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Objectives: Osteoarticular infection (OAI) is a feared complication of Staphylococcus aureus bacteraemia (SAB) and is associated with poor outcomes. We aimed to explore the risk of OAI and death following SAB in patients with and without rheumatoid arthritis (RA) and to identify risk factors for OAI in patients with RA., Methods: Danish nationwide cohort study of all patients with microbiologically verified first-time SAB between 2006-18. We identified RA, SAB, comorbidities, and RA-related characteristics (e.g. orthopaedic implants and antirheumatic treatment) in national registries including the rheumatology registry DANBIO. We estimated the cumulative incidence of OAI and death and adjusted hazard ratios (HRs, multivariate Cox regression)., Results: We identified 18 274 patients with SAB (n = 367 with RA). The 90-day cumulative incidence of OAI was 23.1% (95% CI 18.8; 27.6) for patients with RA and 12.5% (12.1; 13.0) for patients without RA (non-RA) [HR 1.93 (1.54; 2.41)]. For RA patients with orthopaedic implants cumulative incidence was 29.4% (22.9; 36.2) [HR 1.75 (1.08; 2.85)], and for current users of tumor necrosis factor inhibitors (TNFi) it was 41.9% (27.0; 56.1) [HR 2.27 (1.29; 3.98) compared with non-users]. All-cause 90-day mortality following SAB was similar in RA [35.4% (30.6; 40.3)] and non-RA [33.9% (33.2; 34.5), HR 1.04 (0.87; 1.24)]., Conclusion: Following SAB, almost one in four patients with RA contracted OAI corresponding to a doubled risk compared with non-RA. In RA, orthopaedic implants and current TNFi use were associated with approximately doubled OAI risk. One in three died within 90 days in both RA and non-RA. These findings encourage vigilance in RA patients with SAB to avoid treatment delay of OAI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Seasonal trends in hospitalization for childhood bone and joint infection (BJI) are reported inconsistently. True seasonal variation would suggest an element of disease risk from environmental factors. This review evaluates all reported seasonal variations in childhood BJI, with additional analysis of seasonal trends for diseases secondary to Kingella kingae., Methods: A systematic review of the literature was undertaken from January 1, 1980, to August 1, 2024. Data were extracted on the hospitalization rate by season and/or month. Pathogen-specific studies for BJI secondary to K. kingae were examined separately., Results: Twenty studies met inclusion criteria encompassing 35,279 cases of childhood BJI. Most studies reported seasonal variation (n = 15, 75%). Eight studies specifically considered disease secondary to K. kingae, and all reported more frequent hospitalization in autumn and/or winter. This is in keeping with the role of respiratory pathogens and seasonal viruses in disease etiology for K. kingae BJI. Findings from other studies on the seasonality of childhood BJI were inconsistent. There were reported seasonal peaks in autumn/winter (4 studies), summer/spring (5 studies), or no variation (5 studies). Where microbiologic data were available, Staphylococcus aureus was the primary pathogen. The quality assessment demonstrated confounding and heterogeneous inclusion criteria affecting the seasonal analysis., Conclusion: For childhood BJI caused by K. kingae, there appears to be a higher risk of hospitalization in autumn and/or winter months. This may relate to the seasonal circulation of respiratory viruses. There is currently insufficient evidence to support other forms of seasonal variation. Reported findings are likely affected by regional disease and pathogen characteristics., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B167)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Introduction: Sickle cell disease (SCD) is a genetic disorder with a high infectious morbidity and mortality and a heterogeneous distribution in France. One of the challenges is to differentiate a bone and joint infection (BJI) from a vaso-occlusive crisis. This challenge is particularly prevalent in French Guiana, an overseas territory with the highest incidence of SCD in France. The aim of this study was to describe the epidemiology of BJI in children with SCD in French Guiana., Method: This was a retrospective multicentric descriptive study of SCD patients living in French Guiana aged under 18 and diagnosed with a BJI between 2010 and 2022. These BJI were divided into 2 groups: those with microbiological documentation (d-BJI) and those without microbiological identification (ud-BJI)., Results: A total of 53 episodes of BJI in 42 patients (mean age 7.2 years) were reported. Clinical symptoms on arrival were comparable between the d-BJI and ud-BJI groups. Patients in the d-BJI group had longer average hospital stays (40.4 days vs. 16.8 days, P = 0.01) and Salmonella spp. were the most identified bacteria (n = 8/13). White blood cell count was greater in the d-BJI group (30.3 G/L vs. 18.G/L, P = 0.01) and a collection was more frequently identified on imaging (11/13 vs. 16/40, P = 0.01) in this group. Initial in-hospital antibiotic therapy was longer in the d-BJI group (17.2 days vs. 12.8, P = 0.02), as were infection-related complications (9/13 vs. 12/40 P = 0.01)., Conclusion: BJI in children with SCD is not sufficiently microbiologically documented. Progress must be made to improve the documentation of BJI., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In recent years, there has been an increase in Neisseria gonorrhoeae infections in Europe and Spain. Disseminated gonococcal infection is an uncommon clinical presentation that includes gonococcal arthritis. Improved antibiotic treatment has reduced the incidence of gonococcal arthritis. However, the increase in gonococcal infections may have increased the frequency of this clinical entity in recent times. We report five cases of gonococcal arthritis in patients in a tertiary-care hospital in the northern area of Madrid (Spain) from October 2022 to October 2023. Major cases occurred in male patients with unprotected sex and polyarticular symptoms requiring hospital admission and treatment with ceftriaxone and cefixime. The use of molecular techniques has allowed the detection of a greater number of culture-negative cases of gonococcal arthritis, as well as the detection of mutations associated with resistance to fluoroquinolone for switching to oral treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

According to the 2021 CDC sexually transmitted disease surveillance report, national cases of syphilis and gonorrhea continue to rise. Currently, South Dakota ranks #1 in syphilis and #2 in gonorrhea cases per 100,000 population. The higher incidence increases the likelihood South Dakota clinicians will encounter different presentations of syphilis and gonorrhea. Recently, we have seen patients presenting with acute STI related inflammatory arthritis. This review discusses the acute arthritic presentations associated with gonorrhea and syphilis and its treatment., (Copyright© South Dakota State Medical Association.)

Background: This study aimed to analyze the distribution of pathogens and antimicrobial resistance in bone and joint infections (BJIs) among children under four years old., Methods: A retrospective analysis was conducted on the clinical data of children under four years old who received inpatient treatment for BJIs at the Children's Hospital of Soochow University between January 2016 and December 2022. Results of bacterial culture and antimicrobial resistance were analyzed., Results: Among the 131 patients, 52 (39.7%) showed positive bacterial culture results. There were Gram-positive (G+) bacteria detected in 38 strains (73.07%), Gram-negative (G-) bacteria in 12 strains (23.08%), and fungi in 2 strains (3.85%). Thirty-one strains of Staphylococcus aureus (S. aureus) were detected (59.62%), including 7 MRSA strains (22.58%). The resistance rate of G+ bacteria to penicillin was 72.97%, while resistance to erythromycin and clindamycin was approximately 50%. No resistance was found against linezolid, vancomycin, and teicoplanin. G- bacteria showed a sensitivity of 100% to carbapenems, including meropenem, ertapenem, and imipenem, a resistance rate of 91.67% to ampicillin-sulbactam, and relatively high resistance rates to compound sulfamethoxazole, ampicillin/sulbactam, and piperacillin., Conclusions: Regional variations existed in the distribution of pathogens and antimicrobial resistance in children under four years old with BJIs. In our hospital, the most common pathogen is S. aureus, with MRSA accounting for approximately one-fourth of all S. aureus patients. Additionally, extended-spectrum β-lactamase (ESBL)-producing G- bacteria have been identified, underscoring the importance of careful consideration during empirical antibiotic therapy.

Background: We aimed to investigate the clinical features, antimicrobial susceptibility and pvl gene expression in Staphylococcus aureus causing acute hematogenous bone and joint infections (BJIs) in children in Vietnam., Methods: In this prospective study, the demographics, microbiology and clinical outcomes of pediatric patients with acute hematogenous BJIs were collected from September 2022 to September 2023. Antimicrobial susceptibility profiles were determined using VITEK2 Compact system. The pvl gene encoding the Panton-Valentine leukocidin (PVL) toxin was detected by using polymerase chain reaction. Mann-Whitney, χ 2 and Fisher test were used for statistical analysis., Results: In total, 78 patients (46 boys) with S. aureus acute hematogenous BJIs were recruited at the National Children's Hospital, Hanoi, Vietnam. Of all S. aureus isolates, 84.6% were methicillin-resistant S. aureus . All S. aureus isolates were susceptible to vancomycin, ciprofloxacin and levofloxacin; 97% of methicillin-resistant S. aureus isolates was resistant to clindamycin (minimum inhibitory concentration ≥8 μg/mL). The pvl gene was detected in 83.3% of isolates, including 57 methicillin-resistant S. aureus isolates. Patients in the pvl -positive group had significantly higher C-reactive protein levels than those in the pvl -negative group ( P = 0.04). In addition, all 8 children with septic shock were infected with pvl -positive S. aureus ., Conclusions: PVL is a prevalent virulence factor of S. aureus in Vietnam. Furthermore, high inflammatory parameters (C-reactive protein) may be present at the time of diagnosis in PVL positivity-related acute hematogenous BJIs. Further research is necessary to enhance our understanding of the varying correlations between virulence factors and outcomes of S. aureus BJIs., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends., Methods: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices., Results: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted., Conclusions: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aim: To quantify and characterise patients with coexistent septic arthritis (SA) and crystal arthritis (CA) (SACA) in an emergency department (ED) setting., Methods: A single-centre, retrospective, 10-year observational study was conducted at a major referral centre. Patients with a positive joint aspirate for CA or SA carried out in ED, were included. The Newman criteria were utilised to define SA., Results: Of the 567 patients included in the final analysis, 427 had CA and 140 had a final diagnosis of SA. Twenty-three point six percent of patients diagnosed with SA had concomitant CA, while 7.2% of patients diagnosed with CA had concomitant SA. The greatest predisposing factors for SACA were previous history of gout, rheumatoid arthritis, being immunocompromised or having joint metalware. Synovial fluid (SF) white cell count (WCC) showed excellent predictive capability for joint infection with the area under the receiver operating characteristic curves (AUROCs) of 0.81 and 0.87 for SA and SACA respectively. The receiver operating characteristic curves (ROCs) reported a SF WCC cutoff of 32,000/mm3 allowed for 100% sensitivity and approximately 50% specificity., Conclusions: SACA remains a small but important sub-group of patients at risk of misdiagnosis of CA alone. SF WCC of 32,000/mm3 may be a better cutoff than the traditionally accepted 50,000/mm3, possibly warranting inpatient admission for investigation and management of presumed SA., Competing Interests: We declare that there exist no conflicts of interest for this study., (© PMA.)

Purpose: This study is aimed at determining the rates and predictors of re-operation and re-admission in children with septic arthritis treated at an institution without routine clinical practice guidelines., Methods: This is a retrospective cohort study of patients less than 18 years old who underwent surgery for septic arthritis between January 1, 2009, and January 1, 2019, at a single tertiary-care paediatric institution. Uni- and multivariate analysis was performed to identify any risk factors associated with re-operation or unplanned visits to the emergency department after hospital admission compared to patients who had an uncomplicated post-operative course., Results: One hundred and forty-four patients were included. The mean age was five years (range 1 month-17 years), and the most commonly affected joint was the hip. The re-admission rate was 1% (n = 2), and the re-operation rate was 8% (n = 12). Twenty percent of patients (n = 29) had unplanned presentations to the emergency department (ED) after discharge. Discharge CRP level was not significantly higher in patients with unplanned presentations to the ED or re-operation. Positive joint fluid culture and infection of any other joint than the hip increased the likelihood of re-operation. Patients who had septic arthritis of the hip were more likely to have an unplanned ED presentation., Conclusions: Rates of re-admission and re-operation were similar to literature despite lack of a standardized treatment pathway or discharge protocol. Outcomes of pediatric septic arthritis did not correlate with discharge CRP level. There was a high rate of unplanned ED visits after discharge., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

We investigated the prevalence of osteomyelitis and septic arthritis in individuals with osteogenesis imperfecta (OI) as compared to the general population. We performed a retrospective cohort study utilizing the TriNetX Analytics platform, a federated, aggregated electronic health record (EHR) research network containing national, deidentified EHR data. We queried patients with OI, based on encounter diagnoses. Patients in this group with any occurrence of osteomyelitis or septic arthritis were recorded. A control cohort was established to compare the prevalence in patients without OI. Of 8444 individuals with OI, 433 (5.13%) had encounter diagnoses for osteomyelitis and 61 (0.72%) had encounter diagnoses for septic arthritis. In comparison, of 79 176 436 patients without OI, 352 009 (0.44%) had encounter diagnoses for osteomyelitis, while 106 647 (0.13%) had encounter diagnoses for septic arthritis. The relative risk for osteomyelitis in OI patients was 11.53 (95% CI: 10.52-12.64), while the relative risk for septic arthritis was 5.36 (95% CI: 4.18-6.89). The relative risk for osteomyelitis in pediatric OI patients was 30.55 (95% CI: 24.35-38.28). To our knowledge, this is the first study investigating musculoskeletal infections in patients with OI, as well as the first to report the overall prevalence in the general population. Clinicians may benefit from a high index of suspicion for musculoskeletal infections in OI patients with corresponding symptoms. Further study is warranted to investigate if modifications to conventional diagnostic pathways and criteria are valuable in this population. Level of evidence: Retrospective Cohort Study - Level II., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Kingella kingae causes bacteremia, endocarditis, osteomyelitis, septic arthritis, meningitis, spondylodiscitis, and lower respiratory tract infections in pediatric patients. Usually it demonstrates disease after inflammation of mouth, lips or infections of the upper respiratory tract. To date, therapeutic targets in this bacterium remain unexplored. We have utilized a battery of bioinformatics tools to mine these targets in this study. Core genes were initially inferred from 55 genomes of K. kingae and 39 therapeutic targets were mined using an in-house pipeline. We selected aroG product (KDPG aldolase) involved in chorismate pathway, for inhibition analysis of this bacterium using lead-like metabolites from traditional Chinese medicinal plants. Pharmacophore generation was done using control ZINC36444158 (1,16-bis[(dihydroxyphosphinyl)oxy]hexadecane), followed by molecular docking of top hits from a library of 36,000 compounds. Top prioritized compounds were ZINC95914016, ZINC33833283 and ZINC95914219. ADME profiling and simulation of compound dosing (100 mg tablet) was done to infer compartmental pharmacokinetics in a population of 300 individuals in fasting state. PkCSM based toxicity analysis revealed the compounds ZINC95914016 and ZINC95914219 as safe and with almost similar bioavailability. However, ZINC95914016 takes less time to reach maximum concentration in the plasma and shows several optimal parameters compared to other leads. In light of obtained data, we recommend this compound for further testing and induction in experimental drug design pipeline.Communicated by Ramaswamy H. Sarma.

Background: The primary purpose of this retrospective case series was to describe the prevalence and outcomes of single-stage hip arthroplasty in patients who were previously treated for septic arthritis of the native hip at our institution over a 20-year period. This study also examined rates of persistent or recurrent infection, reoperation, and mortality for septic arthritis of the native hip., Methods: Adult patients treated for septic arthritis of the native hip at our institution from 1995 to 2015 were retrospectively identified. Exclusion criteria included age <18 years, missing or incomplete medical records, treatment at an outside institution, and prior surgery of the hip., Results: 97 patients were included in this study. 3 patients (3.1%) who were previously treated for septic arthritis of the native hip underwent single-stage hip arthroplasty an average of 40 ± 25 months from the date of infection. 3 of the 18 (16.7%) patients who were treated with resection arthroplasty underwent second-stage joint reconstruction. There were no cases of periprosthetic joint infection (PJI). 1 patient who underwent single-stage arthroplasty experienced implant-induced metallosis, necessitating removal of the implant. There were no other cases of revision arthroplasty., Conclusions: The prevalence of single-stage hip arthroplasty in patients with a history of septic arthritis of the native hip joint was 3.1%, which is higher than the prevalence of hip arthroplasty in the United States general population, suggesting that a history of septic arthritis may increase the risk of requiring hip arthroplasty. In the small number of patients who went on to receive a hip replacement, there were no reported cases of PJI. This study suggests that hip arthroplasty is a viable option for patients with symptomatic osteoarthritis and a history of septic arthritis of their hip., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SJM: Paid consultant for: DePuy Synthes, a Johnson & Johnson Company, Exactech Inc.; Research support from Exactech Inc.All other authors declare that there is no conflict of interest.

Objectives: The purpose of this study was to determine whether a significant difference existed in the rate of infection after ballistic traumatic arthrotomy managed operatively compared with those managed without surgery., Design: Retrospective cohort study., Setting: Academic Level I Trauma Center., Patient Selection Criteria: Patients with ballistic traumatic arthrotomies of the shoulder, elbow, wrist, hip, knee, or ankle who received operative or nonoperative management., Outcome Measures and Comparisons: The rates of infection and septic arthritis in those who received operative or nonoperative management., Results: One hundred ninety-five patients were studied. Eighty patients were treated nonoperatively (Non-Op group), 16 patients were treated with formal irrigation and debridement in the operating room (I&D group), and 99 patients were treated with formal I&D and open reduction and internal fixation (ORIF) (I&D + ORIF group). Patients in all 3 groups received local wound care and systemic antibiotics. No patients in the Non-Op or I&D group developed an infection. Six patients in the I&D + ORIF group developed extra-articular postoperative infections requiring additional interventions., Conclusions: The infection rate in the I&D + ORIF group was consistent with the infection rates reported in orthopaedic literature after fixation alone. In addition, none of the infections were cases of septic arthritis. This suggests that traumatic arthrotomy does not increase the risk for infection beyond what is expected after fixation alone. Importantly, the Non-Op group represented a series of 80 patients who were treated nonoperatively without developing an infection, indicating that I&D may not be necessary to prevent infection after ballistic arthrotomy. The results suggest that septic arthritis after civilian ballistic arthrotomy is a rare complication regardless of the choice of treatment., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Tularemia is caused by the highly infectious bacterium Francisella tularensis, which is recognized as a Tier 1 bioterrorism agent. Tularemia has a range of recognized clinical manifestations, but fewer than 20 bone or joint infections from 6 countries have been reported in the literature to date. This series includes 13 cases of F. tularensis septic arthritis or osteomyelitis in the United States during 2004-2023 and describes exposures, clinical presentation, diagnosis, and outcomes for this rare but severe form of tularemia. Clinicians should consider F. tularensis in patients with compatible exposures or a history of joint replacement or immunosuppression., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Mycobacterium avium complex (MAC) prosthetic joint infection (PJI) has been rarely reported., Methods: This study aimed to investigate the epidemiology and outcomes of MAC PJI. A systematic review of the literature regarding the MAC infection following total joint arthroplasty including hip and knee joint was performed. Multiple databases were searched for published English-written articles up to May 2023. Studies that reported cases of PJI by MAC were reviewed., Results: A total of 17 patients were identified and analyzed from 11 published studies. All patients presented with joint symptom of pain or swelling prior to the diagnosis and MAC was confirmed by culture. The most of the patients (16/17 patients, 94.1%) were noted to have underlying medical condition(s) that might have affected immunity. Treatment consisted of anti-MAC medication therapy only in two patients and anti-MAC medication therapy plus surgery in 15 patients. Among the patients who underwent surgery, 14 patients (82.3%) had removal of the prosthesis including seven patients who had two-stage surgery to have reimplantation of the prosthesis. No relapse of MAC infection was reported despite of one case of relapse of infection caused by different pyogenic bacteria. The rate of overall mortality was 29.4%, however, identified attributable mortality due to MAC infection was low (5.9%)., Conclusion: PJI by MAC is a rare disease. However, MAC needs to be considered in the differential diagnosis in immunocompromised patients presenting with symptoms of PJI. Two-stage exchange arthroplasty may result in successful treatment outcomes without higher risks of relapse of infection if undertaken in association with appropriate active anti-MAC antibiotic therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. FundingThe author(s) received no financial support for the research, authorship, and/or publication of this article.

Background: Manipulation under anesthesia (MUA) is an established option for improving motion in patients presenting with early stiffness following total knee arthroplasty (TKA). Intra-articular corticosteroid injections (IACI) are sometimes administered adjunctively, yet literature examining their efficacy and safety remains limited., Study Design: Retrospective, Level IV., Methods: A total of 209 patients (TKA = 230) were retrospectively examined to determine the incidence of prosthetic joint infections within 3 months following manipulation with IACI. Approximately 4.9% of initial patients had inadequate follow-up where the presence of infection could not be determined. Range of motion was assessed in patients who had follow-up at or beyond one year (n = 158) and was recorded over multiple time points., Results: No infections (0 of 230) were identified within 90 days of receiving IACI during TKA MUA. Before receiving TKA (preindex), patients averaged 111° of total arc of motion and 113° of flexion. Following index procedures, just prior to manipulation (pre-MUA), patients averaged 83° and 86° of total arc and flexion motion, respectively. At final follow-up, patients averaged 110° of total arc of motion and 111° of flexion. At six weeks following manipulation, patients had gained a mean of 25° and 24° of their total arc and flexion motion found at 1 year. This motion was preserved through a 12-month follow-up period., Conclusion: Administering IACI during TKA MUA does not harbor an elevated risk for acute prosthetic joint infections. Additionally, its use is associated with substantial increases in short-term range of motion at six weeks following manipulation, which remain preserved through long-term follow-up., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although the infection rates for bone-patellar tendon-bone autograft (BTB), hamstring tendon autograft (HT), and allograft have been reported previously, there are limited data available for a large cohort of individuals undergoing anterior cruciate ligament (ACL) reconstruction (ACLR) using quadriceps tendon autograft (QT)., Purpose: The aims of this study are (1) to compare rates of septic arthritis after primary and revision ACLR with QT, BTB, HT, and allograft and (2) to evaluate the association between an infection after ACLR and potential risk factors in a large single-system analysis., Study Design: Cohort study; Level of evidence, 3., Methods: All ACLR cases performed by 10 high-volume sports medicine fellowship-trained ACL surgeons between January 2000 and January 2022 were retrospectively analyzed. Minimum follow-up was 90 days after ACLR, and all multiligament reconstructions were excluded. Demographic information, surgical variables, infection characteristics, and rate of ACL graft retention were collected for all included patients. Independent samples t test, chi-square test, or Fisher exact tests with adjusted Benjamini-Hochberg post hoc procedure were used for group comparisons., Results: In total, 6652 patients were included in this study. The most commonly used graft was allograft (n = 2491; 37.4%), followed by HT (n = 1743; 26.2%), BTB (n = 1478; 22.2%), and QT (n = 940; 14.1%). The overall postoperative rate of septic arthritis was 0.34% (n = 23). Septic arthritis rates based on graft type were 0.74% (n = 13) for HT, 0.24% (n = 6) for allograft, 0.20% (n = 3) for BTB, and 0.10% (n = 1) for QT. While a statistically significant difference with regard to graft type ( P = .01) was observed, no significant relationships were found between postoperative septic arthritis and age, sex, revision ACLR, ACLR surgical technique, and accompanying intra-articular procedures for all septic arthritis patients ( P > .05). The average time from the onset of the symptoms of infection to surgical irrigation and debridement (I&D) was 2 days (minimum, 0; maximum, 6). ACL grafts were retained during I&D procedures in all patients with postoperative septic arthritis., Conclusion: The postoperative rate of septic arthritis was 0.1% after use of the QT autograft. While graft choice may affect rates of septic arthritis after ACLR, patient characteristics, ACLR technique, revision ACLR, and accompanying intra-articular procedures during ACLR were not associated with postoperative septic arthritis with the numbers available for analysis.

Acute septic arthritis is on the rise among all patients. Acute septic arthritis must be extensively assessed, identified, and treated to prevent fatal consequences. Antimicrobial therapy administered intravenously has long been considered the gold standard for treating acute osteoarticular infections. According to clinical research, parenteral antibiotics for a few days, followed by oral antibiotics, are safe and effective for treating infections without complications. This article focuses on bringing physicians up-to-date on the most recent findings and discussions about the epidemiology, etiology, diagnosis, and treatment of acute septic arthritis. In recent years, the emergence of antibiotic-resistant, particularly aggressive bacterial species has highlighted the need for more research to enhance treatment approaches and develop innovative diagnosis methods and drugs that might combat better in all patients. This article aims to furnish radiologists, orthopaedic surgeons, and other medical practitioners with contemporary insights on the subject matter and foster collaborative efforts to improve patient outcomes. This review represents the initial comprehensive update encompassing patients across all age groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 He, Arthur Vithran, Pan, Zeng, Yang, Lu and Zhang.)

Background: A prior history of a septic knee may predispose patients to a periprosthetic joint infection (PJI) after total knee arthroplasty (TKA). We performed multivariate analyses of known risk factors that portend a periprosthetic infection for patients who have a history of septic arthritis (SA). The focus of the study was an assessment of the incidence of TKA PJIs at various time intervals after the onset of a septic knee (0 to 3 months, 3 to 6 months, 6 to 9 months, and 9 months to 1-year)., Methods: We queried a national database to identify patients who underwent a primary TKA between 2010 and 2021 (n = 1.9 million). Patients who had a prior septic knee ipsilateral to the primary TKA were characterized (n = 4,251) and were put into four specific cohorts based on the interval between the SA diagnosis and TKA: less than 3 months; 3 to 6 months; 6 to 9 months; and 9 to 12 months. A cohort of patients who did not have history of septic knee were used for comparison (n = 5,000). The incidence of PJIs from 90 days to 1 year was identified and compared using multivariate analyses., Results: All time cohorts were more likely to require revisions due to PJI, as compared to the comparison group. Significant differences were demonstrated among all time cohorts who had prior SA compared to patients who did not have a history of SA (odds ratio [OR] range, 90.0 to 113.0, P < .001)., Conclusion: This study has shown an increased PJI risk in the first year after SA (P < .05). The surgeon should be aware of the increased PJI risk after SA within the first year after TKA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Acute infections of bone and joints are medical emergencies. Early diagnosis and treatment are essential for limb salvage and prevention of deformities. Data from developing countries are essential to develop region-specific treatment guidelines including choice of empiric antibiotics. We reviewed electronic medical records of children (≤ 12 years old) admitted to the pediatrics or orthopedics department of a tertiary care hospital in South India from 2013 to 2017 with a diagnosis of septic arthritis and/or osteomyelitis. Clinical, microbiological, and follow-up data were collected and analyzed. The median (interquartile range, IQR) age of the children (N = 207) was 48 (7.5-105) months. Acute infections were more common in infants, whereas chronic cases were common in children > 5 years of age. Staphylococcus aureus (71%) was the most common organism identified. Gram-negative organisms were more frequently isolated in infants compared with older children. Blood and/or wound culture positivity was 78% (N = 161) overall and 78% (N = 31) in chronic cases. The median (IQR) duration of antibiotics was 7 (5-8) weeks. Sequelae and readmissions occurred in 47% (N = 81) of the 172 patients followed for a year. Culture positivity rates especially of wound were high even after receiving antibiotics.

Background: The presence of seasonal patterns in pediatric septic arthritis cases is a common orthopaedic teaching. Seasonal variation has been seen in centers outside of the United States and with other inflammatory and infectious joint-related conditions within the country, but it is unknown if a seasonal pattern exists among different regions of the United States. The purpose of this study was to examine the seasonal variation of septic arthritis within specific regions across the United States., Methods: The Pediatric Health Information System database was queried for all patients 19 years or younger who were treated for septic arthritis. Data from 34 pediatric hospitals in the Pediatric Health Information System initiative were included. Centers were organized by geographical region, and season of presentation was determined using equinoxes/solstices. χ 2 tests were performed to detect seasonal differences in septic arthritis for the entire cohort and separated by geographical region. Proportion differences along with 95% CIs were provided., Results: Between 2016 and 2019, there were 5764 cases of septic arthritis. Median age at diagnosis was 6.2 years (range: 0 to 19.0 y). Each season contributed 24% to 25% of the total septic arthritis cases, and there were no significant differences detected between the 4 seasons ( P =0.66). There was no seasonal variation seen in the Midwest, South, or West ( P =0.71, 0.98, 0.36, respectively). However, there was seasonal variation in the Northeast ( P =0.05), with fall and summer having a higher percentage of cases (28%) than the winter (21%)., Conclusions: This study showed no clear seasonal variation in septic arthritis in children across the United States using a national database of pediatric hospital centers. However, there is regional seasonal variation in the Northeast, which may relate to climate differences. With no clear seasonal variation across the United States, continued diligence is needed in diagnosing septic arthritis throughout the year., Level of Evidence: Prognostic II., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Septic arthritis Abstract. A painful, red, and swollen joint may have different causes. Septic arthritis is one of the most serious conditions and should be diagnosed and treated right away. In the native joint, an infection can damage the cartilage within the first 24 hours with impacts on joint function including lingering joint problems leading to possible future joint destruction. An interdisciplinary approach is essential for achieving optimal results. Most infections are caused by bacteria from the patient's own microbiome. In general, the incidence of native joint infections is growing, whether it is due to more appropriate diagnostics, or an actual increase cannot be determined at this point. In case of an acute infection, the patients usually describe a relatively short and acute period of pain, redness, and swelling of the affected joint. For diagnostic purposes the common blood serum laboratory work-up serves as a basis, complemented by puncture of the affected joint. Cell count and cell differentiation in the synovial liquid, microbiological and histopathological workup serve as gold standard in detecting septic arthritis. Septic arthritis lacks a distinctive presentation and other inflammatory conditions, like CPPD and gout must be considered. Prior to antibiotic therapy, joint lavage is the most important method to reduce bacterial load, leading to an improved outcome. Prognosis is determined by a swift diagnosis and initiation of therapy. The patient's comorbidities are significant, especially immunocompromising factors such as rheumatoid arthritis, diabetes or immunomodulating therapy. In case of a second focus of infection, chronic kidney disease or older age, patients are at greater risk for an inferior outcome.

Intra-articular injections prior to total hip arthroplasty (THA) have been associated with postoperative infections. The purpose of this study was to determine whether a temporal relationship exists between hip injections prior to THA and infection. Specifically, we asked (1) Do patients who receive hip injections within 3 months of THA have a higher incidence of prosthetic joint infections (PJIs) or surgical site infections (SSIs)? and (2) Do these patients incur higher 90-day costs? Patients with hip injections prior to THA were identified using a national database from 2010 to 2019. Three laterality-specific groups (injection 0 to 3 months, 3 to 6 months, and 6 to 12 months prior to THA)were compared with a matched cohort without prior injection (n=277,841). Primary outcomes included PJIs, SSIs, and costs. Patients who had injections within 3 months of THA had a higher incidence of PJIs at 90 days (5.1% vs 1.6%, P <.01) and 1 year (6.8% vs 2.1%, P <.01), when compared with the matched cohort. They also had a higher incidence of SSIs at 90 days (2.8% vs 1.2%, P <.01) and 1 year (3.7% vs 1.7%, P <.01). Mean costs were 13.7% higher in this injection cohort. Patients who had injections between 3 and 6 months prior to THA had higher incidence and odds of postoperative PJIs at 90 days (2.6% vs 1.6%, P <.04), whereas those with injections beyond 6 months had no differences in PJIs ( P ≥.46). Patients who receive hip injections within 3 months of undergoing primary THA are at increased risk for postoperative PJIs, SSIs, and higher costs. This study reaffirms guidelines for when to perform THAs in these populations. [ Orthopedics . 2023;46(1):19-26.].

Sternoclavicular joint septic arthritis is rarely seen in the general population. The majority of cases are seen in intravenous drug users. Given the lack of reported cases in the literature, there is no standardized treatment algorithm for this disease. Described treatment methods range from medical management to wide local debridement. The incidence of sternoclavicular joint septic arthritis will likely continue to increase with rising usage of intravenous drugs in the United States. Within the past year, our institution treated four cases., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: There is limited information on the presentation and management of upper extremity septic arthritis (UESA) in children. Our purpose was to report on the characteristics and short-term treatment outcomes of pediatric UESA from a multicenter database., Methods: Patients with UESA were identified from a multicenter retrospective musculoskeletal infection database. Demographics, laboratory tests, culture results, number of surgeries, and complications were collected., Results: Of 684 patients with septic arthritis (SA), 68 (10%) patients had UESA. Septic arthritis was most common in the elbow (53%), followed by the shoulder (41%) and wrist (4%). The median age at admission was 1.7 years [interquartile range(IQR, 0.8-8.0 y)] and 66% of the cohort was male. Blood cultures were collected in 65 (96%) patients with 23 (34%) positive results. Joint aspirate and/or tissue cultures were obtained in 66 (97%) patients with 49 (72%) positive results. Methicillin-sensitive Staphylococcus aureus (MSSA) was the most common causative organism overall, but Streptococcus was the most common pathogen in the shoulder. Sixty-six (97%) patients underwent irrigation and debridement, with 5 (7%) patients requiring 2 surgeries and 1 patient (1%) requiring 3 surgeries. The median length of stay was 4.9 days (IQR, 4.0-6.3 d). Thirty-one (46%) children had adjacent musculoskeletal infections and/or persistent bacteremia. No patients experienced venous thromboembolism, and 4 patients with associated osteomyelitis experienced a musculoskeletal complication (3 avascular necrosis, 1 pathologic fracture). One child had re-admission and 3 children with associated osteomyelitis had a recurrence of UESA. Comparison between elbow and shoulder locations showed that children with septic arthritis of the shoulder were younger (4.6 vs. 1.0 y, P =0.001), and there was a difference in minimum platelet count (280 vs. 358 ×10 9 cells/L, P =0.02)., Conclusions: UESA comprises 10% of cases of septic arthritis in children. The elbow is the most common location. Shoulder septic arthritis affects younger children. MSSA is the most common causative organism in UESA, but Streptococcus is common in shoulder septic arthritis. Irrigation and debridement result in excellent short-term outcomes with a low complication rate. Re-admissions and repeat surgical interventions are rare., Level of Evidence: Level IV, prognostic., Competing Interests: Li is currently receiving a grant from the Scoliosis Research Society, has received consulting fees from Medtronic, has received support for travel from Zimmer Biomet, is the Chair of the Scoliosis Research Society’s Morbidity and Mortality Committee, and is the Chair of the Pediatric Orthopaedic Society of North America’s Membership Committee. Denning has received a speaker honorarium from OrthoPediatrics. Goldstein is a Member At Large of the Board of Directors of the Pediatric Orthopaedic Society of North America. Johnson is currently receiving grants from the Scoliosis Research Society and the Pediatric Orthopaedic Society of North America. Truong is currently receiving grants from the National Institutes of Health and the Gillette Foundation. Shore is on the Board of Directors of the American Academy of Cerebral Palsy and Developmental Medicine and the Advisory Board of the International Pediatric Orthopaedic Symposium. The remaining authors have no conflicts of interest or source of funding to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Staphylococcus aureus is the main aetiologic agent of osteoarticular infections (OAIs) in paediatric patients. The aim of this prospective unicenter study was to describe the phenotypic and genotypic characteristics of S. aureus isolates obtained from OAIs in paediatric patients admitted to tertiary care hospital. Through a surveillance program called OsteoCode , a multidisciplinary team was created and we identified 27 patients with OAIs caused by S. aureus from 2019 to 2021. The susceptibility profile, virulence factors, biofilm formation, pulsed-field gel electrophoresis (PFGE), clonal complex (CC) and sequence type (ST) were determined. In addition, the clinical characteristics and evolution of the patients presented six months after the diagnosis of OAIs were described. Ninety-two percent of the isolates were methicillin-sensitive S. aureus (MSSA). In methicillin-resistant S. aureus (MRSA), SCC mec- II and SCC mec- V were detected. The pvl gene was only observed in MSSA (18.5%) and was associated with highest fever ( p =0.015), multiple localization ( p= 0.017), and soft tissue sites of infection beyond the bone (pyomyositis, pulmonary abscess) ( p= 0.017). Biofilm formation was detected in 55.6% of isolates. The most common CC were CC5 and CC30 which represent the most common linages for bone and joint infections worldwide. The isolates were distributed in different STs, and ST672 was predominant. MRSA were associated with a longer duration of intravenous treatment and a prolonged hospital stay ( p= 0.023). Recurrent infection occurred in five children and orthopaedic complications in 33.3% of patients. This is the first study that reflects the epidemiology of S. aureus in OAIs in paediatric patients in Mexico; a clear predominance of MSSA distributed in different STs was observed. Our findings highlight that a multidisciplinary team is required for the diagnosis and treatment of OAIs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aguilar-Gómez, Merida-Vieyra, Isunza-Alonso, Morales-Pirela, Colín-Martínez, Juárez-Benítez, García de la Puente and Aquino-Andrade.)

Aim: Early diagnosis of osteoarticular infections (OAI) in children and effective treatment prevents complications. The objective of this study was to evaluate effectiveness and safety of shortened intravenous antibiotic treatment of OAI. Incidence, diagnostics and pathogens of paediatric OAI were assessed., Methods: This retrospective study included all paediatric OAI admissions to The Children's Hospital Iceland in 2006-2020. The treatment was evaluated by dividing the study cohort into two groups. The simplified treatment group received intravenous antibiotics for less than 7 days. The longer intravenous group received intravenous antibiotics for a minimum of 7 days., Results: In total, 205 cases of OAI were included: 106 osteomyelitis, 83 septic arthritis and 16 with both. Age standardised incidence was 17 per 100,000 children and decreased over the study period (p = 0.004). A pathogen was identified in 37% (75/205) of cases of which 65% (49/75) were Staphylococcus aureus and 12% (9/75) Kingella kingae. Simplified treatment was not associated with increased risk of complications., Conclusion: This study supports claims that simplified treatment for OAI is safe and effective. Further simplification of treatment might be viable. For uncertain reasons the incidence of OAI was decreasing in Iceland, predominantly in young children., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objectives: To analyze clinical meningococcal strains associated with meningococcal septic arthritis cases in England and Wales, and to identify associations between patient age, the synovial joint affected and strain characteristics., Methods: IMD cases confirmed by the Meningococcal Reference Unit (UK Health Security Agency) between January 2010 and December 2020 were included in the analysis. Septic arthritis cases were defined as those featuring detection and/or isolation of N. meningitidis from an articular site. Capsular grouping was performed by serology on clinical isolates and/or real-time PCR on clinical samples., Results: We identified 162 cases of meningococcal septic arthritis, representing 2% of all invasive meningococcal disease cases during the study period. The knee and the hip were the most commonly affected joints, with the former significantly more frequent in adults and the latter seen more commonly in children and adolescents. Group B strains were between 2 and 6 times less likely to cause septic arthritis in relation to groups W, C and Y strains., Conclusions: Meningococcal septic arthritis remains a rare manifestation of invasive meningococcal disease. Strain and age associations identified in this study remain unexplained. Future analyzes including clinical case information may help to explain these findings., Competing Interests: Declaration of Competing Interest GGB, SAC, AW, LW, LLW, JL, XB and RB have performed contract research on behalf of the UK Health Security Agency for Pfizer, GlaxoSmithKline and Sanofi-Pasteur, but received no personal renumeration. No other authors have any conflict of interest to declare., (Copyright © 2022. Published by Elsevier Ltd.)

Study Objective: Children with a bacterial musculoskeletal infection (MSKI) require prompt identification and treatment. In Lyme disease endemic areas, children with an MSKI can present similarly to those with Lyme arthritis. Our goal was to derive a clinical prediction rule to accurately identify children at a low risk for an MSKI., Methods: We enrolled children with monoarthritis presenting to 1 of 6 Pedi Lyme Net centers and performed a procalcitonin (PCT) and a first-tier Lyme C6 enzyme immunoassay (EIA) test. Our primary outcome was an MSKI (septic arthritis, osteomyelitis, or pyomyositis). Using recursive partitioning with k-fold cross validation, we derived a clinical prediction rule to identify children at a low risk of an MSKI. We calculated the accuracy of our novel rule in a derivation cohort., Results: Of the 735 children in the derivation cohort with an available research biosample, 39 (5%) had an MSKI (18 had septic arthritis, 20 had osteomyelitis, and 1 had pyomyositis), 260 (37%) had Lyme arthritis, and 436 (53%) had other inflammatory arthritis. Children with a PCT level of more than or equal to 0.50 ng/mL and those with a C-reactive protein (CRP) level of more than or equal to 0.6 mg/dL with a negative Lyme C6 EIA were classified as not low risk for an MSKI. Of the 451 (61%) children categorized as low risk, none had an MSKI (sensitivity 100%, 95% confidence interval 91.0% to 100%; specificity 74.2%, 95% confidence interval 70.5% to 77.6%)., Conclusion: A novel clinical decision rule that includes PCT, CRP, and a first-tier Lyme EIA was highly sensitive for MSKIs. Although broader external validation is required, the application of this rule may safely reduce invasive testing, procedures, and treatment for low risk children., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Septic arthritis of the temporomandibular joint (SATMJ) is acute or chronic bacterial or fungal infection involving temporomandibular joint (TMJ) space. It is a disease with high mortality in whole body joints, and about three-fourths of survivors have residual malfunctioning of the affected joint., Objective: The aim of this review was to search systematically, evaluate and then summarize scientific literature about etiology, signs and symptoms, diagnosis, treatment and prognosis of the SATMJ in adults., Methods: After registration at PROSPERO this systematic review was conducted and reported according to the PRISMA checklist. The following databases were systematically searched: MEDLINE, EBSCO, The Cochrane Central Register of Controlled Trials (Central), SCIndex, Scopus, Google Scholar and Registry of clinical studies with human participants., Results: In total 37 studies with 91 patients were included in the review. Dominant signs and symptoms of SATMJ were pain and trismus, while fever was infrequent. The most frequent isolates from the TMJ were Staphylococcus aureus and Streptococci; however, less than 20% of patients had data about susceptibility of the isolates to antibiotics. Combination of third generation cephalosporin and metronidazole was the most frequently prescribed empirically, and antibiotics especially active against S. aureus (glycopeptides and anti-staphylococcal beta-lactams) were under-prescribed. Administration of antibiotics was prolonged (median over 30 days), although two weeks are sufficient treatment for SATMJ if right choice of antibiotics was made. There was high rate of repeated surgical interventions (53.5%), which were linked to higher risk of long-term functional defects., Conclusions: The SATMJ is serious infection that requires early empiric administration of antibiotics with good coverage of Gram-positive bacteria, and subsequent correction of antibiotic therapy according to susceptibility of isolates. Appropriate antibiotic therapy decreases risk of long-term functional disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objectives: Extra-genital manifestations of gonococcal infection are rare (0.5-3%). Among them, gonococcal arthritis (GA) is the most frequent, accounting for 30-90% of disseminated infections. Our study aimed to describe all hospital cases of GA in Reunion Island, a French overseas territory., Methods: We conducted a retrospective, multicentric, observational study of all cases of certain, probable or possible GA from 2008 to 2020., Results: We identified 58 cases of GA, mostly certain cases (n = 48). Sex ratio was balanced, but men were older than women (51 vs 27 years, p < 0.001). A total of 41% had travelled abroad during the previous 3 months, mostly in Madagascar or South-East Asia. The most frequently infected joint was the knee, followed by ankle, wrist and fingers or carpal joints. Only 16% of cases had genital symptoms, but 50% had another extra-genital manifestation, mainly skin lesions (40%). Positivity rate of joint puncture was 91%, with a purulent liquid. Only 58% had a positive culture, and 33% had only a positive PCR. There was no 3GC-resistant strain. In comparison with gonococcal infection without arthritis, patients were older and had fewer genital but more extra-genital symptoms. On discharge 60% had persistent articular symptoms. GA represented 18% of all hospitalised septic arthritis cases with microbial identification in 2019., Conclusions: GA is rare but it is important to make an early diagnosis and treat promptly, as joint destruction may be important, leading to persistent symptoms after discharge. PCR use in joint puncture is useful in cases with negative culture., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

This study aimed to analyze the risk factors for mortality of septic knee arthritis in Korea through a large nationwide data research. The National Health Insurance Service-Health Screening database was used to analyze 89,120 hospitalizations for septic knee arthritis between 2005 and 2018. In-hospital, thirty-day, and ninety-day mortality, and their association with patient's demographic factors, various comorbidities (i.e., cerebrovascular disease, congestive heart failure, and myocardial infarction) and Charlson Comorbidity Index (CCI) were assessed. Secondary outcomes of complications (osteomyelitis, knee arthroplasty, recurrence) were analyzed. The number of hospitalization with septic knee arthritis increased from 1847 cases in 2005 to 8749 cases in 2018. There was no significant difference in mortality after diagnosis of septic knee arthritis between years. The risk of mortality in patients who hospitalized with septic knee arthritis increased in comorbidities like Congestive heart failure, dementia, myocardial infarction, chronic kidney disease. Hazard ratio (HR) decreased in patients who have comorbidities such as rheumatoid arthritis, liver disease, rheumatologic disease. HR for mortality in septic knee arthritis increased in patients with CCI more than 1. The risk factors for mortality in all periods were male sex, old age, high CCI, comorbidities such as congestive heart failure, dementia, myocardial infarction, chronic kidney disease. Efforts to reduce mortality should be concentrate more on patients with these risk factors., (© 2022. The Author(s).)

Purpose: To compare the rates of reoperation and 90-day perioperative complications between open arthrotomy and arthroscopy for the treatment of septic ankle arthritis using a national all-payer claims database., Methods: Patients with a diagnosis of septic ankle arthritis who underwent irrigation and debridement through arthroscopy or arthrotomy were identified in a national data set from 2015-2020 through an all-payer claims database. Demographic and comorbidity characteristics including age, sex, infectious etiologies, and Elixhauser comorbidities were obtained. The rate of reoperation, defined as a proxy for failure of initial intervention, was the primary outcome. Secondary outcomes including readmissions, surgical-site infections, amputations, wound complications, and 90-day medical complications were compared between the 2 cohorts., Results: In total, 168 patients undergoing arthroscopy and 794 patients undergoing arthrotomy for septic ankle arthritis were identified. There were no significant differences in reoperation rates between patients who underwent open arthrotomy and those who underwent arthroscopy (P = .997). However, the rates of surgical-site infection (P = .014) and hospital readmission (P < .001) were significantly higher in the open arthrotomy cohort compared with the arthroscopy cohort., Conclusions: Although there was no significant difference in reoperation rates between arthroscopic and open irrigation and debridement for the treatment of septic ankle arthritis, this study showed significantly higher odds of surgical-site infection and hospital readmission in patients who underwent open arthrotomy when compared with arthroscopy. Case-specific patient and technical considerations should guide the surgical decision-making process to limit secondary complications because this study exemplifies similar reoperation rates between the 2 surgical modalities., Level of Evidence: Level III, nonrandomized cohort analysis., (Copyright © 2022 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: A high prevalence of gonococcal infections has been reported from remote parts of Western Australia, but the occurrence of disseminated infection leading to arthritis has not been studied., Aims: To investigate the frequency, risk factors and long-term outcome of gonococcal arthritis (GA) in Western Australia (WA)., Methods: A population-based data linkage study of patients with a hospital-based diagnosis of GA in WA between 1990 and 2014. Demographics, standardised incidence rates per million and comorbidity accrued before (lookback 186 months, interquartile range (IQR) 86-267) and after the index hospital contact for GA (follow up 100 months, IQR 60-209) are presented as frequency (%), median (IQR) or rates /1000 months., Results: In total, 98 patients were diagnosed with GA. The annual incidence of GA increased from 1.35 to 2.10 per million between 1990 and 2014, but the rate of GA complicating all gonococcal infections was stable around 0.25%. Female patients with GA (54%; n = 53/98) were younger (24 vs 38 years) and more frequently identified as indigenous (88% vs 49%) than male patients (46%; n = 45/98; P = 0.002). Female patients had higher rates of prior infections (15.5 vs 8.1 per 1000 months; P = 0.002) and diabetes mellitus (15.9% vs 2.5%; P = 0.03) and a longer hospital stay (10 vs 8 days; P = 0.02). GA recurrence rate during follow up was low (2%), but a broad range of comorbidities developed contributing to a 14% crude death rate., Conclusions: GA stably complicates 0.25% of gonococcal infections in WA with young indigenous females and middle-aged non-indigenous males most affected. Prior infectious disease and diabetes mellitus are potential risk factors for GA in females. GA recurs rarely, but its development reflects a high risk of morbidity and mortality over the following 10 years., (© 2020 Royal Australasian College of Physicians.)

Introduction: Septic arthritis (SA) is a devastating infection with a high rate of sequelae. The aim of this retrospective study was to determine the epidemiology, clinically significant sequelae and risk factors for developing these sequelae in children admitted to our hospital with SA., Methods: Patients with bacteriologically and/or radiologically confirmed SA from January 1999 to December 2014 were identified from discharge and laboratory records. Data was collected through a retrospective review of the case notes., Results: A total of 75 patients (62.7% male) met the inclusion criteria. The median age at presentation was six years (range two weeks to 15 years), and six patients were neonates. Microbiologic aetiology was determined in 40 (53.3%) patients, with Staphylococcus aureus being the most common organism. 68.0% of the patients underwent arthrotomy, and the average hospital stay was 15.3 days. Sequelae of SA were observed in nine patients on follow-up. Univariate and multivariate statistical analyses showed that young age, pyogenic bacterial isolation and concomitant osteomyelitis were significant risk factors for developing sequelae., Conclusion: Our study demonstrated that young age, pyogenic bacterial isolation and concomitant osteomyelitis are associated with a high risk of sequelae. Timely microbiologic diagnosis by novel polymerase chain reaction methods and the use of magnetic resonance imaging in high-risk children to identify adjacent infection could possibly prevent lifelong disabling sequelae in SA., (Copyright: © Singapore Medical Association.)

Periprosthetic joint infection (PJI) remains a major source of morbidity after total knee arthroplasty (TKA). The risk of recurrent infection has been more extensively studied than the risk of mechanical failure. We sought to define the incidence of instability after revision TKA for PJI and to compare this incidence with that for revision TKA for instability. We retrospectively reviewed patients treated by 4 arthroplasty surgeons at 1 institution. The primary outcome was a new diagnosis of clinical instability after index revision. We analyzed potential risk factors that may contribute to postoperative instability after PJI, including demographic characteristics, implant alignment, number of previous procedures, level of constraint during index revision, and type of spacer used. Patients were matched 1:1 with patients undergoing revision TKA for instability. Continuous variables were compared with Student's t test for normally distributed variables and Mann-Whitney U test for non-normal variables. Categorical variables were compared with Fisher's exact test. Thirty-seven patients who underwent revision TKA for PJI were identified. Twelve (32.4%) had clinical instability after revision, compared with only 3 (8.1%) in the matched cohort ( P =.019). Use of a revision, midlevel constraint device in the PJI cohort did not correlate with a lower risk of instability ( P =.445). A greater number of previous surgical procedures increased the likelihood of instability ( P =.041). Revision TKA for PJI is associated with a high risk of subsequent instability. Midlevel constrained implants may not be sufficient to prevent instability. A focus on soft tissue tension and a lower threshold for increasing constraint may be prudent in this cohort. [ Orthopedics . 2022;45(3):145-150.].

Objectives: To compare the risk of five nonpulmonary infections leading to hospitalization between spondyloarthritis (SpA) and nonspecific back pain (NSBP), and to identify the risk factors., Methods: A total of 3018 patients with SpA and 2527 patients with NSBP were identified. Data from December 1995 to June 2019 was retrieved from a centralized electronic medical record system. The date of onset of five types of nonpulmonary infections including: urinary tract infection (UTI), skin infection, gastroenteritis (GE), septic arthritis, and pancreato-hepatobiliary tract infection were identified. Demographic data, comorbidities, and medications used were also retrieved. Comparative risk of each type of infection between SpA and NSBP was determined using propensity score adjustment method. Cox regression model was used to identified risk factors., Results: Patients with SpA were younger in age, predominantly male, with fewer comorbid diabetes mellitus (DM), renal impairment, and depression. Compared with NSBP, patients with SpA had higher risk of UTI (hazard ratio [HR] 1.91; p < .001), skin infection (HR 1.79; p < .001), and septic arthritis (HR 4.57; p = .04). Risk of GE (HR 1.42; p = 1.00), and pancreato-hepatobiliary tract infection (HR 1.67; p = .06) were not increased. Infliximab was an independent risk factor for UTI (HR 2.21; p = .04). Duration of steroid therapy >6 months (HR 2.22; p < .001), smoker (HR 1.81; p < .001), and psoriasis (HR 2.47; p < .001) were risk factors for skin infection., Conclusion: SpA was associated with increased risk of UTI, skin infection, and septic arthritis. Infliximab, prolonged steroid therapy, smoking, and psoriasis were associated risk factors., (© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background and Objectives: Iron-deficiency anemia (IDA) could predispose the afflicted individuals to various infections and musculoskeletal disorders. This study attempted to investigate the association between IDA and septic arthritis (SA), a musculoskeletal disease. Materials and Methods: We investigated all the eligible subjects in the Taiwanese longitudinal health insurance database (LHID) between 2000 and 2012. Subjects with the diagnosis of IDA (International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM): 280) were allocated to the IDA cohort. The control subjects were randomly matched to every subject with IDA coding by age and sex at the 1:4 ratio. All of the recruited subjects were followed since the index date to the onset of SA (ICD-9-CM: 711.0), withdrawal from the insurance (including death), or 31 December 2013. Results: The cumulative incidence of SA was assessed. We showed that the cumulative incidence of SA was higher in the IDA cohort than in the control cohort (p-value < 0.0001). After adjustment of the comorbidities, the IDA patients had a 2.53-fold risk of SA compared to control subjects (aHR = 2.53, 95% CI = 1.89−3.38). Conclusions: IDA was associated with an increased risk of SA.

Background: The epidemiological characteristics of the common pathogens underlying acute haematogenous osteoarticular infection (AHOI) and their resistance to drugs have temporal and regional differences., Aims: To determine the antimicrobial treatment most effective for culture-negative AHOI patients and those without bacterial cultures., Methods: Retrospective analysis of clinical data of children with AHOI who were culture positive from January 2007 to December 2021. And the distribution of the main pathogens and the drug resistance Staphylococcus aureus were analysed in different time periods, age groups and infection types., Results: A total of 188 cases met the inclusion criteria, including 97 cases of acute haematogenous osteomyelitis (AHO), 75 cases of septic arthritis (SA) and 16 cases of AHO concomitant with SA. The commonest causative pathogen in local children was S. aureus of Gram-positive cocci, followed by Streptococcus, and occasionally Gram-negative bacilli. The distribution of S. aureus had no significant correlation with age or infection type. Staphylococcus aureus accounted for 81.82%, 90.91% and 96.15% of all pathogens, and methicillin-resistant S. aureus (MRSA) accounted for 24.22%, 53.33% and 76.00% of S. aureus in 2007-11, 2012-16 and 2017-21, respectively. The frequency of MRSA infection showed an increasing trend over time., Conclusion: Staphylococcus aureus is still the main pathogen of AHOI in local children. The proportion of MRSA in S. aureus has also increased over time to 76% in the last 5 years, and the increased proportion of MRSA can affect the choice of initial empirical medication., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Traumatic arthrotomy (TA) is a rare but serious condition associated with a high morbidity and mortality that can be mitigated with prompt diagnosis and appropriate management., Objective: This review highlights the pearls and pitfalls of the emergency department (ED) evaluation of TA, including diagnostic procedures, imaging, and management based on current evidence., Discussion: Traumatic arthrotomy occurs when the joint capsule is disrupted during a penetrating injury. This exposes the intra-articular contents to contamination and poses a serious risk for development of septic arthritis. All periarticular injuries should prompt evaluation for TA, as missing this diagnosis can lead to significant morbidity and possibly mortality. ED evaluation options include plain radiographs, computerized tomography, and the saline load test. Each of these diagnostic modalities has unique limitations, and as such it is difficult to determine optimal practice or a standard of care. This is further complicated by the limited number of studies evaluating joints other than the knee. ED management includes orthopedic surgery consultation, wound care including irrigation, tetanus prophylaxis, and antibiotic administration., Conclusions: An understanding of an evidenced-based approach to TA can assist emergency clinicians in diagnosing and managing this challenging clinical presentation., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Inc.)

Background and Objectives: Septic arthritis is a medical emergency associated with high morbidity and mortality. The incidence rate of septic arthritis among dialysis patients is higher than the general population, and dialysis patients with bacteremia frequently experience adverse outcomes. The aim of this study was to identify the clinical features and risk factors for longer hospital length of stay (LOS), positive blood culture, and in-hospital mortality in dialysis patients with septic arthritis. Materials and Methods: The medical records of 52 septic arthritis dialysis patients admitted to our hospital from 1 January 2009 to 31 December 2020 were analyzed. The primary outcomes were bacteremia and in-hospital mortality. Variables were compared, and risk factors were evaluated using linear and logistic regression models. Results: Twelve (23.1%) patients had positive blood cultures. A tunneled cuffed catheter for dialysis access was used in eight (15.4%) patients, and its usage rate was significantly higher in patients with positive blood culture than in those with negative blood culture (41.7 vs. 7.5%, p = 0.011). Fever was present in 15 (28.8%) patients, and was significantly more frequent in patients with positive blood culture (58.3 vs. 20%, p = 0.025). The most frequently involved site was the hip (n = 21, 40.4%). The most common causative pathogen was Gram-positive cocci, with MRSA (n = 7, 58.3%) being dominant. The mean LOS was 29.9 ± 25.1 days. The tunneled cuffed catheter was a significant predictor of longer LOS (Coef = 0.49; Cl 0.25−0.74; p < 0.001). The predictors of positive blood culture were fever (OR = 4.91; Cl 1.10−21.83; p = 0.037) and tunneled cuffed catheter (OR = 7.60; Cl 1.31−44.02; p = 0.024). The predictor of mortality was tunneled cuffed catheter (OR = 14.33; Cl 1.12−183.18; p = 0.041). Conclusions: In the dialysis population, patients with tunneled cuffed catheter for dialysis access had a significantly longer hospital LOS. Tunneled cuffed catheter and fever were independent predictors of positive blood culture, and tunneled cuffed catheter was the predictor of in-hospital mortality. The recognition of the associated factors allows for risk stratification and determination of the optimal treatment plan in dialysis patients with septic arthritis.

Introduction: Bone and Joint Infections (BJI) are medically important, costly and occur in native and prosthetic joints. Arthroplasties will increase significantly in absolute numbers over time as well as the incidence of Prosthetic Joint Infections (PJI). Diagnosis of BJI and PJI is sub-optimal. The available diagnostic tests have variable effectiveness, are often below standard in sensitivity and/or specificity, and carry significant contamination risks during the collection of clinical samples. Improvement of diagnostics is urgently needed., Areas Covered: We provide a narrative review on current and future diagnostic microbiology technologies. Pathogen identification, antibiotic resistance detection, and assessment of the epidemiology of infections via bacterial typing are considered useful for improved patient management. We confirm the continuing importance of culture methods and successful introduction of molecular, mass spectrometry-mediated and next-generation genome sequencing technologies. The diagnostic algorithms for BJI must be better defined, especially in the context of diversity of both disease phenotypes and clinical specimens rendered available., Expert Opinion: Whether interventions in BJI or PJI are surgical or chemo-therapeutic (antibiotics and bacteriophages included), prior sensitive and specific pathogen detection remains a therapy-substantiating necessity. Innovative tests for earlier and more sensitive and specific detection of bacterial pathogens in BJI are urgently needed.

Introduction: Despite the current trend toward less aggressive therapeutic approaches, acute haematogenous osteomyelitis (AHO) continues to be a challenge and is associated with significant morbidity worldwide. Our aim was to assess whether compliance with the current protocol was achieved in 80% of cases, to identify complications and the associated risk factors, and to analyse trends in the aetiology and management of AHO in the paediatric population., Methods: We conducted a longitudinal, observational, single-centre study in patients with AHO aged less than 18 years admitted to a paediatric hospital between 2008 and 2018 divided in 2 cohorts (before and after 2014). We analysed data concerning demographic and clinical characteristics and outcomes., Results: The study included 71 children with AHO, 56% male, with a median age of 3 years (interquartile range, 1-11). We found a 1.8-fold increase of cases in the last 5 years. The causative agent was identified in 37% of cases: MSSA (54%), MRSA (4%), S. pyogenes (19%), K. kingae (12%), S. pneumoniae (8%), and N. meningitidis (4%). Complications were identified in 45% of patients and sequelae in 3.6%. In recent years, there was an increase in myositis (30% vs 7%; P=.02), septic arthritis (68 vs 37.2%; p=0.012) and in the proportion of patients treated for less than 4 weeks (37 vs 3.5%; p=0.012), with a similar sequelae rates. The risk factors associated with complications were age 3 or more years, C-reactive protein levels of 20mg/L or higher, time elapsed between onset and admission of 5 or more days and positive culture, although the only factor that continued to be significantly associated in the multivariate analysis was positive culture. The presence of complications was a risk factor for sequelae at 6 months., Conclusions: Our study confirms that AHO can be aggressive. The identification of risk factors for complications is essential for management., (Copyright © 2021. Published by Elsevier España, S.L.U.)

Background: Identifying the causative pathogen for acute hematogenous musculoskeletal infections (MSKIs) allows for directed antimicrobial therapy and diagnostic confidence. However, 20% to 50% of children with acute MSKIs remain culture negative. The objective of this study was to compare characteristics of culture negative MSKI patients to those where a pathogen is identified., Methods: Electronic medical records of children admitted between July 2014 to September 2018 to a single quaternary care pediatric hospital with acute MSKIs were retrospectively reviewed. Clinical and demographic characteristics were compared between culture positive and culture negative MSKIs., Results: A total of 170 patients were included of whom 43 (25%) were culture negative. All culture negative patients had at least 1 culture type obtained, and the majority (84%) had both blood and source cultures performed. When compared with patients with a causative pathogen identified, culture negative patients were younger (2.3 vs. 9.8 y), smaller (13.5 vs. 31.6 kg), less likely to be febrile on arrival (56% vs. 77%), less likely to have an abscess on imaging (23% vs. 48%), and were more likely to have uncomplicated septic arthritis (35% vs. 8%). No critically ill patient was culture negative. Seven culture negative patients had additional Kingella kingae testing performed, none of which were positive., Conclusions: Despite targeted and standardized efforts to identify causative bacteria, 25% of children with acute MSKIs never have a pathogen identified. Culture negative patients are younger, less febrile, are less likely to have an abscess, and more likely to have isolated septic arthritis., Level of Evidence: This is a retrospective cohort study interested in identifying patient characteristics that predict rate of culture positivity for acute MSKIs. This study meets criteria for Level II evidence., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Septic arthritis is important to consider in any patient who presents with joint pain because it is a medical emergency with an 11% fatality rate. Diagnosis and treatment may improve prognosis; however, many patients do not regain full joint function. In patients with end-stage renal disease (ESRD), immune dysfunction due to uremia and chronic vascular access leads to increased risk of infection. We examined the incidence, risk factors and sequelae of septic arthritis in a cohort of hemodialysis patients. The US Renal Data System was queried for diagnoses of septic arthritis and selected sequelae using International Statistical Classification of Diseases and Related Health Problems-9 and Current Procedural Terminology-4 codes in patients who initiated hemodialysis between 2005 and 2010. Multivariable logistic regression was used to determine potential risk factors for septic arthritis and its sequelae. 7009 cases of septic arthritis were identified, an incidence of 514.8 per 100,000 persons per year. Of these patients, 2179 were diagnosed with a documented organism within 30 days prior to or 14 days after the septic arthritis diagnosis, with methicillin-resistant Staphylococcus aureus infections (57.4%) being the most common. Significant risk factors for septic arthritis included history of joint disease, immune compromise (diabetes, HIV, cirrhosis), bacteremia and urinary tract infection. One of the four sequelae examined (joint replacement, amputation, osteomyelitis, Clostridioides difficile infection) occurred in 25% of septic arthritis cases. The high incidence of septic arthritis and the potential for serious sequelae in patients with ESRD suggest that physicians treating individuals with ESRD and joint pain/inflammation should maintain a high clinical suspicion for septic arthritis., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Kingella kingae is an important cause of septic arthritis in young children, with modern laboratory methods leading to increased detection. Prevalence of this pathogen in New Zealand, where there are high rates of childhood infections due to Staphylococcus aureus and Streptococcus pyogenes, is not known., Methods: We conducted a retrospective review of children <5 years with septic arthritis (without osteomyelitis) at a tertiary children's hospital in Auckland, over 10 years (2005-2014). Data were collected on demographics, microbiology, clinical presentation, investigations and management., Results: Of the 68 cases of septic arthritis, 57 (83.8%) occurred in children aged <24 months. Among those <3 months, Streptococcus agalactiae (Group B streptococcus) was predominant (45.5% of 11 cases), followed by S. aureus (36.4%). The most common pathogen in those 3 to <12 months was Streptococcus pneumoniae (38.5% of 13 cases). In children aged 12 to <24 months, K. kingae was most common (30.3% of 33 cases). Of the 12 cases of K. kingae, 91.7% were identified from synovial fluid culture. All K. kingae isolates were susceptible to amoxicillin., Conclusions: K. kingae is the leading pathogen in septic arthritis in New Zealand children aged 12 to <24 months. Routine inoculation of synovial fluid into blood culture bottles at time of sample collection, in addition to use of polymerase chain reaction methods, should be encouraged to improve detection rates. For infants and preschool children presenting with single joint septic arthritis, empiric antibiotics should include cover for S. aureus and K. kingae., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objective: In Lyme disease endemic areas, Lyme and septic arthritis often present similarly. A published septic knee arthritis clinical prediction rule includes 2 high-risk predictors: absolute neutrophil count of 10,000 cells/mm3 or greater and erythrocyte sedimentation rate of 40 mm/h or greater. The objective of the study was to externally validate this prediction rule in a multicenter prospective cohort., Methods: We enrolled a prospective cohort of children with knee monoarthritis undergoing evaluation for Lyme disease at 1 of 8 Pedi Lyme Net emergency departments located in endemic areas. We defined a case of septic arthritis with a positive synovial fluid culture or a synovial fluid white blood cell count of 50,000 or greater per high powered field with a positive blood culture and Lyme arthritis with a positive or equivocal C6 EIA, followed by a positive supplemental immunoblot. Other children were classified as having inflammatory arthritis. We report the performance of the septic arthritis clinical prediction rule in our study population., Results: Of the 543 eligible children, 13 had septic arthritis (2.4%), 234 Lyme arthritis (43.1%), and 296 inflammatory arthritis (54.5%). Of the 457 children (84.2%) with available laboratory predictors, all children with septic arthritis were classified as high risk (sensitivity, 100%; 95% confidence interval [CI], 77.2%-100%; specificity, 68.1%; 95% CI, 63.6-73.3; negative predictive value, 278/278 [100%]; 95% CI, 98.6%-100%). Of the 303 low-risk children, 52 (17.2%) underwent diagnostic arthrocentesis., Conclusions: The septic knee arthritis clinical prediction rule accurately distinguished between septic and Lyme arthritis in an endemic area. Clinical application may reduce unnecessary invasive diagnostic procedures., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The presence or absence of an implant has a major impact on the type of joint infection therapy. Thus, the aim of this study was the examination of potential differences in the spectrum of pathogens in patients with periprosthetic joint infections (PJI) as compared to patients with native joint infections (NJI)., Methods: In this retrospective study, we evaluated culture-positive synovial fluid samples of 192 consecutive patients obtained from January 2018 to January 2020 in a tertiary care university hospital. For metrically distributed parameters, Mann-Whitney U was used for comparison between groups. In case of nominal data, crosstabs and Chi-squared tests were implemented., Results: Overall, 132 patients suffered from periprosthetic joint infections and 60 patients had infections of native joints. The most commonly isolated bacteria were coagulase-negative Staphylococci (CNS, 28%), followed by Staphylococcus aureus (S. aureus, 26.7%), and other bacteria, such as Streptococci (26.3%). We observed a significant dependence between the types of bacteria and the presence of a joint replacement (p < 0.05). Accordingly, detections of CNS occurred 2.5-fold more frequently in prosthetic as compared to native joint infections (33.9% vs. 13.4% p < 0.05). In contrast, S. aureus was observed 3.2-fold more often in NJIs as compared to PJIs (52.2% vs. 16.4%, p < 0.05)., Conclusion: The pathogen spectra of periprosthetic and native joint infections differ considerably. However, CNS and S. aureus are the predominant microorganisms in both, PJIs and NJIs, which may guide antimicrobial therapy until microbiologic specification of the causative pathogen., (© 2021. The Author(s).)