bluuebunny/crossref_metadata_2025_split huggingface dataset:
BACTERIOPHAGE THERAPY IN ORTHOPAEDIC AND CARDIOVASCULAR SURGERY: CLINICAL EXPERIENCE IN EIGHT PATIENTS WITH DIFFICULT-TO-TREAT INFECTIONS
Authors: Morovic Paula , Benavente Luis Ponce , Karbysheva Svetlana , Perka Carsten , Trampuz Andrej 
Published: November 2023

AimAntibiotics have limited activity in the treatment of multidrug-resistant or chronic biofilm-associated infections, in particular when implants cannot be removed. Lytic bacteriophages can rapidly and selectively kill bacteria, and can be combined with antibiotics. However, clinical experience in patients with surgical infections is limited. We investigated the outcome and safety of local application of bacteriophages in addition to antimicrobial therapy.Method8 patients (2 female and 6 male) with complex orthopedic and cardiovascular infections were included, in whom standard treatment was not feasible or impossible. The treatment was performed in agreement with the Article 37 of the Declaration of Helsinki. Commercial or individually prepared bacteriophages were provided by ELIAVA Institute in Tbilisi, Georgia. Bacteriophages were applied during surgery and continued through drains placed during surgery three times per day for the following 5–14 days. Follow-up ranged from 1 to 28 months.ResultsMedian age was 57 years, range 33–75 years. Two patients were diagnosed with a persistent knee arthrodesis infection, one chronic periprosthetic joint infection (PJI), one cardiovascular implantable electronic device (CIED) infection and four patients with left ventricular assist device (LVAD) infection. The isolated pathogens were multi-drug-resistant Pseudomonas aeruginosa (n=3), methicillin-sensitive Staphylococcus aureus (n=4), methicillin-resistant Staphylococcus aureus (MRSA) (n=1) and methicillin-resistant Staphylococcus epidermidis (MRSE) (n=1). 4 infections were polymicrobial.5 patients underwent surgical debridement with retention of the implant, 1 patient with PJI underwent the exchange of the prosthesis and one patient with LVAD infection was treated conservatively. All patients received intravenous and oral antibiotic therapy and local application of bacteriophages. At follow-up of 12 month, 5 patients were without signs or symptoms of infection, whereas in one patient with LVAD infection, a relapse was observed with emergence of phage-resistant Pseudomonas aeruginosa. In this patient, no surgical revision was performed.ConclusionsBacteriophage therapy may represent a valid additional approach, when standard antimicrobial and surgical treatment is not possible or feasible, including in difficult-to-treat infections. In our case series, 5 of 6 patients were infection free after 1 year. Further studies need to address the optimal bacteriophage administration route, concentration, duration of treatment and combination with antimicrobials.
CAN A DIABETIC FOOT ULCER BE PREVENTED?
Authors: Tiruveedhula Madhu , Graham Anna , Thapar Ankur , Dindyal Shiva , Mulcahy Michael 
Published: November 2023

AimThe aim of this paper is to analyse the cause of neuropathic diabetic foot ulcers and discuss their preventive measures.MethodsReview of patients with foot ulcers managed in our diabetic MDT clinics since Feb 2018 were analysed. Based on this observation and review of pertinent literature, following observations were made.ResultsForefootProgressive hindfoot equinus from contraction of gastroc-soleus-tendo-Achilles complex, with additional contraction of tibialis posterior and peroneal longus muscles and, progressive plantar flexed metatarsal heads secondary to claw toe deformity results in increased forefoot plantar pressures. In patients with insensate feet, this result in ulcer formation under the metatarsal heads from shear stress when walking.Callosity under the metatarsal heads is the earliest clinical sign. Most patients by this time have fixed tightness of the muscle groups as assessed by negative Silfverskiold test. Percutaneous tendo-Achilles lengthening (TAL) has shown to reduce the mid-forefoot plantar pressures by 32% and ulcer healing in 96% of patients within 10 weeks (± 4 weeks). Additional z-lengthening of peroneal longus and tibialis posterior tendons helped in patients with big-toe and 5th metatarsal head ulcers. Proximal metatarsal osteotomies further reduce the forefoot pressures to near normality.MidfootMidfoot ulcers are secondary to rocker-bottom deformity a consequence of Charcot neuroarthropathy (CN). Hindfoot equinus as described and relative osteopenia from neurally mediated increased blood flow (neurovascular theory) and repeated micro-trauma (neurotraumatic theory) result in failure of medial column osseo-ligamentous structures. As the disease progress to the lateral column, the cuboid height drops resulting in a progressive rocker bottom deformity. The skin under this deformity gradually breaks down to ulceration.In the pre-ulcerative stages of midfoot CN, TAL has shown to stabilise the disease progression and in some patents’ regression of the disease process was noted. The lump can excised electively and the foot accommodated in surgical shoes.HindfootThese develop commonly at the pressure areas and bony exostosis in non-ambulatory patients. In ambulatory patients, the most common cause are factors that result in over lengthening of tendo-Achilles such as after TAL, spontaneous tears, or tongue-type fractures.ConclusionsEarly identification of factors that result in plantar skin callosity and treating the deforming forces prevent progression to ulceration. Total contact cast without treatment of these deforming forces results in progression of these callosities to ulceration while in the cast or soon after completion of cast treatment.
BONE AND SOFT-TISSUE CONCENTRATIONS OF PENICILLIN: IS ORAL PENICILLIN V NON-INFERIOR TO INTRAVENOUS PENICILLIN G?
Authors: Rasmussen Hans Christian , Stilling Maiken , Lilleøre Johanne Gade , Petersen Elisabeth , Jørgensen Andrea René , Hvistendahl Magnus A. , Hanberg Pelle , Bue Mats 
Published: November 2023

AimThe β-lactam penicillin is often used in the treatment of soft tissue infections and osteomyelitis caused by penicillin susceptible Staphylococcus aureus. Oral antibiotic treatment has been shown to be non-inferior to intravenous (IV) therapy when used during the first 6 weeks in complex orthopedic infections (OVIVA trial). However, the use of oral β-lactams in osteomyelitis treatment remains a topic of debate due to low and variable bioavailability. The aim was to assess the time for which the unbound penicillin concentration exceeded targeted minimum inhibitory concentrations (fT>MIC) in cancellous bone and subcutaneous tissue after IV (penicillin G) and oral (penicillin V) treatment in a porcine microdialysis model.Method12 female pigs (75kg) were assigned to standard clinical regimens of either three doses of IV penicillin G (1.2g) or oral penicillin V (0.8g) every 6h over 18h. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was collected in the first dosing interval (0–6h; prophylactic situation) and the third dosing interval (12–18h; assumed steady state). Plasma samples were collected for reference. MIC targets of 0.125μg/mL (Staph. aureus breakpoint), 0.25μg/mL (Strep. Group A, B, C and G breakpoint) and 0.5μg/mL (4xMIC) were applied.ResultsFor all investigated MIC targets, IV penicillin G resulted in a longer mean fT>MIC in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral penicillin V. Across compartments, mean fT>MIC for IV penicillin G (MIC: 0.125, 0.25 and 0.5μg/mL) were ≥97%, ≥84% and ≥75% during the first dosing interval, and 100%, ≥95% and ≥88%, during the third dosing interval. The mean fT>MIC for oral penicillin V were ≥40%, ≥24% and ≥7% during the first dosing interval, and ≥42%, ≥36% and ≥18% during the third dosing interval.ConclusionsThe findings suggest that standard clinical dosing of IV penicillin G provides superior fT>MIC in cancellous bone and subcutaneous tissue compared to oral penicillin V, particularly in the third dosing interval. This emphasizes the importance of appropriate route of administration when applying penicillin treatment.AcknowledgementsFunding was received from The Kirsten and Freddy Johansen Foundation, The Novo Nordisk Foundation, The Beckett Foundation, The Hede Nielsen Family Foundation, King Christian the 10th Foundation, The A.P. Møller Foundation, The Dagmar Marshalls Foundation, and The Carl and Ellen Hertz Foundation.
EXTENDED ORAL ANTIBIOTIC PROPHYLAXIS: DO THE SAME CRITERIA APPLY TO PATIENTS UNDERGOING ASEPTIC REVISION ARTHROPLASTY?
Authors: Fowler Mia , Nocon Allina , Chiu Yu-Fen , Tam Kathleen , Carli Alberto 
Published: November 2023

AimProsthetic joint infection (PJI) is a devastating and costly complication of total joint arthroplasty (TJA). Use of extended oral antibiotic prophylaxis (EOAP) has become increasingly popular in the United States following a highly publicized study (Inabathula et al) from a single center demonstrating a significant protective effect (81% reduction) against PJI in ‘high-risk’ patients. However, these results have not been reproduced elsewhere and EOAP use directly conflicts with current antibiotic stewardship efforts. In order to study the role of EOAP in PJI prevention, consensus is needed for what defines ‘high-risk’ patients. The revision TJA (rTJA) population is an appropriate group to study due to having a higher incidence of PJI. The purpose of the current study was to rigorously determine which preoperative conditions described by Inabathula et al. (referred to as Inabathula criteria (IBC)) confer a higher rate of PJI in patients undergoing aseptic rTJA.Method2,256 patients that underwent aseptic rTJA at a single high-volume institution between 2016–2022 were retrospectively reviewed. Patient demographics and comorbidities were recorded to determine if they had 1 or more ‘IBC’, a long list of preoperative conditions including autoimmune diseases, active smoking, body mass index (BMI)>35, diabetes mellitus, and chronic kidney disease (CKD). Reoperation for PJI at 90-days and 1-year was recorded. Chi-squared or Fischer's exact tests were calculated to determine the association between preoperative presence/absence of IBC and PJI. Multivariable logistic regressions were conducted to determine if specific comorbidities within the IBC individually conferred an increased PJI risk.Results1223 patients (54.2%) had at least one IBC condition. IBC-positive patients were more likely to be female, have an increased ASA score, and higher BMI. IBC-positive patients had a significant increase in PJI risk at both 90-days (relative risk (RR)=2.32, p<0.0001) and 1-year (RR=2.14, p=0.002) versus IBC-negative patients. Within IBC-positive patients, every additional IBC condition conferred a 1.8× odds increase for 90-day PJI (p<0.0001), and 1.76× odds increase in 1-year PJI (p<0.0001). Multivariable logistic regression identified active smoking, BMI>35, CKD, and diabetes mellitus as being independently associated with PJI development (p<0.05).ConclusionsOver half of rTJA patients meet IBC and could be eligible to receive EOAP in the United States. However, the specific presence of active smoking, BMI>35, CKD, and diabetes mellitus appear to be responsible for the increased risk of PJI. Prospective studies investigating EOAP use for patients with these specific conditions are urgently needed to prevent unnecessary antibiotic use.
DIRECT HOSPITAL COSTS PER CASE FOR PERIPROSTHETHIC HIP AND KNEE JOINT INFECTION IN EUROPE: A SYSTEMATIC REVIEW
Authors: Szymski Dominik , Walter Nike , Hierl Katja , Rupp Markus , Alt Volker 
Published: November 2023

AimThe number of periprosthetic joint infections (PJI) is increasing due to ageing population and increasing numbers of arthroplasty procedures and treatment is costly. Aim of the study was to analyze the direct healthcare costs of PJI in Europe for total hip arthroplasties (THA) and total knee arthroplasties (TKA).MethodA systematic review in PubMed with search of direct costs of PJI in European countries was performed. Thereby the term cost* AND (infection OR PJI) AND (prosthesis OR knee OR hip OR “TKA” OR “THA” OR arthroplast*) was combined with each European country to detect relevant publications. Publications with definition of performed procedure and joint localization were included into further analysis. The mean value of direct healthcare cost was calculated for the respective joint and the respective operation performed.ResultsScreening revealed 1,274 eligible publications. After review of abstracts and full-texts n=11 manuscripts were included into final analysis (Figure 1). The mean combined direct hospital costs for revision for PJI after TKA and THA was 26,311€. Mean costs for revision procedures for PJI after TKA were 24,617€. Direct costs for TKA-PJI treated with debridement, antibiotics and implant retention (DAIR) were on average 10,121€. For two-stage revisions in knee arthroplasties total average costs were 30,829€. Referring to revision surgery for PJI in THA, the mean hospital costs in Europe were 28,005€. For a DAIR procedure direct healthcare costs of 5,528€ were identified. Two-stage revision cost on average 31,217€.ConclusionsPJIs are associated with significant direct healthcare costs. The financial burden of up to 30,000 € per case underlines the impact of the disease for European health care system. However, the number of detailed reports on PJI costs is limited and the quality of the literature is limited. There is a strong need for more detailed financial data on the costs of PJI treatment.For any tables or figures, please contact the authors directly.
EFFECTIVENESS OF A MULTIDISCIPLINARY TEAM FOR COMPLEX BONE AND JOINT INFECTIONS: ANALYSIS OF ADHERENCE TO TREATMENT DECISION
Authors: Hanssen Jaap L.J. , van der Linden Henrica M.J. , van der Beek Martha T. , van der Wal Robert J.P. , Termaat Marco F. , de Boer Mark G.J. , Scheper Henk 
Published: November 2023

AimMultidisciplinary team (MDT) management of complex bone and joint infections (BJI) is increasingly implemented but studies evaluating this approach are scarce. We assessed the effectiveness of our MDT by analyzing the adherence to its treatment decisions.MethodA cohort study was conducted comprising patients with complex BJI of which the management was discussed during MDT meetings between 2015 and 2022 in a tertiary care academic hospital. Patient characteristics and MDT data were obtained from electronic patient records.ResultsThe analysis included 1321 MDT case decisions on 509 patients. During the study period, the number of patients discussed by the MDT increased from 2.7 to 5.5 per meeting. The percentage of discussed patients with BJI other than prosthetic joint infections (PJI) increased from 26% to 52%. The overall adherence rate to MDT decisions was 92.1%. Reasons for non-adherence were disagreement with the MDT whether cure was achieved or not (34%), new clinical information that was not available during the MDT meeting (12%), preference for suppressive antibiotic treatment over surgery (8%) or not recorded in the patient file (46%).ConclusionsOver the years, the MDT meeting content expanded from mainly PJI to all complex BJI. The high adherence rate to MDT decisions was indicative of an effective MDT. Analysis of adherence is a useful tool to evaluate an MDT and can be used to improve its quality. Different aspects of an MDT need to be evaluated to fully determine its impact and to help improve the care for patients with complex BJI.
WHAT CAN THEY EXPECT? DECREASED QUALITY OF LIFE AND INCREASED POSTOPERATIVE COMPLICATION RATE IN PATIENTS WITH A FRACTURE-RELATED INFECTION
Authors: Buijs Michelle , Haidari Susan , Ijpma Frank , Hietbrink Falco , Govaert Geertje 
Published: November 2023

AimBy gaining insight into the Quality of Life (QoL) status and occurrence of complications, critical facets in the care for patients with Fracture-Related Infection (FRI) can be mitigated and measures can be taken to improve their outcome. Therefore, the aims of this study were to 1) determine the QoL in FRI patients in comparison to non-FRI patients and 2) describe the occurrence of complications in both FRI and non-FRI patients.MethodAn ambidirectional cohort study was conducted in a level-1 trauma centre between January 1st 2016 and November 1st 2021. All patients who underwent surgical stabilisation of a long bone fracture were eligible for inclusion. Patients with an Injury Severity Score (ISS) ≥16 or incomplete follow-up were excluded. QoL was assessed through the use of five-level EuroQol five-dimension (EQ-5D-5L) questionnaires twelve months post-injury.ResultsA total of 134 patients were included, of whom 38 (28%) FRI patients and 96 (72%) non-FRI patients. In comparison to non-FRI patients, FRI patients scored significantly worse on the QoL assessment regarding the index value (p=0.012) and the domains mobility (p<0.001), usual activities (p=0.010) and pain/discomfort (p=0.009). During the median follow-up of 14.5 months (interquartile range (IQR) 9.5–26.5), 25 FRI patients developed a total of 49 distinctive complications besides FRI. The complications nonunion (18%, n=9/49), infection other than FRI (e.g. line infection, urinary tract infection, pneumonia) (18%, n=9/49) and implant failure (14%, n=7/49) were the most frequently described in the FRI group.ConclusionsPatients who suffered from an FRI have a decreased QoL in comparison to those without an FRI. Moreover, patients with an FRI have a higher rate of additional complications. These findings can help in patient counselling regarding the potential physical and mental consequences of having a complicated course of recovery due to an infection.
CLINICAL OUTCOME AND MICROBIOLOGICAL ANALYSIS OF UNEXPECTED POSITIVE INTRAOPERATIVE CULTURES IN PRESUMED ASEPTIC KNEE AND HIP REVISION ARTHROPLASTY: A TEN-YEAR RETROSPECTIVE ANALYSIS WITH A MINIMUM FOLLOW-UP OF TWO YEARS
Authors: Simon Sebastian , Frank Bernhard J.H. , Hartmann Susana Gardete , Mitterer Jennyfer A. , Sujeesh Sebastian , Huber Stephanie , Hofstaetter Jochen G. 
Published: November 2023

AimsThe aim of this study was to assess the incidence the microbiological spectrum and clinical outcome of hip and knee revision arthroplasties with unexpected-positive-intraoperative-cultures (UPIC) at a single center with minimum follow up of 2 years.MethodsWe retrospectively analyzed our prospectively maintained institutional arthroplasty registry. Between 2011 and 2020 we performed presumably aseptic rTHA (n=939) and rTKA (n= 1,058). Clinical outcome, re-revision rates and causes as well as the microbiological spectrum were evaluated.ResultsIn total, 219/939 (23.3%) rTHA and 114/ 1,058 (10.8%) rTKA had a UPIC (p<0.001). Single positive intraoperative cultures were found in 173/219 (78.9%) in rTHA and 99/114 (86.8%) in rTKA, whereas 46/219 (21.0%) rTHA and 15/114 (13.2%) rTKA had positive results in ≥2 intraoperative cultures. A total of 390 microorganisms were found among the 333 cases. Staphylococcus epidermidis 30.9%, CoNS (21.9%), Cutibacterium acnes 21.1%, and Bacillus spp. 7.3% were the most common microorganisms. Overall, detected microorganisms showed high sensitivity to daptomycin (96.6%), vancomycin (97.3%) and linezolid (98.0%).After a minimum follow up of 2 years (rTHA 1,470 (735; 3,738) days; rTKA 1,474 (749; 4,055) days). During the 2-year follow-up, 8 patients died and 5 were lost to follow-up. There were 54/219 (24.7%) re-revision in rTHa and 20/114 (17.5%) in rTKA. Overall, there were 23 (10.5%) septic re-rTHA and 9 (7.9%) septic re-rTKA as well as 31 (14.2%) aseptic re-rTHA and 11 (9.6%) aseptic re-rTKA.Patients with previous septic revisions bevor UPIC procedure showed a significant higher risk for septic re-revision (p<0.05). Moreover, there were less septic re-revisions after single culture positive UPIC (rTHA: 16/173 (9.2%); rTKA 6/99 (6.1%)) compared to ≥2 positive intraoperative cultures UPIC (rTHA: 7/46 (15.2%); rTKA 3/15 (20.0%)).The most common reason for re-revision in the rTHA-group was aseptic loosening of the cup (34.2%) or of the stem (23.3%), dislocation (18.3%) and periprosthetic-fractures (7.8%). In the rTKA-group it was aseptic loosening (40.4%), instability (24.6%) and secondary patella resurfacing (7.9%). There was a higher septic re-revision rate in consecutive revisions than in planned revisions 17.3% vs. 8.5% in the rTHA-group and 14.3% vs. 7.5% in the rTKA-group, p<0.001.ConclusionUPICs are common in rTJA. The rate was higher in hips which may partly explained by the easier pre op joint aspiration in the knee. UPIC may lead to an increase in subsequent re-revisions.
INFERIOR DIAGNOSTIC PERFORMANCE OF SERUM ALBUMIN-GLOBULIN-RATIO IN PERIPROSTHETIC JOINT INFECTION
Authors: Luger Markus , Windhager Reinhard , Sigmund Irene 
Published: November 2023

AimSerum parameters continue to be a focus of research in diagnosing periprosthetic joint infections (PJI). Several workgroups have recently proposed serum Albumin-Globulin-Ratio (AGR) as a potential new biomarker. Due to controversies in the literature, its usability in clinical practice remains uncertain. The aim of this study was to assess the value of serum AGR in diagnosing PJI preoperatively, especially in comparison with the well-established marker C-reactive Protein (CRP).MethodFrom January 2015 to June 2022, patients with indicated revision hip (rTHA) and knee (rTKA) arthroplasty were included in this retrospective cohort study of prospectively collected data. A standardized diagnostic workup was performed using the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI, excluding CRP. Diagnostic accuracies of serum AGR and CRP were calculated by receiver operating characteristic curve (ROC) analysis. A z-test was used to compare the area under the curves (AUC).ResultsA total of 275 patients with rTHA and rTKA were included, 144 joints (52.4%) were identified as septic. Decreased AGR and elevated CRP were strongly associated with PJI, optimal diagnostic thresholds were calculated with 1.253 and 9.4 mg/L, respectively. Sensitivities were 62.5% (95%-confidence interval: 54.3–70.0) and 73.6% (65.8–80.1), and specificities 84.7% (77.5–89.9) and 87.8% (80.9–92.4), respectively. CRP showed a significantly higher AUC than AGR (0.807 (0.761–0.853) and 0.736 (0.686–0.786); p<0.0001).Subgroup analysis of acute versus chronic infections yielded significantly higher diagnostic accuracies in acute PJI for both parameters (p<0.0001). Similar results were observed when focusing on the causative microorganism; a better diagnostic performance was observed in high-virulence PJI compared to low-virulence PJI (p≤0.005). Furthermore, higher AUCs were calculated in knee PJI compared with hip PJI, with a significant difference for AGR (p=0.043).ConclusionsDue to its limited diagnostic accuracy, serum AGR cannot be recommended as an additional marker for diagnosing PJI. Serum parameters are generally unspecific and can be influenced by comorbidities and other foci of infection. Additionally, parameters may remain within normal levels in low-grade PJI. Evaluating AGR, further possible pitfalls must be considered, for example an increased latency until bottom values are reached and the impact of malnutrition.