticular infections and prolonged the hospital stay. In contrast, diarrhea due to C. difficile was rare, while oral rifampin might act protectively against it.

No need for broad-spectrum empirical antibiotic coverage after surgical drainage of orthopaedic implant infections.

PURPOSE: Empirical broad-spectrum antibiotic treatment for orthopaedic implant infections after surgical lavage is common practice while awaiting microbiological results, but lacks evidence. METHODS: This was a single-centre cohort study from 1996 to 2010 with a follow-up of two years. RESULTS: We retrieved 342 implant infections and followed them up for a median of 3.5 years (61 recurred, 18%). Infected implants were arthroplasties (n = 186), different plates, nails or other osteosyntheses. The main pathogens were S. aureus (163, 49 methicillin-resistant) and coagulase-negative staphylococci (60, 45 methicillin-resistant). Median duration of empirical antibiotic coverage after surgical drainage was three days before switching to targeted therapy. Vancomycin was the most frequent initial empirical agent (147), followed by intravenous co-amoxiclav (44). Most empirical antibiotic regimens (269, 79%) proved sensitive to the causative pathogen, but were too broad in 111 episodes (32%). Cephalosporins and penicillins were used only in 44 and ten cases, respectively, although they would have covered 59% of causative pathogens identified later. Multivariate Cox regression analysis showed that neither susceptible antibiotic coverage (compared to non-susceptible; hazard ratio 0.7, 95% confidence interval 0.4-1.2) nor broad-spectrum use (hazard ratio 1.1, 0.8-1.5) changed remission rates. CONCLUSIONS: Provided that surgical drainage is performed, broad-spectrum antibiotic coverage does not enhance remission of orthopaedic implant infections during the first three days. If empirical agents are prescribed from the first day of infection, narrow-spectrum penicillins or cephalosporins can be considered to avoid unnecessary broad-spectrum antibiotic use.

Poor performance of microbiological sampling in the prediction of recurrent arthroplasty infection.

During a two-stage revision for prosthetic joint infections (PJI), joint aspirations, open tissue sampling and serum inflammatory markers are performed before re-implantation to exclude ongoing silent infection. We investigated the performance of these diagnostic procedures on the risk of recurrence of PJI among asymptomatic patients undergoing a two-stage revision. A total of 62 PJI were found in 58 patients. All patients had intra-operative surgical exploration during re-implantation, and 48 of them had intra-operative microbiological swabs. Additionally, 18 joint aspirations and one open biopsy were performed before second-stage reimplantation. Recurrence or persistence of PJI occurred in 12 cases with a mean delay of 218 days after re-implantation, but only four pre- or intraoperative invasive joint samples had grown a pathogen in cultures. In at least seven recurrent PJIs (58%), patients had a normal C-reactive protein (CRP, < 10 mg/l) level before re-implantation. The sensitivity, specificity, positive predictive and negative predictive values of pre-operative invasive joint aspiration and CRP for the prediction of PJI recurrence was 0.58, 0.88, 0.5, 0.84 and 0.17, 0.81, 0.13, 0.86, respectively. As a conclusion, pre-operative joint aspiration, intraoperative bacterial sampling, surgical exploration and serum inflammatory markers are poor predictors of PJI recurrence. The onset of reinfection usually occurs far later than reimplantation.