Sex-related differences in periprosthetic joint infection research.

Introduction: Periprosthetic joint infections (PJIs) have emerged as a focal point in the realm of orthopedics, garnering widespread attention owing to the escalating incidence rates and the profound impact they impose on patients undergoing total joint arthroplasties (TJAs). Year after year, there has been a growing trend in the analysis of multiple risk factors, complication rates, and surgical treatments in the field. This study aims to illuminate the status of the sex-related differences in periprosthetic joint infections and advance research in this field. Methods: A systematic review was carried out following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The final reference list comprised longitudinal studies (both retrospective and prospective) and randomized controlled trials. A sex-based analysis was conducted to assess differences between males and females. Results: A total of 312 studies were initially identified through online database searches and reference investigations. Nine studies were subsequently included in the review. Eight out of nine studies examined the risk of developing PJI after total joint replacement. Notably, only half of these studies demonstrated a statistically significant value, with a p  value  < 0.05 , indicating a higher risk of infectious complications in males compared to females. Conclusion: According to the current literature, there appears to be a propensity for males to develop periprosthetic joint infection after total joint arthroplasty at a higher rate than the female population. Enhancing sex-related analysis in this field is imperative for gathering more robust evidence and insights.

Augmented Articulating Spacers in Infected Total Knee Arthroplasty: Surgical Technique.

Periprosthetic joint infections (PJIs) are a prominent subject of discussion in orthopedics and are frequently debated at conferences and congresses. In the context of PJIs affecting the knee, the decision between following a one-stage or two-stage treatment approach has historically been a pivotal consideration. The first option is limited by indications and potentially devastating complications in case of failure, whereas the second is widely accepted as the gold standard. Initially, the spacer was conceived solely to restore and maintain knee space after removal of the implant. An articulating spacer was introduced to mitigate patient limitations and improve knee function and quality of life. Two main types of articulating spacers are utilized in knee PJI treatment: the mold spacer and the metal-on-poly spacer. This text outlines a technique for metal-on-poly spacer implants. Based on our experience and the existing literature, this approach facilitates early full weight bearing and faster recovery of the knee's range of motion, ultimately improving the quality of life after surgery, thus allowing the spacer retention for an extended period, as suggested by the 1.5-stage revision.

The Effect of Spacer Treatment of Infected Hip and Knee Arthroplasties on Patients' Mental Health: A Narrative Review of the Literature.

BACKGROUND: The gold standard treatment for periprosthetic joint infections is the two-stage revision that includes the spacer placement before definitive reimplantation. The management of PJI affects patients' joint function and, subsequently, their mental health. Even though significant advances have been achieved, little to no attention has been paid to the psychological implications. So, based on standardized patient-reported outcome measures (PROMs), this study aimed to clarify the effect of spacer treatment of infected hip and knee arthroplasties on patients' mental health. METHODS: We performed research on the literature on PJIs in the English language using the MEDLINE database with the search strings "spacer" OR "spacers" AND "hip" OR "knee" AND "SF-12" OR "SF-36" OR "EQ-5" OR "mental" OR "depression" OR "anxiety." The reference lists of selected articles were also hand-searched for any additional articles. RESULTS: A total of 973 published papers were extracted, and 9 papers were finally included. A total of 384 patients who underwent spacer placement for PJI were identified. Of these 384 patients, 54% were female. The mean age ranged from 62 to 78.2 years. Of the11 papers identified for this review, 4 analyzed only hip spacers, including 119 patients; 4 only knee spacers, evaluating 153 patients; while a single study included 112 patients for both joints. CONCLUSIONS: Patients with the spacer are living in a state of mental upset, albeit better than the preoperative state. Clinical improvement with the review is not assured. The alteration of mental state turns out not to be transient for all the patients.

Ideal Timing of Reimplantation in Patients with Periprosthetic Knee Infection Undergoing 2-Stage Exchange: A Diagnostic Scoring System.

BACKGROUND: This study evaluated appropriate thresholds for serum biomarkers, synovial fluid white blood cell (SF-WBC) count, and synovial fluid neutrophil (polymorphonuclear leukocyte [PMN]) percentage to predict infection in a patient group who underwent definitive reimplantation after receiving a continuous course of antibiotic therapy for chronic knee periprosthetic joint infection (PJI). These thresholds were then used to generate a scoring system to predict recurrence (or persistence) of infection. METHODS: The study included 153 patients with a median age of 73 years (range, 46 to 91 years) who underwent 2-stage revision for chronic knee PJI. Staphylococci were identified at baseline in 107 (70%) of the patients. After the 96-week follow-up period, 12% (19) of the 153 patients had recurrence of the PJI. A receiver operating characteristic (ROC) curve analysis was used to assess the predictive value of common serum biomarkers and SF aspiration before reimplantation, and the area under the curve (AUC) was evaluated. Variables that were significantly different between patients with and without infection recurrence were evaluated using a multivariable logistic regression model. A half-integer-point scoring system was created based on the final beta coefficients. RESULTS: Regarding the prediction of recurrent infection, a D-dimer level of >1110 ng/mL yielded a sensitivity of 74%, specificity of 61%, and AUC of 0.69; an SF-WBC count of >934 cells/µL showed a sensitivity of 68%, specificity of 90%, and AUC of 0.79; and an SF-PMN percentage of >52% showed a sensitivity of 73%, specificity of 90%, and AUC of 0.82. The beta coefficients were approximated to 1.5 for the D-dimer level and to 2 for the SF-WBC count and SF-PMN percentage. A total score of >2 was used to classify patients with a high risk of infection recurrence. The ability to discriminate infection recurrence was demonstrated by an AUC of 0.90 (95% confidence interval: 0.82 to 0.99). CONCLUSIONS: Patients with a score of >2 on our proposed scoring system based on serum biomarkers, SF-WBC count, and SF-PMN percentage should not undergo reimplantation, as they are at a high risk for recurrent PJI. Patients with a score of ≤2 can undergo definitive reimplantation with the lowest risk of recurrence. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

High return to sport rate in patients undergoing image-based robotic arm assisted unicompartmental knee arthroplasty.

INTRODUCTION: This study was aimed to assess the return to sport (RTS) rate in patients who underwent CT-based robotic-assisted unicompartmental knee arthroplasty (RA-UKA) and to evaluate the clinical performance and the assocition between patients' sport activity levels and Patient Reported Outcome Measures after surgery. MATERIALS AND METHODS: This retrospective study included 218 patients undergoing medial RA-UKA with fixed-bearing implants, performed at a single center between 2014 and 2019. Patients were allocated into two groups based on sport's practice and were administered the University of California, Los Angeles (UCLA) activity scale, Forgotten Joint Score-12 (FJS-12), Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) and the 5-Level Likert Scale. RESULTS: A total of 136 patients were included for assessment. The overall RTS rate after surgery was 93.1%. Six subjects who did not practice sport preoperatively, were able to start sport activities after surgery and all patients performing sports preoperatively, returned to same activity level. The mean UCLA and FJS-12 scores in the group of patients practicing sports were significantly higher than in the no-sport group (p < 0.001 and p < 0.05, respectively). Patients who practiced sports were more likely to attain higher FJS-12 and UCLA scores than those who were not performing physical activity. CONCLUSIONS: Patients undergoing RA-UKA showed a 93.1% RTS rate after surgery. Differences were detected in terms of postoperative UCLA and FJS-12 scores between patients who performed and who did not practice sport activities after surgery. High levels of postoperative UCLA scores were associated with higher KOOS-JR and patients' satisfaction.

The combined evaluation of fibrinogen and D-dimer levels are a helpful tool to exclude periprosthetic knee infection.

This retrospective study was undertaken to (i) define the most appropriate thresholds for serum d-dimer and fibrinogen for differentiating aseptic failure from periprosthetic joint infection (PJI) and (ii) evaluate the predictive value of our d-dimer and fibrinogen threshold compared to previously proposed thresholds. This observational cohort study included consecutive patients who had undergone total knee arthroplasty (TKA) revision between January 2019 and December 2020. International Consensus Meeting diagnostic criteria were used to identify patients affected by the prosthetic infection. Receiver operating characteristic curve analyses assessed the predictive value of the parameters, and the areas under the curves were evaluated. We included 125 patients with a median age of 69 years (53-82) affected by painful TKA. Fifty-seven patients (47%) had PJI. Patients with PJI had higher median d-dimer, fibrinogen, ESR, and CRP when compared to patients believed to be free of PJI. The best threshold values for d-dimer and fibrinogen were 1063 ng/ml (sensitivity 0.72, specificity 0.74) and 420 mg/dl (sensitivity 0.67 and specificity 0.82), respectively. A d-dimer level >1063 ng/ml combined with a fibrinogen level >420 mg/dl had a sensitivity of 0.52, and a specificity of 0.90. We found that an increased d-dimer beyond 1063 ng/ml showed a better predictive value than the previously proposed threshold. The combined determination of d-dimer and fibrinogen displayed high specificity and should be considered an excellent tool to rule out an infection. The accuracy of the proposed cutoffs is more effective than previously reported.

The Diagnostic Accuracy of Neutrophils to Lymphocytes Ratio, Platelets to Lymphocytes Ratio, Monocytes to Lymphocytes Ratio, and Platelets to Mean Platelet Volume Ratio in Diagnosing Periprosthetic Knee Infections. Are Gender-Specific Cutoff Values Needed?

BACKGROUND: This study aimed to assess the most appropriate thresholds for neutrophils to lymphocytes ratio (NLR), platelets to lymphocytes ratio, monocytes to lymphocytes ratio (MLR), and platelets to mean platelet volume ratio in patients who had a suspected prosthetic knee infection. Furthermore, we evaluated the diagnostic accuracy of our proposed thresholds by men and women. METHODS: A total of 261 consecutive patients affected by painful total knee arthroplasty were included. International Consensus Meeting diagnostic criteria were used to identify periprosthetic infections. Sensitivity, specificity, positive, and negative predictive values were calculated for each cutoff value obtained. The area under the receiver operating characteristic curve was evaluated. RESULTS: NLR reported the best diagnostic accuracy. MLR and NLR reported higher area under the curves in men and women. We obtained an MLR value ≥0.30 (optimal cutoff value for men) and ≥0.17 (optimal cutoff value for women). In men, the sensitivity and the specificity were 0.71 and 0.77, respectively, versus 0.82 and 0.29, in women. For NLR, we obtained a value ≥2.52 (best cutoff value for men) and ≥2.46 (best cutoff value for women). These cutoffs reported a sensitivity and specificity of 0.71 and 0.88 versus 0.54 and 0.76 in men and women, respectively. CONCLUSION: These biomarkers present a low diagnostic accuracy in periprosthetic joint infection detection. Men whose MLR and NLR were above cutoff values had a 77 and 88% probability of presenting a septic prosthetic failure. NLR of at least 2.46 was reasonably sensitive for women who have a periprosthetic knee infection. LEVEL OF EVIDENCE: Diagnostic study, Level II.

Diagnostic Performance of Neutrophil to Lymphocyte Ratio, Monocyte to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Platelet to Mean Platelet Volume Ratio in Periprosthetic Hip and Knee Infections: A Systematic Review and Meta-Analysis.

The current literature on the diagnosis of periprosthetic joint infection provides controversial evidence on the diagnostic accuracy of MLR, NLR, PVR, and PLR. Therefore, this critical literature search and meta-analysis was aimed to summarize the diagnostic accuracy of these biomarkers for the diagnosis of hip and knee prosthetic infection. According to the PRISMA flowchart, we searched MEDLINE, Scopus, and Web of Science, for studies on these ratios for diagnosing PJI. Sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and AUC were analyzed. We included 11 articles in our meta-analysis, including 7537 patients who underwent total hip and knee arthroplasties; among these, 1974 (26%) patients reported a joint infection. The pooled sensitivity and specificity were 0.72 and 0.74, respectively, for NLR, 0.72 and 0.77 for PVR, and 0.77 and 0.75 for PLR. The sensitivity of MLR ranges from 0.54 to 0.81, while the specificity ranges from 0.78 to 0.81. Regarding the evaluation of AUCs, the best diagnostic performance was achieved by MLR (AUC = 0.77) followed by PLR (AUC = 0.75), NLR (AUC = 0.73), and PVR (AUC = 0.70). This meta-analysis demonstrates a fair diagnostic accuracy of these ratios, thus not being useful as a screening tool.

Cell Toxicity Study of Antiseptic Solutions Containing Povidone-Iodine and Hydrogen Peroxide.

The increasing incidence of periprosthetic joint infections (PJIs) has led to a growing interest in developing strategies to prevent and treat this severe complication. The surgical site's application of antiseptic solutions to eliminate contaminating bacteria and eradicate the bacterial biofilm has been increasing over time. Even though it has been proven that combining antimicrobials could enhance their activities and help overcome acquired microbial resistance related to the topical use of antibiotics, the toxicity of integrated solutions is not well described. This study aimed to evaluate the cytotoxicity of solutions containing povidone-iodine (PI) and hydrogen peroxide (H2O2), alone or in combination, after 1.3 and 5 min of exposure. Chondrocytes, tenocytes, and fibroblast-like synoviocytes were used for cytotoxicity analysis. Trypan blue stain (0.4% in PBS) was applied to evaluate the dead cells. All solutions tested showed a progressive increase in toxicity as exposure time increased except for PI at 0.3%, which exhibited the lowest toxicity. The combined solutions reported a reduced cellular killing at 3 and 5 min than H2O2 at equal concentrations, similar results to PI solutions.

Debridement and implant retention in acute hematogenous periprosthetic joint infection after knee arthroplasty: a systematic review.

Debridement, antibiotic, and implant retention (DAIR) can be used as a first surgical procedure for acute infections in patients who have well-fixed components. However, its use in hematogenous or late acute infections is still debated. This systematic review of literature aims to clarify the effectiveness of DAIR procedure in the treatment of hematogenous periprosthetic knee infections. DAIR is an effective way to treat acute hematogenous PJIs of the knee and reaches its best efficacy when performed within one week from the onset of symptoms, modular components are exchanged, and a pathogen-oriented antibiotic therapy can be set. It is safe, economic, and effective technique, but has to be performed in a very narrow temporal window.

The active knee extension after extensor mechanism reconstruction using allograft is not influenced by "early mobilization": a systematic review and meta-analysis.

BACKGROUND: Postoperative rehabilitation after extensor mechanism reconstruction (EMR) with allograft following total knee arthroplasty (TKA) is not standardized. This meta-analysis aimed to evaluate the effectiveness of early and late knee mobilization after EMR. The range of motion (ROM) and extensor lag in both groups were also assessed as the secondary endpoint. METHODS: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, a systematic review of the literature was performed, including studies dealing with the use of allograft for EMR following TKA. Failure was defined as the persistence of extensor lag > 20°. Coleman Methodology Score and Methodological Index for Non-Randomized Studies (MINORS) score were used to assess the quality of studies included. The failure rate was set as the primary outcome in early (4 weeks) and late (8 weeks) mobilization groups after EMR with allograft. Secondary outcomes were postoperative extensor lag and ROM. RESULTS: Twelve articles (129 knees) were finally selected for this meta-analysis. Late and early knee mobilization was described in five and seven studies, respectively. No difference was noted between both groups' failure rates (11/84 vs. 4/38, respectively; p = 0.69). The mean extensor lag at last follow-up was 9.1° ± 8.6 in the early mobilization group, and 6.5° ± 6.1 in the late mobilization group is not significantly different (p > 0.05). The mean postoperative knee flexion was 107.6° ± 6.5 and 104.8° ± 7 in the early and late mobilization group, respectively. CONCLUSION: While immobilization after EMR in TKA is mandatory to allow tissue healing, early knee mobilization after four weeks can be recommended with no additional risk of failure and increased extensor lag compared to a late mobilization protocol. LEVEL OF EVIDENCE: IV, therapeutic study. Registration PROSPERO (International Prospective Register of Systematic Reviews): CRD42019141574.

On the Necessity of a Customized Knee Spacer in Peri-Prosthetic Joint Infection Treatment: 3D Numerical Simulation Results.

Peri-prosthetic joint infections (PJIs) dramatically affect human health, as they are associated with high morbidity and mortality rates. Two-stage revision arthroplasty is currently the gold standard treatment for PJI and consists of infected implant removal, an accurate debridement, and placement of antimicrobial impregnated poly-methyl-metha-acrylate (PMMA) spacer. The use of antibiotic-loaded PMMA (ALPMMA) spacers have showed a success rate that ranges from 85% to 100%. ALPMMA spacers, currently available on the market, demonstrate a series of disadvantages, closely linked to a low propensity to customize, seen as the ability to adapt to the patients' anatomical characteristics, with consequential increase of surgical complexity, surgery duration, and post-operative complications. Conventionally, ALPMMA spacers are available only in three or four standard sizes, with the impossibility of guaranteeing the perfect matching of ALPMMA spacers with residual bone (no further bone loss) and gap filling. In this paper, a 3D model of an ALPMMA spacer is introduced to evaluate the cause- effect link between the geometric characteristics and the correlated clinical improvements. The result is a multivariable-oriented design able to effectively manage the size, alignment, stability, and the patients' anatomical matching. The preliminary numerical results, obtained by using an "ad hoc" 3D virtual planning simulator, clearly point out that to restore the joint line, the mechanical and rotational alignment and the surgeon's control on the thicknesses (distal and posterior thicknesses) of the ALPMMA spacer is mandatory. The numerical simulations campaign involved nineteen patients grouped in three different scenarios (Case N° 1, Case N° 2 and Case N° 3) whose 3D bone models were obtained through an appropriate data management strategy. Each scenario is characterized by a different incidence rate. In particular, the observed rates of occurrence are, respectively, equal to 17% (Case N° 1), 74% (Case N° 2), and 10% (Case N° 3).