Background: Acetylsalicylic acid (ASA) may cause difficult-to-treat symptoms of the airways, skin, or gastrointestinal tract in hypersensitive patients. Due to the chemical relationship between salicylic acid and ASA, a role of a low-salicylate diet has been discussed.

Methods: This review evaluates whether low salicylate diets are meaningful from an allergological or nutritional–physiological perspective.

Results: The body’s arachidonic acid metabolism plays a crucial role in the pathogenesis of ASA intolerance. Despite their chemical affinity, ASA and salicylic acid affect the arachidonic pathway differently. The intake of salicylic acid with food is low compared to therapeutic doses of ASA. There is increasing evidence that protective effects of a high fruit and vegetables diet is related in part to the intake of salicylates. In salicylatelow diets, fruit and vegetables are reduced, harboring the risk of an insufficient diet and malnutrition.

Conclusion: Dietary therapy in ASA-intolerant patients is not recommended.

Background: Promoting a disruptive innovation in microsurgery, exoscopes promise alleviation of physical strain and improved image quality through digital visualization during microneurosurgical interventions. This study investigates the impact of a novel 3D4k hybrid exoscope (i.e., combining digital and optical visualization) on surgical performance and team workflow in preclinical and clinical neurosurgical settings.

Methods: A pre-clinical workshop setting has been developed to assess usability and implementability through skill-based scenarios (neurosurgical participants n = 12). An intraoperative exploration in head and spine surgery (n = 9) and a randomized clinical study comparing ocular and monitor mode in supratentorial brain tumor cases (n = 20) followed within 12 months. Setup, procedure, case characteristics, surgical performance, and user experience have been analyzed for both ocular group (OG) and monitor group (MG).

Results: Brain tumor cases using frontal, frontoparietal, or temporal approaches have been identified as favorable use cases for introducing exoscopic neurosurgery. Mean monitor distance and angle were 180 cm and 10°. Surgical ergonomics when sitting improved significantly in MG compared with OG (P = .03). Hand-eye coordination required familiarization in MG. Preclinical data showed a positive correlation between lateral camera inclination and impact on hand-eye coordination (rs = 0.756, P = .01). There was no significant added surgical time in MG. Image quality in current generation 3D4k monitors has been rated inferior to optic visualization yet awaits updates.

Conclusions: The hybrid exoscopic device can be integrated into established neurosurgical workflows. Currently, exoscopic interventions seem most suited for cranial tumor surgery in lesions that are not deep-seated. Ergonomics improve in monitor mode compared to conventional microsurgery.

Background: Increasing technico-manual complexity of procedures and time constraints necessitates effective neurosurgical training. For this purpose, both screen- and model-based simulations are under investigation. Approaches including 3D printed brains, gelatin composite models, and virtual environments have already been published. However, quality of brain surgery simulation is limited due to discrepancies in visual and haptic experience. Similarly, virtual training scenarios are still lacking sufficient real-world resemblance. In this study, we introduce a novel simulator for realistic neurosurgical training that combines real brain tissue with 3D printing and augmented reality.

Methods: Based on a human CT scan, a skull base and skullcap were 3D printed and equipped with an artificial dura mater. The cerebral hemispheres of a calf’s brain were placed in the convexity of the skullcap and tumor masses composed of aspic, water, and fluorescein were injected in the brain. The skullcap and skull base were placed on each other, glued together, and filled up with an aspic water solution for brain fixation. Then, four surgical scenarios were performed in the operating room as follows: (1) simple tumor resection, (2) complex tumor resection, (3) navigated biopsy via burr hole trepanation, and (4) retrosigmoidal craniotomy. Neuronavigation, augmented reality, fluorescence, and ocular—as well as screen-based (exoscopic)—surgery were available for the simulator training. A total of 29 participants performed at least one training scenario of the simulator and completed a 5-item Likert-like questionnaire as well as qualitative interviews. The questionnaire assessed the realism of the tumor model, skull, and brain tissue as well as the capability for training purposes.

Results: Visual and sensory realism of the skull and brain tissue were rated,”very good,” while the sensory and visual realism of the tumor model were rated “good.” Both overall satisfaction with the model and eligibility of the microscope and neurosurgical instruments for training purposes were rated with “very good.” However, small size of the calf’s brain, its limited shelf life, and the inability to simulate bleedings due to the lack of perfusion were significant drawbacks.

Conclusion: The combination of 3D printing and real brain tissue provided surgical scenarios with very good real-life resemblance. This novel neurosurgical model features a versatile setup for surgical skill training and allows for efficient training of technological support like image and fluorescence guidance, exoscopic surgery, and robotic technology.

Background: Minimally invasive surgery (MIS) for evacuation of spontaneous intracerebral hemorrhage (ICH) has shown promise but there remains a need for intraoperative performance assessment considering the wide range of evacuation effectiveness. In this feasibility study, we analyzed the benefit of intraoperative 3-dimensional imaging during navigated endoscopy-assisted ICH evacuation by mechanical clot fragmentation and aspiration.

Methods: 18 patients with superficial or deep supratentorial ICH underwent MIS for clot evacuation followed by intraoperative computerized tomography (iCT) or cone-beam CT (CBCT) imaging. Eligibility for MIS required (a) availability of intraoperative iCT or CBCT, (b) spontaneous lobar or deep ICH without vascular pathology, (c) a stable ICH volume (20–90 ml), (d) a reduced level of consciousness (GCS 5–14), and (e) a premorbid mRS ≤ 1. Demographic, clinical, and radiographic patient data were analyzed by two independent observers.

Results: Nine female and 9 male patients with a median age of 76 years (42–85) presented with an ICH score of 3 (1–4), GCS of 10 (5–14) and ICH volume of 54 ± 26 ml. Clot fragmentation and aspiration was feasible in all cases and intraoperative imaging determined an overall evacuation rate of 80 ± 19% (residual hematoma volume: 13 ± 17 ml; p < 0.0001 vs. Pre-OP). Based on the intraoperative imaging results, 1/3rd of all patients underwent an immediate re-aspiration attempt. No patient experienced hemorrhagic complications or required conversion to open craniotomy. However, routine postoperative CT imaging revealed early hematoma re-expansion with an adjusted evacuation rate of 59 ± 30% (residual hematoma volume: 26 ± 37 ml; p < 0.001 vs. Pre-OP).

Conclusions: Routine utilization of iCT or CBCT imaging in MIS for ICH permits direct surgical performance assessment and the chance for immediate re-aspiration, which may optimize targeting of an ideal residual hematoma volume and reduce secondary revision rates.

Purpose: With the spread of transjugular intrahepatic portosystemic shunts (TIPS), portosystemic shunt surgery (PSSS) has decreased and leaves more complex patients with great demands for accurate preoperative planning. The aim was to evaluate the role of imaging for predicting the most suitable PSSS approach.

Material and methods: Forty-four patients who underwent PSSS (2002 to 2013) were examined by contrast-enhanced CT (n = 33) and/or MRI (n = 15) prior to surgery. Imaging was analyzed independently by two observers (O1 and O2) with different levels of experience (O1 > O2). They recommended two shunting techniques (vessels and anastomotic variant) for each patient and ranked them according to their appropriateness and complexity. Findings were compared with the actually performed shunt procedure and its outcome.

Results: The first two choices taken together covered the performed PSSS regarding vessels in 88%/100% (CT/MRI, O1) and 76%/73% (O2); and vessels + anastomosis in 79%/73% (O1) and 67%/60% (O2). The prediction of complex surgical procedures (resection of interposing structures, additional thrombectomy, use of a collateral vessel, and use of a graft interposition) was confirmed in 87%, resulting in 80% sensitivity and 96% specificity. Larger shunt vessel distances were associated with therapy failure (p = 0.030) and a vessel distance of ≥ 20 mm was identified as optimal cutoff, in which a graft interposition was used. There was no significant difference between MRI and CT in predicting the intraoperative decisions (p = 0.294 to 1.000).

Conclusion: Preoperative imaging and an experienced radiologist can guide surgeons in PSSS. CT and MRI provide the information necessary to identify technically feasible variants and complicating factors.

Background: Obesity is associated with chronic low-grade inflammation leading to metabolic and cardiovascular diseases, but a subset of obese individuals is considered insulin sensitive (IS). The underlying pathophysiologic mechanisms remain elusive and clinical studies on the relationship between inflammatory markers and metabolically healthy obesity (MHO) are scarce.

Methods: In this cross-sectional analysis, we included a sample of 437 older participants (60-84 years) from the Berlin Aging Study II (BASE-II). Peripheral blood mononuclear cells were isolated, immune cell subsets were analyzed with multiparameter flow cytometry and systemic cytokine levels were measured. Immune cell parameters were correlated with metabolic measures and multiple linear regression analysis was conducted and adjusted for various demographic and clinical factors.

Results: We found that frequencies of naive and memory CD4(+) and CD8(+) T cells inversely correlated with measures for insulin sensitivity in the older population. Moreover, the percentages of naive CD4(+) and CD8(+) T cells were significantly higher, whereas activated T cells and IL-6 levels were lower in IS compared to insulin resistant (IR) obese individuals. The percentages of naive CD4(+) and CD8(+) T cells were predictive for impaired insulin sensitivity (ss = 0.16, p = 0.01 and ss = 0.11, p = 0.04), and the association of naive CD4(+) T cells with insulin sensitivity persisted after multivariate adjustment (ss = 0.14, p = 0.02).

Conclusions: These findings support the hypothesis that parameters of systemic inflammation can differentiate IS from IR obese individuals that are at higher risk for cardiometabolic diseases and may have clinical implications with regard to obesity treatment stratification.

Background: In clinical trials with fixed study designs, statistical inference is only made when the trial is completed. In contrast, group sequential designs allow an early stopping of the trial at interim, either for efficacy when the treatment effect is significant or for futility when the treatment effect seems too small to justify a continuation of the trial. Efficacy stopping boundaries based on alpha spending functions have been widely discussed in the statistical literature, and there is also solid work on the choice of adequate futility stopping boundaries. Still, futility boundaries are often chosen with little or completely without theoretical justification, in particular in investigator initiated trails. Some authors contributed to fill this gap. In here, we rely on an idea of Schüler et al. (2017) who discuss optimality criteria for futility boundaries for the special case of trials with (multiple) time-to-event endpoints. Their concept can be adopted to define "optimal" futility boundaries (with respect to given performance indicators) for continuous endpoints.

Methods: We extend Schülers' definition for "optimal" futility boundaries to the most common study situation of a single continuous primary endpoint compared between two groups. First, we introduce the analytic algorithm to derive these futility boundaries. Second, the new concept is applied to a real clinical trial example. Finally, the performance of a study design with an "optimal" futility boundary is compared to designs with arbitrarily chosen futility boundaries.

Results: The presented concept of deriving futility boundaries allows to control the probability of wrongly stopping for futility, that means stopping for futility even if the treatment effect is promizing. At the same time, the loss in power is also controlled by this approach. Moreover, "optimal" futility boundaries improve the probability of correctly stopping for futility under the null hypothesis of no difference between two groups.

Conclusions: The choice of futility boundaries should be thoroughly investigated at the planning stage. The sometimes met, arbitrary choice of futility boundaries can lead to a substantial negative impact on performance. Applying futility boundaries with predefined optimization criteria increases efficiency of group sequential designs. Other optimization criteria than proposed in here might be incorporated.

Background and objective: The number of people suffering from dementia is increasing worldwide and so is the need for reliable and economical diagnostic instruments. Therefore, the aim of this study was to compare the processing times of the neuropsychological tests Trail Making Tests A and B (TMT-A/B) and Color-Word Interference Test (CWIT), which were performed in both digital and paper versions.

Methods: The pilot study was conducted among 50 healthy participants (age 65–83 years) using a randomized crossover design. The correlations and differences in the individual processing times of the two test versions were statistically analyzed. Further research questions concerned the influence of the individual usage of technology and the technology commitment of participants as well as the influence of the assessed usability on participants’ performance.

Results: Between the two versions (paper-based vs. digital) statistically significant correlations were found in all tests, e.g., TMT-A r(48) = 0.63, p < 0.01; TMT-B rs(48) = 0.77, p < 0.001). The mean value comparison showed statistically significant differences, e.g., interference table (CWIT) t(49) = 11.24, p < 0.01). Correlations with medium effect were found between the differences in processing times and the individual usage of computer (e.g., rs(48) = − 0.31) and smartphone (rs(48) =  − 0.29) and between the processing times of the TMT-B and the usability (rs(48) = 0.29).

Conclusions: The high correlations between the test procedures appear promising. However, the differences found in the processing times of the two test versions require validation and standardization of digitized test procedures before they can be used in practice.

Background: Cardiovascular magnetic resonance (CMR) strain imaging is an established technique to quantify myocardial deformation. However, to what extent left ventricular (LV) systolic strain, and therefore LV mechanics, reflects classical hemodynamic parameters under various inotropic states is still not completely clear. Therefore, the aim of this study was to investigate the correlation of LV global strain parameters measured via CMR feature tracking (CMR-FT, based on conventional cine balanced steady state free precession (bSSFP) images) with hemodynamic parameters such as cardiac index (CI), cardiac power output (CPO) and end-systolic elastance (Ees) under various inotropic states.

Methods: Ten anaesthetized, healthy Landrace swine were acutely instrumented closed-chest and transported to the CMR facility for measurements. After baseline measurements, two steps were performed: (1) dobutamine-stress (Dobutamine) and (2) verapamil-induced cardiovascular depression (Verapamil). During each protocol, CMR images were acquired in the short axisand apical 2Ch, 3Ch and 4Ch views. MEDIS software was utilized to analyze global longitudinal (GLS), global circumferential (GCS), and global radial strain (GRS).

Results: Dobutamine significantly increased heart rate, CI, CPO and Ees, while Verapamil decreased them. Absolute values of GLS, GCS and GRS accordingly increased during Dobutamine infusion, while GLS and GCS decreased during Verapamil. Linear regression analysis showed a moderate correlation between GLS, GCS and LV hemodynamic parameters, while GRS correlated poorly. Indexing global strain parameters for indirect measures of afterload, such as mean aortic pressure or wall stress, significantly improved these correlations, with GLS indexed for wall stress reflecting LV contractility as the clinically widespread LV ejection fraction.

Conclusion: GLS and GCS correlate accordingly with LV hemodynamics under various inotropic states in swine. Indexing strain parameters for indirect measures of afterload substantially improves this correlation, with GLS being as good as LV ejection fraction in reflecting LV contractility. CMR-FT-strain imaging may be a quick and promising tool to characterize LV hemodynamics in patients with varying degrees of LV dysfunction.

Purpose: This study aimed to calculate an applicable relative ratio threshold value instead of the absolute threshold value for simultaneous 68Ga prostate-specific membrane antigen/positron emission tomography ([68Ga]Ga-PSMA-11 PET) in patients with prostate cancer (PCa).

Materials and methods: Our study evaluated thirty-two patients and 170 focal prostate lesions. Lesions are classified into groups according to Prostate Imaging Reporting and Data System (PI-RADS). Standardized uptake values maximum (SUVmax), corresponding lesion-to-background ratios (LBRs) of SUVmax, and LBR distributions of each group were measured based on regions of interest (ROI). We examined LBR with receiver operating characteristic analysis to determine threshold values for differentiation between multiparametric magnetic resonance imaging (mpMRI)-positive and mpMRI-negative lesions.

Results: We analyzed a total of 170 focal prostate lesions. Lesions number of PI-RADS 2 to 5 was 70, 16, 46, and 38. LBR of SUVmax of each PI-RADS scores was 1.5 (0.9, 2.4), 2.5 (1.6, 3.4), 3.7 (2.6, 4.8), and 6.7 (3.5, 12.7). Based on an optimal threshold ratio of 2.5 to be exceeded, lesions could be classified into MRI-positive lesion on [68Ga]Ga-PSMA PET with a sensitivity of 85.2%, a specificity of 72.0%, with the corresponding area under the receiver operating characteristic curve (AUC) of 0.83, p < 0.001. This value matches the imaging findings better.

Conclusion: The ratio threshold value of SUVmax, LBR, has improved clinical and research applicability compared with the absolute value of SUVmax. A higher threshold value than the background’s uptake can dovetail the imaging findings on MRI better. It reduces the bias from using absolute background uptake value as the threshold value.

Background: Today immersive environments such as Virtual Reality (VR) offer new opportunities for serious gaming in exercise therapy and psychoeducation. Chronic back pain (CBP) patients could benefit from exergames in VR. The requirements in older CBP patients for a VR pain therapy have not yet been determined in studies. The aim of the study was to perform a requirements analysis for the user group of geriatric patients with CBP for a VR exergame. The objective was to find out the expectations, desires, preferences and barriers in order to collect them as requirements for this vulnerable group and to determine frameworks of therapy by physiotherapists and psychotherapists.

Methods: We conducted a requirements analysis through semi-structured interviews with 10 elderly participants with CBP. Furthermore, two focus groups were conducted with three physiotherapists and two psychotherapists to determine frameworks of therapy programs for the target group. The qualitative data were transcribed and examined through a structuring content analysis. Subsequently, the results of the analysis were prioritized by all participants of the study.

Results: The results of the requirements analysis indicate mandatory requirements for the overall system, hardware, software and gamification elements. The key requirements were target-group-specific applications of the VR exergame through e.g. individual briefing, user-friendly handling, inclusion of movement limitations, presentation of everyday scenarios in combination with biofeedback, age-appropriate feedback through praise and awards and a maximum exercise duration of 30 min and 15 min of relaxation.

Conclusion: It should be possible to use the determined requirements productively to create user-friendly VR exergames that motivate elderly chronic back pain patients to perform exercises regularly.

Trial registration: The study is registered in the German Clinical Trials Register (DRKS-ID: DRKS00015294 12.10.2018).

Background: The haematoma block (HB) has been successfully used to minimise pain prior to otherwise painful closed reduction manoeuvres for distal radius fractures. However, the invasive manner of the procedure, which technically produces an open fracture, still raises the question, whether HBs increase the risk of infection compared to conventional intravenous analgesia (IA). The purpose of this study was to assess complication rates and safety of the HB procedure for the closed reduction of surgically treated distal radius fractures. Methods: We included 176 distal radius fractures in 170 patients in a retrospective mono-centric study, who underwent closed reduction and casting followed by definitive surgical care over a period of two years. Patients either received a HB or IA before closed reduction and were evaluated for minor and major complications over a follow-up period of four years. Results: Overall, 42 distal radius fractures were treated with a HB (23.9%) and 134 with IA (76.1%) before closed reduction. There were a single major (2.3%) and eight minor (19%) complications observed in the HB group compared to two major (1.4%) and 24 minor (17.9%) complications in the IA group. No significant differences were identified between the two groups. Sex and type of fracture had no effect on complication rates, however, younger patients experienced higher complication rates in comparison to older ones (p = 0.035). Conclusion: According to our data, the apprehensions that clinicians may have of creating open fractures through HB procedures, are unnecessary and may be abandoned confidently.

The aim of this document is to provide specific recommendations on the use of cardiovascular magnetic resonance (CMR) protocols in the era of the COVID-19 pandemic. In patients without COVID-19, standard CMR protocols should be used based on clinical indication as usual. Protocols used in patients who have known / suspected active COVID-19 or post COVID-19 should be performed based on the specific clinical question with an emphasis on cardiac function and myocardial tissue characterization. Short and dedicated protocols are recommended.

Background: EQ-5D health state utilities (HSU) are commonly used in health economics to compute quality-adjusted life years (QALYs). The EQ-5D, which is country-specific, can be derived directly or by mapping from self-reported health-related quality of life (HRQoL) scales such as the PROMIS-29 profile. The PROMIS-29 from the Patient Reported Outcome Measures Information System is a comprehensive assessment of self-reported health with excellent psychometric properties. We sought to find optimal models predicting the EQ-5D-5L crosswalk from the PROMIS-29 in the United Kingdom, France, and Germany and compared the prediction performances with that of a US model.

Methods: We collected EQ-5D-5L and PROMIS-29 profiles and three samples representative of the general populations in the UK (n = 1509), France (n = 1501), and Germany (n = 1502). We used stepwise regression with backward selection to find the best models to predict the EQ-5D-5L crosswalk from all seven PROMIS-29 domains. We investigated the agreement between the observed and predicted EQ-5D-5L crosswalk in all three countries using various indices for the prediction performance, including Bland-Altman plots to examine the performance along the HSU continuum.

Results: The EQ-5D-5L crosswalk was best predicted in France (nRMSEFRA = 0.075, nMAEFRA = 0.052), followed by the UK (nRMSEUK = 0.076, nMAEUK = 0.053) and Germany (nRMSEGER = 0.079, nMAEGER = 0.051). The Bland-Altman plots show that the inclusion of higher-order effects reduced the overprediction of low HSU scores.

Conclusions: Our models provide a valid method to predict the EQ-5D-5L crosswalk from the PROMIS-29 for the UK, France, and Germany.

Background: Asphericity (ASP) of the primary tumor's metabolic tumor volume (MTV) in FDG-PET/CT is independently predictive for survival in patients with non-small cell lung cancer (NSCLC). However, comparability between PET systems may be limited. Therefore, reproducibility of ASP was evaluated at varying image reconstruction and acquisition times to assess feasibility of ASP assessment in multicenter studies.

Methods: This is a retrospective study of 50 patients with NSCLC (female 20; median age 69 years) undergoing pretherapeutic FDG-PET/CT (median 3.7 MBq/kg; 180 s/bed position). Reconstruction used OSEM with TOF4/16 (iterations 4; subsets 16; in-plane filter 2.0, 6.4 or 9.5 mm), TOF4/8 (4 it; 8 ss; filter 2.0/6.0/9.5 mm), PSF + TOF2/17 (2 it; 17 ss; filter 2.0/7.0/10.0 mm) or Bayesian-penalized likelihood (Q.Clear; beta, 600/1750/4000). Resulting reconstructed spatial resolution (FWHM) was determined from hot sphere inserts of a NEMA IEC phantom. Data with approx. 5-mm FWHM were retrospectively smoothed to achieve 7-mm FWHM. List mode data were rebinned for acquisition times of 120/90/60 s. Threshold-based delineation of primary tumor MTV was followed by evaluation of relative ASP/SUVmax/MTV differences between datasets and resulting proportions of discordantly classified cases.

Results: Reconstructed resolution for narrow/medium/wide in-plane filter (or low/medium/high beta) was approx. 5/7/9 mm FWHM. Comparing different pairs of reconstructed resolution between TOF4/8, PSF + TOF2/17, Q.Clear and the reference algorithm TOF4/16, ASP differences was lowest at FWHM of 7 versus 7 mm. Proportions of discordant cases (ASP > 19.5% vs. ≤ 19.5%) were also lowest at 7 mm (TOF4/8, 2%; PSF + TOF2/17, 4%; Q.Clear, 10%). Smoothing of 5-mm data to 7-mm FWHM significantly reduced discordant cases (TOF4/8, 38% reduced to 2%; PSF + TOF2/17, 12% to 4%; Q.Clear, 10% to 6%), resulting in proportions comparable to original 7-mm data. Shorter acquisition time only increased proportions of discordant cases at < 90 s.

Conclusions: ASP differences were mainly determined by reconstructed spatial resolution, and multicenter studies should aim at comparable FWHM (e.g., 7 mm; determined by in-plane filter width). This reduces discordant cases (high vs. low ASP) to an acceptable proportion for TOF and PSF + TOF of < 5% (Q.Clear: 10%). Data with better resolution (i.e., lower FWHM) could be retrospectively smoothed to the desired FWHM, resulting in a comparable number of discordant cases.

Background: [68Ga]Ga-FAPI-46 is a promising radiopharmaceutical for in vivo detection of the fibroblast activation protein by positron emission tomography. Until now, the synthesis of [68Ga]Ga-FAPI-46 has been only performed manually. Our aim was to evaluate the automated synthesis of this radiopharmaceutical on two different commercially available synthesis modules in order to make the tracer readily available for clinical application.

Results: The synthesis of [68Ga]Ga-FAPI-46 with different amounts of precursor (10-50 μg) on the Modular Lab PharmTracer (MLPT) and Modular Lab eazy (ML eazy) from Eckert & Ziegler with a customized synthesis template and a customized single-use cassette yielded best results with 50 μg FAPI-46 for clinical multi-dose application. All relevant quality control parameters tested (e.g. sterility, stability and radiochemical purity) were in accordance with the European Pharmacopoeia.

Conclusions: [68Ga]Ga-FAPI-46 was successfully synthesized fully-automated on the synthesis modules Modular Lab PharmTracer and ML eazy and is, thus, available for multi-dose application in clinical settings.

Background: The purpose of this meta-analysis was to evaluate the diagnostic value of D-dimer in detecting periprosthetic joint infection (PJI).

Methods: A systematic search and screening of relevant studies was performed in the databases PubMed, Web of Science, and Embase using the following medical subject headings (MeSH) or keywords: “arthroplasty or joint prosthesis or joint replacement or periprosthetic joint or prosthetic joint”, “infection or infectious or infected”, and “D-dimer or serum D-dimer or plasma D-dimer or fibrin degradation products”. Data were subsequently analysed and processed using Meta-Disc.

Results: Seven studies with 1285 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.75 (95% confidence interval [CI] 0.70–0.79), 0.69 (95% CI 0.66–0.72), 3.01 (95% CI 1.84–4.93), 0.32 (95% CI 0.19–0.53), and 10.20 (95% CI 3.63–28.64), respectively. Subgroup analyses showed that the use of serum D-dimer had better sensitivity and specificity than plasma D-dimer for the diagnosis of PJI.

Conclusions: Serum D-dimer was shown to have a better diagnostic value than plasma D-dimer for the diagnosis of PJI. Further research is required for clarification.

Background: Because there is no single gold standard method for the diagnosis of periprosthetic joint infection (PJI), the combination of valuable methods to evaluate infection appears to achieve a better diagnostic result. The objective of the present study was to evaluate the diagnostic value of serum interleukin (IL)-6 and C-reactive protein (CRP) for the diagnosis of PJI.

Methods: PubMed, Embase, and the Web of Science databases were searched for articles describing PJI diagnosis using serum IL-6 and CRP published between January 1990 and December 2019.

Results: Eight studies were included in the meta-analysis. The pooled sensitivity was 0.84 (95% confidence interval [CI], 0.80−0.88) for the combined method (serum IL-6 and CRP) in series and parallel approaches, 0.87 (95% CI, 0.82−0.90) for IL-6, and 0.84 (95% CI, 0.79−0.88) for CRP. The pooled specificity was 0.85 (95% CI, 0.82−0.88) for the combined method, 0.83 (95% CI, 0.79−0.87) for IL-6, and 0.83 (95% CI, 0.79−0.87) for CRP. The combined method had the highest value for the area under the curve (0.9453), followed by IL-6 (0.9237) and CRP (0.9074). Subgroup analyses showed that the sensitivity of the combined method in parallel tests was higher than that in IL-6 or CRP (94% vs. 89% and 84%, respectively). Serial testing of the combined method showed increased specificity compared to a single indicator (96% vs. 83% and 80%).

Conclusion: The combination of serum IL-6 and CRP was a reliable tool for the diagnosis of periprosthetic hip and knee infection, demonstrating a better diagnostic accuracy than single marker analysis.