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  1. Article ; Online: HUNTER: Sensitive Automated Characterization of Proteolytic Systems by N Termini Enrichment from Microscale Specimen.

    Uzozie, Anuli C / Tsui, Janice / Lange, Philipp F

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2456, Page(s) 95–122

    Abstract: Proteolysis occurs at low frequency in the cellular environment. Protein N termini reveal essential mechanisms associated with cellular functions, and are useful indicators to track dysfunctional regulation of proteins and pathways in diseases. N ... ...

    Abstract Proteolysis occurs at low frequency in the cellular environment. Protein N termini reveal essential mechanisms associated with cellular functions, and are useful indicators to track dysfunctional regulation of proteins and pathways in diseases. N terminomics has so far relied on labor-intensive methods, which require relatively large starting sample amounts rendering it ill-suited for high-throughput systems biology studies. Here, we describe protocols for the first scalable and automatable method for sensitive enrichment and identification of N termini from minute samples.
    MeSH term(s) Peptide Hydrolases/metabolism ; Protein Processing, Post-Translational ; Proteolysis ; Proteome/metabolism ; Proteomics/methods
    Chemical Substances Proteome ; Peptide Hydrolases (EC 3.4.-)
    Language English
    Publishing date 2022-05-25
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2124-0_8
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  2. Article ; Online: Current pharmacotherapy management of children and adults with pericarditis: Prospectus for improved outcomes.

    Schwier, Nicholas C / Tsui, Janice / Perrine, Jordan A / Guidry, Corey M / Mathew, Julia

    Pharmacotherapy

    2021  Volume 41, Issue 12, Page(s) 1041–1055

    Abstract: ... such as C-reactive protein and adverse drug event monitoring, are also important toward balancing efficacy ...

    Abstract Pericarditis is the most common inflammatory pericardial disease in both children and adults. Since the 2015 European Society of Cardiology Guidelines for the diagnosis and management of pericardial disease were published, there have been significant updates to management. Pharmacotherapy has been historically reserved for idiopathic pericarditis (IP). However, there has been increasing use of pharmacotherapies, such as anti-inflammatory therapies, colchicine, and immunotherapies for other causes of pericarditis, such as post-cardiac injury syndromes (PCIS). Nevertheless, the quality of data varies depending on PCIS or idiopathic etiologies, as well as the adult and pediatric population. High-dose anti-inflammatory therapies should be used to manage symptoms associated with either etiology of pericarditis in both adults and children, but do not ameliorate the inflammatory disease process. Choice of anti-inflammatory should be guided by drug-drug/disease interactions, cost, tolerability, patient age, and should be tapered accordingly over several weeks to months. Colchicine should be added as adjuvant therapy to anti-inflammatory therapies in adults and children with IP, as it has been shown to lower the risk of recurrence, reduce pericarditis symptoms, and improve morbidity. Colchicine is also reasonable to add to adults and children with pericarditis secondary to PCIS. Systemic glucocorticoids increase risk of recurrence in adults and children with IP and are reserved for second-line treatment in acute and recurrent IP; they are generally avoided in PCIS. Immunotherapies are regarded as third-line for recurrent IP in adults and children. Limited evidence exists to support their use in patients with pericarditis from PCIS. Pharmacovigilance strategies, such as C-reactive protein and adverse drug event monitoring, are also important toward balancing efficacy and safety of the various strategies used to manage pericarditis in adults and children.
    MeSH term(s) Adult ; Child ; Humans ; Pericarditis/drug therapy ; Treatment Outcome
    Language English
    Publishing date 2021-12-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 603158-4
    ISSN 1875-9114 ; 0277-0008
    ISSN (online) 1875-9114
    ISSN 0277-0008
    DOI 10.1002/phar.2640
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  3. Article: Multi-omic profiling of the leukemic microenvironment shows bone marrow interstitial fluid is distinct from peripheral blood plasma.

    Nierves, Lorenz / Guo, Jian / Chen, Siyuan / Tsui, Janice / Uzozie, Anuli C / Bush, Jonathan W / Huan, Tao / Lange, Philipp F

    Experimental hematology & oncology

    2022  Volume 11, Issue 1, Page(s) 56

    Abstract: Background: The bone marrow is the place of hematopoiesis with a microenvironment that supports lifelong maintenance of stem cells and high proliferation. It is not surprising that this environment is also favourable for malignant cells emerging in the ... ...

    Abstract Background: The bone marrow is the place of hematopoiesis with a microenvironment that supports lifelong maintenance of stem cells and high proliferation. It is not surprising that this environment is also favourable for malignant cells emerging in the bone marrow or metastasizing to it. While the cellular composition of the bone marrow microenvironment has been extensively studied, the extracellular matrix and interstitial fluid components have received little attention. Since the sinusoids connect the bone marrow interstitial fluid to the circulation, it is often considered to have the same composition as peripheral blood plasma. Stark differences in the cellular composition of the bone marrow and peripheral blood with different secretory capacities would however suggest profound differences.
    Methods: In this study we set out to better define if and how the bone marrow interstitial fluid (BMIF) compares to the peripheral blood plasma (PBP) and how both are remodeled during chemotherapy. We applied a multi-omic strategy to quantify the metabolite, lipid and protein components as well as the proteolytic modification of proteins to gain a comprehensive understanding of the two compartments.
    Results: We found that the bone marrow interstitial fluid is clearly distinct from peripheral blood plasma, both during active pediatric acute lymphoblastic leukemia and following induction chemotherapy. Either compartment was shaped differently by active leukemia, with the bone marrow interstitial fluid being rich in extracellular vesicle components and showing protease dysregulation while the peripheral blood plasma showed elevation of immune regulatory proteins. Following chemotherapy, the BMIF showed signs of cellular remodeling and impaired innate immune activation while the peripheral blood plasma was characterized by restored lipid homeostasis.
    Conclusion: This study provides a comprehensive examination of the fluid portion of the acute lymphoblastic leukemia microenvironment and finds the contribution of either microenvironment to tumourigenesis.
    Language English
    Publishing date 2022-09-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2669066-4
    ISSN 2162-3619
    ISSN 2162-3619
    DOI 10.1186/s40164-022-00310-0
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  4. Article ; Online: Experimental models of abdominal aortic aneurysms.

    Tsui, Janice C

    The open cardiovascular medicine journal

    2010  Volume 4, Page(s) 221–230

    Abstract: Despite being a leading cause of death in the West, the pathophysiology of abdominal aortic aneurysms (AAA) is still incompletely understood. Pharmacotherapy to reduce the growth of small AAAs is limited and techniques for repairing aneurysms continue to ...

    Abstract Despite being a leading cause of death in the West, the pathophysiology of abdominal aortic aneurysms (AAA) is still incompletely understood. Pharmacotherapy to reduce the growth of small AAAs is limited and techniques for repairing aneurysms continue to evolve. Experimental models play a key role in AAA research, as they allow a detailed evaluation of the pathogenesis of disease progression. This review focuses on in vivo experimental models, which have improved our understanding of the potential mechanisms of AAA development and contributed to the advancement of new treatments.
    Language English
    Publishing date 2010-11-26
    Publishing country United Arab Emirates
    Document type Journal Article
    ZDB-ID 2396047-4
    ISSN 1874-1924 ; 1874-1924
    ISSN (online) 1874-1924
    ISSN 1874-1924
    DOI 10.2174/1874192401004010221
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  5. Article ; Online: 'No-touch' saphenous vein harvesting improves graft performance in patients undergoing coronary artery bypass surgery: a journey from bedside to bench.

    Dashwood, Michael R / Tsui, Janice C

    Vascular pharmacology

    2013  Volume 58, Issue 3, Page(s) 240–250

    Abstract: The saphenous vein is the most commonly used conduit in patients undergoing coronary artery bypass surgery yet its patency is inferior to the internal thoracic artery. Vascular damage inflicted to the vein when using conventional harvesting techniques ... ...

    Abstract The saphenous vein is the most commonly used conduit in patients undergoing coronary artery bypass surgery yet its patency is inferior to the internal thoracic artery. Vascular damage inflicted to the vein when using conventional harvesting techniques affects its structure. Endothelial denudation is associated with early vein graft failure while damage of the outermost vessel layers has adverse long-term effects on graft performance. While many in vitro and in vivo experimental studies aimed at improving vein graft patency have been performed to date no significant 'bench to bedside' advances have been made. Among experimental strategies employed is the use of pharmacological agents, gene targeting and external stents. A 'no-touch' technique, where the saphenous vein is removed with minimal trauma and normal architecture preserved, produces a superior graft with long term patency comparable to the internal thoracic artery. Interestingly, many experimental studies are aimed at repairing or replacing those regions of the saphenous vein damaged when harvesting conventionally. 'No-touch' harvesting is superior in coronary artery bypass patients with long-term data published 5years ago. Here we describe a 'bedside to bench' situation where the mechanisms underlying the improved performance of 'no touch' saphenous vein grafts in patients have been studied in the laboratory.
    MeSH term(s) Animals ; Coronary Artery Bypass/methods ; Coronary Artery Disease/surgery ; Endothelium, Vascular/metabolism ; Humans ; Mammary Arteries/transplantation ; Saphenous Vein/transplantation ; Time Factors ; Tissue and Organ Harvesting/methods ; Treatment Outcome ; Vascular Patency
    Language English
    Publishing date 2013-03
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2082846-9
    ISSN 1879-3649 ; 1537-1891 ; 1879-3649
    ISSN (online) 1879-3649 ; 1537-1891
    ISSN 1879-3649
    DOI 10.1016/j.vph.2012.07.008
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    Zs.A 591: Show issues Location:
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  6. Article ; Online: A patient-specific multi-modality abdominal aortic aneurysm imaging phantom.

    Little, Callum D / Mackle, Eleanor C / Maneas, Efthymios / Chong, Debra / Nikitichev, Daniil / Constantinou, Jason / Tsui, Janice / Hamilton, George / Rakhit, Roby D / Mastracci, Tara M / Desjardins, Adrien E

    International journal of computer assisted radiology and surgery

    2022  Volume 17, Issue 9, Page(s) 1611–1617

    Abstract: Purpose: Multimodality imaging of the vascular system is a rapidly growing area of innovation and research, which is increasing with awareness of the dangers of ionizing radiation. Phantom models that are applicable across multiple imaging modalities ... ...

    Abstract Purpose: Multimodality imaging of the vascular system is a rapidly growing area of innovation and research, which is increasing with awareness of the dangers of ionizing radiation. Phantom models that are applicable across multiple imaging modalities facilitate testing and comparisons in pre-clinical studies of new devices. Additionally, phantom models are of benefit to surgical trainees for gaining experience with new techniques. We propose a temperature-stable, high-fidelity method for creating complex abdominal aortic aneurysm phantoms that are compatible with both radiation-based, and ultrasound-based imaging modalities, using low cost materials.
    Methods: Volumetric CT data of an abdominal aortic aneurysm were acquired. Regions of interest were segmented to form a model compatible with 3D printing. The novel phantom fabrication method comprised a hybrid approach of using 3D printing of water-soluble materials to create wall-less, patient-derived vascular structures embedded within tailored tissue-mimicking materials to create realistic surrounding tissues. A non-soluble 3-D printed spine was included to provide a radiological landmark.
    Results: The phantom was found to provide realistic appearances with intravascular ultrasound, computed tomography and transcutaneous ultrasound. Furthermore, the utility of this phantom as a training model was demonstrated during a simulated endovascular aneurysm repair procedure with image fusion.
    Conclusion: With the hybrid fabrication method demonstrated here, complex multimodality imaging patient-derived vascular phantoms can be successfully fabricated. These have potential roles in the benchtop development of emerging imaging technologies, refinement of novel minimally invasive surgical techniques and as clinical training tools.
    MeSH term(s) Aortic Aneurysm, Abdominal/diagnostic imaging ; Aortic Aneurysm, Abdominal/surgery ; Blood Vessel Prosthesis Implantation ; Endovascular Procedures ; Humans ; Phantoms, Imaging ; Printing, Three-Dimensional
    Language English
    Publishing date 2022-04-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2365628-1
    ISSN 1861-6429 ; 1861-6410
    ISSN (online) 1861-6429
    ISSN 1861-6410
    DOI 10.1007/s11548-022-02612-4
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  7. Article ; Online: Histopathological analysis of vascular malformations.

    Pang, Calver / Abu-Hanna, Jeries / Lim, Chung Sim / Brookes, Jocelyn / Tsui, Janice / Hamilton, George / Onuba, Louisa / Deroide, Florence

    Phlebology

    2023  Volume 38, Issue 6, Page(s) 370–379

    Abstract: Objective: To propose and develop a histopathological criteria to help diagnose vascular malformations.: Methods: All patients who underwent surgical resection and had a confirmed histopathological diagnosis of vascular malformations from 01 March ... ...

    Abstract Objective: To propose and develop a histopathological criteria to help diagnose vascular malformations.
    Methods: All patients who underwent surgical resection and had a confirmed histopathological diagnosis of vascular malformations from 01 March 2018-26 February 2020 were included. A criteria based on 10 parameters was developed to help diagnose vascular malformations. Discrepancies between clinical and histopathological diagnosis were evaluated.
    Results: A total of 18 cases were identified. There was a discrepancy between the clinical diagnosis and the initially reported histopathological diagnosis in 16 cases (88.9%). This was reduced to 7 (38.9%) and 6 cases (33.3%) with first and second time revised histopathological analysis using proposed criteria.
    Conclusions: The discrepancy between clinical and histopathological diagnoses of vascular malformations has highlighted the requirement of an agreed criteria for histopathologists to help formulate their diagnosis. The proposed criteria may be used as a guide in addressing this and guide treatment and improve clinical practice.
    MeSH term(s) Humans ; Arteriovenous Malformations/surgery ; Vascular Malformations/diagnosis
    Language English
    Publishing date 2023-05-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 645172-x
    ISSN 1758-1125 ; 0268-3555
    ISSN (online) 1758-1125
    ISSN 0268-3555
    DOI 10.1177/02683555231175022
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  8. Article ; Online: Efficacy and safety of embolo-sclerotherapy of arteriovenous malformations with foam sodium tetradecyl sulphate.

    Pang, Calver / Arasakumar, Donald R / Evans, Nicholas / Papadopoulou, Anthie / Khalifa, Mohamed / Tsui, Janice / Hamilton, George / Lim, Chung-Sim / Brookes, Jocelyn

    International angiology : a journal of the International Union of Angiology

    2023  Volume 42, Issue 3, Page(s) 268–275

    Abstract: Background: To evaluate the efficacy and safety of embolo-sclerotherapy (EST) particularly with foamed sclerotherapy in the treatment of arteriovenous malformations (AVMs).: Methods: All patients with AVM who underwent interventional therapy i.e. EST ...

    Abstract Background: To evaluate the efficacy and safety of embolo-sclerotherapy (EST) particularly with foamed sclerotherapy in the treatment of arteriovenous malformations (AVMs).
    Methods: All patients with AVM who underwent interventional therapy i.e. EST from January 1
    Results: A total of 65 patients were included. There was no statistical difference amongst the volume of foam STS 3% or alcohol used across all types of AVM. Overall, majority of patients (86.2%) reported some degree of improvement following interventional therapy. Six (9.2%) patients experienced complications including necrosis and amputation. The proportions of complication were significantly different across the categories (P=0.009). Patients with type III AVM seemed to report more complications than others.
    Conclusions: Foam sclerotherapy was clinically effective and safe for patients with AVM. This study showed that foam sclerotherapy with STS 3% provided a safe and efficacious alternative sclerosant to ethanol despite it was not often reported to be used to treat AVM. However, a combination of embolic agents is likely required to treat type IV AVMs.
    MeSH term(s) Humans ; Sclerotherapy/adverse effects ; Sodium Tetradecyl Sulfate/adverse effects ; Treatment Outcome ; Arteriovenous Malformations/therapy ; Sclerosing Solutions/adverse effects ; Ethanol
    Chemical Substances Sodium Tetradecyl Sulfate (Q1SUG5KBD6) ; Sclerosing Solutions ; Ethanol (3K9958V90M)
    Language English
    Publishing date 2023-04-17
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 604910-2
    ISSN 1827-1839 ; 0392-9590
    ISSN (online) 1827-1839
    ISSN 0392-9590
    DOI 10.23736/S0392-9590.23.04993-3
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    Zs.A 1833: Show issues Location:
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  9. Article ; Online: PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways.

    Uzozie, Anuli C / Ergin, Enes K / Rolf, Nina / Tsui, Janice / Lorentzian, Amanda / Weng, Samuel S H / Nierves, Lorenz / Smith, Theodore G / Lim, C James / Maxwell, Christopher A / Reid, Gregor S D / Lange, Philipp F

    Journal of experimental & clinical cancer research : CR

    2021  Volume 40, Issue 1, Page(s) 96

    Abstract: Background: Murine xenografts of pediatric leukemia accurately recapitulate genomic aberrations. How this translates to the functional capacity of cells remains unclear. Here, we studied global protein abundance, phosphorylation, and protein maturation ... ...

    Abstract Background: Murine xenografts of pediatric leukemia accurately recapitulate genomic aberrations. How this translates to the functional capacity of cells remains unclear. Here, we studied global protein abundance, phosphorylation, and protein maturation by proteolytic processing in 11 pediatric B- and T- cell ALL patients and 19 corresponding xenografts.
    Methods: Xenograft models were generated for each pediatric patient leukemia. Mass spectrometry-based methods were used to investigate global protein abundance, protein phosphorylation, and limited proteolysis in paired patient and xenografted pediatric acute B- and T- cell lymphocytic leukemia, as well as in pediatric leukemia cell lines. Targeted next-generation sequencing was utilized to examine genetic abnormalities in patients and in corresponding xenografts. Bioinformatic and statistical analysis were performed to identify functional mechanisms associated with proteins and protein post-translational modifications.
    Results: Overall, we found xenograft proteomes to be most equivalent with their patient of origin. Protein level differences that stratified disease subtypes at diagnostic and relapse stages were largely recapitulated in xenografts. As expected, PDXs lacked multiple human leukocyte antigens and complement proteins. We found increased expression of cell cycle proteins indicating a high proliferative capacity of xenografted cells. Structural genomic changes and mutations were reflected at the protein level in patients. In contrast, the post-translational modification landscape was shaped by leukemia type and host and only to a limited degree by the patient of origin. Of 201 known pediatric oncogenic drivers and drug-targetable proteins, the KMT2 protein family showed consistently high variability between patient and corresponding xenografts. Comprehensive N terminomics revealed deregulated proteolytic processing in leukemic cells, in particular from caspase-driven cleavages found in patient cells.
    Conclusion: Genomic and host factors shape protein and post-translational modification landscapes differently. This study highlights select areas of diverging biology while confirming murine patient-derived xenografts as a generally accurate model system.
    MeSH term(s) Animals ; Disease Models, Animal ; Homeodomain Proteins/metabolism ; Humans ; Mice ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Proteome/metabolism ; Trans-Activators/metabolism ; Xenograft Model Antitumor Assays
    Chemical Substances Homeodomain Proteins ; Proteome ; Trans-Activators ; pancreatic and duodenal homeobox 1 protein
    Language English
    Publishing date 2021-03-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 803138-1
    ISSN 1756-9966 ; 0392-9078
    ISSN (online) 1756-9966
    ISSN 0392-9078
    DOI 10.1186/s13046-021-01835-8
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    Zs.A 2065: Show issues Location:
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  10. Article ; Online: Efficacy and safety of foam sclerotherapy with sodium tetradecyl sulfate as preferred sclerosant of venous malformations based on experience from a single specialist center.

    Arasakumar, Donald Rubakan Benedict / Pang, Calver / Evans, Nicholas / Papadopoulou, Anthie / Khalifa, Mohamed / Tsui, Janice / Hamilton, George / Brookes, Jocelyn / Lim, Chung Sim

    Journal of vascular surgery. Venous and lymphatic disorders

    2022  Volume 11, Issue 2, Page(s) 379–388

    Abstract: Objective: We have assessed the efficacy and safety of interventional therapy for venous malformations (VMs), with foam sclerotherapy as the treatment of choice according to our experience at a single specialist center.: Methods: All the patients ... ...

    Abstract Objective: We have assessed the efficacy and safety of interventional therapy for venous malformations (VMs), with foam sclerotherapy as the treatment of choice according to our experience at a single specialist center.
    Methods: All the patients with VMs who had undergone interventional therapy (ie, embolo-sclerotherapy and/or open surgery) from January 1, 2015 to December 31, 2019 were identified through a prospective database. The VM types were classified according to the Puig classification. The outcome measures assessed included the efficacy and complications. The former was divided into four groups: no response, mild response, moderate response, and complete response. The complications were defined as any tissue or functional damage, distal embolization, or tissue reaction. The continuous variables were compared using the analysis of variance F test, and discrete variables were analyzed using the χ
    Results: A total of 207 patients were included. Puig type I lesions were significantly less likely to have received foam sclerotherapy using sodium tetradecyl sulfate (STS) 3% (P ≤ .001) and more likely to have been surgically excised (P ≤ .001). At the patient's first procedure during the study period, the volumes of foam STS 3% were significantly different across all types of VM (P ≤ .001). The patients with type I VMs had received a lower volume of STS 3% compared with those with type II and III VMs. The efficacy outcome categories were significantly different across all types of VMs (P ≤ .001). Overall, only 14 patients (6.8%) had reported no improvement in efficacy, and 38 patients (18%) had not attended follow-up. Therefore, 154 patients (74.8%) had experienced some form of efficacious outcome. Ten patients (4.8%) had developed complications such as hematoma, thrombophlebitis, and ulceration. The incidence of complications differed significantly across the categories (P = .030), with more complications reported for those with type I VMs.
    Conclusions: We found that intervention with foam sclerotherapy using STS 3% is clinically effective and safe for patients with VMs and was most successful for those with Puig type I and II VMs.
    MeSH term(s) Humans ; Sclerosing Solutions/adverse effects ; Sclerotherapy/adverse effects ; Sodium Tetradecyl Sulfate ; Treatment Outcome ; Vascular Malformations/therapy ; Retrospective Studies
    Chemical Substances Sclerosing Solutions ; Sodium Tetradecyl Sulfate (Q1SUG5KBD6)
    Language English
    Publishing date 2022-10-31
    Publishing country United States
    Document type Journal Article
    ISSN 2213-3348
    ISSN (online) 2213-3348
    DOI 10.1016/j.jvsv.2022.10.008
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