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Background Standard sentinel lymph node procedure (SNP) in pediatric cancer consists of a preoperative injection with 99mtechnetium nanocolloid in combination with an optional intraoperative injection with blue dye. However, blue dye has disadvantages, and the detection rate is low, with only 60% of sentinel lymph nodes (SLNs) staining blue. In adult oncology, fluorescence imaging using indocyanine green (ICG) has been shown to be a safe and accurate method for visual detection of SLNs, with a higher sensitivity (up to 97%) compared with blue dye. Therefore, our aim is to determine the feasibility of the addition of ICG to 99mtechnetium nanocolloid (ICG–TC) for visual detection of SLN in pediatric patients. Methods A total of 15 pediatric patients with melanoma, squamous cell carcinoma, and sarcoma were prospectively included. Preoperatively, patients were injected with ICG–TC and imaging with lymphoscintigraphy and single-photon emission computed tomography– computed tomography was performed. Intraoperatively, SLN was detected with fluorescence and the gamma probe. Postoperatively, fluorescence was quantified by tumor-to-background ratio (TBR) and surgeons evaluated the use of ICG using a standardized questionnaire. Results In 10/15 (67%) patients, SLNs were visible transcutaneously. Of all intraoperatively detected SLNs, 35/37 (95%) were fluorescent and 37/37 (100%) were radioactive. Furthermore, ICG–TC led to the identification of six additional SLNs as compared with preoperative imaging. The median TBR in vivo was 6.5 (IQR 5.3). The surgical evaluation showed that ICG assisted in SLN detection and was easy to use. Conclusions ICG–TC for the SNP is a feasible procedure in pediatric patients. It showed an accurate detection rate, was helpful for visual guidance, and no adverse events occurred.

Background Our aim is to show whether the sentinel node procedure (SNP) is recommendable for pediatric patients with extremity rhabdomyosarcoma (RMS). Lymph node metastases are an important prognostic factor in pediatric patients with extremity RMS. Accurate nodal staging is necessary to treat the patient accordingly. An alternative to the current recommended lymph node sampling is the sentinel node procedure (SNP). Methods A systematic review was performed summarizing all published cases of SNP in addition to 13 cases from our hospital and 8 cases from two other hospitals that have not been published before. Results For all patients (n = 55), at least one SLN was identified, but the SNP technique used was not uniform. The SNP changed the nodal classification of eight patients (17.0%) and had a false-negative rate of 10.5%. Conclusions The SNP is recommendable for pediatric patients with extremity RMS. It can change lymph node status and can be used to sample patients in a more targeted way than nodal sampling alone. Therefore, we recommend use of the SNP in addition to clinical and radiological nodal assessment for pediatric patients with extremity RMS.

The incidence of central venous catheter (CVC)-related bloodstream infections is high in patients requiring a long-term CVC. Therefore, infection prevention is of the utmost importance. The aim of this study was to provide an updated overview of randomized controlled trials (RCTs) comparing the efficacy of taurolidine containing lock solutions (TL) to other lock solutions for the prevention of CVC-related bloodstream infections in all patient populations. On 15th February 2021, PubMed, Embase and The Cochrane Library were searched for RCTs comparing the efficacy of TLs for the prevention of CVC-related bloodstream infections with other lock solutions. Exclusion criteria were non-RCTs, studies describing

Sarcomas are a rare heterogeneous group of malignant neoplasms of mesenchymal origin which represent approximately 13% of all cancers in pediatric patients. The most prevalent pediatric bone sarcomas are osteosarcoma (OS) and Ewing sarcoma (ES). Rhabdomyosarcoma (RMS) is the most frequently occurring pediatric soft tissue sarcoma. The median age of OS and ES is approximately 17 years, so this disease is also commonly seen in adults while non-pleiomorphic RMS is rare in the adult population. The mainstay of all treatment regimens is multimodal treatment containing chemotherapy, surgical resection, and sometimes (neo)adjuvant radiotherapy. A clear resection margin improves both local control and overall survival and should be the goal during surgery with a curative intent. Real-time intraoperative fluorescence-guided imaging could facilitate complete resections by visualizing tumor tissue during surgery. This review evaluates whether non-targeted and targeted fluorescence-guided surgery (FGS) could be beneficial for pediatric OS, ES, and RMS patients. Necessities for clinical implementation, current literature, and the positive as well as negative aspects of non-targeted FGS using the NIR dye Indocyanine Green (ICG) were evaluated. In addition, we provide an overview of targets that could potentially be used for FGS in OS, ES, and RMS. Then, due to the time- and cost-efficient translational perspective, we elaborate on the use of antibody-based tracers as well as their disadvantages and alternatives. Finally, we conclude with recommendations for the experiments needed before FGS can be implemented for pediatric OS, ES, and RMS patients.

Sentinel node procedures (SNP) are performed with the use of tracer-agents, mainly radio-colloid and/or blue dye. Fluorescent agents have emerged as a new tracer-agent to identify the SLN intra-operatively with near-infrared imaging. Our aim is to compare the detection rate of fluorescent agents to current "golden standards" (blue dye and/or radio-colloid) for the SNP by means of a systematic review and meta-analysis without any restrictions based on tumor type.A systematic search in PubMed, Embase and The Cochrane Library was performed. Articles that compared the detection rates of fluorescent agents with radio-colloid and/or blue dye were included. Meta-analyses were performed for breast, gynecological and dermatological cancer using a random effects model.In total 6195 articles were screened which resulted in a final inclusion of 55 articles. All studies used indocyanine green (ICG) as fluorescent agent. Meta-analyses comparing ICG with blue dye showed a significant and clinically relevant difference in detection rate in favor of ICG, for both breast, dermatological and gynecological cancer. Meta-analyses comparing ICG with radio-colloid did not show any significant differences, with the exception of ICG versus radio-colloid + blue dye for the bilateral SLN detection in gynecological cancer.Near-infrared fluorescence imaging using ICG provides a higher detection rate compared to blue dye for the SNP in a range of different tumor types. SLN detection rates of ICG are comparable to radiocolloid. Due to their complementary characteristics in terms of spatial resolution and transdermal sensitivity, we suggest to use a combination of both ICG and a radio-colloid. (C) 2020 The Authors. Published by Elsevier Ltd.

The protein clusterin has been implicated in the molecular alterations that occur in articular cartilage during osteoarthritis (OA). Clusterin exists in two isoforms with opposing functions, and their roles in cartilage have not been explored. The secreted form of clusterin (sCLU) is a cytoprotective extracellular chaperone that prevents protein aggregation, enhances cell proliferation and promotes viability, whereas nuclear clusterin acts as a pro-death signal. Therefore, these two clusterin isoforms may be putative molecular markers of repair and catabolic responses in cartilage and the ratio between them may be important. In this study, we focused on sCLU and used established, pathophysiologically relevant, in vitro models to understand its role in cytokine-stimulated cartilage degradation. The secretome of equine cartilage explants, osteochondral biopsies and isolated unpassaged chondrocytes was analyzed by western blotting for released sCLU, cartilage oligomeric protein (COMP) and matrix metalloproteinases (MMP) 3 and 13, following treatment with the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α. Release of sulfated glycosaminoglycans (sGAG) was determined using the dimethylmethylene blue assay. Clusterin messenger RNA (mRNA) expression was quantified by quantitative real-time polymerase chain reaction. MMP-3, MMP-13, COMP, and sGAG release from explants and osteochondral biopsies was elevated with cytokine treatment, confirming cartilage degradation in these models. sCLU release was attenuated with cytokine treatment in all models, potentially limiting its cytoprotective function. Clusterin mRNA expression was down-regulated 7-days post cytokine stimulation. These observations implicate sCLU in catabolic responses of chondrocytes, but further studies are required to evaluate its role in OA and its potential as an investigative biomarker.

Background Among the currently available biochemical markers for osteoarthritis (OA), urinary collagen type II C-telopeptide (uCTX-II) is one of the most frequently investigated markers1. Much research has been performed into the performance of uCTX-II, but most of it in relatively small cohort studies1. Therefore, we performed a meta-analysis to summarize uCTX-II studies in a quantitative way. Objectives To perform a meta-analysis of the performance of uCTX-II as a biomarker for diagnosing knee osteoarthritis (KOA) and its association with radiographic KOA severity. Furthermore, to look for patient and study characteristics that determine uCTX-II performance. Methods Medline and Embase databases were searched for studies into uCTX-II levels in adult subjects with radiographic KOA according to the Kellgren and Lawrence (K&L) classification system. uCTX-II levels were compared between subjects with KOA K&L ≥2 versus healthy control subjects and between subjects with KOA K&L 2 versus K&L 3–4 (i.e. moderate vs severe KOA). Controls were either selected based on lack of knee symptoms, based on K&L score, or were randomly selected from the general population. Differences between KOA subgroups were expressed as standardized mean differences (SMD). Subgroup analyses were performed to compare uCTX-performance between genders, ethnicities, and large and small studies. Differences between subgroups were considered relevant when SMDs differed >25% between groups. Results 2035 Studies were screened for eligibility, of which ten studies were included. A moderate pooled SMD of 0.52 (confidence interval (CI): 0.40–0.65, P Conclusions This is the first meta-analysis of uCTX-II performance in subjects with radiographic KOA. It appeared that uCTX-II levels can distinguish with moderate strength between radiographic KOA subjects and controls. Moreover, uCTX-II levels are consistently increased in severe versus moderate radiographic KOA. Female gender and Caucasian ethnicity were found to enhance uCTX-II performance in distinguishing radiographic KOA from controls. Yet, the number of studies was relatively small and criteria for KOA and control subjects differed between studies. References Van Spil WE, DeGroot J, Lems WF, Oostveen JCM, Lafeber FPJG. Serum and urinary biochemical markers for knee and hip-osteoarthritis: A systematic review applying the consensus BIPED criteria. Osteoarthr Cartil 2010;18(5):605–12. Doi: 10.1016/j.joca.2010.01.012. Disclosure of Interest None declared

Background It is hypothesized that patients with knee osteoarthritis (OA) can be classified into different phenotypes. Knowledge of these phenotypes may contribute to developing effective targeted treatment strategies. Objectives To identify different longitudinal phenotypes of knee OA using biochemical markers and to compare these phenotypes with regard to radiographic joint space loss (JSL) and/or pain progression. Methods Baseline, 1-year, and 2-year biochemical marker data from the FNIH OA Biomarker Consortium were used. This consortium is a nested case-control study of 600 subjects with one symptomatic index knee showing radiographic OA changes of Kellgren and Lawrence grade 1 to 3 1 . Subjects were classified as either JSL progressors, pain progressors, JSL+pain progressors, or non-progressors according to predefined criteria (pain progression=persistent increase in WOMAC pain≥9 points (0–100 scale) from baseline to 2, 3 or 4 years, JSL progression=decrease in JSW≥0.7mm from baseline to 2, 3 or 4 years). Biochemical markers included in the current analysis were sCTX-I, uαCTX-I, uβCTX-I, sNTX-I, uCTX-II, sCPII, sC2C, sC1,2C, sColl2–1 NO2, sCOMP, sHA, and sMMP (u=urinary, s=serum). First, using principal component analysis (PCA), the individual markers were reduced into a number of clusters of markers (components) that may represent common underlying domains. Second, a hierarchical cluster analysis (HCA) was performed to differentiate between longitudinal courses (phenotypes) of these marker clusters. The optimum number was determined from the additive value of each newly identified phenotype as compared to already identified phenotypes. Third, these longitudinal phenotypes were compared with regard to percentages of patients in each of the JSL and/or pain progression categories. Results PCA showed an optimal solution of three components. Looking at the markers that loaded maximally onto each of the components, they were interpreted as cluster of bone (sCTX-I, uαCTX-I, uβCTX-I, sNTX-I, uCTX-II), cartilage (sCPII, sC2C, sC1,2C, sColl2–1 NO2), and synovial (sCOMP, sHA, and sMMP) metabolism, respectively. HCA revealed an optimum of seven longitudinal phenotypes. Based on the relative predominance of the component(s) throughout follow-up, phenotypes were named “high bone”, “high cartilage”, “high synovium”, “low cartilage”, “low synovium”, “low bone, cartilage and synovium” and “low bone and high synovium” phenotype, respectively (Figure 1, dendrogram and heatmap). Phenotypes differed with regard to percentages of patients in JSL and/or pain progression categories (Figure 1, pie charts) as well as other demographic, clinical, and radiographic parameters (data not shown). Conclusions Seven longitudinal phenotypes of knee OA could be identified based on biochemical markers representing bone, cartilage and synovial metabolism. These phenotypes showed relevant differences in other characteristics, such as JSL and/or pain progression. References Kraus VB, Collins JE, Hargrove D, et al. Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium. Ann Rheum Dis. 2016. Disclosure of Interest None declared