Upcoming evidence in clinical practice of two-stage revision arthroplasty for prosthetic joint infection.

Total joint arthroplasty is the recommended treatment for patients with end-stage osteoarthritis, as it reduces disability and pain and restores joint function. However, prosthetic joint infection is a serious complication of this procedure, with the two-stage exchange being the most common treatment method. While there is consensus on diagnosing prosthetic joint infection, there is a lack of agreement on the parameters that can guide the surgeon in performing definitive reimplantation in a two-stage procedure. One approach that has been suggested to improve the accuracy of microbiologic investigations before definitive reimplantation is to observe a holiday period from antibiotic therapy to improve the accuracy of cultures from periprosthetic tissues, but these cultures report some degree of aspecificity. Therefore, several pieces of evidence highlight that performing reimplantation using continuous antibiotic therapy should be considered a safe and effective approach, leading to higher cure rates and a shorter period of disability. Dosage of C-reactive protein (CRP), erythrocyte sedimentation rate (ERS) and D-dimer are helpful in diagnosing prosthetic joint infection, but only D-dimer has shown sufficient accuracy in predicting the risk of infection recurrence after a two-stage procedure. Synovial fluid analysis before reimplantation has been shown to be the most accurate in predicting recurrence, and new cutoff values for leukocyte count and neutrophil percentage have shown a useful predictive rule to identify patients at risk of unfavourable outcome. A new scoring system based on a numerical score calculated from the beta coefficient derived through multivariate analysis of D-dimer levels, synovial fluid leukocytes and relative neutrophils percentage has demonstrated high accuracy when it comes to guiding the second step of two-stage procedure. In conclusion, reimplantation may be a suitable option for patients who are on continuous therapy without local symptoms, and with CRP and ERS within the normal range, with low synovial fluid leukocytes (< 952/mL) and a low relative neutrophil percentage (< 52%) and D-dimer below 1100 µg/mL. A numerical score derived from analysing these three parameters can serve as a valuable tool in determining the feasibility of reimplantation in these patients.

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.

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.

Barbed sutures and skin adhesives improve wound closure in hip and knee arthroplasty.

PURPOSE: This study aimed to formulate evidence-based recommendations for optimising wound management in hip and knee arthroplasty by exploring alternative methods such as barbed sutures and skin adhesives. METHODS: A Delphi panel, comprising seven orthopaedic surgeons, one musculoskeletal infectious disease specialist, and one health economics expert, was convened to evaluate the use of barbed sutures and skin adhesives for wound closure in hip and knee arthroplasty. Two systematic reviews informed the development of questionnaires, with panelists ranking their agreement on statements using a 5-point Likert scale. Consensus was achieved if ≥75% agreement. Unresolved statements were revisited in a second round. RESULTS: Consensus was reached on 11 statements, providing evidence-based recommendations. The expert panel advocates for a multilayer watertight technique using barbed sutures to prevent surgical site infections (SSI), reduce complications, shorten surgical times, optimise resources and improve cosmetic appearance. For skin closure, the panel recommends topical adhesives to decrease wound dehiscence, enhance cosmetic appearance, promote patient compliance, prevent SSIs, and optimise resources. CONCLUSION: The Delphi consensus by Italian total joint arthroplasty experts underscores the pivotal role of barbed sutures and skin adhesives in optimising outcomes. While guiding clinical decision-making, these recommendations are not prescriptive and should be adapted to local practices. The study encourages further research to enhance current evidence. LEVEL OF EVIDENCE: Level III.

Preclinical discovery and development of nirmatrelvir/ritonavir combinational therapy for the treatment of COVID-19 and the lessons learned from SARS-COV-2 variants.

INTRODUCTION: Nirmatrelvir/ritonavir (Paxlovid®) represent an oral antiviral therapy approved for the treatment of COVID-19. Extensive in vitro and in vivo studies have reported the promising activity of nirmatrelvir/ritonavir against numerous emerging viruses. This combination consists of nirmatrelvir, a protease reversible inhibitor of coronavirus 3CLpro mainly metabolized by cytochrome P450 (CYP)3A4, and ritonavir, an inhibitor of the CYP3A isoforms that enhances the efficacy of nirmatrelvir by fixing its suboptimal pharmacokinetic properties. AREAS COVERED: This review comprehensively examines the efficacy of nirmatrelvir/ritonavir through rigorous analysis of in vitro and in vivo studies. Moreover, it thoroughly assesses its safety, tolerability, pharmacokinetics, and antiviral efficacy against SARS-COV-2 infection, based on the main pre-authorization randomized controlled trials. EXPERT OPINION: Nirmatrelvir/ritonavir has a good tolerability profile. Its administration during the early stages of mild-to-moderate COVID-19 holds potential benefits, as it can help prevent the onset of an aberrant immune response that could lead to pulmonary and extra-pulmonary complications. However, its drug - drug interactions can be a factor limiting its use, at least in populations on some chronic therapies, along with the risk of infection relapse after treatment.

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.

Effect of remdesivir on mortality rate and clinical status of COVID-19 patients: a systematic review with meta-analysis.

Remdesivir (RDV) is a broad-spectrum antiviral drug, now approved by Regulatory Agencies for COVID-19 treatment. RDV is associated with improvements in clinical outcomes, but no conclusive studies have shown an effect in reducing mortality. This study aimed to carry out a systematic review with meta-analysis to investigate whether RDV can significantly modify the outcome of COVID-19 patients evaluating its effects on mortality, length of stay, time to clinical improvement and need for oxygen supplementation. No significant improvement in terms of survival in patients treated with standard therapy (ST)+RDV as compared to ST alone (P = 0.24) was found. The duration of oxygen support was significantly lower in patients treated with ST + RDV compared with ST alone (P = 0.03). Further investigations should be planned to assess the real impact of RDV in the management of COVID-19 patients.

The preclinical discovery and development of molnupiravir for the treatment of SARS-CoV-2 (COVID-19).

INTRODUCTION: Molnupiravir (MOV) is a broad-spectrum oral antiviral agent approved for the treatment of COVID-19. The results from in vitro and in vivo studies suggested MOV activity against many RNA viruses such as influenza virus and some alphaviruses agents of epidemic encephalitis. MOV is a prodrug metabolized into the ribonucleoside analog ß-D-N4-hydroxycytidine. It is incorporated into the viral RNA chain causing mutations impairing coding activity of the virus, thereby inhibiting viral replication. AREAS COVERED: This review analyzes the in vitro and in vivo studies that have highlighted the efficacy of MOV and the main pre-authorization randomized controlled trials evaluating its safety, tolerability, and pharmacokinetics, as well as its antiviral efficacy against SARS-COV-2 infection. EXPERT OPINION: MOV is an antiviral agent with an excellent tolerability profile with few drug-drug interactions. Treatment of mild-to-moderate COVID-19 can benefit from MOV administration in the precocious phases of the disease, prior to the trigger of an aberrant immune response responsible for the parenchymal damage to pulmonary and extrapulmonary tissues. However, its suspected mutagenic effect can be a factor limiting its use at least in selected populations and studies on its teratogen effects should be planned before it is authorized for use in the pediatric population or in pregnant women.

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.

Synovial fluid alpha-defensin in periprosthetic knee infection workup : liquid chromatography-mass spectrometry detection of alpha-defensin in synovial fluid.

AIMS: The diagnosis of periprosthetic joint infection (PJI) continues to present a significant clinical challenge. New biomarkers have been proposed to support clinical decision-making; among them, synovial fluid alpha-defensin has gained interest. Current research methodology suggests reference methods are needed to establish solid evidence for use of the test. This prospective study aims to evaluate the diagnostic accuracy of high-performance liquid chromatography coupled with the mass spectrometry (LC-MS) method to detect alpha-defensin in synovial fluid. METHODS: Between October 2017 and September 2019, we collected synovial fluid samples from patients scheduled to undergo revision surgery for painful total knee arthroplasty (TKA). The International Consensus Meeting criteria were used to classify 33 PJIs and 92 aseptic joints. LC-MS assay was performed to measure alpha-defensin in synovial fluid of all included patients. Sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) were calculated to define the test diagnostic accuracy. RESULTS: The AUC was 0.99 (95% confidence interval (CI) 0.98 to 1.00). Receiver operating characteristic (ROC) analysis showed that the optimal cut-off value of synovial fluid alpha-defensin was 1.0 µg/l. The sensitivity of alpha-defensin was 100% (95% CI 96 to 100), the specificity was 97% (95% CI 90 to 98), the positive predictive value was 89.2% (95% CI 82 to 94), and negative predictive value was 100% (95% CI 96 to 100). ROC analysis demonstrated an AUC of 0.99 (95% CI 0.98 to 1.0). CONCLUSION: The present study confirms the utility of alpha-defensin in the synovial fluid in patients with painful TKA to select cases of PJI. Since LC-MS is still a time-consuming technology and is available in highly specialized laboratories, further translational research studies are needed to take this evidence into routine procedures and promote a new diagnostic approach.Cite this article: Bone Joint J 2022;104-B(9):1047-1051.

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.

An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).

INTRODUCTION: Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment. AREAS COVERED: In this review, the authors describe the main investigations leading to the discovery of RDV and its subsequent development as an antiviral agent, focusing on the main clinical trials investigating its efficacy in terms of symptom resolution and mortality reduction. EXPERT OPINION: RDV is the most widely investigated antiviral drug for the treatment of COVID-19. This attention on RDV activity against SARS-CoV-2 is justified by promising in vitro studies, which demonstrated that RDV was able to suppress viral replication without significant toxicity. Such activity was confirmed by an investigation in an animal model and by the results of preliminary clinical investigations. Nevertheless, the efficacy of RDV in reducing mortality has not been clearly demonstrated.

West Nile Virus diffusion in temperate regions and climate change. A systematic review.

West Nile virus (WNV) is a member of the Japanese encephalitis serocomplex, which was first described in 1937 as neurotropic virus in Uganda in 1937. Subsequently, WNV was identified in the rest of the old-world and from 1999 in North America. Birds are the primary hosts, and WNV is maintained in a bird-mosquito-bird cycle, with pigs as amplifying hosts and humans and horses as incidental hosts. WNV transmission is warranted by mosquitoes, usually of the Culex spp., with a tendency to spill over when mosquitoes' populations build up. Other types of transmissions have been described in endemic areas, as trough transplanted organs and transfused blood, placenta, maternal milk, and in some occupational settings. WNV infections in North America and Europe are generally reported during the summer and autumn. Extreme climate phenomena and soil degradation are important events which contribute to expansion of mosquito population and consequently to the increasing number of infections. Draught plays a pivotal role as it makes foul water standing in city drains and catch basins richer of organic material. The relationship between global warming and WNV in climate areas is depicted by investigations on 16,298 WNV cases observed in the United States during the period 2001-2005 that showed that a 5°C increase in mean maximum weekly temperature was associated with a 32-50% higher incidence of WNV infection. In Europe, during the 2022 season, an increase of WNV cases was observed in Mediterranean countries where 1,041 cases were reported based on ECDC data. This outbreak can be associated to the climate characteristics reported during this period and to the introduction of a new WNV-1 lineage. In conclusion, current climate change is causing an increase of mosquito circulation that supports the widest spread of some vector-borne virus including WNV diffusion in previously non-permissible areas. This warrant public health measures to control vectors circulation to reduce WNV and to screen blood and organ donations.

Management of septic arthritis of the hip joint in adults. A systematic review of the literature.

BACKGROUND: The septic arthritis of the hip is a complex condition characterized by a variety of clinical presentations, a challenging diagnosis and different surgical treatment options, including arthroscopy, resection arthroplasty and one and two-stage total hip replacement. Each technique reports variable results in terms of infection eradication rate. The aim of this systematic review is to compare the most relevant studies available in current literature and to assess if a better treatment outcome can be predicted based on the microbiology, history, and type of infection (active vs quiescent) of each case. METHODS: A systematic review of the literature was performed in accordance with the PRISMA guidelines, including the studies dealing with the treatment of hip septic arthritis in adult patients. Electronic databases, namely the MEDLINE, Scopus, and Web of Science, were reviewed using a combination of following keywords "septic arthritis" AND "hip joint" OR "hip" AND "adult". RESULTS: The total number of patients included in this review was 1236 (45% of which females), for 1238 hips. The most common pathogen isolated was Staphylococcus aureus in its Methicillin-sensitive variant ranging from 2 to 37% of cases. Negative cultures were the second most common finding. It was also differentiated the type of infection of the hip, 809 and 417 patients with active and quiescent hip infection, respectively, were analyzed. Eradication rates for two-stage revision arthroplasty ranged between 85 and 100%, for one-stage approach between 94 and 100%, while for arthroscopic debridement/lavage between 89 and 100%. CONCLUSION: Staphylococcus aureus is the most common microorganism isolated followed by culture negative infections. Arthroscopic, one and two stage procedures can be effective in the treatment of hip septic arthritis when the indication is consistent with the type of infection retrieved. LEVEL OF EVIDENCE: IV, therapeutic study.

Synovial Cell Count Before Reimplantation Can Predict the Outcome of Patients with Periprosthetic Knee Infections Undergoing Two-stage Exchange.

BACKGROUND: Although synovial fluid can be used to diagnose periprosthetic joint infections (PJI) effectively, only the cutoff values adopted at the time of PJI diagnosis have been standardized, and few data are currently available about effectiveness of synovial fluid examination before definitive reimplantation. QUESTIONS/PURPOSES: We asked: (1) What are the most appropriate thresholds for synovial fluid leukocyte counts (WBC) and neutrophil percentage (PMN percentage) in a patient group undergoing definitive reimplantation after an uninterrupted course of antibiotic therapy for chronic PJI? (2) What is the predictive value of our synovial WBC and PMN percentage threshold compared with previously proposed thresholds? METHODS: In all, 101 patients with PJI were evaluated for inclusion from January 2016 to December 2018. Nineteen percent (19 of 101) of patients were excluded because of the presence of a chronic inflammatory disease, acute/late hematogenous infection, low amount of synovial fluid for laboratory investigations or infection persistence after spacer placement, and adequate antibiotic therapy. Finally, 81% (82 of 101) of patients with a median (range) age of 74 years (48 to 92) undergoing two-stage revision for chronic TKA infection, who were followed up at our institution for a period 96 weeks or more, were included in this study. The patients did not discontinue antibiotic treatment before reimplantation and were treated for 15 days after reimplantation if intraoperative cultures were negative. No patient remained on suppressive treatment after reimplantation. Synovial fluid was aspirated aseptically with a knee spacer in place to evaluate the cell counts before reimplantation. Thirteen percent (11 of 82) of patients had persistent or recurrent infection, defined as continually elevated erythrocyte sedimentation rate or C-reactive protein levels coupled with local signs and symptoms or positive cultures. The synovial fluid WBC counts and PMN percentage from the 11 patients with persistent or recurrent PJI were compared with the 71 patients who were believed to be free of PJI. Receiver operating characteristic (ROC) curve analyses assessed the predictive value of the parameters, and the areas under the curves (AUCs) were evaluated. The sensitivities, specificities, and positive and negative predictive values were determined for the WBC count and PMN percentage. Patients with persistent or recurrent infection had higher median WBC counts (471 cells/µL versus 1344 cells/µL; p < 0.001) and PMN percentage (36% versus 61%; p < 0.001) than did patients believed to be free of PJI. RESULTS: ROC curve analysis identified the best threshold values to be a WBC count of 934 cells/µL or more (sensitivity 0.82 [95% CI 0.71 to 0.89], specificity 0.82 [95% CI 0.71 to 0.89]) as well as a PMN percentage of at least 52% (sensitivity 0.82 [95% CI 0.71 to 0.89] and specificity 0.78 [95% CI 0.67 to 0.86]. We found no difference between the AUCs for the WBC count and the PMN percentage (0.87 [95% CI 0.79 to 0.96] versus 0.84 [95% CI 0.73 to 0.95]. Comparing the sensitivities and specificities of the synovial fluid WBC count and PMN percentage proposed by other authors, we find that a PMN percentage more than 52% showed better predictive value than previously reported. CONCLUSION: Based on our findings, we believe that patients with WBC counts of at least 934 and PMN percentage of 52% or more should not undergo reimplantation but rather a repeat debridement, as their risk of persistent or recurrent PJI appears prohibitively high. The accuracy of the proposed cutoffs is better than previously reported. LEVEL OF EVIDENCE: Level III, diagnostic study.

The role of D-dimer in periprosthetic joint infection: a systematic review and meta-analysis.

OBJECTIVES: The current literature on diagnosis of periprosthetic joint infection (PJI) provides controversial evidence on the diagnostic accuracy of D-dimer. Therefore, this critical literature search and meta-analysis was aimed to summarize the diagnostic accuracy of D-dimer for diagnosing PJI. CONTENT: We searched MEDLINE, Scopus, and Web of Science, for studies on D-dimer for diagnosing PJI, according to the PRISMA flowchart. QUADAS was used for assessing study quality. Sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were analyzed using bivariate diagnostic random-effects model. The area under the receiver-operating curve (AUC-ROC) was calculated. Subgroup analysis and univariate meta-regression were carried out for detecting potential sources of heterogeneity. SUMMARY: We included 12 articles, totaling 1,818 patients (539 with PJI). The pooled sensitivity and specificity of D-dimer for diagnosing PJI were 0.739 (95% CI: 0.616-0.833) and 0.785 (95% CI: 0.679-0.863). The pooled PLR, NLR, DOR were 3.359 (95% CI, 2.340-4.821), 0.295 (95% CI, 0.180-0.484), and 11.787 (95% CI, 5.785-24.018). The cumulative ROC plot displayed an AUC of 0.688 (95% CI, 0.663-0.713; p<0.001). No threshold effects could be observed. The type of blood sample was identified as possible source of heterogeneity for DOR (p=0.01). OUTLOOK: Evidence emerged from this meta-analysis suggests that D-dimer displays sufficient diagnostic accuracy to rule out PJI. The type of blood sample (plasma vs. serum) and the study design could influence the results in terms of DOR and sensitivity. However, further perspective studies would be needed to validate its potential diagnostic usefulness.

Experimental Pharmacotherapy for COVID-19: The Latest Advances.

The coronavirus infectious disease-2019 (COVID-19) has overwhelmed like a shock wave in a completely unprepared world. Despite coronavirus infections were involved in previous epidemic outbreaks, no antiviral agent was developed for specific treatment. As a consequence, since the beginning of this pandemic, both repositioned and experimental drugs were used to treat the infected patients without evidence of clinical efficacy. Just based on experience coming from the use of antiviral agents to treat other viruses (eg, lopinavir/ritonavir, remdesivir) and supposed antiviral or immunomodulatory activities of drugs with no approved antiviral indications (eg hydroxychloroquine, tocilizumab), clinicians have faced the ongoing pandemic. Currently, after about 9 months from the COVID-19 spread, there is still no antiviral agent capable of ensuring the cure of this syndrome. Clinical trials are beginning to confirm the benefits of some drugs, while for other compounds, efficacy and safety have not yet been confirmed. Randomized clinical trials (RCT) have denied or downsized the beneficial effects attributed to certain molecules, such as aminoquinolines, largely used in clinical practice at the beginning of COVID-19 spread. Conversely, at the same time, they have provided evidence for unexpected effectiveness of other agents that have been underutilized, such as steroids, which were not used in SARS treatment because of the threatened effect on viral replication. Evidence deriving from pathologic studies have demonstrated that the prothrombotic effects of SARS-CoV-2 can be prevented by heparin prophylaxis, underlining the need for personalized treatment for patients with severe disease. The main aim of this review is to synthesize the available information and evidence on both repositioned and experimental drugs for the treatment of COVID-19, focusing on the need to exercise caution on the use of unproven medical therapies.

An Evolution of Shoulder Periprosthetic Infections Management: MicroDTTect, Bioactive Glass and Tantalum Cones Employment.

Periprosthetic joint infections of the shoulder (PJIS) are the major cause for revision within the first two post-operative years, and are challenging both to diagnose and treat. Success depends on early identification of microorganisms, appropriate surgical procedures and efficient antibiotic administration. The peculiar microbiology of the shoulder may render the criteria for hip/knee PJI management inappropriate. In addition, later cases with clinically subtle signs often present diagnostic challenges. In recent years, specific issues of PJIS have been managed through the use of new instruments, such as MicroDTTect in pathogen detection and Bioactive Glass and tantalum cones in humeral bone loss. In the literature to date, no reports have been found that discuss the application in shoulder revisions and infections. The early identification of the microorganisms that cause infection may help improve both treatment strategies and the efficacy of therapy. MicroDTTect proved to be more efficient than swab collection for bacterial identification in orthopedic surgery, thus reducing analysis costs. The increasing number of shoulder arthroplasties is associated with an increase in the number of revisions. In cases of massive metaphyseal humeral bone loss, several techniques have been described; no reports have been reported regarding tantalum in humeral bone loss management. In some cases the tantalum cones required adaptation for femoral diaphysis in the augmentation of the humerus metaphysis and bone loss management improvement. Obtaining stable osseointegration of prosthetic implants is one of the greatest issues in orthopedic surgery, and even more crucial in revisions. Bioactive glasses demonstrated good regenerative and osseointegration properties, and an excellent candidate as a bone graft, scaffold and antibiotics deliverer. The Bioactive glasses were used to increase prosthesis-bone interface stability and fill bone defects in PJIS revision surgeries, contributing to the prevention of re-infection. Longer-term follow-up will be necessary to determine if construction durability is improved in the long term.