bluuebunny/crossref_metadata_2025_split huggingface dataset:
PROSTHETIC JOINT INFECTIONS DUE TO CANDIDA SPP.: A MULTICENTRE INTERNATIONAL OBSERVATIONAL STUDY
Authors: Dinh Aurélien , Chatillon Emma D'anglejan , Ho Rosemary , McNally Martin , Dudareva Maria , Scarborough Matthew , Jesuthasan Gerald , Escolà-Vergé Laura , Lora-Tamayo Jaime , Mancheño-Losa Mikel , Thill Pauline , Giordano Gérard , Fourcade Camille , Duran Clara , Bonnet Eric , Hascoet Julie Lourtet 
Published: November 2023

AimProsthetic joint infection (PJI) due to Candida spp. is a severe complication of arthroplasty but is little reported. This study describes Candida PJI epidemiology, management, and outcome.MethodWe performed a retrospective, observational multinational study with support of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Patients diagnosed with PJI due to Candida spp. between 1990 and 2021 were included. Demographic, clinical, laboratory, imaging, medical/surgical treatment, and outcome data were collected within a standardized database. Treatment failure was defined either as a Candida infection recurrence, superinfection, or death due to infection.ResultsData from 151 patients across 18 centers were analyzed. Mean age was 69.5 ± 13.1yo, 78 (51.7%) patients were male, and 21 (13.9%) were immunosuppressed. Site of infection included hip (55.0%), knee (41.7%), shoulder (2.6%), and femur (0.7%). Twenty-five (16.6%) patients were febrile, and 58 (38.4%) had fistula. Mean number of previous surgeries on the same anatomical site was 3.3±2.3. Surgeries were DAIR (33.8%), one-stage exchange (19.9%), two-stage exchange (39.1%), and implant removal (6.0%). Candida species identified were C. albicans (60.3%), C. parapsilosis (26.5%), C. glabrata (7.3%), and C. tropicalis (5.3%).Co-infection with bacteria was found in 69 (45.7%) cases. Fluconazole (62.9%) and caspofungin (14.6%) were the main antifungal agents prescribed for 148.6 ± 167.5 days. Favorable outcome was found in 54/144 (37.5%) cases. Failure was associated with the number of previous surgeries (OR 1.249, 95%CI 1.061–1.469; p-value=0.007), while treatment by fluconazole was associated with cure (OR 0.336, 95%CI 0.160–0.707; p-value=0.004).ConclusionsThis study provides epidemiologic and outcome data on Candida PJIs. Although poor overall, the prognosis did not seem associated with immunosuppression, type of surgery, fungal species or treatment duration.
HOSPITALIZATIONS DUE TO PROSTHETIC JOINT INFECTION IN SPAIN DURING THE PERIOD 2000 TO 2015
Authors: Gómez-Junyent Joan , Redó Maria Luisa Sorli , Pelegrín Ivan , Millat-Martínez Pere , Pérez-Prieto Daniel , Alier Albert , Verdié Lluis Puig , Poblet Judith , Pardos Sonia Luque , Montero María Milagro , Horcajada Juan Pablo 
Published: November 2023

AimProsthetic joint infection (PJI) is a devastating complication of joint replacement, having an impact on morbimortality but also on national health systems and their budgets. The current situation of PJI-related hospitalizations in Spain and their changes over time are unknown. Therefore, we aimed to analyze the hospitalization burden of PJI, including costs and trends in recent decades.MethodsRetrospective observational study including data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. During the period 2000–2015, hospitalizations due to PJI (ICD-9-CM 996.66) as main diagnosis were included. Epidemiological trends were evaluated during four periods: P1, 2000–2003; P2, 2004–2007; P3, 2008–2011; P4, 2012–2015. Annual hospitalization rates per 100,000 inhabitants and trends were also calculated.ResultsAmong 5,721,6725 hospitalizations, 49,835 were PJI related, which represented 8.71/10,000 admissions. We observed a significant increase in the number of PJI-related hospitalizations per 10,000 admissions during the study period: 6.43 P1, 8.53 P2, 9.60 P3, 10.05 P4 (p<0.001). The annual hospitalization rate was 6.9/100,000 inhabitants (95%CI 6.9–7), which also increased over time (p<0.001). The median age was 72 years (IQR 65–78) and 58.12% were women. Hospitalization rates were higher in women (7.95 vs 5.90; p<0.001) and also increased with patients’ age (p<0.001). Whereas the median length of stay was 7 days (IQR 7–8) in the global cohort, it was 18 days (IQR 10–31) in those with PJI-related hospitalization; however, the median length of stay in PJI-related hospitalizations decreased during the study period (P1 20 days, P4 16 days, p<0.001). The total cost for the healthcare system was 366 million euros and the median cost per patient was 6937 euros (IQR 3584–10505), which significantly increased from 4804 euros in P1 to 8534 in P4 (p<0.001). The majority of patients (90.32%) were discharged home and the case-fatality rate was 2.70%, without significant differences during the study (p=0.384).ConclusionsIn Spain, PJI-related hospitalizations have increased in recent decades, with higher costs despite the decrease in length of stay. PJI is a first magnitude healthcare problem, which should be prioritized in health systems and budgets.
INFECTION AFTER INTRACAPSULAR FEMORAL NECK FRACTURE: DOES ANTIBIOTIC-LOADED BONE CEMENT REDUCE INFECTION RISK AFTER HEMIARTHROPLASTY AND TOTAL HIP ARTHROPLASTY? DATA FROM THE GERMAN ARTHROPLASTY REGISTRY
Authors: Szymski Dominik , Walter Nike , Krull Paula , Melsheimer Oliver , Grimberg Alexander , Alt Volker , Steinbrück Arnd , Rupp Markus 
Published: November 2023

AimThe aim of this investigation was to compare risk of infection in both cemented and cementless hemiarthroplasty (HA) as well as total hip arthroplasty (THA) following femoral neck fracture.MethodsData collection was performed using the German Arthroplasty Registry (EPRD) In HA and THA following femoral neck fracture fixation method was divided into cemented and cementless protheses and paired according to age, sex, body mass index (BMI), and the Elixhauser score using Mahalanobis distance matching.ResultsOverall in 13,612 cases of intracapsular femoral neck fracture, with 9,110 (66.9 %) HAs and 4502 (33.1 %) THAs were analyzed. Infection rate in HA was significantly reduced in cases with use of antibiotic-loaded cement compared to cementless fixated prosthesis (p=0.013). In patients with THA no statistical difference between cemented and cementless prothesis was registered, however after one year 2.4 % of infections were detected in cementless and 2.1 % in cemented THA. In the subpopulation of HA after one year 1.9 % of infections were registered in cemented and 2.8 % in cementless HA. BMI (p=0.001) and Elixhauser-Comorbidity-Score (p<0.003) were identified as risk factors of PJI, while in THA also cemented prosthesis demonstrated within the first 30 days an increased risk (HR=2.728; p=0.010).ConclusionThe rate of infection after intracapsular femoral neck fracture was significantly reduced in patients treated by antibiotic-loaded cemented hemiarthroplasty. In particular for patients with multiple risk factors for the development of a PJI the usage of antibiotic-loaded bone cement seems to be a reasonable procedure for prevention of infection.
OUTCOMES OF FRACTURE-RELATED INFECTIONS: DO ORGANISM, DEPTH OF INVOLVEMENT, AND TEMPORALITY COUNT?
Authors: Wong Janus , Lee Alfred , Fang Christian , Yung Colin , Leung Henry , Liu Alicia , So Ryan , Leung Frankie 
Published: November 2023

AimTo determine mortality and outcomes of patients diagnosed with fracture-related infections (FRIs).MethodFRI patients treated at a trauma centre between 2001 and 2020 were analysed. The primary outcome was 1-year mortality; mortality associations with FRI organism, depth of involvement, and temporality were investigated with multivariable survival analysis. Healthcare-associated and serological outcomes were reported as secondary outcomes.Results311 FRIs with mean age of 67.0 and median Charlson comorbidity index of 0 were analysed. Methicillin-sensitive Staphylococcus aureus (MSSA) (29.9%) was the most frequently implicated organism. The majority of FRIs were deep infections (62.7%). FRIs were diagnosed at a median of 40 (IQR 15–200) days post index surgery. The mean follow-up was 5.9 years.One-year mortality amounted to 17.7%. MSSA FRIs were associated with better survival (adj HR 0.34, 95%CI 0.15–0.76, p=0.008). There was no difference in survivorship between deep or superficial FRI (adj HR 0.86, 95%CI 0.62–1.19, p=0.353) or in relation to onset time (adj HR 1.0, 95%CI 0.99–1.00, p=0.943). Implant removal or debridement alone was performed in 61.7% and 17% respectively. Antibiotics was prescribed for 53 (IQR 23–110) days, and patients were hospitalised for 39 (IQR 19–78) days. CRP and ESR normalised in 70.3% (median 46 days) and 53.8% (median 86 days) patients respectively.ConclusionsFracture-related infections are associated with significant mortality and morbidity regardless of depth and temporality. Non-MSSA FRIs are associated with inferior survival.
TREATMENT AND OUTCOME OF FRACTURE-RELATED INFECTION OF THE CLAVICLE
Authors: Sliepen Jonathan , Hoekstra Harm , Onsea Jolien , Bessems Laura , Depypere Melissa , Herteleer Michiel , Sermon An , Nijs Stefaan , Vranckx Jan , Metsemakers Willem-Jan 
Published: November 2023

AimThe number of operatively treated clavicle fractures has increased over the past decades. Consequently, this has led to an increase in secondary procedures required to treat complications such as fracture-related infection (FRI). The primary objective of this study was to assess the clinical and functional outcome of patients treated for FRI of the clavicle. The secondary objectives were to evaluate the healthcare costs and propose a standardized protocol for the surgical management of this complication.MethodAll patients with a clavicle fracture who underwent open reduction and internal fixation (ORIF) between 1 January 2015 and 1 March 2022 were retrospectively evaluated.This study included patients with an FRI who were diagnosed and treated according to the recommendations of a multidisciplinary team at the University Hospitals Leuven, Belgium.ResultsWe evaluated 626 patients with 630 clavicle fractures who underwent ORIF. In total, 28 patients were diagnosed with an FRI. Of these, eight (29%) underwent definitive implant removal, five (18%) underwent debridement, antimicrobial treatment and implant retention, and fourteen patients (50%) had their implant exchanged in either a single-stage procedure, a two-stage procedure or after multiple revisions. One patient (3.6%) underwent resection of the clavicle. Twelve patients (43%) underwent autologous bone grafting (tricortical iliac crest bone graft (n=6), free vascularized fibular graft (n=5), cancellous bone graft (n=1)) to reconstruct the bone defect. The median follow-up was 32.3 (P25-P75: 23.9–51.1) months. Two patients (7.1%) experienced a recurrence of infection. The functional outcome was satisfactory, with 26 out of 28 patients (93%) having full range of motion. The median healthcare cost was € 11.506 (P25-P75: € 7.953–23.798) per patient.ConclusionFRI is a serious complication that can occur after the surgical treatment of clavicle fractures. Overall, the outcome of patients treated for FRI of the clavicle is good, when management of this complication is performed by using a multidisciplinary team approach. The median healthcare costs of these patients are up to 3.5 times higher compared to non-infected operatively treated clavicle fractures. Expert opinion considers factors such as the size of the bone defect, the condition of the soft tissue, and patient demand to guide surgical decision making.
MASQUELET TECHNIQUE FOR INFECTED SEGMENTAL DEFECTS OF LONG BONES IN A LOW-RESOURCE SETTING OF SUB-SAHARAN AFRICA: TECHNICAL ADAPTATIONS AND OUTCOME
Authors: Loïc Fonkoue , Sylvain Wembou , Kennedy Muluem , Theophile Nana , Olivier Ngongang Franck , Marie-Ange Ngo Yamben , Jean Bahebeck 
Published: November 2023

Aiminfected segmental bone defect (ISBD) is frequent in developing countries. The aim of this study was to assess the efficacy of the Masquelet technique in the treatment of ISBD in a low-resource setting.Patients and MethodWe performed a prospective cohort study during the period from 2018 to 2022. Patients with infected bone defect of long bones were included. Management protocol consisted of two stages in all patients. The first stage consisted in debridement, tissues biopsy for microbiological culture, stabilization with external fixator and defect filling with gentamicin cement spacer. The second stage consisted of reconstruction using a cancellous bone autograft alone, or a mixture of autograft with allograft (demineralized bone matrix + tricalcium phosphate) and 1 gram of vancomycin powder. All patients were followed-up for at least one year. The results were assessed based on both objective (clinical and radiographic evaluation) and subjective (limb function and patient satisfaction) criteria. Main outcomes were bone union, reoperation and failure rates, union time, and limb function.ResultsWe included 31 patients in this study (80.6% men), with a median age of 35 [9 – 80] years. The tibia was affected in 12 cases and the femur in 15 cases. The median size of bone defect was 4 [1.5 – 12] cm. The most prevalent microorganisms were Klebsiella pneumoniae and Staphylococcus aureus. The mean interval between both stages was 14 (8 – 36) weeks and the median follow-up period after the second stage was 20 [12-62] months. External fixation was used in both stages in 25(80%) cases. Bone union was achieved in 26 (83.8%) patients of whom 24 without recurrence of infection, over a median time of 9 [6 – 16] months. All patients with a mixed graft (allograft and autograft) impregnated with local antibiotics achieved bone union. Two patients needed reoperation for relapse of infection between both stages, and subsequently achieved bone union without recurrence of infection. There were three cases of failure related to persistent infection or insufficient fixation stability in the second stage.ConclusionsMasquelet technique is a reliable procedure that can be safely performed in limited resources settings with satisfactory results. The mixture of autograft and allograft when available, all mixed with vancomycin seems to give promising results.
DEBRIDEMENT, ANTIBIOTICS, IRRIGATION, AND IMPLANT RETENTION IN A SHEEP FRACTURE-RELATED INFECTION MODEL
Authors: Siverino Claudia , Gens Lena , Ernst Manuela , Buchholz Tim , Windolf Markus , Richards Geoff , Zeiter Stephan , Moriarty Fintan 
Published: November 2023

AimDebridement, Antibiotics, Irrigation, and implant Retention (DAIR) is a surgical treatment protocol suitable for some patients with fracture related infection (FRI). Clinically relevant pre-clinical models of DAIR are scarce and none have been developed in large animals. Therefore, this project aimed to develop a large animal model for FRI including a DAIR approach and compare outcomes after 2 or 5 weeks of infection.MethodSwiss Alpine sheep (n=8), (2–6 years, 50–80 kg) were included in this study. This study was approved by cantonal Ethical authorities in Chur, Switzerland. A 2 mm osteotomy was created in the tibia and fixed with a 10-hole 5.5 mm steel plate. Subsequently, 2.5 mL of saline solution containing 106 CFU/mL of Staphylococcus aureus MSSA (ATCC 25923) was added over the plate. Sheep were observed for 2 (n=3) or 5 weeks (n=5) until revision surgery, during which visibly infected or necrotic tissues were removed, and the wound flushed with saline. All samples were collected for bacterial quantification. After revision surgery, the sheep were treated systemically for 2 weeks with flucloxacillin and for 4 weeks with rifampicin and cotrimoxazole. After 2 further weeks off antibiotics, the animals were euthanized. Bacteriological culture was performed at the end of the study. Bone cores were isolated from the osteotomy site and processed for Giemsa & Eosin and Brown and Brenn staining. A radiographical examination was performed every second week.ResultsBacteriological evaluation of the retrieved samples during revision surgery showed no significant difference between the 2 vs 5 weeks infection periods in term of total CFU counts. At the end of the study, radiographical examination showed callus formation over the osteotomy site in both groups, although the osteotomy was not completely healed in either group. At euthanasia, the 2 weeks infection group showed a higher soft tissue burden compared to the 5 weeks group, whereby the infection in the 5 weeks group was primarily located in the bone and bone marrow.ConclusionsThe large animal model of FRI and DAIR was successfully established. Bacteriological outcomes highlight that the increasing duration of the infection does not change the outcome but the location of the infection from a predominantly soft tissue infection to a deeper bone and intramedullary (IM) channel infection. The debridement of the IM channel could potentially reduce the infection burden by eliminating those bacteria not easily reached by systemic antibiotics, though is not practical using conventional techniques.
LONGITUDINAL INTRAVITAL IMAGING TO QUANTIFY THE “RACE FOR THE SURFACE” BETWEEN HOST IMMUNE CELL AND BACTERIA FOR ORTHOPAEDIC IMPLANTS WITH S. AUREUS COLONIZATION IN A MURINE MODEL
Authors: Xie Chao , Ren Youliang , Weeks Jason , Lekkala Sashank , Rainbolt Joshua , Xue Thomas , Shu Ye , Lee Kevin , de Mesy Bentley Karen L. , Yeh Shu-Chi , Schwarz Edward 
Published: November 2023

TitleLongitudinal Intravital Imaging to Quantify the “Race for the Surface” Between Host Immune Cell and Bacteria for Orthopaedic Implants with S. aureus Colonization in a Murine ModelAimTo assess S. aureus vs. host cell colonization of contaminated implants vis intravital multiphoton laser scanning microscopy (IV-MLSM) in a murine model.MethodAll animal experiments were approved by IACUC. A flat stainless steel or titanium L-shaped pin was contaminated with 105 CFU of a red fluorescent protein (RFP) expressing strain of USA300LAC, and surgically implanted through the femur of global GFP-transgenic mice. IV-MLSM was performed at 2, 4, and 6 hours post-op. Parallel cross-sectional CFU studies were performed to quantify the bacteria load on the implant at 2,4,6,12,18 and 24 hours.Results1) We developed a high-fidelity reproducible IV-MLSM system to quantify S. aureus and host cell colonization of a bone implant in the mouse femur. Proper placement of all implants were confirmed with in vivo X-rays, and ex vivo photos. We empirically derive the ROI during each imaging session by aggregating the imaged volume which ranges from (636.4um × 636.4um × 151um) = 0.625 +/- 0.014 mm3 of bone marrow in a global GFP-transgenic mouse.2) IV-MLSM imaging acquisition of the “race for the surface”.In vitro MPLSM images of implants partially coated with USA300LAC (RFP-MRSA) were verified by SEM image. Results from IV-MLSM of RFP-MRSA and GFP+ host cell colonization of the contaminated implants illustrated the mutually exclusive surface coating at 3hrs, which to our knowledge is the first demonstration of “the race for the surface” between bacteria and host cells via intravital microscopy.3) Quantifying the “race for the surface” with CFU verification of S. aureus on the implant. 3D volumetric rendering of the GFP+ voxels and RFP+ voxels within the ROI were generated in Imaris. The voxel numbers suggeste that the fight for the surface concludes ∼3hrs post-infection, and then transitions to an aggressive MRSA proliferation phase. The results of WT control demonstrate a significant increase in CFU by 12hrs post-op for both stainless steel (P<0.01) and titanium (P<0.01).ConclusionsWe developed IV-MLSM to quantify the “Race for the Surface” between host cells and contaminating S. aureus in a murine femur implant model. This race is remarkably fast, as the implant surface is completely covered with 3hrs, peak bacterial growth on the implant occurs between 2 and 12 hours and is complete by 12hrs.
ANTIBODY-DRUG CONJUGATE THERAPY AGAINST S. AUREUS IMPLANT-ASSOCIATED INFECTION IN A MURINE MODEL
Authors: Tvilum Anne , Johansen Mikkel Illemann , Glud Lærke , Malskær Diana , Khamas Amanda , Carmali Sheiliza , Mhatre Snehit , Søgaard Ane , Faddy Emma , de Vor Lisanne , Rooijakkers Suzan , Østergaard Lars , Meyer Rikke , Zelikin Alexander , Jørgensen Nis 
Published: November 2023

AimInfections represent a serious threat to the successful utilization of implants in modern medicine. Implant-associated infections are difficult to treat, because they involve biofilms that protect bacteria from the immune system and harbour antibiotic-tolerant persister cells.In this work, we developed an antibody-drug conjugate (ADC) containing the anti-neoplastic drug mitomycin C (MMC) as a novel treatment paradigm for implant-associated infections. MMC was chosen as it is a potent antimicrobial against biofilms and its synthesis into an ADC was chosen to alleviate toxicity. Following development and synthesis of the ADC, stability and release of MMC was measured. We then used the ADC to kill bacteria in suspension and in biofilms, in vitro and in vivo.MethodMitomycin C was conjugated to a commercially available antibody against S. aureus via a disulfide linkage, with a drug release occurred via thiol-disulfide exchange.ADC as tested against S. aureus under various growth conditions (planktonic, persisters and biofilm). In vitro toxicity of ADC vs MMC was measured using a human cell line (MOLT-4).Finally, two independent in vivo experiments were performed in a murine implant-associated osteomyelitis model. In experiment one ADC treatment was compared NaCl, vancomycin and vancomycin + ADC (n=10 for all groups). Subsequently, ADC was compared to NaCl, the antibody used in the ADC construction, MMC and a novel ADC constructed with a non-S. aureus antibody (n=10 for all groups). All treatments were started day 7 post inoculation and were administered for 3 days. CFU enumeration was done following sonication to quantify bacterial load.ResultsDrug release could be triggered on demand with N-acetyl cysteine and release occurred, once in contact with free thiols on S. aureus cell surface.The ADCs exhibited a concentration-dependent antimicrobial effect against S. aureus with doses exceeding 0.5 mg/l reducing amount of CFU to below detection limit (p< 0.001). 15 minutes exposure to ADC resulted in an approx. 2 log CFU/ml reduction compared to untreated biofilms (p < 0.01).In vivo ADC treatment was effective compared to NaCl treatment and the vancomycin treatment (p≤ 0.001). Further ADC and MMC treatment were comparable in efficacy, but both were superior than NaCl, pure antibody and the non-specific ADC (p≤ 0.05). Finally, in vitro cytotoxicity was significantly lower for ADC than MMC.ConclusionsIn this study we have demonstrated that ADCs can be a novel treatment approach to combat implant-associated infections caused by S. aureus.