3D-Printed Osteoinductive Polymeric Scaffolds with Optimized Architecture to Repair a Sheep Metatarsal Critical-Size Bone Defect.

The reconstruction of critical-size bone defects in long bones remains a challenge for clinicians. A new osteoinductive medical device is developed here for long bone repair by combining a 3D-printed architectured cylindrical scaffold made of clinical-grade polylactic acid (PLA) with a polyelectrolyte film coating delivering the osteogenic bone morphogenetic protein 2 (BMP-2). This film-coated scaffold is used to repair a sheep metatarsal 25-mm long critical-size bone defect. In vitro and in vivo biocompatibility of the film-coated PLA material is proved according to ISO standards. Scaffold geometry is found to influence BMP-2 incorporation. Bone regeneration is followed using X-ray scans, µCT scans, and histology. It is shown that scaffold internal geometry, notably pore shape, influenced bone regeneration, which is homogenous longitudinally. Scaffolds with cubic pores of ≈870 µm and a low BMP-2 dose of ≈120 µg cm-3 induce the best bone regeneration without any adverse effects. The visual score given by clinicians during animal follow-up is found to be an easy way to predict bone regeneration. This work opens perspectives for a clinical application in personalized bone regeneration.

Comparison of MRI-based response criteria and radiomics for the prediction of early response to transarterial radioembolization in patients with hepatocellular carcinoma.

PURPOSE: The purpose of this study was to evaluate the capabilities of radiomics using magnetic resonance imaging (MRI) data in the assessment of treatment response to 90yttrium transarterial radioembolization (TARE) in patients with locally advanced hepatocellular carcinoma (HCC) by comparison with predictions based on European Association for the Study of the Liver (EASL) criteria. PATIENTS AND METHODS: Twenty-two patients with HCC (19 men, 3 women; mean age: 66.7 ± 9.8 [SD]; age range: 37-82 years) who underwent contrast-enhanced MRI 4 ± 1 weeks before and 4 ± 4 weeks after TARE, were enrolled in this retrospective study. Regions of interest were placed manually along the contours of the treated tumor on each axial slice of arterial and portal phase images using the ITK-SNAP post-processing software. For each MRI, the Pyradiomics Python package was used to extract 107 radiomics features on both arterial and portal phases, and resulting delta-features were computed. The Mann-Whitney U test with Bonferroni correction was used to select statistically different features between responders and non-responders (i.e., those with progressive or stable disease) at 6-month follow-up, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Finally, for each selected feature, univariable logistic regression with leave-one-out cross validation procedure was used to perform receiver operating characteristic (ROC) curve analysis and compare radiomics parameters with MRI variables. RESULTS: According to mRECIST, 14 patients (14/22; 64%) were non-responders and 8 (8/22; 36%) were responders. Four radiomics parameters (long run emphasis, minor axis length, surface area, and gray level non-uniformity on arterial phase images) were the only predictors of early response. ROC curve analysis showed that long run emphasis was the best parameter for predicting early response, with 100% sensitivity (95% CI: 68-100) and 100% specificity (95% CI: 78-100). EASL morphologic criteria yielded 75% sensitivity (95% CI: 41-96%) and 93% specificity (95% CI: 69-100%). CONCLUSION: Radiomics allows identify marked differences between responders and non-responders, and could aid in the prediction of early treatment response following TARE in patients with HCC.

Cytocompatibility / Antibacterial Activity Trade-off for Knittable Wet-Spun Chitosan Monofilaments Functionalized by the In Situ Incorporation of Cu2+ and Zn2.

The wet spinning of cytocompatible, bioresorbable, and knittable chitosan (CTS) monofilaments would be advantageous for a variety of surgical applications. The complexation capacity of chitosan with Cu2+ or Zn2+ can be leveraged to enhance its antibacterial activity, but not at the expense of cytocompatibility. In this work, a wet-spinning process was adapted for the in situ incorporation of Cu2+ or Zn2+ with chitosan dopes to produce monofilaments at different drawing ratios (τtot) with various cation/glucosamine molar ratios, evaluated in the fibers (rCu,f and rZn,f). Cytocompatibility and antibacterial activity of wet-spun monofilaments were, respectively, quantified by in vitro live-dead assays on balb 3T3 and by different evaluations of the proliferation inhibition of Staphylococcus epidermidis (Gram+) and Escherichia coli (Gram-). Knittability was tested by a specific tensile test using a knitting needle and evaluated with an industrial knitting machine. It was found that rCu,f = 0.01 and rZn,f = 0.03 significantly increase the antibacterial activity without compromising cytocompatibility. Wet spinning with τtot = 1.6 allowed the production of knittable CTS-Cu monofilaments, as confirmed by knitting assays under industrial conditions.

Myocardial blood flows and reserves on solid state camera: Correlations with coronary history and cardiovascular risk factors.

OBJECTIVES: Study designed to test association between stress-induced myocardial blood flow (sMBF), resting MBF (rMBF), and MBF reserve (MFR) and coronary artery disease (CAD) in a population of CAD and non-coronary patients. Secondary objectives were to confront visual analysis and dynamic analysis and to explore potential association between MBF and several cardiovascular risk factors METHODS: A total of 155 patients who underwent dynamic myocardial perfusion imaging on a CZT camera were included. sMBF, rMBF, and MFR were evaluated, and cardiovascular risk was assessed. RESULTS: Significantly lower total sMBF and MFR were observed in CAD patient vs non-CAD patient. In comparison with visual analysis, lower sMBF were found in pathologic territory, lower rMBF in necrotic territory and lower MFR in necrotic ones. A significant correlation between total sMBF, rMBF and diabetes was found. CONCLUSION: sMBF and MFR as assessed on CZT gamma-cameras can be used to determine the coronary state. Low total sMBF might be an independent risk factor of coronaropathy. An inverse correlation was suggested between total sMBF and rMBF with diabetes.

Key Role of Personalized Dosimetry in Dose Adjustment for Selective Internal Radiotherapy: Retrospective Study of Patients Treated With 90Y Resin Microspheres.

PURPOSE: Selective internal radiotherapy with 90Y microspheres is widely used for the treatment of patients with liver cancer. A dosimetric analysis using the dosimetry software Simplicit90y (Boston Scientific, Natick, MA) was conducted to define doses to the tumor and healthy liver, and to determine a threshold tumor dose that could predict progression-free survival. METHODS: Patients experiencing hepatocellular carcinoma and treated with 90Y-labeled resin microspheres were included in a retrospective study. The time-to-progression of the target lesions (TTPLs) and overall survival (OS) were evaluated using Kaplan-Meier tests, and this comparison was based on a log-rank test. RESULTS: Twenty-four procedures for patients with portal vein thrombosis were realized. Median follow-up was 16 months. A threshold tumor dose of 125 Gy was determined with a sensitivity of 89% and a specificity of 100%. For patients with a tumor dose of less than 125 Gy, the median OS was 7.5 months (95% confidence interval [CI], 5-14 months) and the TTPL was 3 months (95% CI, 2-6 months) versus 33 months (95% CI, 22-39 months) and 23 months (95% CI, 7-38 months), respectively, for those with a tumor dose of 125 Gy or more (P = 0.002 and P = 0.0004). CONCLUSIONS: Personalized dosimetry based on 99mTc-MAA SPECT/CT is predictive of TTPL and OS in patients with hepatocellular carcinoma. Customized dosimetry software is essential to optimize treatment planning.

Prospective Comparison of 18-FDG PET/CT and Whole-Body MRI with Diffusion-Weighted Imaging in the Evaluation of Treatment Response of Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplant.

To compare the prognostic values of 18-FDG PET/CT (FDG-PET) and Whole-Body MRI with Diffusion-Weighted Imaging (WB-DW-MRI) in the evaluation of treatment response of Multiple Myeloma (MM) patients eligible for ASCT. Thirty patients with newly diagnosed MM prospectively underwent FDG-PET and WB-DW-MRI at baseline, after induction chemotherapy and after ASCT. Response on WB-DW-MRI was evaluated with the MY-RADS criteria. FDG-PET was considered positive if residual uptake was superior to liver uptake. Imaging results were not used for treatment modification. The impact of imaging results on PFS was analyzed. After a median follow-up of 32 months, 10 patients relapsed. With WB-DW-MRI, post-induction examination was positive in 3/25 and post-ASCT examination was positive in 3/27 patients. However, neither study showed prognostic impact on PFS. FDG-PET was positive in 5/22 post-induction and 3/26 patients post-ASCT, respectively. Positivity of FDG-PET, post-induction or post-ASCT, was associated with a shorter PFS (post-induction: median PFS 19 months vs. not reached, log-rank p = 0.0089; post-ASCT: median PFS 18 months vs. not reached, log-rank p = 0.0005). Preliminary results from this small, single-center, prospective study show that, whether performed post-induction or post-ASCT, FDG-PET has a higher prognostic value than WB-DW-MRI for treatment response evaluation of newly diagnosed MM.

18F-choline PET-computed tomography for the prediction of early treatment responses to transarterial radioembolization in patients with hepatocellular carcinoma.

BACKGROUND: Transarterial radioembolization (TARE) is widely used for the treatment of hepatocellular carcinoma (HCC), but early treatment response can be very difficult to assess. The aim was to evaluate 18F-fluorocholine PET/computed tomography (CT) to assess the treatment response in patients with intermediate or locally advanced HCC. METHODS: Between March 2019 and July 2020, nine HCC patients treated with TARE, who underwent PET/CT at baseline and 1 month after treatment, were enrolled. The maximum, mean (SUVmean), and peak (SUVpeak) standardized uptake value (SUV), SUV normalized by lean body mass (SUL), and total lesion glycolysis (TLG) were measured. Statistical analysis used the Mann-Whitney test to evaluate the differences in parameters between responders (partial and complete response) and nonresponders (stable or progressive disease) at the 6-month follow-up, according to the modified Response Evaluation Criteria in Solid Tumors. RESULTS: Three patients were nonresponders (progressive disease and stable disease) and six were responders. Delta SUVmean, delta SUL, and delta TLG could predict an early response (P = 0.02, P = 0.04, and P = 0.02, respectively). None of the pre-therapeutic parameters were correlated with the response. Post-therapeutic SUL, SUVmean, TLG, and SUVpeak were also predictive of the response. CONCLUSIONS: Our preliminary results showed that changes in certain metabolic parameters (from baseline PET to 1-month PET) are predictive of the response to TARE in HCC (Delta SUVmean, delta TLG, and delta SUL). The absence of post-treatment inflammation could lead to a better prediction than MRI evaluation. This study suggests that 1-month 18F-choline PET/CT could modify the clinical management predicting responders.Video Abstract: http://links.lww.com/NMC/A193.

Multicenter Pilot Study to Assess a Biphasic Calcium Phosphate Implant for Functional and Aesthetic Septorhinoplasty.

Importance: A validated biomaterial would have several medical advantages in septorhinoplasties requiring a large-volume graft such as avoiding donor site morbidity, making ambulatory surgery possible, and reducing surgical costs. Objective: To assess the safety and efficacy of a ceramic to treat saddle and crooked noses. The main endpoint was the biocompatibility of the implant. The secondary endpoint was its functional and aesthetic efficacy. Design, Setting, and Participants: The nasal septum (NASEPT) study is a pilot multicenter noncomparative prospective phase IIa clinical trial. The biomaterial tested was a biphasic calcium phosphate implant composed of 75% hydroxyapatite and 25% beta tri calcium phosphate. This versatile material can be used to replace septal skeleton when it is absent or nonusable. We included 25 patients with a multifractured osseous and cartilaginous framework after several traumas or surgeries. The implant placement technique was identical to an extracorporeal septoplasty through the external approach. Main Outcomes and Measures: The primary endpoint was the occurrence of expected adverse and severe adverse events. The secondary endpoints were clinical functional and aesthetic results and histological microscopic modifications. Results: Any extrusion, infection, pain, and epistaxis were observed. All implants were placed in a sagittal, straight, and solid position without extralobular depression. Comparisons between pre- and postoperative symptoms showed that nasal comfort (p < 10-4) and quality of life (p < 10-4) were dramatically improved in all patients. The nasolabial angle (p = 0.047) and the columellar projection (p = 0.024) were improved after surgery. Histological data showed little submucosal inflammation at 6 months with well-differentiated epithelium. The mean follow-up was 23 months: three patients underwent revision surgery for functional or aesthetic details and four implants were removed (16%) owing to a foreign body reaction between 17 and 74 months. Conclusion and Relevance: The NASEPT implant meets functional and aesthetic requirements in complex septorhinoplasties but its long-term biocompatibility needs to be improved. It could potentially avoid donor site morbidity.

Prospective Comparison of 18F-Choline Positron Emission Tomography/Computed Tomography (PET/CT) and 18F-Fluorodeoxyglucose (FDG) PET/CT in the Initial Workup of Multiple Myeloma: Study Protocol of a Prospective Imaging Trial.

BACKGROUND: The International Myeloma Working Group recommends the use of 18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for treatment response evaluation, as it is superior to magnetic resonance imaging (MRI). However, at initial staging, the sensitivity of FDG-PET remains inferior to that of MRI. Therefore, there is a need for an imaging technique that could have a sensitivity equal to that of MRI at diagnosis and could serve to evaluate therapy. 18F-choline has shown increased sensitivity when compared with 18-FDG, with about 75% more lesions detected in patients with relapsed or progressive multiple myeloma (MM). OBJECTIVE: Our primary objective is to prospectively compare the detection rate of bone lesions by 18F-choline PET/CT (FCH-PET) and FDG-PET in newly diagnosed MM. Our secondary objectives are to assess the accuracy of both PET modalities for the detection of bone lesions and the diagnosis of diffuse disease, to assess the detection rate of extramedullary lesions. METHODS: We will prospectively include 30 patients in a paired comparative accuracy study. Patients with de novo MM will undergo FCH-PET, FDG-PET, and whole-body MRI (WB-MRI) within a 3-week period. WB-MRI will be composed of conventional sequences on the spine and pelvis and of whole-body diffusion axial sequences. The following 6 skeletal areas will be defined: skull, sternum/costal grid, spine, pelvis, superior limbs, and inferior limbs. The number of focal lesions, their respective localization, and intensity of uptake will be retrieved for each skeletal area. Readings will be performed blinded from other imaging techniques. The reference standard will be WB-MRI. Focal lesions present on PET/CT but not on WB-MRI will require a decision made with a consensus of experts based on clinical and imaging data. The number of bone lesions and number of extramedullary lesions will be compared using the Wilcoxon test. The accuracy of FCH-PET and FDG-PET will be compared using the McNemar test. RESULTS: The study started in September 2019, and enrollment is ongoing. As of June 2020, 8 participants have been included. Data collection is expected to be completed in June 2021, and the results are expected to be available in December 2021. CONCLUSIONS: This study will assess if FCH-PET is superior to FDG-PET for the evaluation of MM tumor burden. This will pave the way for future prospective evaluations of the prognostic value of 18-FCH for treatment response evaluation in MM patients. Additionally, this work may provide new perspectives for better assessment of the risk of smoldering MM progressing to MM. TRIAL REGISTRATION: ClinicalTrials.gov NCT03891914; https://clinicaltrials.gov/ct2/show/NCT03891914. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17850.

Prospective comparison of 18-FDG PET/CT and whole-body diffusion-weighted MRI in the assessment of multiple myeloma.

Magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG 18F-FDG PET-CT) are standard procedures for staging multiple myeloma (MM). Diffusion-weighted sequences applied to whole-body MRI (WB-DWI) improve its sensitivity. We compared the number of MM bone focal lesions (FLs) detected by 18F-FDG PET-CT and WB-DWI and evaluated the diagnostic performance of 18F-FDG PET-CT for diffuse infiltration. Thirty newly diagnosed MM patients prospectively underwent 18F-FDG PET-CT and WB-DWI. The criteria for skeletal region positivity were ≥ 1 focal bone lesions (FLs) and/or diffuse disease. MRI with the MY-RADS criteria was used as a reference standard for the diagnosis of diffuse infiltration. 18F-FDG PET-CT and WB-DWI were both interpreted as positive in 28/30 patients with an agreement of 1.00 (95% CI 0.77-1.00) between the two methods. The mean numbers of FLs were 16.7 detected by 18F-FDG PET-CT and 23.9 detected by WB-DWI (P = 0.028). WB-DWI detected more FLs in the skull (P = 0.001) and spine (P = 0.006). Agreement assessed using the prevalence and bias-corrected kappa index was moderate (0.40-0.60) for the spine, sternum-ribs and upper limbs and substantial (0.60-0.80) for the pelvis and lower limbs. As regards the diagnosis of diffuse bone marrow infiltration, the sensitivity, specificity and accuracy of 18F-FDG PET-CT were 0.75, 0.79 and 0.77, respectively. Although WB-DWI detected more FLs than did 18F-FDG PET-CT, there was no difference in the detection of bone disease on a per-patient basis. 18F-FDG PET-CT showed high performance, including for evaluation of diffuse infiltration.

Comparison of Two Percutaneous Atrial Septal Defect Occluders for Device Healing and Nickel Release in a Chronic Porcine Model.

AIMS: To investigate the healing process and nickel release of the Hyperion occluder (Comed BV, Netherlands), as compared to the Amplatzer septal occluder (ASO) (St. Jude Medical Inc., St. Paul, MN, USA) in a chronic swine model. BACKGROUND: Some long-term complications occurring after percutaneous atrial septal defect (ASD) closure may be partially associated with an inappropriate healing of the device and increased nickel release. There is no direct comparative study of different occluders for healing and nickel release. METHODS: After percutaneous ASD creation, 12 pigs were implanted with 15 mm Hyperion (n = 6) and 15 mm ASO (n = 6) devices. After 1 month (n = 3 for each device) and 3 months (n = 3 for each device) of follow-up, device explantation was performed and healing was assessed using histopathological workup. Systemic and tissular nickel release was performed. RESULTS: Implantation was successful in 100% without complications. Device coverage was observed as early as 1 month after implantation and was almost complete after 3 months. A granulation tissue with a predominantly mononuclear inflammatory reaction was observed in contact with nitinol wires while an inflammatory reaction was seen in contact with textile fibers. We found no statistically significant difference between the 2 devices whether for histological grading scores or systemic nickel release, regardless to follow-up duration. CONCLUSIONS: In this preclinical study, we demonstrated that Amplatzer septal occluder and Hyperion occluder were not significantly different for device healing and nickel release processes.

In vitro comparison of three percutaneous atrial septal defect closure devices for endothelialisation and haemocompatibility.

BACKGROUND: Percutaneous device closure of atrial septal defect (ASD) is the gold-standard treatment, but several delayed complications may occur as a result of incomplete device endothelialisation. AIMS: In this in vitro study, we compared three ASD closure devices [Nit-Occlud® ASD-R (device 1); Hyperion™ ASDO (device 2); and Amplatzer™ Septal Occluder (device 3)] in terms of the endothelialisation process, using human endothelial progenitors cells (EPCs), and haemocompatibility. METHODS: EPCs from umbilical cord blood were extracted, cultured and characterised. Device samples were seeded with 100,000 cells/cm2. EPC adhesion was investigated at 3 and 24hours, and EPC proliferation was monitored, which allowed longitudinal follow-up (days 1-12). Haemocompatibility of device samples was assessed using a complement C3a assay and platelet and coagulation activation. RESULTS: With regard to EPC adhesion and proliferation, no statistically significant differences were found between the three devices. We observed for each device a significant time-dependent EPC proliferation, appearing at day 8 for devices 2 and 3 and day 10 for device 1. No complement or platelet activation occurred within 15minutes of contact with devices. However, there was minimal activation of coagulation for the three devices. CONCLUSIONS: In this in vitro study we showed that, despite the three ASD occluders having different device designs and coatings, adhesion and proliferation of human endothelial cells was similar for all devices. This should be further confirmed by similar studies including shear stress forces and anti-thrombotic treatments.

Choline PET/CT in Multiple Myeloma.

The field of multiple myeloma (MM) imaging has evolved. The International Myeloma Working Group recently recommended performing 18F-fluorodeoxyglucose glucose (18FDG) positron emission tomography/computed tomography (PET/CT) with the aim of staging MM patients at baseline and evaluating response to therapy. Novel oncological radiotracers such as 11C-Choline and 18F-Fluorocholine, have been studied in comparison with 18FDG, mostly in MM patients presenting with refractory disease or suspected relapse. Choline-based tracers may overcome some limitations of 18FDG, which include a lack of sensitivity in depicting skull lesions and the fact that 10% of MM patients are FDG-negative. The majority of MM lesions display a higher uptake of Choline than FDG. Also, in many situations, Choline may offer better lesion visualization, with a higher tumor to background ratio; however, various patterns of Choline and FDG uptake have been observed in MM and some limitations, notably as regards liver lesions, should be recognized. Overall, Choline may provide additional detection of up to 75% more lesions. This article aims to provide a comprehensive review of the potential role of Choline in multiple myeloma, as compared to FDG, encompassing Choline physiopathology as well as data from clinical studies.

Bioactive micropatterning of biomaterials for induction of endothelial progenitor cell differentiation: Acceleration of in situ endothelialization.

Synthetic grafts do not provide an appealing surface for endothelial cells to adhere and colonize the inner surface. To promote in situ endothelialization the following aspect has to be taken into account, endothelial progenitor cells (EPCs) needs to be mobilized on the surface of the graft. The surface of the graft has to be sufficiently biocompatible to create a prone environment for the EPCs to adhere, proliferate and, differentiate to form a layer and subsequently improve graft patency. In this work, two active molecules GRGDS and sitagliptin, were chosen for their abilities to recruit, enhance adhesion and induce differentiation of endothelial progenitor cells. They were grafted on PET surfaces in order to provide restrained cues triggering cell alignment and evaluate the influence of such structuration on EPCs fate. We then analyze cell behavior onto functionalized biomaterials. Their abilities to control EPCs fate were demonstrated via RT-qPCR, immunofluorescence, and enzymatic tests. The GRGDS/sitagliptin 100 × 10 surface enables to reduce the stemness phenotype on EPCs and induce the expression of endothelial lineage markers. These results highlight the importance of spatial patterning cues in guiding EPCs organization and function, which may have clinical relevance in the development of vascular grafts that promote patency.

Computational fluid dynamics simulation to compare large volume irrigation and continuous spraying during nasal irrigation.

BACKGROUND: Nasal irrigation is now widely recognized as a treatment for chronic rhinosinusitis and during the postoperative period. However, there are no guidelines for performing irrigation. This study used computational fluid dynamics (CFD) simulation objective physical parameters to optimize and increase the efficiency of nasal irrigation and to compare large-volume, manual, and gravity pressure irrigation vs small-volume continuous spraying. METHODS: A 3-dimensional (3D) sinonasal model was constructed from a healthy adult high-resolution computed tomography (CT) scan. The 3D nasal model was constructed using a tetrahedral and hex-dominant mesh grid with TGRID™ 16 (ANSYS Inc., Villeurbanne, France) software. A structured hex mesh was created inside the domain using the Hexcore meshing method. The final mesh had a total of 9.6 × 106 cells with an average size of 0.29 mm3 , or an average volume of 2.42 × 10-2 mm3 . Navier-Stokes equations were resolved with the standard k - ε model. RESULTS: Large-volume irrigation (15 mL/s) covered all zones (136 to 310 cm2 ) rapidly with strong shear stress and prolonged contact time (310 mPa 3.26 seconds for gravity mode and 280 mPa 3.35 seconds for manual pressure mode). Continuous spraying (3 mL/second) covered all areas (76 to 310 cm2 ) but with far less volume, more slowly, with low shear stress (50 mPa), and with shorter contact time (1.84 seconds). The surface wetted by time in contact was 135.4, 113.9, and 46.6 cm2 for gravity, manual pressure mode, and continuous spraying, respectively. CONCLUSION: CFD simulation visualizes the circulation of water during nasal irrigation and makes it possible to determine objective parameters to decide which mode of irrigation may be used.

Prognostic utility of pre-transplantation [18 F] fluorodeoxyglucose positron emission tomography/computed tomography in patients with diffuse large B-cell lymphoma who underwent rituximab, dexamethasone, high-dose cytarabine, carboplatin salvage chemotherapy.

We analysed the outcomes of 62 patients with refractory/relapsed diffuse large B-cell lymphoma (rrDLBCL) who had pre-transplantation fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after R-DHAC (rituximab, dexamethasone, high-dose cytarabine, carboplatin) salvage chemotherapy, and were evaluated using Deauville criteria and total lesion glycolysis (TLG). A positive pre-transplantation PET/CT with Deauville score of 5 was associated with shorter progression-free survival (PFS) (P = 0·01), while a Deauville score of 4 was not predictive of outcome. Only pre-transplant TLG was significantly associated with both PFS (P = 0·005) and overall survival (P = 0·03). TLG deserves to be further investigated in prospective studies.

Retrospective Study Comparing WBC scan and 18F-FDG PET/CT in Patients with Suspected Prosthetic Vascular Graft Infection.

OBJECTIVES: Prosthetic vascular graft infections (PVGIs) are associated with high mortality rates. To improve treatment outcome, an early and definite diagnosis is critical, and current diagnostic criteria are often insufficient. The accuracy of 2-deoxy-2-[fluorine-18]-fluoro-d-glucose positron emission tomography integrated with computed tomography (18F-FDG PET/CT) and white blood cell (WBC) scan for the diagnosis of PVGI were compared. METHODS: A retrospective single centre study was conducted on patients undergoing WBC scan and 18F-FDG PET/CT for a suspected PVGI between April 2013 and June 2016 at the Bordeaux University Hospital, France. The diagnostic value of both imaging tests was assessed for all grafts, using receiver operating characteristic (ROC) curve analysis. Images were independently interpreted by two nuclear medicine physicians blinded to the patients' clinical and other imaging data. RESULTS: Thirty-nine patients were included, of whom 15 had PVGI. Antibiotic treatment was started before nuclear imaging for 16 patients, including nine patients with a PVGI. The 96 grafts of these patients were analysed, and 19 were infected. The diagnostic value of the WBC scan was significantly higher than 18F-FDG PET/CT (ROC AUC = 0.902, 95% CI 0.824-0.980, and 0.759, CI 95% (0.659-0.858), respectively, p = .0071). Interobserver agreement was good for 18F-FDG PET/CT and excellent for WBC scan (kappa value of 0.76, 95% CI 0.62-0.9, and 0.97, 95% CI 0.92-1, respectively). Only one patient had a false negative 18F-FDG PET/CT result under antibiotic therapy. CONCLUSION: The WBC scan has a better diagnostic value than 18F-FDG PET/CT for PVGI diagnosis.

Cell and tissue responses at the interface with a chitosan hydrogel intended for vascular applications: in vitro and in vivo exploration.

AIMS: The need for small caliber vessels to treat cardiovascular diseases has grown. However, synthetic polymers perform poorly in small-diameter applications. Chitosan hydrogels can provide a novel biological scaffold for vascular engineering. The goal of this study was to explore host cell and tissue behavior at the interface with chitosan-based scaffolds in vitro and in vivo. METHODS AND RESULTS: in vitro, we assessed the ability of endothelial cells lining chitosan hydrogels to produce tissue factor (TF), thrombomodulin (TM) and nitric oxide. We showed that endothelial cells behave as a native endothelium since under stimulation, TF and TM expression increased and decreased, respectively. Endothelial cells seeded on chitosan produced nitric oxide, but no change was observed under stimulation. After in vivo subcutaneous implantation of chitosan hydrogels in rats, macrophage activation phenotypes, playing a crucial role in biomaterial/tissue, were explored by immunohistochemistry. Our results suggested a balance between pro- and anti-inflammatory signals since we observed an inflammatory response in favor of macrophage M2 phenotype. CONCLUSION: in vitro exploration of endothelial cell response at the interface with chitosan hydrogel showed a functional endothelium and in vivo exploration of tissue response revealed a biointegration of chitosan hydrogels.

In vitro Evidence of Improved Antimicrobial Efficacy of Silver and Triclosan Containing Vascular Grafts Compared with Rifampicin Soaked Grafts.

OBJECTIVES: The aim was to compare the antimicrobial efficacy of four different grafts: a standard graft (Intergard, IG), an IG graft soaked in rifampicin (IGrif), a silver impregnated graft (Intergard Silver, IGS), and a silver + triclosan impregnated graft (Intergard Synergy, IGSy). METHODS: This was a seven day in vitro study. The IG, IGrif, IGS, and IGSy grafts were each contaminated separately with the following microorganisms: Staphylococcus epidermidis, Methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans from both clinical and American Type Culture Collection (ATCC) origins. The in vitro antimicrobial efficacy was evaluated by time to kill assays at T0, T24h, T48h, T72h, and T168h. Bactericidal activity was defined as >3 log10 reduction factor (logRF). Additionally, Rifampicin, triclosan and silver resistance development were screened. RESULTS: As anticipated for the non-antimicrobial IG, all microorganism strains proliferated. The IGSy and the IGS showed a seven day bactericidal efficacy (>3 logRF) for all tested microorganisms. This efficacy was confirmed at all time points for IGSy only, demonstrating faster bactericidal efficacy than IGS. The IGrif demonstrated a seven day bactericidal efficacy against the ATCC MRSA only, while showing no activity against C. albicans and ATCC E. coli. Regarding ATCC S. epidermidis, clinical MRSA and clinical E. coli, IGrif, although bactericidal at earlier time points, lost its antimicrobial efficacy at seven days leading to the emergence of rifampicin resistant mutants in four of six, two of six, and two of six assays, respectively. Mutant strains were also detected in ATCC MRSA in one of six assays. No triclosan or silver resistance has emerged at T7days. CONCLUSION: For all microorganisms tested, the Synergy graft combining silver with triclosan demonstrated a more sustainable and efficient seven day antimicrobial activity than the rifampicin soaked graft. The emergence of rifampicin resistant mutants suggests preference for a Synergy graft over a graft soaked in rifampicin, to prevent or treat an infection when a biological solution is not feasible.