Risk of Major Amputation Following Application of Paclitaxel Coated Balloons in the Lower Limb Arteries : A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Objective: There have been concerns about the long term safety of paclitaxel coated devices in the lower limbs. A formal systematic review and meta-analysis of randomised controlled trials (RCTs) was performed to examine the long term risk of major amputation using paclitaxel coated balloons in peripheral arterial disease (PAD). Method: This systematic review was registered with PROSPERO (ID 227761). A broad bibliographic search was performed for RCTs investigating paclitaxel coated balloons in the peripheral arteries (femoropopliteal and infrapopliteal) for treatment of intermittent claudication or critical limb ischaemia (CLI). The literature search was last updated on 20 February 2021 without any restrictions on publication language, date, or status. Major amputations were analysed with time to event methods employing one and two stage models. Sensitivity and subgroup analyses, combinatorial meta-analysis, and a multivariable dose response meta-analysis to examine presence of a biological gradient were also performed. Results: In all, 21 RCTs with 3 760 lower limbs were analysed (52% intermittent claudication and 48% CLI; median follow up two years). There were 87 major amputations of 2 216 limbs in the paclitaxel arms (4.0% crude risk) compared with 41 major amputations in 1 544 limbs in the control arms (2.7% crude risk). The risk of major amputation was significantly higher for paclitaxel coated balloons with a hazard ratio (HR) of 1.66 (95% CI 1.14 - 2.42; p = .008, one stage stratified Cox model). The prediction interval was 95% CI 1.10 - 2.46 (two stage model). The observed amputation risk was consistent for both femoropopliteal (p = .055) and infrapopliteal (p = .055) vessels. Number needed to harm was 35 for CLI. There was good evidence of a significant non-linear dose response relationship with accelerated risk per cumulative paclitaxel dose (chi square model p = .007). There was no evidence of publication bias (p = .80) and no significant statistical heterogeneity between studies (I-2 = 0%, p = .77). Results were stable across sensitivity analyses (different models and subgroups based on anatomy and clinical indication and excluding unpublished trials). There were no influential single trials. Level of certainty in evidence was downrated from high to moderate because of sparse events in some studies. Conclusion: There appears to be heightened risk of major amputation after use of paclitaxel coated balloons in the peripheral arteries. Further investigations are warranted urgently.Peer reviewe

Dataset on FAP-induced emergence of spontaneous metastases and on the preparation of activatable FAP-targeting immunoliposomes to detect the metastases

The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma. The raw and processed data presented herein is related to a research article entitled “Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases” (F.L. Tansi, R. Rüger, C. Böhm, R.E. Kontermann, U.K. Teichgraeber, A. Fahr, I. Hilger, 2016) [1]. Furthermore, evidence for the detection of FAP-expressing tumor cells and cells of the tumor stroma by activatable FAP-targeting liposomes is presented in this dataset

The role of gadolinium in magnetic resonance imaging for early prostate cancer diagnosis: A diagnostic accuracy study.

ObjectiveProstate lesions detected with multiparametric magnetic resonance imaging (mpMRI) are classified for their malignant potential according to the Prostate Imaging-Reporting And Data System (PI-RADS™2). In this study, we evaluate the diagnostic accuracy of the mpMRI with and without gadolinium, with emphasis on the added diagnostic value of the dynamic contrast enhancement (DCE).Materials and methodsThe study was retrospective for 286 prostate lesions / 213 eligible patients, n = 116/170, and 49/59% malignant for the peripheral (Pz) and transitional zone (Tz), respectively. A stereotactic MRI-guided prostate biopsy served as the histological ground truth. All patients received a mpMRI with DCE. The influence of DCE in the prediction of malignancy was analyzed by blinded assessment of the imaging protocol without DCE and the DCE separately.ResultsSignificant (CSPca) and insignificant (IPca) prostate cancers were evaluated separately to enhance the potential effects of the DCE in the detection of CSPca. The Receiver Operating Characteristics Area Under Curve (ROC-AUC), sensitivity (Se) and specificity (Spe) of PIRADS-without-DCE in the Pz was 0.70/0.47/0.86 for all cancers (IPca and CSPca merged) and 0.73/0.54/0.82 for CSPca. PIRADS-with-DCE for the same patients showed ROC-AUC/Se/Spe of 0.70/0.49/0.86 for all Pz cancers and 0.69/0.54/0.81 for CSPca in the Pz, respectively, p>0.05 chi-squared test. Similar results for the Tz, AUC/Se/Spe for PIRADS-without-DCE was 0.75/0.61/0.79 all cancers and 0.67/0.54/0.71 for CSPca, not influenced by DCE (0.66/0.47/0.81 for all Tz cancers and 0.61/0.39/0.75 for CSPca in Tz). The added Se and Spe of DCE for the detection of CSPca was 88/34% and 78/33% in the Pz and Tz, respectively.ConclusionDCE showed no significant added diagnostic value and lower specificity for the prediction of CSPca compared to the non-enhanced sequences. Our results support that gadolinium might be omitted without mitigating the diagnostic accuracy of the mpMRI for prostate cancer

Dataset on the role of endoglin expression on melanin production in murine melanoma and on the influence of melanin on optical imaging

The underlying data demonstrates that the expression of endoglin in murine melanoma cells influences melanin production in the cells. Also, the data shows that melanin production is further increased when the cells are subcutaneously implanted in mice models and that the high melanin production prevents detection of the cells by fluorescence imaging. The processed data presented herein is related to a research article by Tansi et al. (2018) entitled “Endoglin based in vivo near-infrared fluorescence imaging of tumor models in mice using activatable liposomes”

Risk of Major Amputation Following Application of Paclitaxel Coated Balloons in the Lower Limb Arteries: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Objective: There have been concerns about the long term safety of paclitaxel coated devices in the lower limbs. A formal systematic review and meta-analysis of randomised controlled trials (RCTs) was performed to examine the long term risk of major amputation using paclitaxel coated balloons in peripheral arterial disease (PAD). Method: This systematic review was registered with PROSPERO (ID 227761). A broad bibliographic search was performed for RCTs investigating paclitaxel coated balloons in the peripheral arteries (femoropopliteal and infrapopliteal) for treatment of intermittent claudication or critical limb ischaemia (CLI). The literature search was last updated on 20 February 2021 without any restrictions on publication language, date, or status. Major amputations were analysed with time to event methods employing one and two stage models. Sensitivity and subgroup analyses, combinatorial meta-analysis, and a multivariable dose response meta-analysis to examine presence of a biological gradient were also performed. Results: In all, 21 RCTs with 3 760 lower limbs were analysed (52% intermittent claudication and 48% CLI; median follow up two years). There were 87 major amputations of 2 216 limbs in the paclitaxel arms (4.0% crude risk) compared with 41 major amputations in 1 544 limbs in the control arms (2.7% crude risk). The risk of major amputation was significantly higher for paclitaxel coated balloons with a hazard ratio (HR) of 1.66 (95% CI 1.14 - 2.42; p = .008, one stage stratified Cox model). The prediction interval was 95% CI 1.10 - 2.46 (two stage model). The observed amputation risk was consistent for both femoropopliteal (p = .055) and infrapopliteal (p = .055) vessels. Number needed to harm was 35 for CLI. There was good evidence of a significant non-linear dose response relationship with accelerated risk per cumulative paclitaxel dose (chi square model p = .007). There was no evidence of publication bias (p = .80) and no significant statistical heterogeneity between studies (I-2 = 0%, p = .77). Results were stable across sensitivity analyses (different models and subgroups based on anatomy and clinical indication and excluding unpublished trials). There were no influential single trials. Level of certainty in evidence was downrated from high to moderate because of sparse events in some studies. Conclusion: There appears to be heightened risk of major amputation after use of paclitaxel coated balloons in the peripheral arteries. Further investigations are warranted urgently

Modification of Aminosilanized Superparamagnetic Nanoparticles: Feasibility of Multimodal Detection Using 3T MRI, Small Animal PET, and Fluorescence Imaging

The aim of our study was to modify an aminosilane-coated superparamagnetic nanoparticle for cell labeling and subsequent multimodal imaging using magnetic resonance imaging (MRI), positron emission tomography (PET), and fluorescent imaging in vivo

Ultrashort echo time MRI of the lung in children and adolescents: comparison with non-enhanced computed tomography and standard post-contrast T1w MRI sequences

Objectives!#!To compare the diagnostic value of ultrashort echo time (UTE) magnetic resonance imaging (MRI) for the lung versus the gold standard computed tomography (CT) and two T1-weighted MRI sequences in children.!##!Methods!#!Twenty-three patients with proven oncologic disease (14 male, 9 female; mean age 9.0 + / - 5.4 years) received 35 low-dose CT and MRI examinations of the lung. The MRI protocol (1.5-T) included the following post-contrast sequences: two-dimensional (2D) incoherent gradient echo (GRE; acquisition with breath-hold), 3D volume interpolated GRE (breath-hold), and 3D high-resolution radial UTE sequences (performed during free-breathing). Images were evaluated by considering image quality as well as distinct diagnosis of pulmonary nodules and parenchymal areal opacities with consideration of sizes and characterisations.!##!Results!#!The UTE technique showed significantly higher overall image quality, better sharpness, and fewer artefacts than both other sequences. On CT, 110 pulmonary nodules with a mean diameter of 4.9 + / - 2.9 mm were detected. UTE imaging resulted in a significantly higher detection rate compared to both other sequences (p < 0.01): 76.4% (84 of 110 nodules) for UTE versus 60.9% (67 of 110) for incoherent GRE and 62.7% (69 of 110) for volume interpolated GRE sequences. The detection of parenchymal areal opacities by the UTE technique was also significantly higher with a rate of 93.3% (42 of 45 opacities) versus 77.8% (35 of 45) for 2D GRE and 80.0% (36 of 45) for 3D GRE sequences (p < 0.05).!##!Conclusion!#!The UTE technique for lung MRI is favourable in children with generally high diagnostic performance compared to standard T1-weighted sequences as well as CT. Key Points • Due to the possible acquisition during free-breathing of the patients, the UTE MRI sequence for the lung is favourable in children. • The UTE technique reaches higher overall image quality, better sharpness, and lower artefacts, but not higher contrast compared to standard post-contrast T1-weighted sequences. • In comparison to the gold standard chest CT, the detection rate of small pulmonary nodules small nodules ≤ 4 mm and subtle parenchymal areal opacities is higher with the UTE imaging than standard T1-weighted sequences