bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Aim

The 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.

Methods

Data 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.

Results

Overall 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).

Conclusion

The 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

Aim

To determine mortality and outcomes of patients diagnosed with fracture-related infections (FRIs).

Method

FRI 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.

Results

311 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.

Conclusions

Fracture-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

Aim

The 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.

Method

All 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.

Results

We 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.

Conclusion

FRI 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

Aim

infected 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 Method

We 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.

Results

We 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.

Conclusions

Masquelet 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

Aim

Debridement, 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.

Method

Swiss 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.

Results

Bacteriological 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.

Conclusions

The 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

Title

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

Aim

To assess S. aureus vs. host cell colonization of contaminated implants vis intravital multiphoton laser scanning microscopy (IV-MLSM) in a murine model.

Method

All 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.

Results

1) 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).

Conclusions

We 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

Aim

Infections 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.

Method

Mitomycin 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.

Results

Drug 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.

Conclusions

In this study we have demonstrated that ADCs can be a novel treatment approach to combat implant-associated infections caused by S. aureus.
A TWO-STAGE APPROACH IN MANAGING DIABETIC NEUROPATHIC FOREFOOT ULCERS
Authors: Tiruveedhula Madhu , Graham Anna , Thapar Ankur , Dindyal Shiva , Mulcahy Michael
Published: November 2023

Aim

To 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.

Methods

Forefoot 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.

Results

One 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.

Conclusion

The 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

Aim

Calcaneal 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.

Method

A 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.

Results

33 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.

Conclusions

Single 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

Aim

Antibiotic 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.

Method

Usually 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.

Results

During 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.

Conclusions

With 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 aim

Implant-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.

Method

Six 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.

Results

Time 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.

Conclusions

To 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

Aim

The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality.

Method

A 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.

Results

15 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).

Conclusions

Due 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

Aim

The 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.

Method

This 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.

Results

The 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).

Conclusions

The 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

Aim

Synovial 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.

Methods

Overall, 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).

Results

An 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.

Conclusion

The 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 aim

In 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.

Method

Adult 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.

Results

We 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).

Conclusions

The 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

Aim

There 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.

Methods

17 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.

Results

The 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).

Conclusion

Our 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).
„Das is ja wohl eh klar.“
Authors: Stückler Lena
Published: November 2023

This article is dedicated to the particle subclass of modal particles and their supposed function of indicating the social proximity between speakers. This assumption stems mostly from the reference to shared knowledge of modal particles. This marking of the relations between the speakers occurs on the one hand through a high frequency of modal particles in conversational situations characterised by proximity, and on the other hand through the occurrence of certain modal particles. This paper deals with an empirical test of these assumptions. For this purpose, a corpus of twenty-two conversations in two different settings was used, one setting characterised by a close relationship and the other by unfamiliarity and social distance between the speakers. Within these conversations the frequencies of modal particles were collected and analysed in terms of their quantity and distribution. The results of the case study show that it is not all modal particles for which a function as relational markers can be assumed. Only the two particles ja and eh occur more frequently in the conversations characterised by social proximity. In addition to this, other factors like age and gender are highlighted that may influence the distribution of modal particles in this case study.
Temperature-controlled spectral tuning of a single wavelength polymer-based solid-state random laser
Authors: Kumar Bhupesh , Schulz Sebastian A. , Sebbah Patrick
Published: November 2023

We demonstrate temperature-controlled spectral tunability of a partially-pumped single-wavelength random laser in a solid-state random laser based on DCM [4-dicyanomethylene-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran] doped PMMA (polymethyl methacrylate) dye. By carefully shaping the spatial profile of the pump, we first achieve a low-threshold, single-mode random lasing with an excellent side lobe rejection. Notably, we show how temperature-induced changes in the refractive index of the PMMA-DCM layer result in a blue shift of this single lasing mode. We demonstrate spectral tunability over an 8nm-wide bandwidth.
On-demand flat-top wideband OAM mode converter based on a cladding-etched helical fiber grating
Authors: Zhu Chengliang , Tang Chengfeng , Piao Qingxia , Meng Xinyue , Wang Peng , Zhao Yong
Published: November 2023

A new method enabling to provide an on-demand flat-top wideband orbital angular momentum (OAM) mode converter is proposed and experimentally demonstrated, which is based on utilization of a cladding-etched helical long-period fiber grating (CEHLPG). By appropriately selecting the grating period and precisely controlling the diameter of the CEHLPG in-situ, both the radial order and central wavelength of the flat-top band for the generated OAM mode can be flexibly tailored according to specific requirements. As typical examples, the first azimuthal order OAM modes with a flat-top bandwidth of 95 nm at -20 dB, a central operating wavelength of ∼1500 nm, and the radial-orders of 9, 8, 5, and 2, respectively, have been demonstrated consecutively. The proposed method provides an excellent flexibility and robustness in controlling both the radial order and the central wavelength of the resulting flat-top wideband OAM mode conversion, which may support a variety of practical optical vortex applications.
Enhanced second harmonic generation by an atomically thin MoS2 sheet attached to a resonant metasurface
Authors: Khazaee Sara , Peschel Ulf
Published: November 2023

Two-dimensional transition metal dichalcogenides have shown large second-order nonlinear responses due to their broken crystal inversion symmetry. However, their nonlinear interaction with light is restricted to an atomically thin layer. Placing a sheet of transition metal dichalcogenides on a resonant metasurface enhances the field interacting with the nonlinear material thus compensating for this shortcoming. But, it remains a challenge to tune resonances such, that they coincide with fundamental and second harmonic frequencies simultaneously. Here we demonstrate two independent methods to achieve that goal and numerically illustrate our findings for a MoS2 layer combined with silicon nitride photonic crystals. We numerically demonstrate 20-fold and 170-fold enhancement of second-harmonic generation compared with a design based on a single resonant structure. Although we focus on that specific configuration our approach can likewise be applied to other dielectrics combined with highly nonlinear 2D materials.
Incoherent nonlinear deconvolution using an iterative algorithm for recovering limited-support images from blurred digital photographs
Authors: Rosen Joseph , Anand Vijayakumar
Published: November 2023

Recovering original images from blurred images is a challenging task. We propose a new deconvolution method termed incoherent nonlinear deconvolution using an iterative algorithm (INDIA). Two inputs are introduced into the algorithm: one is a random or engineered point spread function of the scattering system, and the other is a blurred or distorted image of some object produced from this system. The two functions are Fourier transformed, and their phase distributions are processed independently of their magnitude. The algorithm yields the image of the original object with reduced blurring effects. The results of the new method are compared to two linear and two nonlinear algorithms under various types of blurs. The root mean square error and structural similarity between the original and recovered images are chosen as the comparison criteria between the five different algorithms. The simulation and experimental results confirm the superior performance of INDIA compared to the other tested deblurring methods.