International Consensus Meeting Research Articles

Clinical applications of metagenomic next-generation sequencing in the identification of pathogens in periprosthetic joint infections: a retrospective study

BackgroundThis study aimed to evaluate the application of metagenomic next-generation sequencing (mNGS) technology to identify pathogens in periprosthetic joint infection (PJI).MethodsA retrospective analysis was conducted on 65 patients suspected of having PJI between April 2020 and July 2023. The patients were categorized into PJI (46 patients) and non-PJI (19 patients) groups based on the 2018 International Consensus Meeting criteria. Clinical data were collected, and both conventional bacterial culture and mNGS were performed. The diagnostic performance of the two methods was compared and analyzed.ResultsmNGS exhibited a sensitivity of 89.13%, a specificity of 94.74%, a positive predictive value of 97.62%, a negative predictive value of 78.26%, and an overall diagnostic accuracy of 90.77%. Compared to microbial culture, mNGS demonstrated superior diagnostic sensitivity while maintaining similar specificity. A total of 48 pathogens were successfully identified using mNGS, with Coagulase-negative staphylococci, Streptococci, Staphylococcus aureus, and Cutibacterium acnes being the most common infectious agents. Notably, mNGS was used to identify 17 potential pathogens in 14 culture-negative PJI samples, highlighting its ability to detect rare infectious agents, including Cutibacterium acnes (n = 5), Granulicatella adiacens (n = 1), Mycobacterium tuberculosis complex (n = 1), and Coxiella burnetii (n = 1), among others, which are not detectable by routine culture methods. However, mNGS failed to detect the pathogen in 4 culture-positive PJI patients, indicating its limitations. Among the 46 PJI patients, 27 had positive culture and mNGS results. The results of mNGS were concordant with those of culture at the genus level in 6 patients with PJI and at the species level in 18 patients. Furthermore, the present study revealed a significantly greater proportion of Staphylococcus aureus in the sinus tract group (45.45%) than in the non-sinus tract group (14.29%), indicating the association of this pathogen with sinus formation in PJI (P = 0.03). Additionally, there was no significant difference in the occurrence of polymicrobial infections between the sinus tract group (27.27%) and the non-sinus tract group (33.33%) (P = 0.37).ConclusionsMetagenomic next-generation sequencing can serve as a valuable screening tool in addition to traditional culture methods to improve diagnostic accuracy through optimized culture strategies.

Low-Dose Aspirin Is the Safest Prophylaxis for Prevention of Venous Thromboembolism After Total Knee Arthroplasty Across All Patient Risk Profiles.

The International Consensus Meeting on Venous Thromboembolism (ICM-VTE) in 2022 proclaimed low-dose aspirin as the most effective agent in patients across all risk profiles undergoing joint arthroplasty. However, data on large patient populations assessing trends in chemoprophylactic choices and related outcomes following total knee arthroplasty (TKA) remain scant. The present study was designed to characterize the clinical use of various chemoprophylactic agents in patients undergoing TKA and to determine the efficacy of aspirin compared with other agents in patient groups stratified by VTE risk profiles. This study utilized a national database to determine the proportion of patients undergoing TKA who received low-dose aspirin versus other chemoprophylaxis between 2012 and 2022. VTE risk profiles were determined on the basis of comorbidities established in the ICM-VTE. The odds ratios (ORs) and 95% confidence intervals (CIs) between various classes of thromboprophylaxis in patients with high and low risk of VTE were calculated. The odds of deep-vein thrombosis (DVT), pulmonary embolus (PE), bleeding events, infections, mortality, and hospitalizations were also assessed in the 90-day postoperative period for propensity-matched cohorts receiving low-dose (81 mg) aspirin only versus other prophylaxis, segregating patients by VTE risk profile. A total of 126,692 patients undergoing TKA across 60 health-care organizations were included. The proportion of patients receiving low-dose aspirin increased from 7.65% to 55.29% between 2012 and 2022, whereas the proportion of patients receiving other chemoprophylaxis decreased from 96.25% to 42.98%. Low-dose-aspirin-only use increased to approximately 50% in both high-risk and low-risk populations but was more likely in low-risk populations (OR, 1.17; 95% CI, 1.15 to 1.20) relative to high-risk populations. Both low-risk and high-risk patients in the low-dose-aspirin-only cohorts had decreased odds of DVT, PE, bleeding, infections, and hospitalizations compared with other prophylaxis regimens. The findings of the present study on a very large population of patients undergoing TKA support the recent ICM-VTE statement by showing that low-dose aspirin is a safe and effective method of prophylaxis in patients across various risk profiles. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Results of a monocentric field study: value of histology compared to sonication method and conventional tissue culture in the diagnosis of periprosthetic joint infection (PJI).

To confirm the diagnosis of periprosthetic joint infection (PJI), the Infectious Diseases Society of America (IDSA) and the International Consensus Meeting (ICM) have defined criteria that include histology as a minor criterion and the sonication method only as an additional criterion. The aim of this monocentric, retrospective study was to investigate the value of histology and whether sonication leads to a more accurate diagnosis. All revision surgeries for knee and hip arthroplasty between 2017 and 2020 were included. With regard to microbiological diagnostic, conventional culture of periprosthetic biopsies and sonication of explant material were performed. In addition, histology and non-specific inflammatory markers (CRP, leukocytes) were recorded. A total of 78 patients with PJI and 62 aseptic controls were included. From both microbiological methods (conventional culture / sonication), Staphyloccus (S.) epidermidis and S. aureus were detected most frequently. However, compared to the conventional microbiology, a higher sensitivity was calculated for sonication, albeit with a lower specificity in relation to a PJI. In two logistic regression models for the significance of all diagnostic parameters in PJI, the AUC was 0.92 and 0.96 with histology in particular making the decisive contribution in both models (p < 0. 001, both models). Since histology showed the highest accuracy in the current study, its importance in the PJI criteria should be reevaluated. Sonication shows a high sensitivity for germ detection with a lower specificity and should only be used in combination with the conventional culture for microbiolgical diagnostics.

Commercial Synovial Antigen Testing is Inferior to Traditional Culture for the Diagnosis of Periprosthetic Joint Infection in Patients Undergoing Revision Total Knee Arthroplasty

BackgroundDespite its limitations, a culture remains the “gold standard” for pathogen identification in patients who have periprosthetic joint infection (PJI). Recently, a synovial fluid antigen test has been introduced by a commercial entity. The purpose of this multicenter study was to determine the accuracy of the antigen test in the diagnosis of PJI. MethodsThis retrospective study identified 613 patients undergoing revision total knee arthroplasty who had undergone preoperative synovial fluid analysis. A PJI was defined using the 2018 International Consensus Meeting (ICM) criteria. Patients who had an extended period (> 180 days) from aspiration to revision procedure (n = 62), those presenting within 90 days of their index arthroplasty procedure (n = 17), and patients who had an inconclusive ICM score (n = 8) were excluded. Using receiver operator characteristic curve analyses, we examined the utility of the microbial identification (MID) antigen test and any positive culture (either preoperative or intraoperative) in the diagnosis of PJI. ResultsA total of 526 patients were included. Of these, 125 (23.8%) were ICM positive and 401 (76.2%) were ICM negative. Culture demonstrated an area under the curve (AUC) of 0.864, sensitivity of 75.2%, and specificity of 97.5%. On the other hand, the MID test exhibited an AUC of 0.802, sensitivity of 61.6%, and specificity of 98.8%. The AUC of culture was significantly higher than that of the MID test (P = .037). The MID test was positive in 41.9% of culture-negative PJI cases. We also observed a high rate of discordance (29.7%) when both culture and the MID test were positive in the ICM-positive group. ConclusionsSynovial fluid antigen testing does not provide additional clinical benefit when compared to traditional cultures for the diagnosis of PJI. The antigen test had low sensitivity in the diagnosis of PJI and a relatively high rate of discordance with culture. Level of EvidenceLevel III.

Does retained cement or hardware during 2-stage revision shoulder arthroplasty for infection increase the risk of recurrent infection?

IntroductionWhen treating chronic prosthetic joint infection (PJI) after shoulder arthroplasty, removal of the implants and cement is typically pursued because they represent a potential nidus for infection. However, complete removal can increase morbidity and compromise bone stock that is important for achieving stable revision implants. The purpose of this study is to compare the rates of repeat infection after 2-stage revision for PJI in patients who have retained cement or hardware compared to those who had complete removal. Material and MethodsWe retrospectively analyzed all two-stage revision total shoulder arthroplasties (TSAs) performed for infection at two institutions between 2011 and 2020 with minimum two-year follow-up from completion of the two-stage revision. Patients were included if they met the International Consensus Meeting (ICM) criteria for probable or definite infection2. Postoperative radiographs after the first-stage of the revision consisting of prosthesis and cement removal and placement of an antibiotic spacer were reviewed to evaluate for retained cement or hardware. Repeat infection was defined as either ≥2 positive cultures at the time of second-stage revision with the same organism cultured during the first-stage revision or repeat surgery for infection after the two-stage revision in patients that again met the ICM criteria for probable or definite infection. The rate of repeat infection among patients with retained cement or hardware was compared to the rate of infection among patients without retained cement or hardware. ResultsThirty-seven patients met inclusion criteria and were included in the analysis. Six (16%) patients had retained cement and one patient (3%) had two retained broken glenoid baseplate screws after first-stage revision. Of the ten cases of recurrent infection, one case (10%) involved retained cement/hardware. Age at revision (60.9±10.6 vs. 65.0±9.6, p=0.264), BMI (33.4±7.2 vs. 29.7±7.3, p=0.184), Charlson Comorbidity Index (2 (0-8) vs. 3 (0-6), p=0.289), male sex (7 vs. 16, p=0.420) and presence of diabetes (1 vs. 3, p=0.709) were not associated with repeat infection. Retained cement or hardware was also not associated with a repeat risk of infection (1 vs. 6, OR=0.389, p=0.374). DiscussionWe did not find an increased risk of repeat infection in patients with retained cement or hardware compared to those without. Therefore, we believe that surgeons should consider leaving cement or hardware that is difficult to remove and may lead to increased morbidity and future complications.

Cervical Cancer Associated with Pregnancy: Current Challenges and Future Strategies.

Cancer during pregnancy is defined as a tumor diagnosed in a pregnant woman or up to 1-year post-partum. While being a rare disease, cervical cancer is probably one of the most challenging medical conditions, with the dual stake of treating the cancer without compromising its chances for cure, while preserving the pregnancy and the health of the fetus and child. To date, guidelines for gynecological cancers are provided through international consensus meetings with expert panels, giving insights on both diagnosis, treatment, and obstetrical care. However, these expert guidelines do not discuss the various approaches than can be found within the literature, such as alternative staging modalities or innovative surgical approaches. Also, the obstetrical care of women diagnosed with cervical cancer during pregnancy requires specific considerations that are not provided within our current standard of care. This systematic review aims to fill the gap on current issues with regards to the management of cervical cancer during pregnancy and provide future directions within this evolving landscape.

The False-Positive Rate of Synovial Fluid Culture at a Single Clinical Laboratory Using Culture Bottles.

Introduction Synovial fluid (SF) cultures can yield false-positive or negative results when diagnosing periprosthetic joint infection (PJI). False-positives may arise during sample collection or from laboratory contamination. Understanding false-positive SF culture rates is crucial for interpreting PJI laboratory data, yet clinical laboratories rarely report these rates. This study aimed to define the false-positive SF culture rate at a major specialized clinical laboratory. Methods This study retrospectively analyzed prospectively collected data at a single clinical laboratory that receives SF for clinical testing for PJI. A total of 180,317 periprosthetic SF samples from the hip, knee, and shoulder were identified from January 2016 to December 2023, which met the inclusion criteria for this study. Samples were classified by both a modified 2018 International Consensus Meeting (ICM) score and an inflammation score that combined the SF-C-reactive protein, alpha-defensin, SF-white blood cell count, and SF-polymorphonuclear% into one standardized metric. Logistic regression was utilized to evaluate the impact of various collection-based characteristics on culture positivity, including inflammation biomarkers, the source joint, quality control metrics, and days of specimen transport to the laboratory. SF culture false-positivity was calculated based on the ICM category of "not-infected" or low inflammation score. Results Overall, 13.3% (23,974/180,317) of the samples were associated with a positive culture result: 12.5% for knee samples, 20.3% for hip samples, and 14.7% for shoulder samples. The false-positive SF culture rate among 131,949 samples classified as "not-infected" by the modified 2018 ICM definition was 0.47% (95%CI: 0.43 to 0.51%). Stratification by joint revealed a false-positive rate of 0.34% (95%CI: 0.31 to 0.38%) for knee samples, 1.24% (95%CI: 1.05 to 1.45%) for hip samples, and 3.02% (95%CI: 2.40 to 3.80%) for shoulder samples, with p < 0.0001 for all comparisons. The false-positive SF culture rate among 90,156 samples, representing half of all samples with the lowest standardized inflammation scores, was 0.47% (95%CI: 0.43 to 0.52%). Stratification by joint revealed a false-positive rate of 0.33% (95%CI: 0.29 to 0.37%) for knee samples, 1.45% (95%CI: 1.19 to 1.77%) for hip samples, and 3.09% (95%CI: 2.41 to 3.95%) for shoulder samples, with p<0.0001 for all comparisons. Multivariate logistic regression demonstrated the joint source (hip, shoulder) and poor sample quality as collection-based factors associated with a false-positive culture. Evaluation of a cohort of samples selected to minimize collection-based causes of false-positive culture demonstrated a false-positive rate of 0.30%, representing the ceiling limit for laboratory-based SF culture false-positivity. Conclusions This study utilizes two methods to estimate the false-positive SF culture rate at a single specialized clinical laboratory, demonstrating an overall false-positive rate of approximately 0.5%. Stratification of samples by source joint demonstrated that periprosthetic SF from the shoulder and hip have a substantially higher false-positive culture rate than that of the knee. The lowest false-positive SF culture rate (0.30%) was observed among samples from the knee-passing quality control. Culture positivity due to contamination at this specific laboratory is less than 0.30% because all specimens undergo identical processing.

Humeral stem loosening is not always prosthetic joint infection

BackgroundAseptic humeral stem loosening is an uncommon complication of shoulder arthroplasty, and its presence has been considered a highly specific predictor of prosthetic joint infection (PJI). Literature on aseptic humeral stem loosening is sparse. The primary purpose of this study was to determine the rate of aseptic humeral loosening in revision shoulder arthroplasty. Secondarily, we sought to identify predictors of septic and aseptic humeral loosening. MethodsOur institutional revision shoulder arthroplasty database was reviewed. Inclusion criteria were patients with humeral stem loosening as indicated in the operative report. Patient demographics, index surgery and indication, revision surgery and indication, and operative data were recorded. Charts were manually reviewed, and PJI scores were calculated using the International Consensus Meeting (ICM) scoring criteria. ICM classifications of PJI “unlikely” and “possible” were considered aseptic, and PJI “probable” and “definite” were considered septic. Statistical analysis was performed to determine associations between the abovementioned variables and aseptic humeral loosening. ResultsForty-six patients with forty-eight shoulders were included in our analysis. Ten cases (21%) were classified as definite PJI, thirteen cases (27%) were classified as probable PJI, four cases (8%) were classified as possible PJI, and twenty-one cases (44%) were classified as PJI unlikely. On analysis of stem design, there were no statistically significant associations with aseptic loosening; although, a lack of proximal porous ingrowth surface trended toward higher rates of aseptic loosening in all patients and in ATSA and RTSA subgroup analyses. In the index RTSA subgroup, aseptic loosening was associated with female sex (p=0.005). Seventeen of 39 shoulders (44%) that underwent either index ATSA or RTSA demonstrated concomitant glenoid loosening. The absence of glenoid loosening was associated with aseptic humeral loosening in index ATSA and RTSA (p<0.001). Conclusion52% of revision shoulder arthroplasty cases with humeral loosening performed at our institution were aseptic. There appear to be distinct demographic and radiographic factors that are more commonly associated with aseptic as opposed to septic humeral loosening. Our data demonstrate that demographic predictors of aseptic loosening of RTSA include female sex. The absence of glenoid component loosening is associated with aseptic humeral loosening and concomitant glenoid loosening is associated with septic humeral loosening. Understanding of these factors can guide the preoperative index of suspicion for PJI in the setting of humeral stem loosening.

Finding the Optimal Serological Screening Test for Periprosthetic Joint Infection: A Prospective Study

IntroductionNo single test has demonstrated absolute accuracy in the diagnosis of periprosthetic joint infection (PJI). Serological markers are often used as screening tools to avoid unnecessary joint aspiration in cases with a low probability of infection. This study aimed to determine the utility of standard-of-care serological tests as a screening tool for PJI in patients undergoing revision arthroplasty. MethodsThis prospective study enrolled 502 patients undergoing revision hip or knee arthroplasty between May 2017 and August 2021. A PJI was defined using a modified definition of the 2018 International Consensus Meeting (ICM) criteria. Plasma D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen were measured preoperatively. There were 82 patients undergoing reimplantation who were excluded. Additionally, 8 patients who had an inconclusive ICM score were also excluded. Of the 412 included patients, 317 (76.9%) underwent revision for aseptic failure, and 95 (23.1%) had PJI. Receiver operating characteristic curves were used to assess the diagnostic utility of each serological test. A pairwise comparison with Bonferroni correction was performed in order to determine whether the differences in areas under the curve (AUCs) between the tests were significant. Additional analyses were performed to find the threshold for each test that offered 100% sensitivity, allowing it to be the optimal screening test. ResultsAll four serological markers, D-dimer (AUC 0.860, sensitivity 81.3%, specificity 81.7%), CRP (AUC 0.862, sensitivity 90.4%, specificity 70.0%), ESR (AUC 0.833, sensitivity 73.9%, specificity 85.2%), and fibrinogen (AUC 0.798, sensitivity 74.7%, specificity 75.4%), demonstrated comparable accuracy for the diagnosis of PJI (all P > 0.05). When maximizing sensitivity to 100%, D-dimer demonstrated the highest specificity (AUC 0.860, specificity 40.2%), outperforming ESR (AUC 0.833, specificity 3.3%), fibrinogen (AUC 0.798, specificity 2.3%), and CRP (AUC 0.862, specificity 0%). A plasma D-dimer level of ≥ 244 ng/mL was identified as the optimal cutoff for use as a screening test. ConclusionAlthough plasma D-dimer demonstrated similar diagnostic accuracy as CRP, ESR, and fibrinogen, it outperformed all three aforementioned serological markers when used as a screening test for PJI.

Do one-stage indications predict success following two-stage arthroplasty for chronic periprosthetic joint infection?

Introduction: The 2018 International Consensus Meeting (ICM) proposed criteria for one-stage exchange arthroplasty in treating periprosthetic joint infection (PJI). Our study aimed to determine what proportion of PJI patients met the 2018 ICM criteria and how this affected infection-free survivorship for patients. Methods: All chronic PJI patients treated with two-stage exchange within our institution between 2017-2020 were retrospectively reviewed. Included cases met 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI and had a 2-year minimum follow-up. Treatment success was defined as Tier 1A in the 2019 MSIS working group definition. ICM one-stage criteria included non-immunocompromised host, absence of sepsis, adequate soft tissue for closure, known preoperative pathogen, and susceptibility. Immunocompromised host was analyzed as two separate definitions. Kaplan-Meier survivorship, Cox regression, and univariate analyses were performed. Results: A total of 293 chronic PJI patients were included. Overall, treatment failure occurred in (21.8 %) patients. Only 13 % () met ICM criteria definition no.1 for one-stage exchange; 12 % () met definition no.2. In both definitions, infection-free survivorship at 2years did not differ between patients who met and did not meet criteria (). Cox proportional hazard regression analyses demonstrated that the only variable predicting treatment failure was knee joint involvement (). Conclusions: We found that a very limited number of chronic PJI patients were suitable for a one-stage exchange. Furthermore, the supposition that healthier hosts with known pathogens (the basis of the ICM criteria) yield better PJI treatment outcomes was not observed. These results justify the ongoing multicenter randomized control trial comparing one-stage versus two-stage treatment for chronic PJI.

A machine learning-based model for "In-time" prediction of periprosthetic joint infection.

Previous criteria had limited value in early diagnosis of periprosthetic joint infection (PJI). Here, we constructed a novel machine learning (ML)-derived, "in-time" diagnostic system for PJI and proved its validity. We filtered "in-time" diagnostic indicators reported in the literature based on our continuous retrospective cohort of PJI and aseptic prosthetic loosening patients. With the indicators, we developed a two-level ML model with six base learners including Elastic Net, Linear Support Vector Machine, Kernel Support Vector Machine, Extra Trees, Light Gradient Boosting Machine and Multilayer Perceptron), and one meta-learner, Ensemble Learning of Weighted Voting. The prediction performance of this model was compared with those of previous diagnostic criteria (International Consensus Meeting in 2018 (ICM 2018), etc.). Another prospective cohort was used for internal validation. Based on our ML model, a user-friendly web tool was developed for swift PJI diagnosis in clinical practice. A total of 254 patients (199 for development and 55 for validation cohort) were included in this study with 38.2% of them diagnosed as PJI. We included 21 widely accessible features including imaging indicators (X-ray and CT) in the model. The sensitivity and accuracy of our ML model were significantly higher than ICM 2018 in development cohort (90.6% vs. 76.1%, P = 0.032; 94.5% vs. 86.7%, P = 0.020), which was supported by internal validation cohort (84.2% vs. 78.6%; 94.6% vs. 81.8%). Our novel ML-derived PJI "in-time" diagnostic system demonstrated significantly improved diagnostic potency for surgical decision-making compared with the commonly used criteria. Moreover, our web-based tool greatly assisted surgeons in distinguishing PJI patients comprehensively. Diagnostic Level III.

Diagnostic Test Performances for Identifying Periprosthetic Joint Infection in Hip Hemiarthroplasty.

Periprosthetic joint infection (PJI) is a devastating complication of hip hemiarthroplasty (HHA) that is not well-represented in the literature. Therefore, this study aimed to evaluate diagnostic markers for identifying PJI in patients after HHA and compare them with the most recent 2018 International Consensus Meeting on Musculoskeletal Infection criteria. A total of 98 patients (64 PJIs, 65.3%) were analyzed. Patients were identified by relevant Current Procedural Terminology and International Classification of Diseases-9/10 codes from 2000 to 2021 across a single healthcare system. Preoperative or intraoperative synovial fluid nucleated cell (NC) count, synovial polymorphonuclear (PMN) percentage, serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), and serum white blood cell count were compared with Student t -test between aseptic and septic cohorts. Diagnostic utility and laboratory cutoff values were determined using receiver-operating characteristic curves and Youden index, respectively. Mean values were significantly higher in the septic cohort for synovial NC count (120,992.2 versus 1,498.0 cells/μL, P < 0.001), synovial PMN percentage (91.3% versus 56.2%, P < 0.001), serum ESR (75.6 versus 36.3 mm/hr, P < 0.001), serum CRP (20.2 versus 125.8 mg/L, P < 0.001), and serum white blood cell count (8.5 versus 11.5 cells/μL, P < 0.001). Synovial NC count, synovial PMN percentage, and serum CRP had excellent PJI discriminatory ability with an area under the curve of 0.99, 0.90, and 0.93, respectively. Optimal cutoffs were 2,700 cells/μL for synovial NC count (100% sensitivity and 94% specificity), 81.0% for synovial PMN percentage (96% sensitivity and 89% specificity), 52.0 mm/hr for serum ESR (75% sensitivity and 80% specificity), and 40.0 mg/L for serum CRP (85% sensitivity and 92% specificity). Our findings support the continued use of routine serum and synovial fluid tests for diagnosing PJI in HHA patients. Optimal cutoff values for both synovial fluid biomarkers were very close in alignment with the 2018 International Consensus Meeting criteria. Level III, retrospective comparative study.

2023 International Consensus Meeting on musculoskeletal infection: Summary from the treatment workgroup and consensus on treatment in preclinical models.

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location, and implants used, there are also a wide range of animal models described modeling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to (1) animal model considerations, (2) outcome measurements, and (3) imaging.

International consensus on post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

Unexpected Positive Cultures in Hip and Knee Periprosthetic Fractures

BackgroundThe purpose of this study was to determine the prevalence of unexpected positive cultures noted at the time of revision surgery for periprosthetic fracture (PPF) after total hip or knee arthroplasty. Moreover, we evaluated whether this finding should be considered clinically significant and what type of treatment, if any, was required. MethodsThis was a single-center retrospective review of 270 patients undergoing surgery for PPFs from December 2010 to December 2021. Exclusion criteria included: open fractures; history of infection at fractured joint; non-operatively treated patients; and intraoperative fractures. The primary end point was the prevalence of unexpected positive cultures noted at the time of revision surgery. This was defined as one or more positive cultures in a PPF that the surgeon had preoperatively classified as aseptic according to the 2018 International Consensus Meeting. Data collection included patient demographics, medical histories, preoperative investigations, postoperative microbiology, and treatment. ResultsDuring the study period, 159 patients were admitted with PPFs of the hip and 61 with PPFs of the knee. The mean age was 70 years (range, 32 to 93 years). Unexpected positive cultures were diagnosed postoperatively in 15 patients (6.8%; 10 hips, 5 knees). The most prevalent organism was Staphylococcus epidermidis (35.0%). Of those 15 patients, 6 required a surgical revision for infection. None of the patient-related risk factors were found to be associated with an increased risk of unexpected positive cultures. The comparison between infected and noninfected patients showed a significant association between preoperative C-reactive protein >10 mg/mL (P = .04), loose implant (P = .07), and infection. ConclusionsThe prevalence of unexpected positive cultures was 6.8% in our study cohort. Although surgical treatment may be required, the majority of patients seem to require no treatment. Larger series are required to investigate the clinical importance of this rare finding. Level of EvidenceIII.

What is the diagnostic accuracy of neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio in detecting acute periprosthetic joint infections? A gender-specific analysis.

The accurate and timely diagnosis of periprosthetic joint infection (PJI) is critical for guiding optimal treatment management and success, highlighting the requirement of readily available inexpensive serum biomarkers to increase the diagnostic accuracy for PJI. Many studies have investigated the diagnostic accuracy of neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR). However, there is a lack of existing literature regarding optimal thresholds for acute PJI. The purpose of this study was to reveal the most appropriate cut-off values for MLR and NLR in detecting acute PJI with a gender specific analysis. Patients were classified as having an acute PJI if they met the International Consensus Meeting (ICM) 2018 modified criteria. Patients who had a negative clinical and diagnostic workup for a PJI and the presence of erythema on the index surgical area were included in the erysipelas group (control group). Data obtained from all patients included age, sex, body mass index (BMI), Charlson Comorbidity Index (CCI), procedure type (THA or TKA), serum C-reactive protein (CRP), and blood studies at the admission and culture results were retrieved from the electronic medical record. ROC curve analysis was used to determine the gender-specific optimal threshold values for CRP, NLR, and MLR. Comparing the sensitivities and specificities of NLR and MLR at the identified best thresholds in males and females, the study found similar sensitivities of NLR in males and females with 0.84 and 0.84, respectively. On the other hand, an MLR of 0.67 or more reported a notably higher specificity in male patients [0.90 (95% CI 0.75-0.96) versus 0.70 (95% CI 0.56-0.80)]. NLR and MLR represent commonly ordered, low-cost, simple, and readily available complete cell count laboratory values and should be used as adjunct tests with reasonable diagnostic accuracy in detecting acute PJIs. Moreover, with its excellent specificity and PPV, MLR could provide valuable insight in diagnosing acute PJI, particularly in male patients. Level III Retrospective Cohort analysis.

The 2023 Orthopaedic Research Society's International Consensus Meeting on musculoskeletal infection: Summary from the host immunity section.

Musculoskeletal infections (MSKI), which are a major problem in orthopedics, occur when the pathogen eludes or overwhelms the host immune system. While effective vaccines and immunotherapies to prevent and treat MSKI should be possible, fundamental knowledge gaps in our understanding of protective, nonprotective, and pathogenic host immunity are prohibitive. We also lack critical knowledge of how host immunity is affected by the microbiome, implants, prior infection, nutrition, antibiotics, and concomitant therapies, autoimmunity, and other comorbidities. To define our current knowledge of these critical topics, a Host Immunity Section of the 2023 Orthopaedic Research Society MSKI International Consensus Meeting (ICM) proposed 78 questions. Systematic reviews were performed on 15 of these questions, upon which recommendations with level of evidence were voted on by the 72 ICM delegates, and another 12 questions were voted on with a recommendation of "Unknown" without systematic reviews. Two questions were transferred to another ICM Section, and the other 45 were tabled for future consideration due to limitations of available human resources. Here we report the results of the voting with internet access to the questions, recommendations, and rationale from the systematic reviews. Eighteen questions received a consensus vote of ≥90%, while nine recommendations failed to achieve this threshold. Commentary on why consensus was not achieved on these questions and potential ways forward are provided to stimulate specific funding mechanisms and research on these critical MSKI host defense questions.

Preoperative infection risk assessment in hip arthroplasty a matched-pair study of the reliability of 3 validated risk scales.

Peri-prosthetic infection (PJI) represents one of the most devastating complications of total hip arthroplasty (THA). The aim of this study is to assess the reliability of different PJI risk assessment scales between two matched pairs of THA groups. This study included 37 patients with PJI following THA performed between 2012 and 2020 (Group A). Each patient in this group was matched, based on sex, age, and follow-up duration, with a control patient who underwent the same surgical procedure without any septic complications (Group B) during the same period. Each patient's assessment included the American Society of Anesthesiologists (ASA) score and a retrospective evaluation using three different preoperative, specific PJI risk assessment scales: the International Consensus Meeting (ICM) Preoperative Risk Calculator for PJI, the Mayo PJI Risk Score, and the KLIC-score. The two groups were statistically compared using descriptive analyses, both for binomial data and numerical variables. Statistically significant higher values were observed in the preoperative ASA score and surgical time in Group A. Statistically different higher scores were determined only with the ICM risk calculator score in Group A. No significant differences were found using the KLIC score and Mayo score between the two groups. We emphasize the reliability of the ASA score as a nonspecific preoperative assessment scale for PJI. The ICM risk calculator was confirmed as a reliable, specific preoperative assessment scale for PJI, suggesting its routine adoption in THA clinical practice.

Determinants of Relapse and Treatment-Free Survival Following Splenectomy in Patients with Immune Cytopenias

Background: Splenectomy has historically been a treatment option for patients with immune cytopenia not responding to standard treatment. Despite being a highly effective treatment option, current guidelines recommend this strategy as a third-line treatment. There is a need for more evidence regarding predictive response factors that could help adequately select the ideal candidate for splenectomy, its effectiveness, and related complications. The study aims to identify factors associated with relapse in patients diagnosed with immune cytopenia who have undergone splenectomy. Methods: Retrospective cohort study including patients with immune cytopenia, including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and Evans syndrome (ES), who underwent splenectomy between January 1990 and March 2023 in a tertiary referral center in Mexico City. Response criteria were based on the 2019 American Society of Hematology guidelines for ITP and the 2020 First International Consensus Meeting for AIHA. We defined early surgical complications as those occurring in the first 30 days from splenectomy; a durable response after splenectomy was described as lasting one year or more. Results: With a median follow-up of 100 months (interquartile range [IQR] 55.6 - 141.7 months), 173 patients were analyzed: 70% were female, 83% had primary ITP, 10% AIHA, and 7% ES. Only 15% had secondary autoimmune cytopenia: 4% systemic lupus erythematosus, 4% antiphospholipid antibody syndrome (APS), and 4% both; 3% had other autoimmune diseases; one (0.5%) patient had common variable immunodeficiency (CVI). Before splenectomy, all the patients received corticosteroids as first-line treatment, 13% rituximab, and 10% thrombopoietin receptor analogs (TPO-RA). Splenectomy was performed as the second-line treatment (2L) in 43% of the cases and as a third or later line of therapy (&amp;gt;2L) in 57%. When analyzing periods, there is a decline in the frequency of splenectomy as 2L: 62% from 1990-2010, 48% from 2011-2015, and 33% from 2016-2023. The median time from diagnosis to splenectomy was 6.3 months (IQR 2.6 - 19.9 months), 10.9 months (IQR 3.7 - 30.9 months), and 16.5 months (IQR 3.5 - 49.5 months) in the respective periods. The global response rate after splenectomy was 97.7%: complete response in 91.9%, partial response in 5.8%, and durable responses in 77.5%. The relapse rate after splenectomy was 32.0%, significantly lower in patients undergoing splenectomy as 2L vs. &amp;gt;2L: 20.0% vs. 40.8% (p&amp;lt;0.001). The relapse rate after splenectomy was the same in the different periods (p = 0.244). The number of patients free of a new line treatment after splenectomy at 100 months was significantly higher in patients undergoing splenectomy as 2L vs. &amp;gt;2L: 82.7% vs. 65.3% (p=0.014). When analyzing factors associated with relapse requiring a new line of treatment, splenectomy as the 2L (HR 0.403; 95% CI 0.206-0.788, p = 0.008) and post-splenectomy thrombocytosis (HR 0.301; 95% CI 0.144-0.6, p = 0.001) were associated with higher treatment-free survival in the multivariate analysis (See Table 1 and Figure 1). The rate of early surgical complications was 14%: severe infections (8.7%), bleeding (5.2%), and thrombosis (3.5%). Late surgical complications occurred in 8%: thrombosis (5.8%), infections (2.9%), and bleeding (2.3%). Five patients (3%) died during the follow-up period: 3 related to thrombocytopenia, one to splenectomy (abdominal sepsis in a patient with CVI), and one due to prostate adenocarcinoma. The use of TPO-RA before splenectomy and the diagnosis of APS were associated with post-surgical thrombosis in the multivariate analysis: OR 6.8 (95% CI 1.9 - 23.5, p = 0.002) and OR 4.3 (95% CI 1 - 17.8, p = 0.044), respectively. Conclusions: At our center, splenectomy is frequently employed as a very early 2L treatment. However, this tendency has diminished due to improved access to new drugs. Interestingly, splenectomy as 2L vs. &amp;gt;2L is associated with better outcomes which contrast with current recommendations. In a center where splenectomy is frequently performed, the procedure is associated with a reasonable rate of complications. In patients with immune cytopenia, splenectomy as a second-line treatment is a valid, effective, relatively safe, and cost-effective option, particularly in low-income areas with limited access to new therapies.

Preoperative Prophylactic Antibiotics Administration Does Not Influence Culture Yield in Revision Shoulder Arthroplasty.

The importance of administrating prophylactic antibiotics prior to a surgical procedure is well established. Given the difficulty in diagnosing shoulder periprosthetic infections, which are more indolent in nature, some advocate holding prophylactic antibiotics prior to obtaining cultures as there is a concern antibiotics may lead to a false negative culture result. The purpose of this study is to determine whether administration of antibiotics prior to obtaining cultures in revision shoulder arthroplasty influences culture yield. This was a retrospective analysis of revision shoulder arthroplasty cases performed at a single institution between 2015 and 2021. During the study period, each surgeon had a standardized protocol that dictated whether antibiotics were given or held prior to each revision surgery. Each case was categorized into either a Pre-culture antibiotic group, if antibiotics were administered prior to incision, or a Post-culture antibiotic group if antibiotics were administered after incision and obtaining cultures. Basic demographics and the International Consensus Meeting (ICM) scoring criteria provided by the Musculoskeletal Infection Society was used to categorize the probability of periprosthetic joint infection for each case. Culture positivity was calculated as the ratio of positive cultures and total number of cultures obtained. One hundred and twenty-four patients met inclusion criteria. There were 48 patients in the Pre-culture group and 76 patients in the Post-culture group. No significant difference in patient demographics or ICM criteria (p=0.09) was observed between the two groups. With regards to culture positivity, there was no difference between the Pre-culture antibiotic group and the Post-culture antibiotic group (16% vs 15%, p=0.82, confidence interval= 8-25% vs. 10-20%, respectively). In the setting of revision shoulder arthroplasty, timing of antibiotic administration did not significantly influence culture yield. This study supports the use of prophylactic antibiotics prior to obtaining cultures in revision shoulder arthroplasty.