Globulin and albumin to globulin ratio precisely diagnose periprosthetic joint infection and determine the timing of second-stage reimplantation.

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications of total joint arthroplasty (TJI). An early and accurate diagnosis of PJI is associated with better treatment outcomes. However, whether the platelet-related markers and globulin-related markers can be used to assist the diagnosis of PJI remains elusive. METHODS: A total of 206 patients who underwent revision hip or knee arthroplasty in our institution were divided into two groups: 79 patients in PJI group and 127 patients in aseptic failure group. The levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet-related markers including platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT) and PLT to MPV ratio (PMR) and globulin-related markers such as globulin (GLB), albumin to globulin ratio (AGR) and PLT to AGR ratio were compared. The diagnostic value was measured using area under the curve (AUC) after constructing receiver operating characteristic (ROC) curves. The potential of each marker for determining the timing of second-staged reimplantation was also evaluated. RESULTS: Significantly increased levels of ESR, CRP, PLT, PCT, PMR, GLB and PLT to AGR ratio were identified in PJI group, while decreased levels of MPV and AGR were also found. The diagnostic values of all platelet-related markers and GLB were considered as fair, and good diagnostic values of AGR and PLT to AGR ratio were found, which were comparable to those of ESR and CRP. The levels of GLB and AGR can also be used to predict negative culture result and the timing of second-stage reimplantation. CONCLUSIONS: Globulin and albumin to globulin ratio were found to have good diagnostic values for PJI, and they can precisely predict the culture results and persistent infection.

Diagnostic accuracy of calprotectin in periprosthetic joint infection: a diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI. METHODS: We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values. RESULTS: A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87-0.98), 0.93(95% CI 0.87-0.96), 13.65(95% CI 6.89-27.08), and 0.06(95% CI 0.02-0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52-941.11) and 0.98 (95% CI 0.96-0.99), respectively. CONCLUSION: Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study.

Synovial calprotectin for the diagnosis of periprosthetic joint infection: a diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infections (PJI) are a rare but severe complication of total joint arthroplasty (TJA). However, the diagnosis of PJI remains difficult. It is one of the research that focuses about diagnosis for PJI for majority researchers to discover a novel biomarker. This meta-analysis tried to evaluate diagnostic value of synovial calprotectin for PJI. METHODS: This meta-analysis search of the literature was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. Literature quality was appraised using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) based on RevMan (version 5.3). The diagnostic value of calprotectin for PJI was evaluated by calculating sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), diagnostic score and area under SROC (AUC) based on the Stata version 14.0 software. We conduct subgroup analysis according to the study design, cutoff values, the country of study, and gold standard. RESULTS: Seven studies were included in this meta-analysis. The pooled sensitivity of synovial calprotectin for the diagnosis of PJI was 0.94 (95% CI, 0.87-0.98), and the specificity was 0.93 (95% CI, 0.87-0.96). The pooled AUC, PLR, and NLR for synovial calprotectin were 0.98 (95% CI, 0.96-0.99), 13.65 (95% CI, 6.89-27.07), and 0.06 (95% CI, 0.02-0.15), respectively. The pooled diagnostic score and DOR were 5.4 (95% CI, 3.96-6.85) and 222.32 (95% CI, 52.52-941.12), respectively. CONCLUSION: In summary, this meta-analysis indicates that synovial calprotectin is a promising biomarker of assistant diagnosis for PJI, as well as recommended test for excluding diagnostic tool.

Excess Serum Interleukin-18 Distinguishes Patients With Pathogenic Mutations in PSTPIP1.

OBJECTIVE: Dominantly inherited PSTPIP1 mutations cause a spectrum of autoinflammatory manifestations epitomized by PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome.). The connections between PSTPIP1 and PAPA syndrome are poorly understood, although evidence suggests involvement of pyrin inflammasome activation. Interleukin-18 (IL-18) is an inflammasome-activated cytokine associated with susceptibility to macrophage activation syndrome (MAS). This study was undertaken to investigate an association of IL-18 with PAPA syndrome. METHODS: Clinical and genetic data and serum samples were obtained from patients referred to institutions due to symptoms indicative of PAPA syndrome. Serum IL-18, IL-18 binding protein (IL-18BP), and CXCL9 levels were assessed by bead-based assay, and free IL-18 levels were assessed by enzyme-linked immunosorbent assay. RESULTS: The symptoms of PSTPIP1-positive patients with PAPA syndrome overlapped with those of mutation-negative patients with PAPA-like conditions, but mutation-positive patients had earlier onset and a greater proportion had a history of arthritis. We found uniform elevation of total serum IL-18 in treated PAPA syndrome patients at levels nearly as high as those seen in NLRC4-associated autoinflammation with infantile enterocolitis patients, and well above levels found in most familial Mediterranean fever patients. Serum IL-18 elevation in PAPA syndrome patients persisted despite fluctuations in disease activity. Levels of the soluble IL-18 antagonist IL-18BP were modestly elevated, and PAPA syndrome patients had detectable free IL-18. PAPA syndrome was rarely associated with elevation of CXCL9, an indicator of interferon-γ activity, but no PAPA syndrome patients had a history of MAS. CONCLUSION: PAPA syndrome is a refractory and often disabling monogenic autoinflammatory disease associated with chronic and unopposed elevation of serum IL-18 levels but not with risk of MAS. These findings affect our understanding of the diseases in which IL-18 is overproduced and suggest a link between pyrin inflammasome activation, IL-18, and autoinflammation, without susceptibility to MAS.

The relationship of C-reactive protein/interleukin-6 concentrations between serum and synovial fluid in the diagnosis of periprosthetic joint infection.

BACKGROUND: The relationship of C-reactive protein (CRP)/interleukin-6 (IL-6) concentrations between serum and synovial fluid and whether synovial CRP/IL-6 testing in addition to serum CRP/IL-6 testing would result in a benefit in the diagnosis of periprosthetic joint infection (PJI) deserves to be investigated. METHODS: From June 2016 to July 2019, 139 patients were included in the study. Synovial CRP and IL-6 were tested by ELISA. The serum CRP and IL-6 were obtained from medical records. The definition of PJI was based on the modified Musculoskeletal Infection Society (MSIS) criteria. The relationship of serum and synovial CRP and IL-6 and the value of each index in the diagnosis of PJI were evaluated. RESULTS: The receiver operating characteristic (ROC) curves showed that synovial IL-6 had the highest area under the curve (AUC) at 0.935, which was followed by synovial CRP, serum IL-6 and serum CRP 0.861, 0.847 and 0.821, respectively. When combining serum CRP and synovial CRP to diagnose PJI, the AUC was 0.849, which was slightly higher than the result obtained when using serum CRP alone. In contrast, when combining serum IL-6 and synovial IL-6 to diagnose PJI, the AUC increased to 0.940, which was significantly higher than that obtained using serum IL-6 alone. CONCLUSION: The synovial IL-6 has the highest diagnostic accuracy for PJI. However, inferring the level of CRP/IL-6 in the synovial fluid from the serum level of CRP/IL-6 was not feasible. Synovial CRP testing did not offer an advantage when combined with an existing serum CRP result to diagnose PJI, while additional synovial IL-6 was worthy of testing even if there was an existing serum IL-6 result.

Children with Primary Septic Arthritis Have a Markedly Lower Risk of Adverse Outcomes Than Those with Contiguous Osteomyelitis.

BACKGROUND: It is widely believed that septic arthritis poses a risk of joint destruction and long-term adverse outcomes for children if not treated emergently. In the present study, children who had primary confirmed septic arthritis were compared with those who had septic arthritis and adjacent osteomyelitis to evaluate differences that affect the relative risk of adverse outcomes. METHODS: Children who underwent multidisciplinary treatment for septic arthritis with or without contiguous osteomyelitis between 2009 and 2019 were retrospectively studied. Clinical, laboratory, treatment, and outcome data were compared between cohorts of children with primary confirmed septic arthritis and children with septic arthritis and contiguous osteomyelitis. RESULTS: One hundred and thirty-four children had primary confirmed septic arthritis, and 105 children had septic arthritis with contiguous osteomyelitis. Children with osteomyelitis were older (median, 7.4 versus 2.4 years), had higher initial C-reactive protein (median, 15.7 versus 6.4 mg/dL), and had a higher rate of thrombocytopenia (21.0% versus 1.5%). They also had a higher rate of bacteremia (69.5% versus 20.2%) for a longer duration (median, 2.0 versus 1.0 days). Detected pathogens in children with osteomyelitis as compared with those with primary septic arthritis were more likely to be Staphylococcus aureus (77.1% versus 32.1%) and less likely to be Kingella kingae (2.9% versus 32.1%). Children with contiguous osteomyelitis had longer hospitalizations (median, 8.0 versus 4.0 days), a higher rate of intensive care (21.0% versus 1.5%), a higher readmission rate (17.1% versus 5.2%), and a higher complication rate (38.1% versus 0.7%). CONCLUSIONS: Primary septic arthritis in children is dissimilar to septic arthritis associated with osteomyelitis. The present study demonstrates that long-term adverse outcomes in children with septic arthritis are likely due to the contiguous osteomyelitis. Children with primary septic arthritis are sufficiently distinguishable from those who have contiguous osteomyelitis to guide decisions for magnetic resonance imaging acquisition, duration of antibiotic therapy, and length of outpatient follow-up in order to recognize and address adverse outcomes. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Acute monoarthritis in young children: comparing the characteristics of patients with juvenile idiopathic arthritis versus septic and undifferentiated arthritis.

Acute arthritis is a common cause of consultation in pediatric emergency wards. Arthritis can be caused by juvenile idiopathic arthritis (JIA), septic (SA) or remain undetermined (UA). In young children, SA is mainly caused by Kingella kingae (KK), a hard to grow bacteria leading generally to a mild clinical and biological form of SA. An early accurate diagnosis between KK-SA and early-onset JIA is essential to provide appropriate treatment and follow-up. The aim of this work was to compare clinical and biological characteristics, length of hospital stays, duration of intravenous (IV) antibiotics exposure and use of invasive surgical management of patients under 6 years of age hospitalized for acute monoarthritis with a final diagnosis of JIA, SA or UA. We retrospectively analyzed data from < 6-year-old children, hospitalized at a French tertiary center for acute mono-arthritis, who underwent a joint aspiration. Non-parametric tests were performed to compare children with JIA, SA or UA. Bonferroni correction for multiple comparisons was applied with threshold for significance at 0.025. Among the 196 included patients, 110 (56.1%) had SA, 20 (10.2%) had JIA and 66 (33.7%) had UA. Patients with JIA were older when compared to SA (2.7 years [1.8-3.6] versus 1.4 [1.1-2.1], p < 0.001). Presence of fever was not different between JIA and SA or UA. White blood cells in serum were lower in JIA (11.2 × 109/L [10-13.6]) when compared to SA (13.2 × 109/L [11-16.6]), p = 0.01. In synovial fluid leucocytes were higher in SA 105.5 × 103 cells/mm3 [46-211] compared to JIA and UA (42 × 103 cells/mm3 [6.4-59.2] and 7.29 × 103 cells/mm3 [2.1-72] respectively), p < 0.001. Intravenous antibiotics were administered to 95% of children with JIA, 100% of patients with SA, and 95.4% of UA. Arthrotomy-lavage was performed in 66.7% of patients with JIA, 79.6% of patients with SA, and 71.1% of patients with UA. In children less than 6 years of age with acute mono-arthritis, the clinical and biological parameters currently used do not reliably differentiate between JIA, AS and UA. JIA subgroups that present a diagnostic problem at the onset of monoarthritis before the age of 6 years, are oligoarticular JIA and systemic JIA with hip arthritis. The development of new biomarkers will be required to distinguish JIA and AS caused by Kingella kingae in these patients.

White Blood Cell Count Is the Most Reliable Test for the Diagnosis of Septic Arthritis After Anterior Cruciate Ligament Reconstruction: An Observational Study of 38 Patients.

PURPOSE: (1) To evaluate the diagnostic testing performance of the synovial white blood cell (WBC) count, polymorphonuclear cell percentage, and synovial glucose, synovial protein, synovial lactate dehydrogenase, and synovial C-reactive protein levels as diagnostic markers for the diagnosis of septic arthritis after anterior cruciate ligament (ACL) reconstruction; (2) to define the ideal thresholds of the aforementioned tests, leading to the optimal sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy; and (3) to define the sensitivity of synovial fluid culture and synovial tissue sample culture, as well as determine whether previous antibiotic treatment may affect the accuracy of these tests. METHODS: We performed a retrospective analysis of all patients readmitted from January 2009 to September 2019 with signs suggestive of septic arthritis and undergoing a knee aspiration for synovial fluid analysis and culture. The receiver operating characteristic curve and the associated area under the curve were constructed for the aforementioned synovial markers. Sensitivity, specificity, PPV, NPV, and accuracy were calculated for the obtained optimal values. Sensitivity was also calculated for synovial fluid culture and synovial tissue sample culture, and the influence of previous antibiotic treatments on culture sensitivity was evaluated. RESULTS: Among 3,408 cases of ACL reconstruction, after the exclusion of 13 patients not meeting the inclusion criteria, 24 infected and 14 uninfected patients were reviewed and included in the analysis. The diagnosis was confirmed by the presence of 2 positive culture findings with the same isolated microorganism or at least 3 of the 4 following criteria: elevated serum C-reactive protein level and erythrocyte sedimentation rate, positive results of histologic analysis of synovial tissue, macroscopic evidence of purulence, and 1 positive culture finding. The receiver operating characteristic curve analysis showed that the most reliable marker for the diagnosis of septic arthritis after ACL reconstruction was the synovial WBC count (area under the curve, 0.89). A cutoff value of 28,100 cells/mL presented the highest accuracy (0.85), highest PPV (0.94), and highest NPV (0.76); moreover, with the threshold set at 40,000 cells/mL, postoperative infection could be diagnosed with 100% specificity. The sensitivity of synovial fluid culture was significantly lower than the sensitivity of synovial tissue sample culture (0.63 vs 0.96, P = .0045); moreover, the sensitivity further decreased if patients took antibiotics before aspiration (0.44 vs 0.73), although this decrease was not statistically significant. CONCLUSIONS: The synovial WBC count is the most reliable test for the diagnosis of septic arthritis after ACL reconstruction. Although the sensitivity of synovial fluid culture is affected by previous antibiotic treatment, the synovial WBC count is not influenced and proves to be useful in the diagnosis of this uncommon complication. LEVEL OF EVIDENCE: Level II, diagnostic study.

Elevated plasma D-dimer concentration has higher efficacy for the diagnosis of periprosthetic joint infection of the knee than of the hip-A single-center, retrospective study.

The aim of this study is to evaluate the value of D-dimers in the diagnosis of periprosthetic joint infection (PJI). The analysis was performed for revision total hip (rTHA) and revision total knee arthroplasty (rTKA) together and separately with two thresholds, one calculated by statistical methods and the second adopted from the ICM 2018 definition. The study group comprised 133 patients who underwent rTHA or rTKA: 68 patients diagnosed according to the ICM 2018 definition (PJI group) and 65 with aseptic implant loosening, instability, malposition, or implant failure with the exclusion of infection (aseptic revision total joint arthroplasty or arTJA group). Mean D-dimer concentrations were 0.36 ± 0.25 µg/ml in the arTJA group and 0.87 ± 0.78 µg/ml in the PJI group (p < .001). For rTHA and rTKA together, the sensitivity and specificity of the evaluation were 75% and 73.8% according to the calculated cut-off value (0.45 µg/ml), and 33.8% and 95.4% based on the ICM 2018 threshold (0.85 µg/ml). Separately, for rTHA, sensitivity and specificity were 62.5% and 62.1% for the calculated value (0.43 µg/ml) and 6.3% and 96.6% for the ICM 2018 threshold; for rTKA, sensitivity was 86.1% and specificity was 88.9% for the calculated threshold (0.48 µg/ml) and 58.3% and 94.4% for the ICM 2018 value. Our findings indicate that plasma D-dimers have potential as markers of knee PJI, but moderate to low value for hip PJI.

Elevated HbA1c is not a risk factor for wound complications following total joint arthroplasty: a prospective study.

BACKGROUND: Controversies exist regarding the association of elevated serum glycated haemoglobin (HbA1c) levels and postoperative surgical site infection (SSI) or prosthetic joint infection (PJI) in the setting of total hip and knee arthroplasty (THA and TKA). The purpose of the current study was to determine the prevalence of unknown and uncontrolled diabetes mellitus (DM) in a consecutive series and to investigate the association between postoperative wound complications or SSI/PJI and elevated HbA1c in patients undergoing TJA. METHODS: In this prospective single-centre study, HbA1c was determined for patients undergoing elective primary, aseptic or septic revision THA and TKA, between September 2017 and March 2018. Prevalence of DM, unknown and uncontrolled diabetes were reported. Occurrence of 90-day wound healing disorders (WHD) as well as SSI or PJI were observed. Considering the HbA1c threshold ⩾6.5%, a comparative analysis between patients with and without WHD and SSI or PJI for the whole study cohort, as well as for each arthroplasty group, was performed. Receiver operating characteristic (ROC) curves were developed to quantify the predictive power of HbA1c with regard to WHD and infection complications. A total of 1488 patients were included for final analysis. There were 1127 primary THA and TKA (75.7%), 272 aseptic revisions (18.3%) and 89 septic revisions (6.0%). The known diabetic patients constituted 9.9% of the whole study cohort. RESULTS: The majority had uncontrolled DM (67%). Prevalence of unknown DM was 11.1%. The results reveal the prevalence for the German population and might be different in other regions. A total of 57 patients (3.7%) experienced postoperative wound or infectious complications. PJI occurred in only 5 patients (0.03%). There was no significant difference between patients with HbA1c <6.5% and patients with HbA1c ⩾6.5% (p = 0.092). CONCLUSIONS: We demonstrated that prevalence of unknown and uncontrolled DM in patients undergoing TJA is increasing, however; routine preoperative determination of the HbA1c value to prevent possible postoperative wound or infectious complications remains debatable. Larger studies investigating the optimal HbA1c level, as well as other predictors are required.

Thiol/disulfide homeostasis as a novel indicator of oxidative stress during the treatment process of patients with septic arthritis.

OBJECTIVES: This study aims to investigate dynamic thiol/disulfide homeostasis as a novel indicator of oxidative stress and to find out its association with standard inflammatory markers during the treatment of patients with septic arthritis (SA). PATIENTS AND METHODS: In this prospective study, a new colorimetric method for measuring thiol/disulfide homeostasis was assessed between May 2013 and October 2014 in 24 patients with SA (14 males, 10 females; mean age 14.5±19.1 years; range, 1 to 80 years) at baseline and the end of the third week of the treatment, and in 24 healthy controls (14 males, 10 females; mean age 12.5±18.7 years; range, 1 to 85 years). Also, standard inflammatory markers such as C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell count were evaluated. RESULTS: At baseline, serum disulfide was higher in SA group compared to the control group, whereas native thiol was lower (p<0.05 for all). At the end of the third week of the treatment, serum disulfide level was lower, whereas the native thiol was higher compared to baseline (p<0.05 for all). In addition, serum disulfide level was positively correlated with CRP (r=0.736, p<0.001) and disulfide/native thiol ratio (r=0.779, p<0.001). Furthermore, in multiple regression analyses, the disulfide level was independently associated with CRP (ß=0.226, p=0.005). CONCLUSION: Our results suggest that the elevated levels of serum disulfide and standard inflammatory markers at baseline in patients with SA and decreased levels of these parameters are related with oxidative stress. This homeostasis shifted towards disulfide formation due to thiol oxidation. Therefore, thiol/ disulfide homeostasis may be a helpful biomarker for the follow-up in patients with SA.

Tofacitinib treatment aggravates Staphylococcus aureus septic arthritis, but attenuates sepsis and enterotoxin induced shock in mice.

Tofacitinib, a janus kinase inhibitor, is a novel immunosuppressive drug for treatment of rheumatoid arthritis (RA). Septic arthritis (SA) and sepsis caused by Staphylococcus aureus (S. aureus), for which RA patients are at risk, are infections with high mortality. The aim of this study was to investigate the effect of tofacitinib on S. aureus infections using mouse models. In vitro tofacitinib treated mouse splenocytes were stimulated with S. aureus derived stimuli. Mice pre-treated with tofacitinib were inoculated intravenously with either arthritogenic- or septic doses of S. aureus. Arthritis severity and mortality were compared between groups. Additionally, pre-treated mice were challenged with staphylococcal toxin TSST-1 to induce shock. Tofacitinib inhibited splenocyte proliferation and IFN-γ production in response to TSST-1 and dead S. aureus. In SA, tofacitinib treatment aggravated arthritis with more severe bone erosions. However, in sepsis, treated mice displayed significantly prolonged survival compared to controls. Similarly, in staphylococcal enterotoxin-induced shock tofacitinib pre-treatment, but not late treatment dramatically reduced mortality, which was accompanied by decreased levels of TNF-α and IFN-γ. Our findings show that tofacitinib treatment increase susceptibility of SA in mice, but has a positive effect on survival in S. aureus-induced sepsis and a strong protective effect in toxin-induced shock.

Is Procalcitonin (PCT) a reliable biomarker for preoperative diagnosing of low grade periprosthetic joint infection? A prospective study.

BACKGROUND: Since a "gold-standard" is missing, diagnosing periprosthetic joint infection (PJI) remains a challenge in orthopedic surgery. The purpose of this study was to evaluate the accuracy of serum and synovial fluid Procalcitonin (S-PCT and SF-PCT) as a diagnostic parameter and to compare it to the biomarkers recommended in the 2018 Definition of periprosthetic hip and knee infection. METHODS: Between August 2018 and July 2019, a prospective cohort study was conducted in 70 patients with painful hip, shoulder and knee arthroplasty. Besides medical history, clinical and laboratory data was gathered. PJI was diagnosed based on the 2018 Definition of periprosthetic hip and knee infection. Preoperative blood and synovial joint fluid were taken for PCT measurement. S-PCT and SF-PCT levels were measured using standard quantitative PCT enzyme immunoassays. RESULTS: Twenty three patients (33%) were classified as the PJI group and fourty seven patient (67%) as the aseptic group. The mean levels of S-PCT were significantly (p <  0.001) higher in the PJI group than those in the aseptic group (PJI 0.05 ± 0.21 ng/mL (0.0-1.03) vs. aseptic 0.02 ± 0.03 ng/mL (0.0-0.18)). In synovial fluid, the mean PCT values in the aseptic group were significantly higher (p <  0.001) than those of PJI group (PJI 2.7 ± 1.4 ng/mL (0.53-9.7) vs. aseptic 8.7 ± 2.5 ng/mL (0.25-87.9)). S- PCT, with a cut-off level of 0.5 ng/mL, had a sensitivity of 13.0% and a specificity of 91.0%. SF-PCT, with a cut-off level of 5.0 ng/mL, had a sensitivity of 13.0% and a specificity of 52.0%. CONCLUSION: S-PCT and SF-PCT appeared to be no reliable biomarkers in the differential diagnosis of PJI from aseptic loosening in total joint arthroplasty.

Serum CA72-4 is specifically elevated in gout patients and predicts flares.

OBJECTIVES: Serum CA72-4 levels are elevated in some gout patients but this has not been comprehensively described. The present study profiled serum CA72-4 expression in gout patients and verified the hypothesis that CA72-4 is a predictor of future flares in a prospective gout cohort. METHODS: To profile CA72-4 expression, a cross-sectional study was conducted in subjects with gouty arthritis, asymptomatic hyperuricaemia, four major arthritis types (OA, RA, SpA, septic arthritis) and healthy controls. A prospective gout cohort study was initiated to test the value of CA72-4 for predicting gout flares. During a 6-month follow-up, gout flares, CA72-4 levels and other gout-related clinical variables were observed at 1, 3 and 6 months. RESULTS: CA72-4 was highly expressed in patients with gouty arthritis [median (interquartile range) 4.55 (1.56, 32.64) U/ml] compared with hyperuricaemia patients [1.47 (0.87, 3.29) U/ml], healthy subjects [1.59 (0.99, 3.39) U/ml] and other arthritis patients [septic arthritis, 1.38 (0.99, 2.66) U/ml; RA, 1.58 (0.95, 3.37) U/ml; SpA, 1.56 (0.98, 2.85) U/ml; OA, 1.54 (0.94, 3.34) U/ml; P < 0.001, respectively]. Gout patients with frequent flares (twice or more in the last year) had higher CA72-4 levels than patients with fewer flares (fewer than twice in the last year). High CA72-4 level (>6.9 U/ml) was the strongest predictor of gout flares (hazard ratio = 3.889). Prophylactic colchicine was effective, especially for patients with high CA72-4 levels (P = 0.014). CONCLUSION: CA72-4 levels were upregulated in gout patients who experienced frequent flares and CA72-4 was a useful biomarker to predict future flares.

Mildly decreased preoperative bilirubin levels are associated with infections after shoulder and knee arthroplasty.

Increasing numbers of arthroplasties are also accompanied by postoperative infections. The main purpose was to evaluate preoperative serum bilirubin levels between patients with and without infections after shoulder and knee arthroplasties. For this retrospective case-control single-center study, a total of 108 patients were extracted from a prospectively collected database. Eighteen patients with infections after shoulder (n = 8) and knee (n = 10) arthroplasty were matched by age, gender, and implant type in a 1:5-scenario to 90 patients (40 shoulders and 50 knees) without postoperative infection. Demographic data, preoperative blood parameters, and postoperative infection-related outcomes were evaluated. Total bilirubin was the only preoperative parameter significantly different between the infection (8.21 ± 3.25 µmol/L or 0.48 ± 0.19 mg/dL) and noninfection (10.78 ± 4.62 µmol/L or 0.63 ± 0.27 mg/dL; P = .014) group, while C-reactive protein and other liver parameters were similar between the groups. Significantly more controls (92.1%) had preoperative bilirubin levels above 8.72 µmol/L or 0.51 mg/dL than cases (7.9%; P = .007). The 5-year infection survival-rate was 65.6% for patients with preoperative bilirubin levels < 8.72 µmol/L or < 0.51 mg/dL and 91.2% with ≥ 8.72 µmol/L or ≥ 0.51 mg/dL. Mildly decreased preoperative bilirubin levels with a cutoff at 8.72 µmol/L or 0.51 mg/dL were significantly associated to patients with infections after shoulder and knee arthroplasty. There were no differences in other blood parameters or comorbidities between patients with infections and their matched-controls.

C-reactive protein is not a screening tool for late periprosthetic joint infection.

BACKGROUND: Preoperative diagnosis of periprosthetic joint infection (PJI) is important because of the therapeutic consequences. The aim of the present study is to investigate whether the serum C-reactive protein (CRP) level can be used as a screening tool for late PJI. MATERIALS AND METHODS: A cohort of 390 patients with revision surgery of total hip prostheses (200) or total knee prostheses (190) was assessed for late PJI by determining CRP serum level and performing preoperative aspiration with cultivation and intraoperative tissue analyses with cultivation and histologic examination, using the Musculoskeletal Infection Society (MSIS) and International Consensus Meeting (ICM) criteria. RESULTS: A total of 180 joints were rated as PJI (prevalence 46%). Of these, 42.8% (77) showed a CRP level below 10 mg/L and 28.3% (51) showed a normal CRP level of less than 5 mg/L. The 76.9% of the cases with slow-growing bacteria showed a CRP level below 10 mg/L, and 61.5% showed a normal CRP level. CONCLUSIONS: Serum CRP level should not be used as a screening tool to rule out late PJI. LEVEL OF EVIDENCE: Level 2 (diagnostic study).

Septic arthritis: a 5-year review of admissions to the Orthopedic Department.

OBJECTIVES: Characterization of sociodemographic and clinical aspects of patients admitted to the Orthopedic Department (OD) after observation in the Emergency Room (ER) with the diagnosis of septic arthritis (SA). MATERIAL AND METHODS: A retrospective, monocentric, cross-sectional study was conducted. Sociodemographic and clinical data on patients admitted to the OD with suspected SA between April 2014 and September 2019 were collected. RESULTS: One-hundred and ten patients were included. In the overall sample, most patients were male (n=61; 55.5%) with a median age of 70 (IQR=20) years old. Thirty-six patients (32.7%) had a previous history of hyperuricemia or gout, or had this diagnosis established at the time of their hospital admission. Monoarthritis was the most common form of presentation (n=106; 96.4%), with the knee being the most frequently involved joint (n=60; 54.5%). S. aureus was the most representative microorganism in synovial fluid (SF) cultures (n=33; 30.6%). SF cultures did not allow the identification of a causative microorganism in 53 cases submitted to arthrotomy (50.5%). Serum C-reactive protein (CRP) was a predictive factor for microorganism identification in SF cultures, with values ≥ 17.6 mg/dl presenting a sensibility and specificity of 60.8% and 77.4%, respectively [CI 95% (0.52 - 0.80)]. Patients with a diagnosis of hyperuricemia or gout presented a higher risk for a negative SF culture result (OR = 4.7 [CI 95% =1.9 - 11.5]). CONCLUSIONS: Elderly subjects with multiple comorbidities, namely cardiovascular risk factors, seem more prone to SA. Serum CRP appears to be a predictive factor for the identification of a causative microorganism. The higher risk of a negative SF culture in patients with hyperuricemia or gout should alert us for the possibility of misdiagnosis of SA in patients with an acute gout attack.

Optimizing the Composition of Irrigation Fluid to Reduce the Potency of Staphylococcus aureus α-Toxin: Potential Role in the Treatment of Septic Arthritis.

OBJECTIVE: Septic arthritis is commonly caused by Staphylococcus aureus and is a medical emergency requiring antibiotics and joint irrigation. The bacteria produce α-toxin causing rapid cartilage cell (chondrocyte) death. Saline (0.9%NaCl) lavage is normally used to remove bacteria and toxins, however, its composition might be suboptimal to suppress the lethal effects of α-toxin. We utilized rabbit erythrocyte hemolysis as a sensitive, biologically relevant assay of α-toxin levels to determine if changes to osmolarity, temperature, pH, and divalent cation (Mg2+, Ca2+) concentration were protective. DESIGN: Erythrocytes were incubated in the various conditions and then exposed to α-toxin ("chronic" challenge) or incubated with α-toxin and then exposed to experimental conditions ("acute" challenge). RESULTS: Raising osmolarity from 300 mOsm (0.9%NaCl) to 400, 600, or 900 mOsm (sucrose addition) when applied chronically, significantly reduced hemolysis linearly. As an acute challenge, osmotic protection was significant and similar over 400 to 900 mOsm. Reducing temperature chronically from 37°C to 25°C and 4°C significantly reduced hemolysis, however, when applied as an acute challenge although significant, was less marked. Divalent cations (Mg2+, Ca2+ at 5mM) reduced hemolysis. Varying pH (6.5, 7.2, 8.0) applied chronically marginally reduced hemolysis. The optimized saline (0.9% NaCl; 900 mOsm with sucrose, 5 mM MgCl2 (37°C)) rapidly and significantly reduced hemolysis compared with saline and Hank's buffered saline solution applied either chronically or acutely. CONCLUSIONS: These results on the effect of S. aureus α-toxin on erythrocytes showed that optimizing saline could markedly reduce the potency of S. aureus α-toxin. Such modifications to saline could be of benefit during joint irrigation for septic arthritis.

The serum level of D-Dimer is not suitable for distinguishing between prosthetic joint infection and aseptic loosening.

BACKGROUND: To evaluate the meaning of serum CRP, ESR, and D-Dimer in the diagnosis of prosthetic joint infection. METHODS: In a retrospective study, 101 patients presented with osteoarthritis, PJI, and aseptic loosening were divided into three groups according to the type of operation they received in our department from June 2016 to December 2018: group A, 44 patients treated with primary arthroplasty; group B, 31 PJI patients treated with resection arthroplasty and spacer insertion surgery; group C, 26 aseptic loosening patients treated with revision arthroplasty. Data such as gender, age, preoperative serum CRP, ESR, and D-Dimer level were compared among the three different groups. RESULTS: There are no statistically significant differences when comparing general data such as gender and age in patients from the three different groups. However, Serum CRP level in group B (43.49 ± 10.00 mg/L) is significantly higher than in group A (2.97 ± 0.75 mg/L) and C (4.80 ± 1.26 mg/L). Serum ESR level in group B (49.84 ± 5.48 µg/L) is significantly higher than those in group A (15.28 ± 2.63 µg/L) and C (22.50 ± 3.47 µg/L). Serum D-Dimer level in group B (1.58 ± 0.17 µg/L) is significantly higher than that in group A (0.51 ± 0.50 µg/L), but similar with group C (1.22 ± 0.29 µg/L). There are no statistically significant differences when compared with sensitivity and specificity of CRP, ESR, and D-Dimer in the diagnosis of PJI among patients from the three different groups when D-Dimer > 0.85 µg/L was set as the optimal threshold value for the diagnosis of PJI. CONCLUSION: D-Dimer is not a parameter to distinguish between aseptic loosening and PJI.