bluuebunny/crossref_metadata_2025 huggingface dataset:
A NEW CLASSIFICATION OF FRACTURE-RELATED INFECTION
Authors: McNally Martin , Alt Volker , Wouthuyzen Marjan , Marais Leonard , Metsemakers Willem-Jan , Zalavras Charalampos , Morgenstern Mario
Published: November 2023

Aim

To classify Fracture-related Infection (FRI) allowing comparison of clinical studies and to guide decision-making around the main surgical treatment concepts.

Method

An international group of FRI experts met in Lisbon, June 2022 and proposed a new FRI classification. A core group met during the EBJIS Meeting in Graz, 2022 and on-line, to determine the preconditions, purpose, primary factors for inclusion, format and the detailed description of the elements of an FRI Classification.

Results

Historically, FRI was classified by time from injury alone (early, delayed or late). Time produces pathophysiological changes which affect the bone, the soft-tissues and the patient general health, over a continuum. No definitive cut-off is therefore possible. Also, in several studies, time was not identified as an independent predictor of outcome.

The most important primary factors were characteristics of the fracture (F), relevant systemic co-morbidities of the patient (R) and impairment of the soft-tissue envelope (I). These factors determine FRI severity, choice of treatment method and are predictors of outcome. For the fracture (F), the state of healing, the potential for bone healing and the presence or absence of a bone defect are critical factors. Co-morbidities are listed and the degree of end-organ damage is important (R). The ability to close the wound directly or the need for soft tissue reconstruction determines the impairment of the soft tissue component (I). Hence the FRI Classification was designed.

The final proposal of the FRI Classification is presented here. The new classification has five stages; from simple cases of infected healed fractures, in healthy individuals with good soft tissues (Stage 1), through unhealed fractures with variable potential for bone healing (Stages 2, 3 or 4) to Stage 5, with no limb-sparing or reconstructive options. For instance, the need for a free flap (I4), over a well-healed fracture (F1), in a patient with 2 co-morbidities (R2) gives a classification of F1R2I4 for that patient.

Conclusions

This novel approach to FRI classification builds on previous work in osteomyelitis, PJI and chronic medical conditions. It focusses attention on the elements of the disease which need treatment. It now requires validation in large patient cohorts.

On behalf of the FRI Classification Consensus Group.
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

Aim

Antibiotics 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.

Method

8 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.

Results

Median 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.

Conclusions

Bacteriophage 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

Aim

The aim of this paper is to analyse the cause of neuropathic diabetic foot ulcers and discuss their preventive measures.

Methods

Review 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.

Results

Forefoot

Progressive 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.

Midfoot

Midfoot 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.

Hindfoot

These 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.

Conclusions

Early 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

Aim

The 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.

Method

12 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.

Results

For 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.

Conclusions

The 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.

Acknowledgements

Funding 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

Aim

Prosthetic 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.

Method

2,256 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.

Results

1223 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).

Conclusions

Over 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

Aim

The 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).

Method

A 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.

Results

Screening 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€.

Conclusions

PJIs 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

Aim

Multidisciplinary 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.

Method

A 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.

Results

The 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%).

Conclusions

Over 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

Aim

By 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.

Method

An 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.

Results

A 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.

Conclusions

Patients 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

Aims

The 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.

Methods

We 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.

Results

In 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.

Conclusion

UPICs 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

Aim

Serum 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).

Method

From 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).

Results

A 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).

Conclusions

Due 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.
PLASMA FIBRINOGEN IS A PROMISING FIRST-LINE SCREENING BIOMARKER FOR THE DIAGNOSIS OF PERIPROSTHETIC JOINT INFECTION AND TIMING OF REIMPLANTATION: A MULTICENTRE RETROSPECTIVE STUDY
Authors: Fang Hang , Cai Daozhang , Huang Lisi , He Qiuying
Published: November 2023

Aim

The diagnosis of periprosthetic joint infection (PJI) remains a clinical dilemma, since presentations of PJI usually greatly overlap with aseptic failure (AF). The aim of this study is to evaluate the values of plasma fibrinogen, individually or in combination with CRP, ESR and WBC, for distinguishing PJI from AF.

Method

We retrospectively enrolled 357 cases who underwent revision hip or knee arthroplasties in the Third Affiliated Hospital of Southern Medical University, Sun Yat-sen Memorial Hospital and the First Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2021, including 197 AF, 116 PJI and 44 reimplantation. The diagnostic capacity of preoperative fibrinogen, CRP, ESR and WBC as well as their combinations for differentiating PJI from AF were assessed by ROC curves. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated according to the optimal cutoff value based on the Youden index. All biomarkers were further investigated for their potential ability to predict optimal timing of reimplantation as well as their diagnostic capacity in the subgroups of the knee and hip PJI. Furthermore, the correlations among fibrinogen, CRP and ESR in the patients with PJI and AF were analyzed to further evaluate the potential capacity of fibrinogen in the diagnosis of PJI.

Results

The levels of fibrinogen, CRP, ESR and WBC were significantly higher in PJI group than in AF group. ROC analyses showed that the AUCs of fibrinogen, CRP, ESR and WBC were 0.879, 0.903, 0.879 and 0.685, respectively. The optimal threshold of fibrinogen is 4.04 g/L (74.1% sensitivity, 85.6% specificity, 76.1% PPV, 85.0% NPV and 81.8% accuracy). Combining fibrinogen with CRP and/or ESR (AUC: 0.903∼0.914) yielded almost equivalent diagnostic efficiency compared with the combination of CRP and ESR (AUC: 0.910). Besides, fibrinogen yielded AUCs of 0.869 (cutoff: 3.44 g/L) and 0.887 (cutoff: 4.12 g/L) in the hip and knee subgroups, with higher specificity and PPV of 93.1% and 96.1% in the knee PJI. Intriguingly, as for the cases with CRP < 10mg/L and ESR ≧ 30 mm/h, the specificity and NPV of fibrinogen for diagnosing PJI were 92.2% and 83.9%.

Conclusions

Plasma fibrinogen is considered as a potential first-line screening marker for PJI detection and timing of reimplantation. As for the patients with an increased ESR but normal CRP, a low fibrinogen level (below 4.04 g/L) is more likely to rule out PJI.
THE PREDICTIVE VALUE AND RELIABILITY OF ULTRASOUND-GUIDED BIOPSIES FOR DIAGNOSING PERIPROSTHETIC SHOULDER INFECTIONS
Authors: Heesterbeek Petra , Pruijn Nathalie , Boks Simone , van Bokhoven Steven , Dorrestijn Oscar , Schreurs Wim , Telgt Denise
Published: November 2023

Aim

Diagnosis of periprosthetic shoulder infections (PSI) is difficult as they are mostly caused by low-virulent bacteria and patients do not show typical infection signs, such as elevated blood markers, wound leakage, or red and swollen skin. Ultrasound-guided biopsies for culture may therefore be an alternative for mini-open biopsies as less costly and invasive method. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination polymerase chain reaction (PCR), and/or synovial markers for preoperative diagnosis of PSI in patients undergoing revision shoulder surgery.

Method

A prospective explorative diagnostic cohort study was performed including patients undergoing revision shoulder replacement surgery. A shoulder puncture was taken preoperatively before incision to collect synovial fluid for interleukin-6 (IL-6), calprotectin, WBC, polymorphonuclear cells determination. Prior to revision surgery, six ultrasound-guided synovial tissue biopsies were collected for culture and two additional for PCR analysis. Six routine care tissue biopsies were taken during revision surgery and served as reference standard.

Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV; primary outcome measure), and accuracy were calculated for ultrasound-guided biopsies, and synovial markers, and combinations of these.

Results

Fifty-five patients were included. In 24 patients, routine tissue cultures were positive for infection. Cultures from ultrasound-guided biopsies diagnosed an infection in 7 of these patients, yielding a sensitivity, specificity, PPV, NPV, and accuracy of 29.2%, 93.5%, 77.8%, 63.0%, and 65.6%, respectively.

Ultrasound-guided biopsies in combination with synovial WBC increased the NPV to 76.7% and accuracy to 73.8%. When synovial WBC and calprotectin were combined with ultrasound-guided biopsies, it resulted in a better diagnostic value: sensitivity 69.2%, specificity 80.0%, PPV 69.2%, NPV 80.0%, and accuracy 75.8%. Ultrasound-guided biopsies in combination with calprotectin and ESR yielded a sensitivity of 50.0%, specificity of 93.8%, PPV of 80.0%, NPV of 78.9%, and accuracy of 79.2%.

Synovial fluid was obtained in 42 patients. Sensitivities of WBC, PMN, IL-6, and calprotectin were between 25.0% and 35.7%, specificities between 89.5% and 95.0%, PPVs between 60.0% and 83.3%, NPVs between 65.4% and 69.4%, and accuracies between 64.5% and 70.6%.

Conclusions

In this prospective study we showed that ultrasound-guided biopsies for cultures alone and in combination with PCR and/or synovial markers are not reliable enough to use in clinical practice for the preoperative diagnosis of low grade PSI.
TO SONICATE OR NOT TO SONICATE?
Authors: Hesselvig Anne Brun , Bjarnsholt Thomas , Jørgensen Ann , Gottlieb Hans
Published: November 2023

Aim

To evaluate whether sonication of implant material and subsequent culturing add clinical relevance to culturing of tissue biopsies for improved antibiotic treatment in treatment of bone and joint infection.

Method

A retrospective examination of patients’ charts and microbiological analyses in patients who had explanted material (plates, screws, k-wires and prostheses) send for sonication between December 2020 and April 2022.

Results

77/143 (54 %) patients had complete agreement between the cultures from tissue biopsies and sonication fluid. 66/143 (46 %) patients had partial or no agreement between the cultures from tissue biopsies and sonication fluid.

Of the 66 patients, 31 (47 %) had a culture positive sonication fluid and tissue biopsies that were positive with one or more bacterial isolates. 26/66 (39 %) patients had a culture positive sonication fluid and tissue biopsies that were negative. 9/66 (14 %) patients had negative sonication fluid and positive tissue biopsies.

Of the 26 patients with culture positive sonication fluid and culture negative tissue biopsies, virulent bacteria were found in 5 (19 %) patients, making the diagnosis and treatment of infection straight forward. The remaining 21 (81 %) patients had C. acnes, S. epidermidis and CoNS in the sonication fluid, which made the diagnosis less evident but none the less gave the clinician a relevant treatment option.

Conclusion

In this study a high concordance was found between cultures from tissue biopsies and sonication fluid. Additionally, in a small group of patients with culture negative tissue biopsy, the culture of sonication fluid was essential to the identification infections agent. This indicates that culture of sonication fluid is an important diagnostic tool in bone and joint infection, especially in the absence of positive tissue cultures.
IMPLANT RETENTION IN A RABBIT MODEL OF DELAYED FRACTURE-RELATED INFECTION: SUCCESSFUL ERADICATION BUT IMPAIRED BONE HEALING COMPARED TO EARLY INFECTION
Authors: Puetzler Jan , Vallejo Alejandro , Gosheger Georg , Schulze Martin , Arens Daniel , Zeiter Stephan , Siverino Claudia , Moriarty Fintan
Published: November 2023

Aim

The time to onset of symptoms after fracture fixation is still commonly used to classify fracture-related infections (FRI). Early infections (<2 weeks) can often be treated with debridement, systemic antibiotics, irrigation, and implant preservation (DAIR). Late infections (>10 weeks) typically require implant removal as mature, antibiotic-tolerant biofilms have formed. However, the recommendations for delayed infections (2–10 weeks) are not clearly defined. Here, infection healing and bone healing in early and delayed FRI is investigated in a rabbit model with a standardized DAIR procedure.

Method

Staphylococcus aureus was inoculated into 17 rabbits after plate osteosynthesis in a humerus osteotomy. The infection developed either one week (early group, n=6) or four weeks (delayed group, n=6) before a standardized DAIR procedure and microbiological analysis were performed. Systemic antibiotics were administered for six weeks (two weeks: Nafcillin+Rifampin, four weeks: Levofloxacin+Rifampin). A control group (n=5) also underwent a revision operation (debridement and irrigation) after four weeks, but received no antibiotic treatment. Rabbits were euthanized seven weeks after the revision operation. Bone healing was assessed using a modified radiographic union score for tibial fractures (mRUST). After euthanasia, a quantitative microbiological examination of the entire humerus, adjacent soft tissues, and implants was performed.

Results

All animals were infected at the time of revision surgery, with the bacterial load in the early group (especially in soft tissues) being greater than in the delayed group and control group. This indicates infiltration of bacteria into areas that are more difficult to reach after four weeks of debridement. The infection was eradicated in all animals in both the early and delayed groups at euthanasia, but not in the control group (CFU median (IQR): 2.1×107 (1.3×107-2.6×107). The osteotomy healed in the early group, while bone healing was significantly impaired in both the delayed group and control group (mRUST median (IQR): early group: 16 (14–16), delayed group: 7.5 (6–10), control: 7 (5.5–9); early vs. delayed: p=0.0411, early vs. control p=0.0065).

Conclusion

The maturation of the infection between the first and fourth week does not affect the success of infection eradication in this rabbit FRI model. However, bone healing appears to be impaired with increasing duration of infection.
SEPSIS IN PERIPROSTHETIC JOINT INFECTIONS: EPIDEMIOLOGY, RISK FACTORS, AND OUTCOMES
Authors: Bärtl Susanne , Lovasz David , Li Jing , Alt Volker , Rupp Markus
Published: November 2023

Aim

Sepsis is a life-threatening complication of periprosthetic joint infections (PJI) that requires early and effective therapy. This study aims to investigate the epidemiology, associated risk factors, and outcome of sepsis in the context of periprosthetic joint infections (PJI).

Method

This single-center retrospective cohort study included patients treated for PJI from 2017 to 2020. Patients were classified based on the criteria of the European Bone and Joint Infection Society. The presence of sepsis was determined using the SOFA score and SIRS criteria. The cohort with PJI and sepsis (sepsis) was compared to patients with PJI without sepsis (non-sepsis). Risk factors considered were patient characteristics, affected joints, surgical therapy, microbiological findings, preexisting medical conditions, clinical symptoms, and symptom duration. Outcome parameters were mortality, length of hospital stay, and length of stay in the intensive care unit.

Results

A total of 109 patients with PJI were identified, of whom 45 patients (41.3%) met the criteria for sepsis. Patients with sepsis had more severe preexisting diseases compared with the non-sepsis cohort (Charlson Comorbidity Index 3.8 vs. 2.8; p≤0.001). An increased odds ratio (OR) for a septic course was found for the comorbidities pneumonia (8.2; p=0.001), myocardial infarction (2.0; p=0.02), atrial fibrillation (3.3; p=0.01), diabetes mellitus (1.2; p=0.04), endocarditis (5.5; p=0.01), and renal disease (2.0; p≤0.001). Infection with Staphylococcus aureus (sepsis 20 vs. non-sepsis 10; p=0.002), Streptococcus dysgalactiae (sepsis 7 vs. non-sepsis 2; p=0.002) and Candida albicans (sepsis 5 vs. non-sepsis 0; p=0.01) were more prevalent in patients with sepsis. In the sepsis cohort, further infectious foci were present in addition to PJI in 57.8% of patients, compared to 18.8% in the non-sepsis cohort. The presence of sepsis was associated with a longer hospital stay (sepsis 68 days vs. non-sepsis 38 days; p=0.001) and longer intensive care unit stay (sepsis 12 days vs. non-sepsis 2 days; p=0.001). In-hospital mortality was ten times higher in the sepsis cohort compared to non-septic patients (sepsis 11/42 vs. non-sepsis 2/64; OR 10.3; p=0.01).

Conclusions

In a relevant proportion of patients, PJI can lead to a septic course of disease associated with increased mortality. Particularly in patients with preexisting diseases, increased attention is required, and comprehensive screening for other foci of infection seems mandatory. In addition to highly virulent pathogens such as staphylococci and streptococci, fungal infections should be considered as causative pathogens in septic patients with PJI.
The incidence and risk factors for abnormal postoperative blood tests following primary total joint replacement
Authors: Orfanos Georgios , Nantha Kumar Nakulan , Redfern Daniel , Burston Ben , Banerjee Robin , Thomas Geraint
Published: November 2023

Aims

We aim to evaluate the usefulness of postoperative blood tests by investigating the incidence of abnormal results following total joint replacement (TJR), as well as identifying preoperative risk factors for abnormal blood test results postoperatively, especially pertaining to anaemia and acute kidney injury (AKI).

Methods

This is a retrospective cohort study of patients who had elective TJR between January and December 2019 at a tertiary centre. Data gathered included age at time of surgery, sex, BMI, American Society of Anesthesiologists (ASA) grade, preoperative and postoperative laboratory test results, haemoglobin (Hgb), white blood count (WBC), haematocrit (Hct), platelets (Plts), sodium (Na+), potassium (K+), creatinine (Cr), estimated glomerular filtration rate (eGFR), and Ferritin (ug/l). Abnormal blood tests, AKI, electrolyte imbalance, anaemia, transfusion, reoperation, and readmission within one year were reported.

Results

The study included 2,721 patients with a mean age of 69 years, of whom 1,266 (46.6%) were male. Abnormal postoperative bloods were identified in 444 (16.3%) patients. We identified age (≥ 65 years), female sex, and ASA grade ≥ III as risk factors for developing abnormal postoperative blood tests. Preoperative haemoglobin (≤ 127 g/dl) and packed cell volume (≤ 0.395 l/l) were noted to be significant risk factors for postoperative anaemia, and potassium (≤ 3.7 mmol/l) was noted to be a significant risk factor for AKI.

Conclusion

The costs outweigh the benefits of ordering routine postoperative blood tests in TJR patients. Clinicians should risk-stratify their patients and have a lower threshold for ordering blood tests in patients with abnormal preoperative haemoglobin (≤ 127 g/l), blood loss > 300 ml, chronic kidney disease, ASA grade ≥ III, and clinical concern.

Cite this article: Bone Jt Open 2023;4(11):899–905.
Causal discourse structures in medical referral materials: a humanistic insight
Authors: Chinaguh Emmanuel C. , Akeredolu-Ale Bolanle I. , Adeosun Kehinde G. , Adejumobi Hannah O.
Published: November 2023

Humanistic studies on medical causality from language studies have hardly explored how causality is constructed in medical referral materials, which is the research gap this study intends to fill. For data, forty completed National Health Insurance Authority (NHIA) medical referral forms, comprising 842 words and medical signs, were purposively selected from a healthcare provider in Abeokuta, Ogun State, Nigeria, and subjected to discourse analysis with insights from the causal coherence categories of Mann/Thompson’s (1987) Rhetorical Structure Theory.

The paper identified two causal relations/structures – nonvolitional cause and nonvolitional result – in the data. Each structure reveals the primacy of diagnosis among the medical processes of diagnosing, investigating and treating or referring. The diagnosis proposition is primed as the consequence of pathophysiological causation in a diagnostic schema; while in the medical referral process, it is elevated as the causation for a medical referral, for instance for further specialist review and management, in a medical-referral schema. The construal of the semantic parameter of non-volition in the coherence relations is aided by the reality that illness is not intended, except caused by self-harm or suicide. The relations were signalled by four signal types, which are genre, semantic, syntactic, and semiotic; and six specific signals – mapping, lexical overlap, lexical chain, adverbials, semiotic overlap, and lexical-semiotic chain. These are implicit signals that complement the concise presentation of the medical processes. To conclude, this research provides the causal modeling of some medical processes, which highlights the prominence of diagnosis in medical referrals.
Control of the annular spatial profile of high harmonics using a Bessel-Gaussian beam carrying the nonzero orbital angular momentum
Authors: Han Jiaxin , Tang Xiangyu , Fu Yong , Wang Beiyu , Yin Zhiming , Jin Cheng
Published: November 2023

We propose to generate vortex high harmonics in the extreme ultraviolet (XUV) with a controllable spatial profile by using a Bessel-Gaussian (BG) beam carrying a nonzero orbital angular momentum (OAM). Such BG beam has quite a different intensity profile at the focus compared to the generally used BG beam without carrying the OAM. We show that the BG beam is capable of generating single-ring structured high harmonics, which is quite different from an Laguerre-Gaussian (LG) beam with a similar intensity distribution at the laser focus. We reveal that favorable phase-matching conditions can be achieved off-axis and away from the laser focus because a single-atom intrinsic phase due to the short electron trajectory can be well compensated by a geometric phase of the BG beam. We thus give a general rule that vortex high harmonics with a single annular profile can be efficiently generated when a gas medium is located at 1.5zred to 2.0zred before or after the laser focus of the BG beam, here zred is a reduced length. We also show the validity of this rule when the BG beam carries a higher OAM. This work is expected to be useful for synthesizing attosecond vortex pulses.
Precise parameter control of multicycle terahertz generation in PPLN using flexible pulse trains
Authors: Matlis N. H. , Zhang Z. , Demirbas U. , Rentschler C. , Ravi K. , Youssef M. , Cirmi G. , Pergament M. , Edelmann M. , Mohamadi S. M. , Reuter S. , Kärtner F. X.
Published: November 2023

The low (sub %) efficiencies so-far demonstrated for nonlinear optical down-conversion to terahertz (THz) frequencies are a primary limiting factor in the generation of high-energy, high-field THz-radiation pulses (in particular narrowband, multicycle pulses) needed for many scientific fields. However, simulations predict that far higher conversion efficiencies are possible by use of suitably-optimized optical sources. Here we implement a customized optical laser system producing highly-tunable trains of infrared pulses and systematically explore the experimental optimization of the down-conversion process. Our setup, which allows tuning of the energy, duration, number and periodicity of the pulses in the train, provides a unique capability to test predictions of analytic theory and simulation on the parameter dependences for the optical-to-THz difference-frequency generation process as well as to map out, with unprecedented precision, key properties of the nonlinear crystal medium. We discuss the agreements and deviations between simulation and experimental results which, on the one hand, shed light on limitations of the existing theory, and on the other hand, provide the first steps in a recipe for development of practical, high-field, efficiency-optimized THz sources.
Wavelength-switching performance and thermal lens effect of cryogenic Yb:YAG lasers
Authors: Lang Bing-Tian , Song Yan-Jie , Zong Nan , Chen Zhong-Zheng , Bo Yong , Peng Qin-Jun
Published: November 2023

Wavelength-switching performance and thermal lens effect of cryogenic Yb:YAG lasers pumped by a 940 nm laser diode are presented. A maximum continuous wave output power is reached 13.16 W at 80 K with an optic-optic efficiency of 25.6% at an incident pump power of 60 W. The wavelength-switching performance is observed and explained by absorbed pump power threshold behavior as temperature. Moreover, we directly characterize the thermal lens effect by wavefront measurement with a Shack-Hartmann wavefront sensor. The wavefront peak-to-valley value (PV) is 0.338 µm (about 0.33λ) at 80 K, corresponding to a thermal lens dioptric power of 0.15 m-1. The substantial decrease of the thermal lens effect contributes to the significant improvement of laser performance, which is consistent with the brilliant beam quality factor M2 of about 1.10 at both x and y directions.