Objectives: To investigate the microbiological trends of community-acquired diabetic foot osteomyelitis (DFO) over the past two decades in specialized academic centres in Switzerland, Spain, and Turkey. Methods: A retrospective analysis of DFO cohorts (2000-2019) from five centres (Geneva, Zurich, Las Palmas, Barcelona, Istanbul) stratified into four periods (P1-P4) to assess microbiological changes. Results: Among 1379 DFO episodes (76% male, median age 67 years; 90% type 2 diabetes, median duration 17 years), gram-positive bacteria were identified in 82%, including Staphylococcus aureus (47%). Methicillin-resistant S. aureus (MRSA) was more prevalent in Barcelona (36%), Las Palmas (24%), and Geneva (29%) than in Zurich (7%). Over time, gram-positive bacteria remained stable or decreased, particularly in Las Palmas (83% to 65%, P = 0.03). The proportion of MRSA decreased in Geneva (39% to 16%) and Las Palmas (37% to 9%), but remained stable in Barcelona. Enterobacteriaceae prevalence increased, notably in Geneva (16% to 39%, P < 0.01) and Las Palmas (27% to 41%, P < 0.01). Among gram-negative pathogens quinolone resistance was 12.5%. Enterobacteriaceae-DFO was associated with ischemic necrosis (OR 1.65), Las Palmas cohort (OR 3.14), and 2016-2019 period (OR 2.68). Conclusions: A significant increase in Enterobacteriaceae-related DFOs was observed from 2016 to 2019, particularly in Mediterranean Europe.

In diabetic foot infections (DFI), the clinical virulence of skin commensals are generally presumed to be low. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria) and pathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pathogenic pathogens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxygen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs. 24 %, p = 0.23) or microbiological recurrence (11% vs. 17 %, p = 0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, the isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confidence interval 0.1–3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may also be based on oral non-beta-lactam antibiotic agents effective against the corresponding skin pathogens.

Objective: To assess the outcomes of diabetic foot infections (DFIs) due to Pseudomonas aeruginosa. Patients and Methods: From April 24, 2013 to July 31, 2016, we analyzed data from patients prospectively enrolled in our clinical pathway of DFIs, comparing those with infection due to Pseudomonas with those without infection due to Pseudomonas. Results: Overall, we assessed 1018 cases of DFIs: 392 with osteomyelitis and 626 with only soft tissue infections. The prevalence of P aeruginosa in deep wound cultures was 10% (104/1018); of the 1018 cultures, 22 were monomicrobial, 82 were polymicrobial, and 46 were with osteomyelitis. Overall, the patients were treated with a median of 1 surgical debridement and a total of 20 days of antibiotic therapy. In a comparison of crude groups, the proportion of clinical failures was significantly higher with Pseudomonas than with other pathogens (36/104 [35%] vs 218/914 [24%], respectively; P=.02). A multivariate analysis showed that pseudomonal DFIs did not recur more often than nonpseudomonal DFIs (hazard ratio, 1.0; 95% confidence interval, 0.6-1.7). Among the 104 cases of pseudomonal DFIs, there was no association between failure of treatment and the total duration of antibiotic therapy, duration of intravenous therapy, duration of combined antibiotic therapy with more than 1 agent, or duration of oral (fluoroquinolone) therapy. Among 15 cases of pseudomonal recurrence, 2 (13%) developed resistance to the antibiotic agent used for the index episode. Conclusion: For DFIs caused by P aeruginosa, other than choosing an antibiotic agent that is active against the organism, it does not appear necessary to treat with a different therapeutic regimen compared with the treatment of nonpseudomonal DFIs. There is no difference!

Background Healthcare-associated infections (HAI) are one of the gravest threats to patient safety worldwide. The importance of the hospital environment has recently been revalued in infection prevention and control. Though the literature is evolving rapidly, many institutions still do not consider healthcare environmental hygiene (HEH) very important for patient safety. The evidence for interventions in the healthcare environment on patient colonization and HAI with multidrug-resistant microorganisms (MDROs) or other epidemiologically relevant pathogens was reviewed. Methods We performed a systematic review according to the PRISMA guidelines using the PubMed and Web of Science databases. All original studies were eligible if published before December 31, 2019, and if the effect of an HEH intervention on HAI or patient colonization was measured. Studies were not eligible if they were conducted in vitro, did not include patient colonization or HAI as an outcome, were bundled with hand hygiene interventions, included a complete structural rebuild of the healthcare facility or were implemented during an outbreak. The primary outcome was the comparison of the intervention on patient colonization or HAI compared to baseline or control. Interventions were categorized by mechanical, chemical, human factors, or bundles. Study quality was assessed using a specifically-designed tool that considered study design, sample size, control, confounders, and issues with reporting. The effect of HEH interventions on environmental bioburden was studied as a secondary outcome. Findings After deduplication, 952 records were scrutinized, of which 44 were included for full text assessment. A total of 26 articles were included in the review and analyzed. Most studies demonstrated a reduction of patient colonization or HAI, and all that analyzed bioburden demonstrated a reduction following the HEH intervention. Studies tested mechanical interventions (n = 8), chemical interventions (n = 7), human factors interventions (n = 3), and bundled interventions (n = 8). The majority of studies (21/26, 81%) analyzed either S. aureus , C. difficile , and/or vancomycin-resistant enterococci. Most studies (23/26, 88%) reported a decrease of MDRO-colonization or HAI for at least one of the tested organisms, while 58% reported a significant decrease of MDRO-colonization or HAI for all tested microorganisms. Forty-two percent were of good quality according to the scoring system. The majority (21/26, 81%) of study interventions were recommended for application by the authors. Studies were often not powered adequately to measure statistically significant reductions. Interpretation Improving HEH helps keep patients safe. Most studies demonstrated that interventions in the hospital environment were related with lower HAI and/or patient colonization. Most of the studies were not of high quality; additional adequately-powered, high-quality studies are needed. Systematic registration number : CRD42020204909

Purpose The Actionable Register of Geneva Outpatients and inpatients with SARS-CoV-2 (ARGOS) is an ongoing prospective cohort created by the Geneva Directorate of Health. It consists of an operational database compiling all SARS-CoV-2 test results recorded in the Geneva area since late February 2020. This article aims at presenting this comprehensive cohort, in light of some of the varying public health measures in Geneva, Switzerland, since March 2020. Participants As of 1 June 2021, the database included 360 525 patients, among which 65 475 had at least one positive test result for SARS-CoV-2. Among all positive patients, 37.6% were contacted only once, 10.6% had one follow-up call, 8.5% had two and 27.7% had three or more follow-up calls. Participation rate among positive patients is 94%. Data collection is ongoing. Findings to date ARGOS data illustrates the magnitude of COVID-19 pandemic in Geneva, Switzerland, and details a variety of population factors and outcomes. The content of the cohort includes demographic data, comorbidities and risk factors for poor clinical outcome, self-reported COVID-19 symptoms, environmental and socioeconomic factors, prospective and retrospective contact tracing data, travel quarantine data and deaths. The registry has already been used in several publications focusing on symptoms and long COVID-19, infection fatality rate and re-infection. Future plans The data of this large real-world registry provides a valuable resource for various types of research, such as clinical research, epidemiological research or policy assessment as it illustrates the impact of public health policies and overall disease burden of COVID-19.

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BACKGROUND:Since the beginning of the COVID-19 pandemic, no direct antiviral treatment is effective as post-exposure prophylaxis (PEP). Lopinavir/ritonavir (LPV/r) was repurposed as a potential PEP agent against COVID-19. METHODS:We conducted a pragmatic open-label, parallel, cluster-randomised superiority trial in four sites in Switzerland and Brazil between March 2020 to March 2021. Clusters were randomised to receive LPV/r PEP (400/100 mg) twice daily for 5 days or no PEP (surveillance). Exposure to SARS-CoV-2 was defined as a close contact of >15 minutes in <2 metres distance or having shared a closed space for ≥2 hours with a person with confirmed SARS-CoV-2 infection. The primary outcome is the occurrence of COVID-19 defined by a SARS-CoV-2 infection (positive oropharyngeal SARS-CoV-2 PCR and/or a seroconversion) and ≥1 compatible symptom within 21 days post-enrolment. ClinicalTrials.gov (Identifier: NCT04364022); Swiss National Clinical Trial Portal: SNCTP 000003732. FINDINGS:Of 318 participants, 157 (49.4%) were women; median age was 39 (interquartile range, 28-50) years. A total of 209 (179 clusters) participants were randomised to LPV/r PEP and 109 (95 clusters) to surveillance. Baseline characteristics were similar, with the exception of baseline SARS-CoV-2 PCR positivity, which was 3-fold more frequent in the LPV/r arm (34/209 [16.3%] vs 6/109 [5.5%], respectively). During 21-day follow-up, 48/318 (15.1%) participants developed COVID-19: 35/209 (16.7%) in the LPV/r group and 13/109 (11.9%) in the surveillance group (unadjusted hazard ratio 1.44; 95% CI, 0.76-2.73). In the primary endpoint analysis, which was adjuted for baseline imbalance, the hazard ratio for developing COVID-19 in the LPV/r group vs surveillance was 0.60 (95% CI, 0.29-1.26; p =0.18). INTERPRETATION:The role of LPV/r as PEP for COVID-19 remains unanswered. Although LPV/r over 5 days did not significantly reduce the incidence of COVID-19 in exposed individuals, we observed a change in the directionality of the effect in favour of LPV/r after adjusting for baseline imbalance. LPV/r for this indication merits further testing against SARS-CoV-2 in clinical trials. FUNDING:Swiss National Science Foundation (project no.: 33IC30_166819) and the Private Foundation of Geneva University Hospitals (Edmond Rothschild (Suisse) SA, Union Bancaire Privée and the Fondation pour la recherche et le traitement médical).

Objective: Radiographic imaging is an important diagnostic tool in diabetic foot osteomyelitis (DFO). It is unknown whether DFO cases diagnosed with conventional X-ray versus positive Magnetic Resonance Imaging (MRI) differ regarding epidemiology and treatment outcome. Theoretically, signs of inflammation on MRI without bone lesions might be easier to treat. Methods: Our clinical pathway for diabetic foot infections discourages the use of MRI for the diagnosis of DFO. We compared the epidemiology and therapy of non-amputated DFO with positive features on conventional X-ray, MRI, or both. Radiology specialists interpreted the images. The intraoperative aspect of bone during amputation and the results of bone cultures were considered the gold standard for DFO diagnosis. Results: We prospectively followed 390 DFO episodes in 186 adult patients for a median of 2.9 years and performed 318 conventional X-rays (median costs 100 Swiss Francs; 100 US$) and 47 (47/390; 12%) MRI scans (median 800 Swiss Francs; 800 US $). Among them, 18 episodes were associated with positive MRI findings but lacked bone lesions on X-ray. After debridement, the median duration of systemic antibiotics was 28 days for MRI-only episodes and 30 days for X-ray-positive cases (Wilcoxonranksum- test; p=0.26). The corresponding median numbers of surgical debridements were 1 and 1; and recurrence was witnessed in 25% and 28%, respectively. In multivariate logistic regression analysis, MRI-only episodes did not alter the remission rate (odds ratio 0.5, 95%CI 0.1-5.2). Conclusions: According to our clinical pathway, DFO episodes with positive MRI findings only did not differ epidemiologically from the remaining DFO cases and did not influence the choice of therapy nor remission rate.

INTRODUCTION:Lopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2. METHODS AND ANALYSIS:COPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total. ETHICS AND DISSEMINATION:Ethics approval has been granted by the Commission Cantonale d'Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences. TRIAL REGISTRATION NUMBER:Clinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732). REGISTERED REPORT IDENTIFIER:CCER 2020-0864.

SummaryObjectiveThe appropriate duration of antibiotic therapy for diabetic foot infections (DFI) after surgical amputations in toto is debated. There are discrepancies worldwide.MethodsUsing a clinical pathway for adult DFI patients (retrospective cohort analysis), we conducted a cluster‐controlled Cox regression analysis. Minimum follow‐up was 2 months.ResultsWe followed 482 amputated DFI episodes for a median of 2.1 years after the index episode. The DFIs predominately affected the forefoot (n = 433; 90%). We diagnosed osteomyelitis in 239 cases (239/482; 50%). In total, 47 cases (10%) were complicated by bacteremia, 86 (18%) by abscesses and 139 (29%) presented with cellulitis. Surgical amputation involved the toes (n = 155), midfoot (280) and hindfoot (47). Overall, 178 cases (37%) required revascularization. After amputation, the median duration of antibiotic administration was 7 days (interquartile range, 1‐16 days). In 109 cases (25%), antibiotics were discontinued immediately after surgery. Overall, clinical failure occurred in 90 DFIs (17%), due to the same pathogens in only 38 cases. In multivariate analysis, neither duration of total postsurgical antibiotic administration (HR 1.0, 95% CI 0.99‐1.01) nor immediate postoperative discontinuation altered failure rate (HR 0.9, 0.5‐1.5).ConclusionAccording to our clinical pathway, we found no benefit in continuing postsurgical antibiotic administration in routine amputation for DFI. In the absence of residual infection (ie, resection at clear margins), antibiotics should be discontinued.

Observations of sea surface height (SSH) fields using satellite borne altimeters were conducted starting in the 1990s in various parts of the world ocean. Currently, a long period of 20 years of calibrated and accurate altimeter observations of Sea Surface Height Anomalies (SSHA) is publically available and ready to be examined for determining the rate of westward propagation of these anomalies, which are interpreted as a surface manifestation of linear Rossby waves that propagate westward in the ocean thermocline or as nonlinear eddies. The basis for estimating the speed of westward propagation of SSHA is time-longitude (Hovmöller) diagrams of the SSHA field at fixed latitude. In such a diagram the westward propagation is evident from a left-upward tilt of constant SSHA values (i.e. contours) and the angle between this tilt and the ordinate is directly proportional to the speed of westward propagation. In this work we use synthetically generated noisy data to examine the accuracy of three different methods that have been separately used in previous studies for estimating this slope (angle) of the time-longitude diagram: The first is the application of Radon transform, used in image processing for detecting structures on an image. The second method is the application of 2D Fast Fourier Transform that yields a frequency-wavenumber diagram of the amplitudes so the frequency and wavenumber where the maximum amplitude occurs determine the phase speed i.e. the slope. The third method constitutes an adaptation of Radon transform to a propagating wave in which structures of minimal variance in the image are identified. The three methods do not always yield the same phase speed value and our analysis of the synthetic data shows that an estimate of the phase speed at any given latitude should be considered valid only when at least two of the methods yield the same value. The relevance of the suggested procedure to observed signals is verified by applying it to observed SSHA signals in the ocean.

AimTo assess amoxicillin‐clavulanate (AMC) for the oral therapy of diabetic foot infections (DFIs), especially for diabetic foot osteomyelitis (DFO).MethodsWe performed a retrospective cohort analysis among 794 DFI episodes, including 339 DFO cases.ResultsThe median duration of antibiotic therapy after surgical debridement (including partial amputation) was 30 days (DFO, 30 days). Oral AMC was prescribed for a median of 20 days (interquartile range, 12‐30 days). The median ratio of oral AMC among the entire antibiotic treatment was 0.9 (interquartile range, 0.7‐1.0). After a median follow‐up of 3.3 years, 178 DFIs (22%) overall recurred (DFO, 75; 22%). Overall, oral AMC led to 74% remission compared with 79% with other regimens (χ2‐test; P = 0.15). In multivariate analyses and stratified subgroup analyses, oral AMC resulted in similar clinical outcomes to other antimicrobial regimens, when used orally from the start, after an initial parenteral therapy, or when prescribed for DFO.ConclusionsOral AMC is a reasonable option when treating patients with DFIs and DFOs.

Factors strongly related to the risk of developing diabetic foot infections include vascular, neuropathic and hyperglycemic complications of long-standing diabetes mellitus. These infections are common and serious, posing a worldwide burden on administrative providers of healthcare, patients and physicians. The most appropriate approach to these infections is with a multidisciplinary team. This subchapter summarizes the current state-of the-art concerning therapy, and scientific knowledge, for peripheral arterial insufficiency, hyperglycemia, and peripheral neuropathy of the diabetic foot, with an emphasis on the infectious complications.

Revue du rhumatisme - In Press.Proof corrected by the author Available online since mardi 7 novembre 2017

AimTo determine the most appropriate duration of antibiotic therapy for diabetic foot infections (DFIs).MethodsUsing a clinical pathway for adult patients with DFIs (retrospective cohort analysis), we created a cluster‐controlled Cox regression model to assess factors related to remission of infection, emphasizing antibiotic‐related variables. We excluded total amputations as a result of DFI and DFI episodes with a follow‐up time of <2 months.ResultsAmong 1018 DFI episodes in 482 patients, we identified 392 episodes of osteomyelitis, 626 soft tissue infections, 246 large abscesses, 322 episodes of cellulitis and 335 episodes of necrosis; 313 cases involved revascularization. Patients underwent surgical debridement for 824 episodes (81%), of which 596 (59%) required amputation. The median total duration of antibiotic therapy was 20 days. After a median follow‐up of 3 years, 251 of the episodes (24.7%) were followed by ≥1 additional episode(s). Comparing patients with and without additional episodes, risk of recurrence was lower in those who underwent amputation, had type 1 diabetes, or underwent revascularization. On multivariate analysis including the entire study population, risk of remission was inversely associated with type 1 diabetes (hazard ratio [HR] 0.3, 95% confidence interval [CI] 0.2‐0.6). Neither duration of antibiotic therapy nor parenteral treatment affected risk of recurrence (HR 1.0, 95% CI 0.99‐1.01 for both). Similarly, neither >3 weeks versus <3 weeks of therapy, nor >1 week versus <1 week of intravenous treatment affected recurrence. In stratified analyses for both soft tissue DFIs or osteomyelitis separately, we did not observe associations of antibiotic duration with microbiological or clinical recurrences of DFI. The HRs were 1.0 (95% CI 0.6‐1.8) for an antibiotic duration >3 weeks overall and 0.6 (95% CI 0.2‐1.3) for osteomyelitis cases only. Plotting of duration of antibiotic therapy failed to identify any optimal threshold for preventing recurrences.ConclusionsOur analysis found no threshold for the optimal duration or route of administration of antibiotic therapy to prevent recurrences of DFI. These limited data might support possibly shorter treatment duration for patients with DFI.

Background: After antibiotic therapy of an initial diabetic foot infection (DFI), pathogens isolated from subsequent episodes might become more resistant to commonly prescribed antibiotics. If so, this might require a modification of the current recommendations for the selection of empiric antibiotic therapy. This study investigated whether the Infectious Diseases Society of America (IDSA) DFI guideline recommendations should be modified based on the number of past DFI episodes.Methods: This was a single-centre retrospective cohort survey of DFI patients seen during the years 2010 to 2016.Results: A total 1018 episodes of DFI in 482 adult patients were identified. These patients were followed-up for a median of 3.3 years after the first DFI episode. The total number of episodes was 2257 and the median interval between recurrent episodes was 7.6 months. Among the recurrent DFIs, the causative pathogens were the same as in the previous episode in only 43% of cases (158/365). Staphylococcus aureus was the predominant pathogen in all episodes (range 1 to 13 episodes) and was not more prevalent with the increasing number of episodes. DFIs were treated with systemic antibiotics for a median duration of 20 days (interquartile range 11-35 days). Overall, there was no significant increase in the incidence of antibiotic resistance to methicillin, rifampicin, clindamycin, or ciprofloxacin over the episodes (Pearson's Chi-square test p-values of 0.76, 1.00, 0.06, and 0.46, respectively; corresponding p-values for trend of 0.21, 0.27, 0.38, and 0.08, respectively).Conclusions: After the successful treatment of a DFI, recurrent episodes are frequent. A history of a previous DFI episode did not predict a greater likelihood of any antibiotic-resistant isolate in subsequent episodes. Thus, broadening the spectrum of empiric antibiotic therapy for recurrent episodes of DFI does not appear necessary. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Fever with rash is a frequent reason for consultation. A detailed medical history and thorough physical examination are essential since laboratory tests often lack specificity. Certain infectious and non-infectious causes are considered medical emergencies and must always be investigated upon initial evaluation. In the case of a history of recent travel the differential diagnosis has to be broadened but it should not be forgotten that resurgent « childhood » viral diseases like measles can be acquired while traveling.

Background Alveolar echinococcosis is a potentially lethal zoonosis caused by larval forms of the tapeworm Echinococcus multilocularis . Humans are aberrant intermediate hosts who become infected by ingestion of egg-contaminated food or water or via physical contact with domestic or wild animals that carry the parasite in their small intestine. In humans, the disease usually affects the liver and can spread to other organs causing metastatic infiltration. In this report, we describe an advanced presentation of human alveolar echinococcosis mimicking metastatic malignancy. Case presentation A 62-year-old white woman was evaluated for fever, jaundice, and abdominal pain, associated with significant weight loss. She lived in a rural area in Switzerland and used to eat wild forest fruits and mushrooms. She owned cats that used to hunt rodents. On physical examination, she appeared severely ill with cachexia, altered mental status, jaundice, and massive hepatomegaly. Laboratory tests showed cholestasis with preserved liver function. An abdominal computed tomography scan showed an enlarged liver with a huge cystic mass in the right lobe extending into the left lobe, infiltrating her hepatic hilum, causing intrahepatic bile duct dilation and occlusion of her right portal vein. A chest computed tomography scan showed multiple calcified bilateral pulmonary nodules. Her clinical and radiological presentation resembled an advanced neoplastic disease. Serologic tests for Echinococcus multilocularis were positive. The diagnosis of alveolar echinococcosis was established on her past history of exposure, imaging, and serology results. Conclusions Clinical presentation and radiologic imaging findings of disseminated alveolar echinococcosis can mimic metastatic malignancy, and diagnosis can be challenging in atypically advanced cases. As the incidence of human alveolar echinococcosis appears to be increasing in Europe and Switzerland, physicians should be aware of alveolar echinococcosis, its epidemiology, and its clinical features.

Alarmins are endogenous molecules with homeostatic roles that have reached the focus of research in inflammatory arthritis in the last two decades, mostly due to their ability to indicate tissue related damage after active or passive release from injured cells. From HMGB1, S100A8/A9 and S100A12 proteins, over heat-shock proteins (HSPs) and purine metabolites (e.g. uric acid, ATP) to altered matrix proteins and interleukin-33 (IL-33), a number of alarmins have been determined until now as having a role in rheumatoid arthritis, psoriatic and juvenile idiopathic arthritis, as well as spondyloarthritis and gout. Although formerly being linked to initiation and chronification of inflammatory arthritis, driving auto- and paracrine inflammatory loops, more recent research has also unraveled the alarmins’ role in the crosstalk between innate and adaptive immunity and in resolution of inflammation.Providing a state-of-the-art overview of known alarmins, this review lists the known modes of action and pathologic contribution of alarmins to inflammatory arthritis, as well as biomarker potential of alarmins in the clinical setting for tracking disease severity. Based upon research on animal experimental models (CIA, AIA) and clinical trials, a look is made into potentially viable strategies for modifying alarmin secretion and their target receptor (e.g. TLR, RAGE) interaction with the purpose of attenuating arthritic disease.

Staphylococcus aureus versus streptococci in orthopaedic infections Antonio Tumminello, Dennis Dominguez, Dan Lebowitz, Placido Bartolone, Michael Betz, Didier Hannouche & Ilker Uçkay To cite this article: Antonio Tumminello, Dennis Dominguez, Dan Lebowitz, Placido Bartolone, Michael Betz, Didier Hannouche & Ilker Uçkay (2017): Staphylococcus aureus versus streptococci in orthopaedic infections, Infectious Diseases, DOI: 10.1080/23744235.2017.1318219 To link to this article: http://dx.doi.org/10.1080/23744235.2017.1318219