bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASSESSING THE EFFICACY OF A PRE-FORMULATED IRRIGATION SOLUTION FOR ACUTE PERIPROSTHETIC JOINT INFECTION: INITIAL FINDINGS FROM A RANDOMIZED CONTROLLED TRIAL
Authors: Taltavull Rafael Oleo , Goma-Camps Matías Vicente , Calderer Lluis Carrera , Amat Carles , Corona Pablo 
Published: November 2024

AimThis study aims to evaluate the effectiveness of a pre-formulated irrigation solution1 (containing ethanol, acetic acid, sodium acetate, benzalkonium chloride, and sterile water) compared to saline solution in managing acute periprosthetic joint infections (A-PJI) during Debridement, Antibiotic, and Implant Retention (DAIR) surgeries. The primary objective is to assess the healing rate using this solution1 versus saline in A-PJI patients, with “cure” defined by a set of criteria including no recurrence, wound issues, or need for ongoing suppressive antibiotics after 1 year. Principio del formularioFinal del formularioMethodThis single-center, randomized controlled trial will involve patients with acute periprosthetic infections undergoing standard DAIR surgery, divided into two groups: one receiving saline solution and the other receiving pre-formulated solution1. The study is single-blinded, with patients unaware of their group assignment. The study is registered at ISRCTN: https://doi.org/10.1186/ISRCTN10873696. Inclusion criteria include patients over 18 with hip or knee prostheses suffering from acute or hematogenous periprosthetic infections, while exclusion criteria include a history of prior debridement or multiple infected implants, among others. Principio del formularioFinal del formulario A total of 50 subjects are needed for statistical significance, with a 5% dropout rate anticipated. An interim safety analysis will assess early effectiveness and adverse effects, and the results are presented in this study. Data will be managed in online databases and analyzed using SPSS software, with a significance level of p<0.05ResultsTwenty-four patients were eligible for analysis, twelve in each group. The overall average age was 75 years, and the gender distribution was predominantly female (9 F and 3 M in each group). No significant differences were found at the baseline characteristics level between the two groups (p>0.05). The minimum follow-up of 1 year was achieved in all cases except three due to deaths not related to periprosthetic infection. Regarding efficacy, a non-statistically significant difference was observed (p>0.05), with 58% in the serum group and 42% in the pre-formulated irrigation solution1 group (X2= 0.17, p=0.683). The average hospital stay was 38.42 days (SD 26.32) in the pre-formulated irrigation solution group1 and 24.42 days (SD 18.72) in the serum group, with this difference being not significant (t=1.5, p=0.148).ConclusionsWhile the current analysis indicates no significant differences between both groups in terms of efficacy, the study's ongoing progress and the inclusion of a larger sample size could potentially yield more definitive results.
LIPOSOMES CONJUGATED ON THE BACTERIOPHAGE SURFACE FOR DELIVERING ANTIBIOTICS TO COMBAT MULTIDRUG-RESISTANT BACTERIAL INFECTIONS
Authors: Wang Lei , Trampuz Andrej , Zhang Xianlong 
Published: November 2024

AimTreatment of prosthetic joint infection (PJI) by systemic administration of high doses of long-term antibiotics often proves ineffective, causing severe side effects. Thus, we presented the phage Sb-1, which coding extracellular polymeric substances (EPS) degradation depolymerases, conjugated with rifampicin-loaded liposomes (Lip-RIF@Phage) by bio-orthogonal functionalization strategy to target biofilm (Figure1).MethodMethicillin-resistant Staphylococcus aureus (MRSA) biofilm was grown on porous glass beads for 24 h in vitro. After the biofilm formation, beads were exposed to 0.9% saline, then sonication. Quantitative and qualitative biofilm analyses were performed by colony counting, scanning electron microscopy and isothermal microcalorimetry. A rat model of total knee arthroplasty infected with the bioluminescent MRSA strain was developed as the PJI model to evaluate the efficacy of Lip-RIF@Phage anti-biofilm therapy in vivo, then the creatinine, alanine transaminase, and aspartate transaminase values were evaluated throughout the entire treatment process.ResultsAfter treatment with Lip-RIF@Phage, no bacterial colonies were observed, consistent with findings from scanning electron microscopy. Similarly, isothermal microcalorimetry revealed no detectable heat following Lip-RIF@Phage treatment, aligning with these observations. In vivo experiments demonstrated a significant reduction in biofilm cell load compared to all other tested conditions, with no evidence of systemic toxicity on renal and liver functions attributed to Lip-RIF@Phage.ConclusionsThe innovative depolymerase-phagobot nanosystem (Lip-RIF@Phage) exhibits remarkable efficacy in completely eliminating biofilm cells in vitro. It serves as an excellent carrier for antibiotic delivery, enhancing antibiotic penetration through biofilms and improving biofilm eradication efficacy. Furthermore, it enables personalized treatment strategies against biofilm-associated multidrug-resistant (MDR) infections by maximizing the effectiveness of any remaining sensitive antibiotics.For any tables or figures, please contact the authors directly.
IN VITRO STUDY ON CHEMICAL DEBRIDEMENT DURING PERIPROSTHETIC JOINT INFECTION SURGERY: WHAT IS THE BEST TREATMENT STRATEGY?
Authors: Gómez Miguel Márquez , Guembe María , Díaz-Navarro Marta , Peinado Lourdes Prats , Matas-Díaz Jose-Antonio , Ruiz Pablo Sanz 
Published: November 2024

AimChemical debridement is a fundamental step during Periprosthetic joint infection (PJI) surgery. Antiseptic solutions are commonly used, but evidence on the optimal antiseptic, concentration, and irrigation time is lacking. The aim of this study is to analyze and compare the anti-biofilm capacity of povidone iodine, H202, acetic acid and Bactisure™ after different exposure times, as well as their combinations.MethodSurgical steel discs inoculated with methicillin susceptible (MSSA) and resistant S. aureus (MRSA), P. aeruginosa, and S. epidermidis were exposed to the following antiseptic solutions: 0.3% (PI0.3) and 10% povidone iodine (PI10), H202, 3% Acetic acid (AA3) and Bactisure™. Combinations included AA3, H202, and PI10 in various orders. Exposure time for the antiseptics solutions was 1, 3 and 5 minutes, while combinations had a 9-minute total exposure, 3 minutes per antiseptic sequentially. All experiments were performed in triplicate and with a sterile saline control. nThe reduction in colony-forming units (CFU) was measured after sonication, and biofilm structure was analyzed via scanning electron microscopy.ResultsPI showed the highest antibiofilm activity. PI0.3 eradicated bacteria on the discs after 3 and 5 minutes of exposure, but only achieved a 77.1% reduction after 1 minute. After PI10 treatment, we did not recover any bacteria regardless of exposure time. H202, AA3, and Bactisure™ reached a significantly lower bacterial decrease at all exposure times compared to PI0.3 and PI10. AA3 was less effective against MSSA and S. epidermidis. H202 showed less activity against MRSA than PI0.3, PI10, and Bactisure™. Combinations of antiseptics starting with AA3 showed the best results in terms of CFU reduction and cell viability.ConclusionsWe propose a sequential combination of AA3 + H202 + PI10 with an exposure time of 9 minutes for the chemical debridement in PJI surgery. First, AA3 performs debridement and disruption of the biofilm. Then, H202 has a bactericidal effect and increases the porosity of the cell wall, and PI10 has a final bactericidal effect. If combinations are unavailable, PI is a cost-effective alternative.
REVISION FOR INFECTION AFTER PRIMARY TOTAL HIP ARTHROPLASTY: TIME TRENDS IN SURGICAL STRATEGY
Authors: Høvding Pål , Hallan Geir , Furnes Ove , Dale Håvard 
Published: November 2024

Background and purposePrevious publications have reported an increased but levelling out risk of revision for infection after total hip arthroplasty (THA) in Norway. We assessed the changes in risk of major (cup and/or stem, 1- or 2-stage) and minor revisions (debridement, exchange of modular parts, antibiotics and implant retention (DAIR)) for infection after primary THAs reported to the Norwegian Arthroplasty Register (NAR) over the period 2005-2022.Patients and methodsPrimary THAs reported to the NAR from 2005 to 2022 were included. Time was stratified into time periods (2005-2009, 2010-2018, 2019-2022) based on a previous publication. Cox regression analyses, adjusted for sex, age and ASA-classification, with the first revision for infection were performed.Results140,338 primary THAs met the inclusion criteria. 1.3% (1,785) were revised for infection during the study period. 0.5% (638) had major revisions, whereas 0.8% (1,147) had DAIRs for infection.The risk of revision for infection was 1.2 (95%CI 1.1-1.4) for 2010-2018 and 1.0 (0.8-1.1) for 2019-2022 compared to 2005-2009. Compared to 2010-2018, the risk of revision for infection was 0.8 (0.7-0.9) for 2019-2022.The risk of DAIR for infection was 1.5 (1.3-1.9) for 2010-2018 and 1.2 (1.0-1.4) for 2019-2022 compared to 2005-2009. Compared to 2010-2018, the risk of DAIR for infection was 0.8 (0.7-0.9) for 2019-2022.The risk of major revision for infection was 0.8 (0.7-1.0) for 2010-2018 and 0.8 (0.6-1.0) for 2019-2022 compared to 2005-2009.InterpretationThe overall risk of revision for infection after THA, in Norway, has decreased in the period 2019-2022. The risk for DAIR initially increased in the period 2005-2009, levelled out 2010-2018 before starting to decrease in 2019-2022. The risk of major revision for infection was reduced in the period 2005-2009 before levelling out. This shows changes in revision strategies, but may also reflect a true decrease in periprosthetic joint infection.
A THERAPEUTIC DRUG-MONITORING APPROACH FOR DALBAVANCIN (MONTALBANO)
Authors: Landonio Simona , Galli Lucia , Mariani Chiara , Covizzi Alice , Merli Stefania , Giorgi Riccardo , Coen Massimo , Cattaneo Dario , Passerini Matteo , Gori Andrea 
Published: November 2024

Aimdalbavancin, a lipo-glycopeptide antibiotic effective against Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus), allows extended dosing interval due to its peculiar pharmacokinetics. Despite being registered for treatment of acute skin infections, off-label use has shown promise in various settings, particularly in osteo-articular infections. This study aims to assess dalbavancin's pharmacological efficacy and its safety and clinical success in patients treated according to personalized schedules guided by Therapeutic Drug Monitoring (TDM), particularly in long-term therapies.Methodsnon-interventional, retrospective, single-center pharmacological study. We included adult patients with at least one dalbavancin TDM determination from July 1, 2022 to February 1, 2024 and treated with outpatient parenteral antimicrobial therapy. We recorded dalbavancin trough concentration (Cmin) and its peak concentration (Cmax) and employed log-linear regression models to predict the timing of dalbavancin dosing, aiming to sustain Cmin levels above 4 or 8.04 mg/L, according to recent literature. Data regarding index infections, patients’ characteristics, outcomes, and adverse events were also collected.Resultswe included 32 patients, whose clinical and microbiological characteristics are depicted in Table 1. Regarding the primary outcome, 132/134 (98.5%) trough concentration was >4 mg/L, while 112/134 (83.6%) was >8.04 mg/L. For the secondary outcomes, 2/32 patients experienced an adverse event correlated to dalbavancin: (i) exanthema one week after the start of therapy and (ii) exanthema, conjunctivitis, angioedema, and nausea one month after the start of therapy. Moreover, we observed 4/32 clinical unsuccess (one failure during treatment, one relapse after the end of therapy, one switch to another antibiotic, and one isolation of non-susceptible microorganism).Conclusionsa TDM-based approach with the use of a log-linear regression model allows a more precise timing of dalbavancin administration by maintaining sufficient concentration of circulating drugs. This approach is promising for infections requiring a long-term treatment, such as orthopedic infection where source control is not possible.For any tables or figures, please contact the authors directly.
TROUGH LEVELS OF DALBAVANCIN DURING LONG-TERM TREATMENT OF PERIPROSTHETIC JOINT INFECTIONS
Authors: Söderquist Bo , Möller Max , Salihovic Samira 
Published: November 2024

AimDalbavancin is a lipoglycopeptide with a broad antimicrobial spectrum against Gram-positive bacteria and effect against microorganisms in biofilm in vitro. Its pharmacokinetic properties, with an exceptionally long half-life of approximately 300 hours, allow for simplified administration that may be of value in the long-term treatment of bone and joint infections, such as prosthetic joint infections (PJIs). Several case reports and case series with “off-lable” treatment with dalbavancin of PJIs exist, but the optimal dosing regimen remains to be defined. Therapeutic drug monitoring (TDM) is recommended for treatment with >2 doses of dalbavancin. In the absence of TDM, the Swedish national guidelines for bone and joint infections (2023, www.infektion.net) recommends a loading dose of dalbavancin 1,500 mg on day 1 and 1,500 mg on days 8 – 14, after which from day 28 1,000 mg is given biweekly or 500 mg every week. The aim of the present study was to determine trough levels of dalbavancin in patients with long-term treatment of PJIs according to the national guidelines.MethodTwelve patients with PJI were treated with at least 6 doses of dalbavancin, of which the first two doses were 1500 mg and the following doses were 1000 every second week, and prospectively sampled biweekly for determination of serum concentrations (trough levels) of dalbavancin which was measured by liquid chromatography coupled to electrospray tandem mass spectrometry (LC-MS/MS). The renal function was also examined.ResultsThe median serum concentration 14 days after the first dose of dalbavancin 1500 mg was 36.3 mg/L (range 6.6 – 62.4 mg/L). The median value 14 days after the second dose of 1500 mg (day 27 – 28) was 48.2 mg/L (range 12.2 – 77.3 mg/L). The trough value after the last dose of a total of 6 – 7 doses was as median 43.1 mg/L (range 26.2 – 97.5 mg/L). Three patients showed a tendency towards successive accumulation of dalbavancin during treatment. None of the patients, including those three with increasing through levels during treatment, showed any significant alteration in creatinine nor glomerular filtration rate.ConclusionsTDM during long-term treatment with dalbavancin is recommended to avoid the risk of accumulation and unnecessarily high trough values. With TDM, the dosing interval can be extended in several cases. In addition, with the support of TDM, subtherapeutic serum concentrations, with the risk of developing resistance, can be avoided.
THE IMPACT OF UNTOWARD EVENTS DURING PRIMARY OR REVISION TOTAL HIP OR KNEE ARTHROPLASTY SURGERY
Authors: Trebše Neža , Blas Mateja , Kanalec Tanja , Angelini Kristina , Filipič Tjaša , Levašic Vesna , Trebse Rihard 
Published: November 2024

AimThere is limited data on the frequency and impact of untoward events such as glove perforation, contamination of the surgical field (drape perforation, laceration, detachment), the unsterile object in the surgical field (hair, sweat droplet…), defecation, elevated air temperature…that may happen in the operating theatre. These events should influence the surgical site infection rate but it is not clear to what extent. We wanted to calculate the frequency and measure the impact of these events on the infection and general revision rate.MethodIn our institution, scrub nurses prospectively and diligently record untoward events in the theatres. We have an institutional implant registry with close to 100% data completion since 2001, and surgeons register complications before discharge. We analysed the respective databases and compared the revision and infection rate in the group with untoward events with the outcome of all arthroplasty patients within the same period. Two-tailed Z statistical test was used for analysis.ResultsBetween 1.1.2012 and 31.12.2018 we operated 13574 prosthetic joints: 6232 primary THR (total hip replacement) and 5466 primary KR (total and partial knee replacement) and 1245 and 631 revisions respectively. During this period, we recorded 372 events (2.74%) including 20 (0.15 %) defecations, 40 (0.29 %) unsterile object in the surgical field, 73 (0.54%) field sterility violations, 45 (0.33 %) glove perforations, 45 (0.33 %) occasions with elevated air temperature, 106 (0.78%) with guests in the OR, 11 (0.08%) with wound near the surgical field, and 32 (0.24%) with other events. We followed the patients till 1.1.2022, in this time we recorded 27 (7.26%) reoperations in the cohort with untoward events. There were 9 (2.42%) infections and 18 (4.84%) aseptic revisions in the group with unwanted events.The infection rate for all TJR (total joint replacement) from the period 2012-2018, followed till 1.1.2022 was 2.23%, the revision rate for any reason was 4.37%. For all THR (primary and revision) the infection rate was 0.84%, the overall revision rate was 3.18% and for the KR (primary and revision) 1.71% and 5,82% respectively. The difference is significant at p>0.05 for infection rate.ConclusionsThe potentially serious sterility disruptive events in the operative rooms did result in an increased infection rate but not an increase in revision rate. There is no data about the rate and the impact of these events besides for perforated surgical gloves with higher reported incidences than in our study influencing infection rate if perioperative antibiotic prophylaxis was not used. Ours is the first study reporting the impact of these unwanted events in the operating theatre.Key wordsorthopaedic surgery, unwanted events, revision rate
PREDICTING PERIPROSTHETIC JOINT INFECTION: EXTERNAL VALIDATION OF PREOPERATIVE PREDICTION MODELS
Authors: Yoon Seung-Jae , Jutte Paul , Soriano Alex , Sousa Ricardo , Zijlstra Wierd , Wouthuyzen-Bakker Marjan 
Published: November 2024

AimThis study aimed to externally validate promising preoperative PJI prediction models in a recent, multinational European cohort.MethodThree preoperative PJI prediction models (by Tan et al., Del Toro et al., and Bülow et al.) which previously demonstrated high levels of accuracy were selected for validation. A multicenter retrospective observational analysis was performed of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) between January 2020 and December 2021 and treated at centers in the Netherlands, Portugal, and Spain. Patient characteristics were compared between our cohort and those used to develop the prediction models. Model performance was assessed through discrimination and calibration.ResultsA total of 2684 patients were included of whom 60 developed a PJI (2.2%). Our patient cohort differed from the models’ original cohorts in terms of demographic variables, procedural variables, and the prevalence of comorbidities. The c-statistics for the Tan, Del Toro, and Bülow models were 0.72, 0.69, and 0.72 respectively. Calibration was reasonable, but precise percentage estimates for PJI risk were most accurate for predicted risks up to 3-4%; the Tan model overestimated risks above 4%, while the Del Toro model underestimated risks above 3%.ConclusionsIn this multinational cohort study, the Tan, Del Toro, and Bülow PJI prediction models were found to be externally valid for classifying high risk patients for developing a PJI. These models hold promise for clinical application to enhance preoperative patient counseling and targeted prevention strategies.KeywordsPeriprosthetic Joint Infection (PJI), High Risk Groups, Prediction Models, Validation, Infection Prevention
SYSTEMIC INFLAMMATION RESPONSE INDEX (SIRI) AND MONOCYTE TO LYMPHOCYTE RATIO (MLR) ARE PREDICTORS OF GOOD OUTCOMES IN SURGICAL TREATMENT OF PERIPROSTHETIC JOINT INFECTIONS OF LOWER LIMBS: A SINGLE-CENTRE RETROSPECTIVE ANALYSIS
Authors: Vitiello Raffaele , Smimmo Alessandro , Taccari Francesco , Matteini Elena , Micheli Giulia , Fantoni Massimo , Maccauro Giulio 
Published: November 2024

AimPeriprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA) whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR), while late infections with two-stage revision surgery. Two-stage revision is considered the “gold standard” for treatment of chronic PJI. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to- lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII)], systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI.MethodA single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII and AISI) were evaluated at the explantation time, at 4, 6, 8 weeks after surgery and at reimplantation time. Correlation between laboratory parameters and surgery success was evaluated, defined as infection absence/resolution at the last follow upResults57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nineteen patients completed the two-stage revision process. Among them, none showed signs of re-infection or persistence of infection at the last available follow up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others were submitted to Girdlestone technique or chronic suppressive antibiotic therapy. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7, p-value 0.04) and MLR values (mean 0.4 SD 0.2, p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation of SIRI and PCR, also defined respectively delta-SIRI (mean −2.3 SD 1.8, p-value 0.03) and delta-PCR (mean −46 SD 35.7, p-value 0.03), were associated with favorable outcomesConclusionsThe results of our study suggest that, in patients with PJI undergoing two-stage, SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant.