Purpose. Many studies have found associations between laboratory biomarkers and periprosthetic joint infection (PJI), but it remains unclear whether these biomarkers are clinically useful in ruling out PJI. This meta-analysis compared the performance of interleukin-6 (IL-6) versus procalcitonin (PCT) for the diagnosis of PJI. Materials and Methods. In this meta-analysis, we reviewed studies that evaluated IL-6 or/and PCT as a diagnostic biomarker for PJI and provided sufficient data to permit sensitivity and specificity analyses for each test. The major databases MEDLINE, EMBASE, the Cochrane Library, Web of Science, and SCOPUS were searched for appropriate studies from the earliest available date of indexing through February 28, 2017. No restrictions were placed on language of publication. Results. We identified 18 studies encompassing a total of 1,260 subjects; 16 studies reported on IL-6 [Fig. 1] and 6 studies reported on PCT [Fig. 2]. The area under the curve (AUC) was 0.93 (95% CI, 0.91 to 0.95) for IL-6 and 0.83 (95% CI, 0.79 to 0.86) for PCT. The pooled sensitivity was 0.83 (95% CI, 0.74 to 0.89) for IL-6 and 0.58 (95% CI, 0.31 to 0.81) for PCT. The pooled specificity was 0.91 (95% CI, 0.84 to 0.95) for IL-6 and 0.95 (95% CI, 0.63 to 1.00) for PCT. Both the IL-6 and PCT tests had a high positive likelihood ratio (LR); 9.3 (95% CI, 5.3 to 16.2) and 12.4 (95% CI, 1.7 to 89.8), respectively, making them excellent rule-in tests for the diagnosis of PJI. The pooled negative LR for IL-6 was 0.19 (95% CI, 0.12 to 0.29), making it suitable as a rule-out test, whereas the pooled negative LR for PCT was 0.44 (95% CI, 0.25 to 0.78), making it unsuitable as a rule-out diagnostic tool. Conclusion. Based on the results of the current meta-analysis, IL-6 has higher diagnostic value than PCT for the diagnosis of PJI. Moreover, the specificity of the IL-6 test is higher than its sensitivity. Conversely, PCT is not recommended for use as a rule-out diagnostic tool. For any figures or tables, please contact the authors directly

Anterior cruciate ligament (ACL) injuries have been increasing, especially amongst adolescents. These injuries can increase the risk for early-onset knee osteoarthritis (OA). The consequences of late-stage knee OA include structural joint change, functional limitations and persistent pain. Interleukin-6 (IL-6) is a pro-inflammatory biomarker reflecting knee joint healing, and increasing evidence suggests that IL-6 may play a critical role in the development of pathological pain. The purpose of this study was to determine the relationship between subjective knee joint pain and function, and synovial fluid concentrations of the pro-inflammatory cytokine IL-6, in adolescents undergoing anterior cruciate ligament reconstruction surgery. Seven youth (12-17 yrs.) undergoing anterior cruciate ligament (ACL) reconstruction surgery participated in this study. They completed the Pedi International Knee Documentation Committee (Pedi-IKDC) questionnaire on knee joint pain and function. At the time of their ACL reconstruction surgery, synovial fluid samples were collected through aspiration to dryness with a syringe without saline flushing. IL-6 levels in synovial fluid (sf) were measured using enzyme linked immunosorbent assay. Spearman's rho correlation coefficient was used to determine the correlation between IL-6 levels and scores from the Pedi-IKDC questionnaire. There was a statistically significant correlation between sfIL-6 levels and the Pedi-IKDC Symptoms score (-.929, p=0.003). The correlations between sfIL-6 and Pedi-IKDC activity score (.546, p = .234) and between sfIL-6 and total Pedi-IKDC score (-.536, p = .215) were not statistically significant. This is the first study to evaluate IL-6 as a biomarker of knee joint healing in an adolescent population, reported a very strong correlation (-.929, p=0.003) between IL-6 in knee joint synovial fluid and a subjective questionnaire on knee joint pain. These findings provide preliminary scientific evidence regarding the relationship between knee joint pain, as determined by a validated questionnaire and the inflammatory and healing status of the patient's knee. This study provides a basis and justification for future longitudinal research on biomarkers of knee joint healing in patients throughout their recovery and rehabilitation process. Incorporating physiological and psychosocial variables to current return-to-activity (RTA) criteria has the potential to improve decision making for adolescents following ACL reconstruction to reduce premature RTA thereby reducing the risk of re-injury and risk of early-onset knee OA in adolescents

Aim. Diagnosis of periprosthetic shoulder infections (PSI) is difficult as they are mostly caused by low-virulent bacteria and patients do not show typical infection signs, such as elevated blood markers, wound leakage, or red and swollen skin. Ultrasound-guided biopsies for culture may therefore be an alternative for mini-open biopsies as less costly and invasive method. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination polymerase chain reaction (PCR), and/or synovial markers for preoperative diagnosis of PSI in patients undergoing revision shoulder surgery. Method. A prospective explorative diagnostic cohort study was performed including patients undergoing revision shoulder replacement surgery. A shoulder puncture was taken preoperatively before incision to collect synovial fluid for interleukin-6 (IL-6), calprotectin, WBC, polymorphonuclear cells determination. Prior to revision surgery, six ultrasound-guided synovial tissue biopsies were collected for culture and two additional for PCR analysis. Six routine care tissue biopsies were taken during revision surgery and served as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV; primary outcome measure), and accuracy were calculated for ultrasound-guided biopsies, and synovial markers, and combinations of these. Results. Fifty-five patients were included. In 24 patients, routine tissue cultures were positive for infection. Cultures from ultrasound-guided biopsies diagnosed an infection in 7 of these patients, yielding a sensitivity, specificity, PPV, NPV, and accuracy of 29.2%, 93.5%, 77.8%, 63.0%, and 65.6%, respectively. Ultrasound-guided biopsies in combination with synovial WBC increased the NPV to 76.7% and accuracy to 73.8%. When synovial WBC and calprotectin were combined with ultrasound-guided biopsies, it resulted in a better diagnostic value: sensitivity 69.2%, specificity 80.0%, PPV 69.2%, NPV 80.0%, and accuracy 75.8%. Ultrasound-guided biopsies in combination with calprotectin and ESR yielded a sensitivity of 50.0%, specificity of 93.8%, PPV of 80.0%, NPV of 78.9%, and accuracy of 79.2%. Synovial fluid was obtained in 42 patients. Sensitivities of WBC, PMN, IL-6, and calprotectin were between 25.0% and 35.7%, specificities between 89.5% and 95.0%, PPVs between 60.0% and 83.3%, NPVs between 65.4% and 69.4%, and accuracies between 64.5% and 70.6%. Conclusions. In this prospective study we showed that ultrasound-guided biopsies for cultures alone and in combination with PCR and/or synovial markers are not reliable enough to use in clinical practice for the preoperative diagnosis of low grade PSI

Aim. Diagnosis and isolation of a causative organism is imperative for successful treatment of periprosthetic joint infections (PJI). While there are several diagnostic algorithms using microbiology, serum and synovial markers, the preoperative diagnosis of a low-grade infection remains a challenge, particularly in patients with unsuccessful aspiration. An incisional biopsy may be used in these cases as additional diagnostic tool. In this retrospective study we evaluated microbiological findings, sensitivity, and specificity of open synovial biopsies in cases of inconclusive preoperative diagnostics. Methods. In a retrospective databank analysis (2010–2018), we identified 80 TKAs that underwent an open biopsy because of inconclusive results after applying the CDC Criteria (2010) or the MSIS (2011–2018) for PJI. Infection makers in the serum (C-reactive protein [CRP], leucocytes count and interleukin-6 [IL-6]) and in the synovial aspirate (leucocyte count, percentage of neutrophiles) prior to the biopsy were analyzed. All biopsies were performed by suprapatellar mini-arthrotomy. If a subsequent revision surgery was performed, the isolated organisms in the open biopsy were compared to the results in the revision surgery and sensitivity and specificity were calculated. Serum markers were checked for correlation with a positive result in the open biopsy using Cramer-V and Chi. 2. -Test. Results. A positive result in the open biopsy occurred in 32 cases (40%) while 48 cases (60%) showed no growth of microorganisms. A preoperative elevated serum CRP (≥1mg/dl) showed a significant correlation for a positive biopsy (p=0.04). The odds ratio for a positive biopsy was 2.57 (95% CI 1.02–6.46) with elevated serum CRP. A revision surgery of the TKA with additional tissue sampling was performed in 27 (84%) cases with a positive biopsy and in 32 (67%) cases with a negative biopsy. The intraoperative tissue samples from the revision surgery showed microbial growth in only 52% of cases that were believed to be culture positive from the biopsy results, while positive cultures occurred in 41% of the cases with an initially negative biopsy. Patients with ≥ two cultures of the same microorganism in the biopsy presented a positive result in 73% of their revision surgeries. The open biopsy showed a sensitivity of 48% with a specificity of 62% in our collective if revision surgery was performed. Conclusion. Open biopsy may be considered with inconclusive preoperative serum and synovial fluid diagnostics for PJI, but sensitivity and specificity were rather low in this special collective. Further studies with bigger collectives should be performed to determine potential markers with a higher sensitivity

Aim. In the diagnosis of prosthetic joint infection (PJI), many biomarkers have shown a sound performance in terms of accuracy, sensitivity and specificity. In this study we aimed to test the frequently used serum biomarkers C-reactive Protein (CRP), Fibrinogen, Leukocytes, Interleukin-6 (IL-6), Interferon alpha (IF-alpha) and Procalcitonin (PCT) regarding these qualities. Following that, the optimal multi-biomarker combination was calculated to further improve the diagnostic performance. Method. 124 knee or hip revision arthroplasty procedures were prospectively investigated focusing on preoperative serum blood levels of CRP, Fibrinogen, Leukocytes, IL-6, IF-alpha and PCT. The presence of PJI was determined by a blinded researcher. Logistic regression with lasso-regularization was used for the biomarkers and all their ratios. Following cross-validation on a training sample set to get optimal performance estimates, we performed the final model on a test set (25% of all samples). Results. Out of all evaluated biomarkers, CRP (AUC 0.91, p-value 0.03) and Fibrinogen (AUC 0.93, p-value 0.02) had the best performances. The optimal combination when testing multiple biomarkers in 32 cross-validation runs was calculated including Fibrinogen, CRP, the ratio of Fibrinogen to CRP and the ratio of serum Thrombocytes to CRP (AUC 0.92, accuracy 0.77, specificity 0.92, sensitivity 0.68, cut-off 0.63, p-value 0.04). Conclusions. It was not possible to increase the diagnostic performance by combining multiple biomarkers using sophisticated statistical methods. The calculated Multi-biomarker models did not improve the AUC, accuracy, sensitivity and specificity when compared to single biomarkers

It has been previously shown that Low-Magnitude High-Frequency Vibration (LMHFV) is able to enhance ovariectomy-induced osteoporotic fracture healing in rats. Fracture healing begins with the inflammatory stage, and all subsequent stages are regulated by the infiltration of immune cells such as macrophages and the release of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Therefore, the aim of this study was to investigate the effect of LMFHV treatment on the inflammatory response in osteoporotic fracture healing. In this study, ovariectomy-induced osteoporotic and sham-operated closed-femoral fracture SD-rats were randomized into three groups: sham control (SHAM), ovariectomized control (OVX-C) or ovariectomized vibration (OVX-V) (n=36, n=6 per group per time point). LMHFV (35Hz, 0.3g) was given 20 min/day and 5 days/week to OVX-V group. SHAM operation and ovariectomy were performed at 6-month and closed femoral fracture was performed at 9-month. Callus morphometry was determined by callus width from weekly radiography. Local expressions of inducible nitric oxide synthase (iNOS) (macrophage M1 marker), CD206 (macrophage M2 marker), TNF-α, IL-6 and IL-10 were detected by immunohistochemistry and quantified by colour threshold in ImageJ, assessed at weeks 1 and 2 post-fracture. Significant difference between groups was considered at p≤0.05 by one-way ANOVA. Callus formation was higher in OVX-V than that of OVX-C as shown by callus width at weeks 1 and 2 (p=0.054 and 0.028, respectively). Immunohistochemistry results showed that CD206 positive signal and the M2/M1 ratio which indicates the progression of macrophage polarization were significantly higher in OVX-V rats (p=0.053 and 0.049, respectively) when compared to OVX-C at week 1. Area fraction of TNF-α positive signal was significantly higher in SHAM and OVX-V rats at week 1 (p=0.01 and 0.033, respectively). IL-6 signal was also significantly higher in SHAM and OVX-V groups at week 1 (p=0.004 and 0.029, respectively). IL-10 expression was significantly lower in SHAM and OVX-V groups at week 1 (p=0.013 and 0.05, respectively). Here we have shown that LMHFV treatment promoted the shift from pro-inflammatory stage towards anti-inflammatory stage earlier. It has been reported that the polarization of pro-inflammatory macrophages M1 to anti-inflammatory macrophages M2 was indicative of the endochondral ossification process in the long bone fracture model. Besides, we found that LMHFV treatment enhanced pro-inflammatory markers of TNF-α and IL-6 and suppressed anti-inflammatory marker of IL-10 at week 1, showing that inflammatory response was enhanced at week 1 post-fracture. These inflammatory cytokines involved in fracture healing were shown to coordinate different fracture healing processes such as mesenchymal stem cell recruitment and angiogenesis. Our previous study has demonstrated that ovariectomized rats exhibit lower levels of inflammatory response after fracture creation. Therefore, we report that LMHFV treatment can modulate macrophage polarization from M1 to M2 at an earlier time-point and partly restore the impaired inflammatory response in OVX bones at the early stage of fracture healing that may lead to accelerated healing of osteoporotic fracture as shown by promoted callus formation

Background. The anterior approach for total hip arthroplasty has recently been hypothesized to result in less muscle damage. While clinical outcome studies are essential, they are subject to patient and surgeon bias. We prospectively analyzed biochemical markers of muscle damage and inflammation in patients receiving anterior and posterior minimally-invasive total hip arthroplasty to provide objective evidence of the surgical insult. Methods. 29 patients receiving an anterior and 28 patients receiving a posterior total hip arthroplasty were analyzed. Peri-operative and radiographic data were collected to ensure similar cohorts. Creatine kinase, C-reactive protein, Interleukin-6, Interleukin-1beta, and Tumor necrosis factor-alpha were collected pre-operatively, post-operatively, and on post-operative days 1 and 2. Comparisons between the groups were made using the Student's t-test and Fisher's Exact test. Independent predictors of elevation in markers of inflammation and muscle damage were determined using multivariate logistic regression analysis. Results. Markers of inflammation were slightly decreased in direct anterior group (mean differences in C-reactive protein 27.5 [95% confidence interval −24.7–79.6] mg/dL, Interleukin-6 13.5 [95% confidence interval −11.5–38.4] pg/ml, Interleukin-1beta 42.6 [95% confidence interval −10.4–95.6], and Tumor necrosis factor-alpha 148.6 [95% confidence interval −69.3–366.6] pg/ml). The rise in creatine kinase was 5.5 times higher in the post anesthesia care unit (mean difference 150.3 [95% confidence interval 70.4–230.2] units/L, p < 0.05) and nearly twice as high cumulatively in the miniposterior approach group (305.0 [95% confidence interval −46.7–656.8] units/L, p < 0.05). Conclusion. Anterior total hip arthroplasty caused significantly less muscle damage compared to traditional posterior surgery as indicated by creatine kinase levels. The clinical importance of this rise needs to be delineated by further clinical studies. The overall physiologic burden as measured by markers of inflammation, however, appears to be similar. Objective measurement of muscle damage and inflammation provides an unbiased way of determining the immediate effects of surgical intervention in total hip arthroplasty patients

Purpose. There is controversial whether synovectomy must be done in primary total knee arthroplasty (TKA). The objectivity of the study was to compare the effect of synovectomy on inflammation and clinical outcomes after surgical treatment of knee osteoarthritis. Methods. A total of 240 patients who underwent primary unilateral TKR were randomly divided into a group without (Group A) and with synovectomy (Group B). All operations were performed by the same surgeon and follow-up was for 4 year. Clinical outcomes (including American Knee Society score (AKS), SF-36, and HSS scores) serum inflammatory markers (including interleukin-6 (IL-6), CRP and ESR) and the difference in temperature of the affected knee skin, swelling, ROM, patients VAS satisfaction score and VAS pain score were sequentially evaluated until 4 years after surgery. Result. There were no statistically different clinical parameters between the two groups preoperatively. At the 4 years follow-up, both groups had a similarly significantly improved AKS clinical and functional score. Similar changes in serial inflammatory markers were identified in both groups. In addition, no difference was seen regarding drainage-fluid inflammatory markers at any follow-up time. There was no difference in respect to patients satisfaction score from surgery to 1 year, but Group B showed greater patients satisfaction score from 2 year to four year, with less number of patients suffering from anterior pain. There was no difference with regard to other parameters at any follow-up time. Conclusions. Synovectomy in primary TKA does not seem to have any clinical advantage and shorten the duration of the inflammatory response, but it might increase patient satisfaction score and reduce anterior knee pain

Periprosthetic joint infection (PPJI) following shoulder arthroplasty is uncommon, with an overall rate of 0.98%. However, the rates following revision arthroplasty and reverse arthroplasty are much higher. Given the rapid increase in the prevalence of shoulder arthroplasty and the increasing revision burden, the cost of PPJI to society will likely increase substantially. The most common organisms found in PPJI following shoulder arthroplasty are Staphylococcus aureus, coagulase-negative Staphylococcus, and Propionibacterium acnes (P. acnes). P. acnes is especially common in males. Traditional testing for PPJI includes aspiration, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). Aspiration often yields a dry tap and when fluid is obtained for culture, a positive result is helpful but a negative result does not rule out PPJI. Although WBC, ESR, and CRP are often positive with PPJI in the lower extremity, they are most often negative in shoulder PPJI. Although bone scans and WBC labeled scans are used, they are expensive and have low sensitivity and specificity. New testing and techniques have been reported in an attempt to improve sensitivity and specificity for PPJI. These techniques can be divided into tests on serum, synovial fluid, and tissue. Serum Interleukin-6 (IL-6) is highly specific (94%) for shoulder PPJI but has low sensitivity (14%). Synovial fluid can be tested for leukocyte esterase using a simple and cheap technique. In lower extremity PPJI it has shown to be helpful. It is not as helpful in shoulder PPJI with 30% sensitivity and 67% specificity. Alpha defensin has been reported to be more sensitive (63%) and as specific (95%) as traditional techniques but still lacks predictive value. Testing for specific cytokines (IL-2, IL-6, TNF- α) within synovial fluid is not widely used as yet but has shown promise with 80% sensitivity and 90% specificity. Obtaining tissue for culture and other testing is probably the most reliable way of confirming PPJI for the shoulder. Frozen sections taken at the time of revision can be helpful but is very pathologist dependent and institution specific. With a dedicated musculoskeletal pathologist, the finding of 10 or more WBCs per high powered field has been reported to be 72% sensitive and 100% specific for P. acnes and 63% sensitive and 100% specific for other organisms. Cultures from arthroscopic tissue biopsy have also been found to have high sensitivity (100%) and specificity (100%). Genetic testing of tissue biopsy specimens (PCR/NGS) has recently been reported and shows great promise. The significance of positive cultures and other tests, especially for P. acnes is unclear. There is a high rate of positive intra-operative cultures in primary cases of shoulder arthroplasty. In addition, intra-operative cultures taken at the time of revision, even in cases in which infection is not suspected, are frequently positive for P. acnes with weak correlation with rates of post-operative clinical infection. In conclusion, shoulder PPJI is a difficult problem to deal with. The definition of shoulder PPJI is currently unclear and further study is needed. There is no ideal test to confirm it. A reasonable approach is to aspirate for culture, and perform serum tests for WBC, ESR, and C-reactive protein. If any of these is positive in the setting of a painful arthroplasty, PPJI should be assumed until proven otherwise. Operative tissue cultures are probably the most reliable test but the clinical significance is not always obvious. Synovial fluid cytokine profiles and tissue PCR/NGS show promise for the future

Aims

The worldwide COVID-19 pandemic is directly impacting the field of orthopaedic surgery and traumatology with postponed operations, changed status of planned elective surgeries and acute emergencies in patients with unknown infection status. To this point, Germany's COVID-19 infection numbers and death rate have been lower than those of many other nations.

During the pandemic of COVID-19, some patients with COVID-19 may need emergency surgeries. As spine surgeons, it is our responsibility to ensure appropriate treatment to the patients with COVID-19 and spinal diseases. A protocol for spinal surgery and related management on patients with COVID-19 has been reviewed. Patient preparation for emergency surgeries, indications, and contraindications of emergency surgeries, operating room preparation, infection control precautions and personal protective equipments (PPE), anesthesia management, intraoperative procedures, postoperative management, medical waste disposal, and surveillance of healthcare workers were reviewed. It should be safe for surgeons with PPE of protection level 2 to perform spinal surgeries on patients with COVID-19. Standardized and careful surgical procedures should be necessary to reduce the exposure to COVID-19.