Interleukin-6 and other inflammatory markers in diagnosis of periprosthetic joint infection

Purpose

The purpose of this study was to evaluate the diagnostic value of interleukin-6 (IL-6) and other inflammatory markers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WCC) in diagnosis of PJI.

Methods

The study group included 40 patients (21 males, 19 females) admitted for surgical intervention after knee or hip arthroplasties. Patients were subjected to careful history taking, thorough clinical examination and pre-operative laboratory investigations including serum IL-6, CRP, WCC and ESR. Peri-implant tissue specimens were subjected to microbiological culture and histopathological examination.

Results

The mean age of patients was 58.4 years (range, 38–72 years). Intra-operative cultures and histopathological examination revealed 11 patients had been infected (PJI) and 29 patients were aseptic failure of prosthesis. Four presumed markers of infection were tested preoperatively: ESR, CRP, WCC, and IL-6. ESR (p?=?0.0001), CRP (p?=?0.004), WCC (0.0001), and IL-6 (p?=?0.0001) were significantly higher in patients with septic revision than those with aseptic failure of the prosthesis. Serum IL-6 (>10.4 pg/ml) reportedly had a sensitivity of 100 %, a specificity of 90.9 %, a PPV of 79 %, a NPV of 100 %, and accuracy of 92.5 %.

Conclusions

The present study demonstrated that IL-6 has been found to be the most accurate laboratory marker for diagnosing PJI when compared to ESR, CRP, and WCC. IL-6 above 10.4 pg/ml and CRP level above 18 mg/L will identify all patients with PJI and the combination of CRP?+?IL-6 is an excellent screening test to identify all such patients (sensitivity 100 %, NPV 100 %).     

Lipopolysaccharide-binding protein: A valuable biomarker in the differentiation between periprosthetic joint infection and aseptic loosening?

Purpose

The pre-operative differentiation between periprosthetic joint infection (PJI) and aseptic loosening after total hip (THA) or knee (TKA) arthroplasty is essential for successful therapy and relies in part on the use of molecular markers. The objective of this study was to assess serum levels of lipopolysaccharide-binding protein (LBP) as a diagnostic tool for PJI and to compare its accuracy with standard tests.

Methods

One hundred and twenty patients presenting with a painful TKA or TKA with indication for surgical revision were included in this prospective, controlled, clinical trial at a single centre. Pre-operative blood and serum samples were collected and analysed for white blood cell (WBC) count, C-reactive protein (CRP) and LBP. The definite diagnosis of periprosthetic joint infection was determined on the basis of clinical, microbiological and histopathological examination.

Results

LBP showed significantly higher values in PJI compared with aseptic loosening (p?p?7 ng/ml. In combination with CRP, the positive predictive value for PJI was at 0.67; negative predictive value with both negative was at 0.77.

Discussion

Patients with PJI have elevated serum levels of LBP when compared with patients with aseptic loosening. The use of LBP in serum appears not to be a more accurate marker than CRP level in serum for detecting PJI. On the basis of these results, we cannot recommend the sole use of LBP for differentiating PJI and aseptic loosening following THA and TKA.     

Failure of the first step of two-stage revision due to polymicrobial prosthetic joint infection of the hip

Background

The unsuccessful treatment of prosthetic joint infection (PJI) with two-stage revision leads to infection recurrence. The objectives of the study were to assess the clinical and demographic characteristics of patients with polymicrobial PJI, and to evaluate the role of the microbial profile involved in PJI in the risk of infection recurrence after the first step of two-stage revision surgery.

Materials and methods

A retrospective analysis of 189 cases of culture-positive PJI following total hip replacement over a 5-year period was performed. The demographic characteristics of patients, clinical symptoms, microbiology cultures of intraoperative biopsies, laboratory values of C-reactive protein (CRP), white blood cell count and erythrocyte sedimentation rate were analyzed. Patients were divided into two groups—135 with monomicrobial and 54 with polymicrobial infection.

Results

Of all patients, 68.9 % in the monomicrobial and 83.3 % in the polymicrobial group had a body mass index >25 kg/m² (p = 0.05). The median CRP values were 5.7 mg/L (IQR 4.0–10.0 mg/L) in the monomicrobial compared to 8.8 mg/L (IQR 5.0–27 mg/L) in the polymicrobial group (p = 0.01). The percentage of successful outcomes was 27.8 % in patients with microbial associations (p < 0.0001). Gram-negative pathogens caused polymicrobial PJI in 61.5 % of cases with infection recurrence (OR 4.4; 95 % CI 1.18–16.37; p = 0.03).

Conclusions

Overweight and obese patients or those with elevated CRP had a greater risk of polymicrobial PJI. They were predisposed to recurrence of infection after the first step of two-stage revision. An unsuccessful outcome was more likely in cases with polymicrobial infection compared to those with monomicrobial infection. In addition, the presence of multidrug-resistant strains of Gram-negative bacteria substantially increased the risk of PJI treatment being unsuccessful.

Level of evidence

Level III, therapeutic study.

     

Articular collapse and surgical frequency in corticosteroid-associated osteonecrosis of the femoral head and the knee: an MRI-based prospective study

Background

The purpose of this magnetic resonance imaging (MRI)-based prospective study was to clarify the frequency of articular collapse in, and to define the frequency with which surgical interventions are performed for, osteonecrosis of the femoral head and the knee.

Methods

MRI screening for osteonecrosis of the femoral head and the knee was prospectively performed within 1 year after corticosteroid administration. Those patients with osteonecrosis were conservatively followed with MRI to detect articular collapse by bone marrow edema. Several surgical interventions were considered after articular collapse. The frequencies of collapse and of surgical intervention were compared using the Kaplan–Meier method and the log-rank test.

Results

Of 1,239 joints (623 hips and 616 knees) surveyed in the study, osteonecrosis was identified in 370 (191 hips and 179 knees) by MRI. Thus, the incidence of osteonecrosis was 30 % (31 % in hip and 29 % in knee). Of 155 hips and 154 knees followed for more than 2 years, the frequency of articular collapse was significantly higher in osteonecrosis of the femoral head than in osteonecrosis of the knee (p?<?0.05, 38 % [59 hips] versus 5 % [7 knees]). After articular collapse, surgery was performed significantly more often for osteonecrosis of the femoral head than for osteonecrosis of the knee (p?=?0.024, 63 % [37 femoral heads] versus 29 % [2 knees]).

Conclusions

Osteonecrosis of the femoral head can result in clinically more severe sequelae than osteonecrosis of the knee, and surgery is more often performed for osteonecrosis of the femoral head.     

Elevated Preoperative Systemic Inflammatory Markers Predict Poor Outcome in Localized Soft Tissue Sarcoma

Background

Systemic inflammation has been implicated in cancer development and progression. This study sought to determine whether systemic inflammatory markers can predict postoperative outcome in soft tissue sarcoma (STS).

Methods

A total of 162 cases of primary, localized STS were reviewed. Patients with evidence of infectious or inflammatory diseases were excluded. The mean follow-up period was 46.7 months. The level of serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil-to-lymphocyte ratio (NLR) measured before surgery were evaluated for association with disease-specific survival and local recurrence.

Results

The mean values of CRP, ESR, and NLR were 0.79 mg/dL, 18.8 mm/h, and 2.12, respectively. Cutoff values derived from receiver-operating characteristic curve analysis were 0.20 mg/dL for CRP, 10.0 mm/h for ESR, and 2.50 for NLR. On univariate analysis, all inflammatory markers were associated with disease-specific survival (CRP: P = 0.007; ESR: P = 0.022; NLR: P = 0.030). On multivariate analysis, the CRP level (P = 0.019) and ESR (P = 0.013) remained significant. Elevation of multiple markers was a more significant prognostic factor than elevation of a single marker (P = 0.001). However, none of the inflammatory markers was associated with local recurrence (CRP: P = 0.345; ESR: P = 0.271; NLR: P = 0.570). Histologic grade was strongly correlated with inflammatory marker values (NLR: P < 0.001; ESR: P = 0.002; CRP: P = 0.007).

Conclusions

Preoperative systemic inflammatory status, assessed by using multiple serum markers, predicted disease-specific survival in STS.     

Risk factors and a prognostic model of hip periprosthetic infection recurrence after surgical treatment using articulating and non-articulating spacers

Purpose

The purpose of this study was evaluation of the efficacy of the first step of a two-stage procedure for treatment of hip prosthetic joint infection (PJI) using articulating and non-articulating spacers as well as development of a prediction model and prognostic score for infection recurrence.

Methods

In a cohort of 217 patients treated for PJI of the hip, demographic characteristics, clinical symptoms, body temperature, body mass index (BMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBC), microbiological cultures and the type of the spacer used were retrospectively analyzed for association with the recurrence of PJI.

Results

Patients with infection recurrence had increased levels of ESR and CRP (P?<?0.001) together with higher BMI and shorter infection manifestation period after previous surgery (P?<?0.05). Among these patients, there was no significant difference of clinical characteristics between subjects with articulating and non-articulating spacers. Microbial associations were more often identified in patients with recurrent infection (50 %, P?<?0.01) where Gram-negative bacteria were predominant (61.5 %, P?<?0.01). These patients had higher percentage of Acinetobacter sp. and P. aeruginosa isolates (28.2 %, P?<?0.01).

Conclusions

Efficacy of the first step of two-stage revision was 64.1 %. Placement of either articulating or non-articulating spacers did not influence recovery from PJI. Laboratory values of ESR, CRP, BMI and the type of previous surgery were identified as main factors that affect outcomes of the two-stage procedure. A prognostic model with the calculation of a total risk score for PJI recurrence was developed.

     

Arthroscopic anatomic study of posteromedial joint capsule in knee joint associated with popliteal cyst

Purpose

The purpose of this study was to examine the arthroscopic anatomy of posteromedial capsule and magnetic resonance imaging (MRI) findings in internal derangement of the knee joint and to analyze the relationship between popliteal cysts and the posteromedial capsule.

Methods

From 2011 to 2012, a prospective study included 194 knees of consecutive arthroscopic surgeries for assorted knee problems. The anatomy of the posteromedial joint capsule was evaluated arthroscopically and divided into three types by the presence of capsular fold and opening: no capsular fold and no opening (type I), capsular fold without opening (type II), capsular fold with opening (type III). The presence and size of popliteal cyst were documented by MRI.

Results

Type I was observed in 160 knees (82.5 %), type II in 10 (5.1 %) and type III in 24 (12.4 %). Popliteal cysts were found in 25 knees (12.9 %) by MRI. Of these cases, symptomatic popliteal cysts were identified in 12 knees (6.9 %). On 160 knees demonstrated to be type I, only 3 knees (1.9 %) had popliteal cysts in MRI, 6 knees (60 %) in 10 knees of type II and 16 knees (66.7 %) in 24 knees of type III. Therefore, there was a statistically significant relationship between the type of anatomy in the posteromedial capsule and the popliteal cyst (p < 0.001).

Conclusion

An association between popliteal cyst and arthroscopic anatomy of posteromedial capsule was demonstrated. Comprehensive understanding and knowledge of the arthroscopic anatomy of posteromedial capsule would contribute to the arthroscopic approach in understanding the pathogenesis of popliteal cyst.

Study design

Development of diagnostic criteria on basis of consecutive patients.

Level of evidence

2.     

Impact of Day 2 C-Reactive Protein on Day 3 and 4 Thresholds Associated With Infective Complications Following Curative Surgery for Colorectal Cancer

Background

The postoperative systemic inflammatory response, as evidenced by C-reactive protein (CRP) on days 3 and 4, has been reported to be associated with the development of infective complications following surgery for colorectal cancer. However, patients in enhanced recovery after surgery require earlier assessment at day 2, the peak CRP response to surgery. The aim of the present study was to assess the impact of day 2 CRP on the CRP concentrations on days 3 and 4.

Methods

Patients with colorectal cancer undergoing elective resection were recorded in a prospective database (n = 357). CRP was measured preoperatively and on days 1–4 postoperatively. Correlations between day 2 CRP and day 3 and day 4 CRP concentrations were examined.

Results

The majority of patients were ≥65 (72 %), male (53 %), underwent right or left hemicolectomy (63 %), and had node-negative disease (61 %). Day 2 CRP was not significantly associated with age, sex, operation type, or tumor stage. Day 2 CRP was directly associated with day 3 (r ² = 0.601, p < 0.001) and day 4 (r ² = 0.270, p < 0.001) CRP. The median day 2 CRP that corresponded with the previously described thresholds for predicting infective complications was ~190 mg/L, and for predicting an anastomotic leak 200 mg/L.

Conclusions

A day 2 CRP concentration >190 mg/L was associated with day 3 and 4 CRP concentrations above established CRP thresholds for the development of infective complications.     

Histopathologische Diagnose der periprothetischen Gelenkinfektion nach Hüftgelenkersatz

Background

The distinction between aseptic and septic loosening of a total hip arthroplasty is a diagnostic challenge. Therapy and clinical success depend on the correct diagnosis. Histopathological evaluation of the periprosthetic interface membrane is one possible diagnostic parameter; detailed analysis of tissue characteristics may reflect the cause of failure. This study evaluated the diagnostic value of a published histopathological consensus classification for the periprosthetic interface membrane in the identification of periprosthetic joint infection (PJI).

Methods

Between 2004 and 2008, a prospective analysis was performed in 106 patients who had revisions because of assumed PJI. Based on clinical presentation, radiography, and haematological screening, infection was assumed, and a joint aspiration was performed. Based on these findings, a two-stage revision was performed, with intraoperative samples for culture and histological evaluation obtained. Final diagnosis of infection was based on the interpretation of the clinical presentation and the preoperative and intraoperative findings. The basis for histopathological evaluation was the consensus classification for the periprosthetic interface membrane. Sensitivity, specificity, and accuracy were calculated for each parameter.

Results

In 92 patients, a positive diagnosis of PJI could be made. Histopathology yielded the highest accuracy (0.93) in identification of PJI, identifying 86 of 92 infections (69 type II, 17 type III). In 13 of the 14 noninfected hips, histopathology correlated in 13 (93%) cases (10 type I, three type IV). The accuracies of microbiological culture, C-reactive protein, and aspiration were 0.82, 0.86, and 0.54, respectively.

Conclusion

In the diagnosis of PJI, histopathological evaluation of the periprosthetic interface membrane proved very effective. To analyse the cause of prosthesis loosening, tissue samples of the periprosthetic interface membrane should be evaluated on the basis of the consensus classification in all revision surgeries.     

The Leukocyte Esterase Strip Test has Practical Value for Diagnosing Periprosthetic Joint Infection After Total Knee Arthroplasty: A Multicenter Study

Background

Leukocyte esterase (LE) was recently reported to be an accurate marker for diagnosing periprosthetic joint infection (PJI) as defined by the Musculoskeletal Infection Society (MSIS) criteria. However, the diagnostic value of the LE test for PJI after total knee arthroplasty (TKA), the reliability of the subjective visual interpretation of the LE test, and the correlation between the LE test results and the current MSIS criteria remain unclear.

Infection surveillance in transsphenoidal pituitary surgery - comparison of lipopolysaccharide-binding-protein, interleukin 6, C-reactive protein, white blood cell count, erythrocyte sedimentation rate and body temperature

Background

One of the major concerns in transsphenoidal surgery are infections because the approach to the pituitary includes a route of microbial colonization. To minimize the associated morbidity and mortality, a surveillance program is crucial to monitor for perioperative infections.

Methods

For 1 year, we analysed body temperature (BT), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), C-reactive protein (CRP), interleukin 6 (IL-6) and lipopolysaccharide-binding-protein (LBP) following elective transsphenoidal pituitary surgery. Samples were collected on admission, day 1, 3 and 7 as well as 3 months postoperatively.

Results

In 116 patients, all data were available. No postoperative infections occurred within the first postoperative week. BT (37.6?±?0.6, baseline 37.0?±?0.5 °C), WBC (11,366?±?2,541, baseline 6,861?±?2,123/μl), CRP (25.3?±?22.6, baseline 3.1?±?6 mg/l), IL-6 (12?±?13, baseline 2.7?±?2.6 pg/ml), and LBP (11.3?±?4.9, baseline 5.7?±?2.7 μg/ml) peaked on day 1 postoperatively (each p?=?0.001), while ESR peaked on day 3 (25?±?16, baseline 13?±?11 mm/h, p?=?0.001). BT and IL-6 normalized by day 3 and CRP by day 7, while ESR (23?±?16 mm/h, p?=?0.001), WBC (7,807?±?2,750/μl, p?=?0.001) and LBP (7.3?±?2.6 μg/ml, p?=?0.028) were still increased by day 7.

Conclusion

The present study establishes normative values for an infection surveillance following transsphenoidal pituitary surgery. CRP, a convenient and reasonable priced parameter, is affected by the procedure for the first postoperative week. IL-6 is more robust and allows a close monitoring on the expense of additional pricing. ESR, WBC and LBP are sustained affected by surgery, and do not offer any advantage. Since no infections were observed, we were unable to calculate the respective sensitivity and specificity.     

A new prognostic score for the survival of patients with esophageal squamous cell carcinoma

Purpose

Recent studies have shown that the modified Glasgow Prognostic Score (mGPS), which is an inflammation-based prognostic score, is useful as a prognostic index for some cancer cases. The purpose of this study was to create a prognostic scoring system for patients with esophageal squamous cell carcinoma (ESCC) that was more independent and sensitive than the mGPS.

Methods

One hundred sixty-eight patients who had undergone esophagectomy for ESCC were included in the study. The new mGPS (NmGPS) was calculated based on the following cutoff values: CRP >0.75 mg/dL indicated NmGPS 1 or 2, depending on the absence or presence of hypoalbuminemia (<3.5 g/dL); and CRP ≤0.75 mg/dL indicated NmGPS 0. We also performed an analysis based on cutoff values of 0.5 and 0.25 mg/dL for CRP.

Results

Only the NmGPS with a cutoff CRP value of 0.5 mg/dL was able to divide into three independent patient groups in the survival curves. In the multivariate analyses, a NmGPS (CRP cutoff; 0.5 mg/dL) of 2 was a more significant independent prognostic factor (HR 4.437, 95 % CI 2.000–9.844, p = 0.0002) than a mGPS of 2 (HR 2.726, 95 % CI 1.021–7.112, p = 0.0449).

Conclusions

The new prognostic score NmGPS (CRP cutoff; 0.5 mg/dL) was more independent and sensitive than the mGPS for patients with ESCC.     

Usefulness of knee arthroscopy for diagnosis of knee pain in pediatric patients: comparison with preoperative clinical diagnosis

Purpose

To investigate the knee arthroscopic findings of pediatric patients with knee pain.

Subjects

Ninety-five knees of 94 patients (46 males and 48 females) aged 15 years or younger who underwent knee arthroscopy during a 4-year period from January 2007 were studied. The mean age at surgery was 13.5 (7–15) years. The mean interval from symptom onset to arthroscopic examination was 6.8 months (5 days to 2 years 10 months).

Results

The most common cause of knee pain was sports-related activities (64 knees). Other causes included falling from a moving bicycle (5 knees), while knee pain appeared with no defined reason in 14 knees. The most frequent final diagnosis based on knee arthroscopic findings was anterior cruciate ligament (ACL) injury (35 knees), followed by discoid lateral meniscus (16 knees), lateral meniscal tear (11 knees), and medial plica syndrome (9 knees), while no arthroscopic abnormality was observed in 8 of 95 knees. Among the 95 knees, the diagnosis based on preoperative physical tests and imaging findings was different from the arthroscopic diagnosis in 16 knees, 8 of which were diagnosed preoperatively as medial meniscal tear.

Conclusion

ACL injury and discoid lateral meniscus were the predominant conditions in pediatric patients who underwent knee arthroscopic surgery for knee pain. Knee arthroscopy is useful to provide a definitive diagnosis for knee pain in pediatric patients. Preoperative evaluations had a diagnostic accuracy of only 83.2 % and failed to diagnose conditions such as medial plica syndrome and chondral injury. Therefore, diagnosis before knee arthroscopy has to be interpreted with caution.     

Can Joint Contact Dynamics Be Restored by Anterior Cruciate Ligament Reconstruction?

Background

Rotational kinematics has become an important consideration after ACL reconstruction because of its possible influence on knee degeneration. However, it remains unknown whether ACL reconstruction can restore both rotational kinematics and normal joint contact patterns, especially during functional activities.

Questions/purposes

We asked whether knee kinematics (tibial anterior translation and axial rotation) and joint contact mechanics (tibiofemoral sliding distance) would be restored by double-bundle (DB) or single-bundle (SB) reconstruction.

Methods

We retrospectively studied 17 patients who underwent ACL reconstruction by the SB (n = 7) or DB (n = 10) procedure. We used dynamic stereo x-ray to capture biplane radiographic images of the knee during downhill treadmill running. Tibial anterior translation, axial rotation, and joint sliding distance in the medial and lateral compartments were compared between reconstructed and contralateral knees in both SB and DB groups.

Results

We observed reduced anterior tibial translation and increased knee rotation in the reconstructed knees compared to the contralateral knees in both SB and DB groups. The mean joint sliding distance on the medial compartment was larger in the reconstructed knees than in the contralateral knees for both the SB group (9.5 ± 3.9 mm versus 7.5 ± 4.3 mm) and the DB group (11.1 ± 1.3 mm versus 7.9 ± 3.8 mm).

Conclusions

Neither ACL reconstruction procedure restored normal knee kinematics or medial joint sliding.

Clinical Relevance

Further study is necessary to understand the clinical significance of abnormal joint contact, identify the responsible mechanisms, and optimize reconstruction procedures for restoring normal joint mechanics after ACL injury.