bluuebunny/crossref_metadata_2025_split huggingface dataset:
A TWO-STAGE APPROACH IN MANAGING DIABETIC NEUROPATHIC FOREFOOT ULCERS
Authors: Tiruveedhula Madhu , Graham Anna , Thapar Ankur , Dindyal Shiva , Mulcahy Michael 
Published: November 2023

AimTo describe a 2-stage treatment pathway for managing neuropathic forefoot ulcers and the safety and efficacy of percutaneous tendo-Achilles lengthening (TAL) in out-patient clinics.MethodsForefoot ulcers in patients with diabetic neuropathy are a result of factors that result in increased forefoot plantar pressure. Plantar flexed metatarsal heads secondary to progressive claw toe deformity and hindfoot equinus from changes within the gastrocnemius-soleus-tendo-Achilles complex, with additional contraction of tibialis posterior and peroneal longus, secondary to motor neuropathy results in progressive increase in forefoot plantar pressures.Consecutive patients, who presented to our Diabetic Foot clinic since February 2019 with forefoot ulcers or recurrent forefoot callosity were treated with TAL in the first instance, and in patients with recurrent or non-healing ulcers, by proximal dorsal closing wedge osteotomy; a 2-stage treatment pathway.Patients were followed up at 3, 6, and 12 months to assess ulcer healing and recurrence.ResultsOne hundred and twelve patients (146 feet) underwent TAL by 3 consultants in the out-patient clinics. Of these, 96 feet were followed for a minimum of 12 months (range 12–36 months). None had infection or wound related problems at the tenotomy sites; complete transection of the tendon was noted in 4 patients (4%) and one-patient developed heel callosity suggestive of over-lengthening.In 92 feet (96%), the ulcers healed 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.In 12 feet (10%), the ulcer failed to heal or recurred, the MRI scan in these patients showed plantar flexed metatarsals secondary to progressive claw toe deformity. The ulcer in this group healed after surgical offloading with proximal dorsal closing wedge osteotomy. In patients with osteomyelitis, the intramedullary canal was curetted and filled with local antibiotic eluting agents such as Cerament G®. The osteotomy site was stabilised with a percutaneous 1.6mm k-wire.ConclusionThe described 2-stage treatment pathway results in long-term healing of neuropathic forefoot ulcers, and in 96% of patients, the ulcer healed after out-patient percutaneous TAL alone. TAL is a safe and effective initial out-patient procedure with improved patient outcomes.
SINGLE-STAGE, COMBINED, ORTHO-PLASTICS TREATMENT OF SEVERE CALCANEAL OSTEOMYELITIS WITH LARGE SOFT-TISSUE DEFECTS: LONG-TERM FOLLOW-UP
Authors: Down Billy , Tsang Shao-Ting Jerry , Hotchen Andrew , Ferguson Jamie , Stubbs David , Loizou Constantinos , McNally Martin , Ramsden Alex , Kendal Adrian 
Published: November 2023

AimCalcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below knee amputation; particularly in cases of severe soft tissue destruction. This study assesses the outcomes of combined ortho-plastics treatment of complex calcaneal osteomyelitis.MethodA retrospective review was performed of all patients who underwent combined single stage ortho-plastics treatment of calcaneal osteomyelitis (2008- 2022). Primary outcome measures were osteomyelitis recurrence and BKA. Secondary outcome measures included flap failure, operative time, complications, length of stay.Results33 patients (16 female, 17 male, mean age = 54.4 years) underwent combined ortho-plastics surgical treatment for BACH “complex” calcaneal osteomyelitis with a median follow-up of 31 months (s.d. 24.3). 20 received a local flap, 13 received a free flap. Fracture-related infection (39%) and diabetic ulceration (33%) were the commonest causes. 54% of patients had already undergone at least one operation elsewhere.There were seven cases of recurrent osteomyelitis (21%); all in the local flap group. One patient required a BKA (3%). Recurrence was associated with increased mortality risk (OR 18.8 (95% CI 1.5–227.8), p=0.004) and reduced likelihood of walking independently (OR 0.14 (95% CI 0.02–0.86), p=0.042).Local flap reconstruction (OR 15 (95% CI 0.8–289.6), p=0.027) and peripheral vascular disease (OR 39.7 (95% CI 1.7–905.6), p=0.006) were associated with increased recurrence risk.Free flap reconstruction took significantly longer intra-operatively than local flaps (443 vs 174 minutes, p<0.001), but without significant differences in length of stay or frequency of out-patient appointments.ConclusionsSingle stage ortho-plastic management was associated with 79% eradication of infection and 3% amputation in this complex and co-morbid patient group. Risk factors for failure were peripheral vascular disease and local flap reconstruction. Whilst good outcomes can be achieved, this treatment requires high levels of in-patient and out-patient care.
AMOXICILLIN IN DEEP-SEATED SAMPLES: QUANTIFICATION OF A DELICATE COMPOUND
Authors: Erdmann Joana , Clauss Martin , Khanna Nina , Kühl Richard , Linder Fanny , Mathys Mandy , Morgenstern Mario , Ullrich Kathrin , Rentsch Katharina 
Published: November 2023

AimAntibiotic concentration at the infected site is a relevant information to gain knowledge about deep-seated infections. The combination of antibiotic therapy and debridement is often indicated to treat these infections. At University Hospital Basel the most frequently administered antibiotic before debridement is amoxicillin in combination with clavulanic acid. Amoxicillin is a fragile beta-lactam antibiotic that brings multiple challenges for its quantification.As for many sample materials only little material is available, the aim of this work was to establish a sensitive and reliable quantification method for amoxicillin that only requires a small sample mass. We did not quantify clavulanic acid as we focused on the drug with antibiotic action.MethodUsually discarded sample material during debridement was collected and directly frozen. The thawed tissues were prepared using simple protein precipitation and manual homogenization with micro pestles followed by a matrix cleanup with online solid-phase extraction. Separation was performed by HPLC followed by heated electrospray ionization and tandem mass spectrometry.ResultsDuring method development, amoxicillin showed partial formation of a covalent methanol adduct when performing protein precipitation. Furthermore, multiple in-source products of amoxicillin during ionization could be observed. Adding an aqueous buffer to the samples before protein precipitation and summing up the signals of amoxicillin and its in-source acetonitrile-sodium-adduct led to successful method validation for a calibration range of 1–51 mg/kg using 10 mg of each tissue sample. The imprecision was < 8% over the entire concentration range and the bias was ≤ 10 %. The quantitative matrix effect was < 6 % in six different tissue samples.Until now we measured amoxicillin in samples from nine patients with prosthetic joint infection, bursitis, or an abscess who obtained amoxicillin between 5 hours and 15 minutes before sampling and found concentrations between 1.4 and 35 mg/kg.ConclusionsWith this method, we developed a fast, simple, and sensitive quantification assay for amoxicillin in tissue samples with little material that can now be applied to different study samples.
STEADY-STATE PIPERACILLIN CONCENTRATIONS IN THE PROXIMITY OF AN ORTHOPAEDIC IMPLANT: A MICRODIALYSIS PORCINE STUDY
Authors: Lilleøre Johanne Gade , Jørgensen Andrea , Knudsen Martin , Hanberg Pelle , Öbrink-Hansen Kristina , Tøstesen Sara , Søballe Kjeld , Stilling Maiken , Bue Mats 
Published: November 2023

Background and aimImplant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low it is crucial to achieve adequate antibiotic concentrations proximate to the implant for a sufficient amount of time to protect the implant surface and ensure tissue integration. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant inserted in cancellous bone.MethodSix female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12–18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference.ResultsTime above the minimal inhibitory concentration (fT>MIC) was evaluated for MIC of 8 (low target) and 16 μg/mL (high target). For the low piperacillin target (8 μg/mL), comparable mean fT>MIC across all the investigated compartments (mean range: 54–74%) was found. For the high target (16 μg/mL), fT>MIC was shorter inside the cannulated screw (mean: 16%) than in the cancellous bone next to the screw and plasma (mean range: 49–54%), and similar between the two cancellous bone compartments.ConclusionsTo reach more aggressive piperacillin fT>MIC targets in relation to the implant, alternative dosing regimens such as continuous infusion may be considered.
LOCAL ANTIBIOTIC DELIVERY VIA INTRA-ARTICULAR CATHETER INFUSION FOR THE TREATMENT OF PERIPROSTHETIC JOINT INFECTION: A SYSTEMATIC REVIEW
Authors: Bruyninckx Sander , Vles Georges 
Published: November 2023

AimThe objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality.MethodA comprehensive literature search in accordance with the Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA) guidelines was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Exclusion criteria included patients < 18 years of age, follow-up <11 months, and a score < 6 on the National Institute of Health quality assessment tool.Results15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The quality of many studies was impeded by a retrospective design (14/15), a relative small study population (10 out of 15 studies had less than 50 patients), selection bias, and remarkable heterogeneity in terms of catheter type, antibiotic type, dose and duration of IA antibiotics and techniques of surgical revision. 347 were chronic infections, 66 acute infections and 218 unknown. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (499/631, 79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (77/631, 12.2%), DAIR with adjuvant IA antibiotic infusion (36/631, 5.7%) or two-stage revision with adjuvant IA antibiotic infusion (19/631, 3.0%). Mean duration of IA antibiotic infusion was 19 days (range 3–50), although most patients received a combination of both IA and systemic (IV or PO) antibiotics. An overall failure rate (defined as failures of infection eradication/total PJIs) of approximately 11% was found. The use of IA antibiotic infusion as a stand-alone treatment was associated with a higher failure rate. In total 117 complications occurred in 631 cases (18.5%). Of these, 71 were non-catheter-related (60.7%) and 46 were catheter-related (39.3%). The most common catheter-related complications were premature loss of the catheter (18/46), developing a fistula (5/46), and elevated blood urea nitrogen (BUN) and creatinine levels (12/46).ConclusionsDue to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. From a theoretical point of view it seems likely that is should not be used as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs, labour and catheter-related complications of this treatment modality.
TUBERCULOUS ARTHRITIS OF NATIVE JOINTS: A SYSTEMATIC REVIEW AND EBJIS WORKGROUP REPORT
Authors: Marais Leonard , Nieuwoudt Luan , Nansook Adisha , Menon Aditya , Benito Natividad 
Published: November 2023

AimThe aim of this systematic review was to assess the existing published data on tuberculous arthritis involving native joints in adults aged 18 years and older. The specific research questions focused on the diagnosis and management of the disease.MethodThis study was performed in accordance with the guidelines provided in the Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR). A systematic literature search was undertaken of Pubmed, Web of Science, Scopus and the Cochrane library. Only studies published in English since 1970 were considered. Case series involving less than 10 patients, systematic and narrative reviews, and laboratory or animal studies were excluded. We also excluded reports of TB infections not involving a “native joint” and tuberculosis of the spine. The level of evidence and strength of recommendations was performed in accordance with the GRADE system.ResultsThe systematic review of the literature yielded 2023 potential sources. Following deduplication, screening and full-text review, 20 data sources involving 573 patients from nine countries, were included. There was considerable variation amongst the studies in terms of the approach to diagnosis and management. The most common method used to confirm the diagnosis was microbiological culture of tissue obtained by biopsy, with positive findings in 93% of cases. Medical management involved a median 12 months of antitubercular treatment (IQR 8–16; range 4–18 months). Duration of pre-operative treatment ranged from two to 12 weeks in duration. Surgery was performed in approximately 87% of patients and varied from arthroscopic debridement to complete synovectomy combined with total joint arthroplasty. When arthroplasty and arthrodesis cases are excluded, 80% of patients received an open or arthroscopic debridement. The mean follow-up time of all studies was 26 months, with most studies demonstrating a minimum follow-up of at least six-months (range 3–112 months). Recurrence rates were reported in most studies, with an overall average recurrence rate of 7,4% (35 of 475).ConclusionsThe current literature on TB arthritis highlights the need for the establishment of standardised diagnostic criteria. Further research is needed to define the optimal approach to medical and surgical treatment. The role of early debridement in active tuberculous arthritis needs to be explored further. Specifically, comparative studies are required to address the questions around use of medical treatment alone versus in combination with surgical intervention.
EVALUATION OF AN UPGRADED SYNOVIAL CALPROTECTIN LATERAL FLOW ASSAY IN UNCLEAR CASES OF HIP AND KNEE PROSTHETIC JOINT INFECTIONS
Authors: Gardete-Hartmann Susana , Simon Sebastian , Frank Bernhard J.H. , Sebastian Sujeesh , Loew Marcellino , Sommer Ian , Hofstaetter Jochen 
Published: November 2023

AimSynovial calprotectin point-of-care test (POC) has shown promising clinical value in diagnosing periprosthetic joint infections (PJIs). However, limited data are available in unclear cases. Moreover, cut-off values for calprotectin lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) need to be adapted. The aim of this study was to evaluate the performance of an upgraded and more sensitive version of a synovial calprotectin LFA along with ELISA immunoassay in patients with septic, aseptic, and unclear cases.MethodsOverall, 206 prospectively collected periprosthetic synovial fluid samples from 169 patients (106f/63m; 38 hip/131 knee) who underwent revision surgeries were retrospectively evaluated for calprotectin concentration. The following groups were analyzed: unexpected negative cultures (UNC; 32/206), unexpected positive cultures (UPC; 28/206), and unclear cases (65/206) with conflicting clinical results. In addition, we added a true aseptic (40/206), and true septic (41/206) control groups according to the international consensus meeting (ICM) 2018 PJI classification. Calprotectin concentration was determined by a rapid quantitative LFA (n=206) (Lyfstone®, Norway), and compared to calprotectin ELISA immunoassay (171/206). For the determination of a new calprotectin cut-off value, analysis of the area under the curve (AUC) followed by Youden's J statistic were performed using the calproctectin values from clear septic and aseptic cases. Sensitivity and specificity for calprotectin were calculated. All statistical analyses were performed using IBM-SPSS® version 25 (Armonk, NY, USA).ResultsAn absolute calprotectin value of 43 mg/ml, and 40.15 mg/ml was determined to be the optimal cut-off for PJI diagnosis using the new version of the LFA and ELISA, respectively. With this cut-off, the sensitivity and specificity of synovial calprotectin concentration for PJI were 88.1% (95% CI 77.8 to 94.7) and 76.6% (95% CI 61.9 to 87.7) for LFA, and 97.06% (95% CI 89.8 to 99.64) and 93.6% (95% CI 82.5 to 98.66) for ELISA, respectively. Of the evaluated groups, UNC 30/32 (93.8%) vs 26/27 (96.3%), UPC 6/28 (21.4%) vs 4/21 (19%), and unclear samples 45/65 (69.2%) vs 30/56 (53.6%) displayed a high likelihood of infection by using LFA, and ELISA, respectively.ConclusionThe upgraded version of the calprotectin quantitative LFA with a new suggested cut-off for infected samples showed additional clinical value in identifying cases at high risk of infection in unclear PJI revisions. Additionally, calprotectin ELISA immunoassay had a better performance than LFA. Further large sample-size validation studies are warranted.
WHAT IS THE AGREEMENT BETWEEN PRINCIPLES AND PRACTICE OF ANTIBIOTIC STEWARDSHIP IN THE MANAGEMENT OF DIABETIC FOOT INFECTIONS?
Authors: Reinert Noémie , Wetzel Katinka , Franzeck Fabian , Morgenstern Mario , Clauss Martin , Sendi Parham 
Published: November 2023

Background and aimIn 2019, specific diagnostic and antibiotic treatment recommendations for diabetic foot infection (DFI) and osteomyelitis (DFO) were introduced in our institution. They include principles on numbers of biopsies to obtain for microbiological/histopathological examinations, labeling anatomic localization, and antibiotic treatment (ABT) duration based on the aforementioned findings. ABT should be stopped after complete resection of infected bone. In case of incomplete resection, treatment is continued for 4–6 weeks. Two years after the introduction of these recommendations, we investigated the degree of implementation for hospitalized patients.MethodAdult patients with DFI/DFO undergoing surgical intervention from 01/2019–12/2021 were reviewed retrospectively. Diagnostic procedures were assigned to each episode when performed ≤30 days before surgical invention. Chi-square and Mann-Whitney-U tests were performed where appropriate.ResultsWe included 80 patients with 117 hospital episodes and 163 surgical interventions (mean 1.5 episodes and 2 interventions per patient). The mean age was 69.6 (SD 11.5) years, 75% were male. Vascular examination and MRI were performed in 70.9% and 74.4% of episodes, respectively. Impaired perfusion and DFO were confirmed in 34.9% and 56.3%, respectively. Blood cultures were sampled in 34.2%, bacteremia detected in 7.7% with S. aureus being the most common microorganism. Biopsies were obtained in 71.8% of operations, in 90.5% of those 3–5 samples. These were sent for histological examination in 63.2% of the interventions. In 43.6% the anatomic location was labeled ‘proximal to the resection margin’.Preoperative antibiotics were administered in 41.9% of the episodes because of concomitant soft-tissue infections. The most commonly used compound was amoxicillin/clavulanate (74.4%). ABT duration varied significantly when there were signs of DFO in preoperative MRI (p=0.015). The mean duration of antibiotic therapy was 9 (IQR 5–15) days in surgically cured episodes and 40.5 (IQR 15–42) days in cases with resection margins in non-healthy bone (p<0.0001). The results were similar when analyzing treatment duration with respect to osteomyelitis in histology: 13 (IQR 8–42) versus 29 (IQR 13–42) days, respectively (p=0.026).ConclusionsThe adherence to recommendations in terms of biopsy sampling was excellent, moderate for sending samples to histology and poor for labeling the anatomic location. The adherence to ABT duration was good but can be improved by shortening treatment duration for surgically cured cases. Results of preoperative MRI appear to be influential on the decision-making for treatment duration.
DEVELOPMENT AND VALIDATION OF A SYNTHETIC SYNOVIAL FLUID MODEL AS DIAGNOSTIC TOOL FOR BIOFILM-RELATED PROSTHETIC JOINT INFECTIONS
Authors: De Bleeckere Amber , Vandendriessche Stien , Messiaen Anne-Sophie , Crabbé Aurélie , Boelens Jerina , Coenye Tom 
Published: November 2023

AimThere is growing evidence that bacteria encountered in periprosthetic joint infections (PJI) form surface-attached biofilms on prostheses, as well as biofilm aggregates embedded in synovial fluid and tissues. However, models allowing the investigation of these biofilms and the assessment of their antimicrobial susceptibility in physiologically relevant conditions are currently lacking. To address this, we developed a synthetic synovial fluid (SSF) model and we validated this model in terms of growth, aggregate formation and antimicrobial susceptibility testing, using multiple PJI isolates.Methods17 PJI isolates were included, belonging to Staphylococcus aureus, coagulase negative staphylococci, Cutibacterium acnes, Pseudomonas aeruginosa, enterococci, streptococci, Candida species and Enterobacterales. Growth and aggregate formation in SSF, under microaerophilic or anaerobic conditions, were evaluated using light microscopy. The biofilm preventing concentration (BPC) and minimum biofilm inhibitory concentration (MBIC) of relevant antibiotics (doxycyclin, rifampicin and oxacillin) were determined for the staphylococcal strains (n=8). To this end, a high throughput approach was developed, using a fluorescent viability resazurin staining. BPC and MBIC values were compared to the minimum inhibitory concentration (MIC) obtained with conventional methods.ResultsThe SSF model allowed all isolates to grow well under microaerophilic or anaerobic conditions. When cultured in SSF, all isolates formed biofilm aggregates, varying in size and shape along different species. A susceptibility testing method based on measuring resazurin-derived fluorescence was successfully developed, allowing high throughput determination of the BPC and the MBIC in SSF. For all staphylococci cultured in SSF a reduced susceptibility to the tested antibiotics was observed when compared to susceptibility data obtained in general medium. For rifampicin and doxycyclin the BPC was consistently higher than the MIC (two- to fourfold dilution difference for rifampicin and four- to sixfold dilution difference for doxycyclin). For oxacillin the MIC equaled the BPC for two isolates, while for the other isolates the BPC was higher than the MIC (two- to fourfold dilution difference). Expectedly, the MBIC was higher than the BPC and differences with the MIC were even more pronounced for all antibiotics tested (differences of six- to fourteenfold dilutions were observed).ConclusionOur data indicate that the in vitro SSF model could provide more insight in how PJI-related pathogens form biofilms in physiologically relevant conditions. The BPC and MBIC were consistently and substantially higher than MIC. This model could be a valuable addition to evaluate the antimicrobial susceptibility in biofilms in a PJI context.Sources of funding: FWO-Vlaanderen (grant G066523N).