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Messika J, Belousova N, Parquin F, Roux A. Antibody-Mediated Rejection in Lung Transplantation: Diagnosis and Therapeutic Armamentarium in a 21st Century Perspective. Transpl Int 2024; 37:12973. [PMID: 39170865 PMCID: PMC11336419 DOI: 10.3389/ti.2024.12973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 07/10/2024] [Indexed: 08/23/2024]
Abstract
Humoral immunity is a major waypoint towards chronic allograft dysfunction in lung transplantation (LT) recipients. Though allo-immunization and antibody-mediated rejection (AMR) are well-known entities, some diagnostic gaps need to be addressed. Morphological analysis could be enhanced by digital pathology and artificial intelligence-based companion tools. Graft transcriptomics can help to identify graft failure phenotypes or endotypes. Donor-derived cell free DNA is being evaluated for graft-loss risk stratification and tailored surveillance. Preventative therapies should be tailored according to risk. The donor pool can be enlarged for candidates with HLA sensitization, with strategies combining plasma exchange, intravenous immunoglobulin and immune cell depletion, or with emerging or innovative therapies such as imlifidase or immunoadsorption. In cases of insufficient pre-transplant desensitization, the effects of antibodies on the allograft can be prevented by targeting the complement cascade, although evidence for this strategy in LT is limited. In LT recipients with a humoral response, strategies are combined, including depletion of immune cells (plasmapheresis or immunoadsorption), inhibition of immune pathways, or modulation of the inflammatory cascade, which can be achieved with photopheresis. Altogether, these innovative techniques offer promising perspectives for LT recipients and shape the 21st century's armamentarium against AMR.
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Affiliation(s)
- Jonathan Messika
- Thoracic Intensive Care Unit, Foch Hospital, Suresnes, France
- Physiopathology and Epidemiology of Respiratory Diseases, UMR1152 INSERM and Université de Paris, Paris, France
- Paris Transplant Group, Paris, France
| | - Natalia Belousova
- Paris Transplant Group, Paris, France
- Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France
| | - François Parquin
- Thoracic Intensive Care Unit, Foch Hospital, Suresnes, France
- Paris Transplant Group, Paris, France
| | - Antoine Roux
- Paris Transplant Group, Paris, France
- Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France
- Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France
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2
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Zikou X, Vaia D, Vasiliki P, Panagiotis C, Stavros A. Use of Therapeutic Apheresis methods in ICU. Transfus Apher Sci 2024; 63:103853. [PMID: 38049358 DOI: 10.1016/j.transci.2023.103853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/06/2023]
Abstract
Apheresis is a modern medical approach in which plasma or cellular components are separated from the whole blood. Apheresis can be either diagnostic or therapeutic. Diagnostic apheresis is typically applied in hematology and cancer research. Therapeutic Apheresis (TA) includes a broad spectrum of extracorporeal treatments applied in various medical specialties, including Intensive Care Unit (ICU). Considering the complexity of the pathophysiologic characteristics of various clinical entities and in particular sepsis, apheresis methods are becoming increasingly applicable. Therapeutic Plasma Exchange (TPE) is the most common used method in ICU. It is considered as first line therapy for Thrombotic Thrombocytopenic Purpura (TTP) and Guillain Barre Syndrome, while the current data for sepsis are scarce. Over the last decades, technologic evolution has led to increasing application of new and more selective methods based on adsorptive techniques. In this review we will describe the current data of characteristics of different techniques, safety and clinical impact of apheresis methods used in ICUs.
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3
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Melexopoulou C, Filiopoulos V, Marinaki S. Therapeutic apheresis in renal transplantation: An update. Transfus Apher Sci 2024; 63:103844. [PMID: 37978039 DOI: 10.1016/j.transci.2023.103844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2023]
Abstract
Therapeutic apheresis (TA) plays a significant role in various aspects of renal transplantation. It has been a necessary preconditioning component in ABO incompatible kidney transplants and an important modality in the removal of anti-human leukocyte antigen (HLA) antibodies both in the context of desensitization protocols that have been developed to allow highly sensitized kidney transplant candidates to be successfully transplanted and as treatment of antibody mediated rejection episodes post transplantation. In addition, TA has been used with various results for the management of recurrent focal segmental glomerulosclerosis. The purpose of this review is to examine the evidence supporting the application of TA as an adjunctive therapeutic option to immunosuppressive agents in protocols both before and after kidney transplantation.
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Affiliation(s)
- Christina Melexopoulou
- Department of Nephrology & Renal Transplantation, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
| | - Vassilis Filiopoulos
- Department of Nephrology & Renal Transplantation, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Smaragdi Marinaki
- Department of Nephrology & Renal Transplantation, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
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4
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Melexopoulou C, Filiopoulos V, Marinaki S. WITHDRAWN:Therapeutic apheresis in renal transplantation: An update. Transfus Apher Sci 2023:103852. [PMID: 38008686 DOI: 10.1016/j.transci.2023.103852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2023]
Abstract
The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.transci.2023.103844 of original article. The duplicate article has therefore been withdrawn. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal
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Affiliation(s)
- Christina Melexopoulou
- Department of Nephrology & Renal Transplantation, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
| | - Vassilis Filiopoulos
- Department of Nephrology & Renal Transplantation, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Smaragdi Marinaki
- Department of Nephrology & Renal Transplantation, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
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Moranne O, Cristol JP. With Single Plasma Exchange, a Better Understanding of the Potential Clinical Effects of Albumin Replacement Is Required. Blood Purif 2023; 52:844-846. [PMID: 37611556 DOI: 10.1159/000531186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 05/18/2023] [Indexed: 08/25/2023]
Affiliation(s)
- Olivier Moranne
- Service NDA, Centre Hospitalier Université de Nîmes, Nîmes, France
- IDESP, INSERM, Montpellier, France
| | - Jean-Paul Cristol
- Department of Biochemistry, University Hospital of Montpellier, University of Montpellier, Montpellier, France
- PhyMedExp, INSERM, CNRS, University of Montpellier, Montpellier, France
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6
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Alasfar S, Kodali L, Schinstock CA. Current Therapies in Kidney Transplant Rejection. J Clin Med 2023; 12:4927. [PMID: 37568328 PMCID: PMC10419508 DOI: 10.3390/jcm12154927] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
Despite significant advancements in immunosuppressive therapies, kidney transplant rejection continues to pose a substantial challenge, impacting the long-term survival of grafts. This article provides an overview of the diagnosis, current therapies, and management strategies for acute T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). TCMR is diagnosed through histological examination of kidney biopsy samples, which reveal the infiltration of mononuclear cells into the allograft tissue. Corticosteroids serve as the primary treatment for TCMR, while severe or steroid-resistant cases may require T-cell-depleting agents, like Thymoglobulin. ABMR occurs due to the binding of antibodies to graft endothelial cells. The most common treatment for ABMR is plasmapheresis, although its efficacy is still a subject of debate. Other current therapies, such as intravenous immunoglobulins, anti-CD20 antibodies, complement inhibitors, and proteasome inhibitors, are also utilized to varying degrees, but their efficacy remains questionable. Management decisions for ABMR depend on the timing of the rejection episode and the presence of chronic changes. In managing both TCMR and ABMR, it is crucial to optimize immunosuppression and address adherence. However, further research is needed to explore newer therapeutics and evaluate their efficacy.
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Affiliation(s)
- Sami Alasfar
- Department of Medicine, Mayo Clinic, Phoenix, AZ 85054, USA;
| | - Lavanya Kodali
- Department of Medicine, Mayo Clinic, Phoenix, AZ 85054, USA;
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Yu Y, Ou L. The development of immunosorbents for the treatment of systemic lupus erythematosus via hemoperfusion. Front Med (Lausanne) 2023; 9:1035150. [PMID: 36687455 PMCID: PMC9845935 DOI: 10.3389/fmed.2022.1035150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 11/29/2022] [Indexed: 01/05/2023] Open
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease (AID) that involves multiple organ systems and is characterized by elevated levels of autoantibodies (ANA) and immune complexes. The immunoadsorption technique uses an extracorporeal clearance process to remove pathogenic toxins from patients' blood and alleviate disease symptoms. An immunosorbent is a key component of the immunoadsorption system that determines therapeutic efficacy and safety. Immunosorbents are prepared by immobilizing antibodies, antigens, or ligands with specific physicochemical affinities on a supporting matrix. Immunosorbents and pathogenic toxins bind via affinity adsorption, which involves electrostatic interactions, hydrogen bonds, hydrophobic interactions, and van der Waals forces. Immunosorbents are classified on the basis of their interaction mechanism with toxins into three categories: non-selective, semi-selective, and highly selective. This review aimed to summarize the current status of various commercial immunosorbents that are used to treat SLE. Moreover, recent developments in immunosorbents have heightened the need for a brief discussion about specific ligands and a supporting matrix.
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Affiliation(s)
- Yameng Yu
- Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China,Beijing Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, Department of Dental Materials, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital, Material Technology of Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, Beijing, China
| | - Lailiang Ou
- Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China,*Correspondence: Lailiang Ou ✉
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Tseke P, Griveas I. IMMUNOADSORPTION AND COVID 19 PANDEMIC. Transfus Apher Sci 2022; 61:103599. [PMID: 36372733 PMCID: PMC9624060 DOI: 10.1016/j.transci.2022.103599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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9
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Torres DD, Fontò G, Guastamacchia L, Santangelo L, Carbone V, Piscopo G, Spadaccino F, Ranieri E, Netti GS, Giordano M. Therapeutic Approach for Recurrent Focal Segmental Glomerulosclerosis in Pediatric Renal Transplant Recipients: A Single-Center Experience. Blood Purif 2022; 51:847-856. [DOI: 10.1159/000521311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 12/02/2021] [Indexed: 11/19/2022]
Abstract
<b><i>Introduction:</i></b> Recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KTx) develops in 40% of patients, leading to graft loss in half of cases. Extracorporeal apheretic treatments, combined with immunosuppressive drugs, seem to be the most promising therapies, but at now limited reports are available, mainly in pediatric patients. <b><i>Objective:</i></b> We aimed to assess the efficacy of immunoadsorption (IA) to treat recurrent FSGS in pediatric patients. <b><i>Methods:</i></b> We report a case series of 4 pediatric patients (aged 4–12 years) followed at our institution for early recurrent FSGS after KTx. FSGS recurrence was treated with early and intensive apheretic treatments IA. <b><i>Results:</i></b> After IA initiation, a partial remission (PR) of proteinuria at 24-month follow-up was achieved only in 1 patient. The others showed a mild reduction of nephrotic proteinuria, without PR, but gained a significant improvement in clinical signs of nephrotic syndrome (reduction of edema, increased serum albumin, and total protein levels). After a median follow-up of 38 (22–48) months, renal function was almost stable over time in all patients, except one who returned to hemodialysis after 22 months. No severe IA-related complications occurred. <b><i>Conclusions:</i></b> According to our clinical experience, IA revealed as a safe and effective therapy to treat patients with recurrent FSGS after KTx and it could maintain stable renal function in 75% of patients.
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10
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Schossee N, Veit G, Gittel J, Viebahn J, Niklaus M, Klingler P, Üçeyler N, Klinker E, Kobsar A, Boeck M, Koessler J. Profile of the single-use, multiple-pass protein A adsorber column in immunoadsorption. Vox Sang 2021; 117:393-398. [PMID: 34545576 DOI: 10.1111/vox.13205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 08/25/2021] [Accepted: 08/31/2021] [Indexed: 11/27/2022]
Abstract
BACKGROUND AND OBJECTIVES Immunoadsorptions (IA) are used to remove autoantibodies from the plasma in autoimmune disorders. In this study, we evaluated the effects of a single-use, recombinant staphylococcal protein A-based immunoadsorber on blood composition of the patient. MATERIALS AND METHODS In a cohort of patients with myasthenia gravis or stiff-person syndrome, essential parameters of blood cell count, coagulation, clinical chemistry or plasma proteins and immunoglobulins (Ig) were measured before and after IA (n = 11). RESULTS In average, IA reduced the levels of total IgG, IgG1, IgG2 and IgG4 by approximately 60%, the acetylcholine receptor autoantibody levels by more than 70%. IgG3, IgA or IgM were diminished to a lower extent. In contrast to fibrinogen or other coagulation factors, the column markedly removed vitamin K-dependent coagulation factors II, VII, IX and X by approximately 40%-70%. Accordingly, international normalized ratio and activated partial thromboplastin time were increased after IA by 59.1% and 32.7%, respectively. Coagulation tests almost returned to baseline values within 24 h. Blood cell count, electrolytes, total protein or albumin were not essentially affected. No clinical events occurred. CONCLUSION The single-use, multiple-pass protein A adsorber column is highly efficient to remove IgG1, IgG2 and IgG4 or specific acetylcholine receptor autoantibodies from the plasma. Coagulation parameters should be monitored, since the column has the capacity to largely reduce vitamin K-dependent factors.
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Affiliation(s)
- Nadine Schossee
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Gabriele Veit
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Julia Gittel
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Johannes Viebahn
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Marius Niklaus
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Philipp Klingler
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Nurcan Üçeyler
- Department of Neurology, University of Wuerzburg, Wuerzburg, Germany
| | - Erdwine Klinker
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Anna Kobsar
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Markus Boeck
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Juergen Koessler
- Institute of Transfusion Medicine and Haemotherapy, University of Wuerzburg, Wuerzburg, Germany
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11
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Chen J, Feng L, Zhou H, Shen C, Sun X, Wang H, Lai R, Huang X, Feng H. Immunoadsorption with staphylococcal protein A column in autoimmune encephalitis. Transfusion 2021; 61:3272-3276. [PMID: 34469028 DOI: 10.1111/trf.16644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 07/30/2021] [Accepted: 08/17/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Early treatment has a positive effect on autoimmune encephalitis. However, different treatments have individual differences and corresponding contraindications in the clinical. Few reports have described the application of immunoadsorption with Staphylococcal Protein A Column (SPA-IA) in neuroimmune diseases. We aimed to observe the safety and efficiency of SPA-IA in autoimmune encephalitis. PATIENTS AND METHODS We retrospectively analyzed three cases of autoimmune encephalitis wherein the first-line treatment was ineffective or contraindicated. The clinical features and prognosis during and after SPA-IA are described in detail. RESULTS All patients were definitely diagnosed with autoimmune encephalitis. After treated with SPA-IA, all antibody titers, except for the serum antibody titer in Patient 2, were markedly decreased in both the cerebral spinal fluid and serum. The mean fibrinogen levels before and after SPA-IA were stable, and there were no clinical bleeding events. The modified Rankin Scale scores and their symptoms improved significantly after the last SPA-IA session or 3 months later. CONCLUSIONS SPA-IA may be a viable, efficacious, and safe treatment alternative for autoimmune encephalitis with contraindications to traditional treatment or poor response.
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Affiliation(s)
- Jiaxin Chen
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Li Feng
- Department of Neurological Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Hongyan Zhou
- Department of Neurological Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Cunzhou Shen
- Department of Neurological Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Xunsha Sun
- Department of Neurological Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Haiyan Wang
- Department of Neurological Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Rong Lai
- Department of Neurological Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Xin Huang
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Huiyu Feng
- Department of Neurological Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
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12
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Fuchs K, Rummler S, Ries W, Helmschrott M, Selbach J, Ernst F, Morath C, Gauly A, Atiye S, Stauss-Grabo M, Giefer M. Performance, clinical effectiveness, and safety of immunoadsorption in a wide range of indications. Ther Apher Dial 2021; 26:229-241. [PMID: 33914397 PMCID: PMC9291474 DOI: 10.1111/1744-9987.13663] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/22/2021] [Accepted: 04/25/2021] [Indexed: 12/14/2022]
Abstract
Immunoadsorption is well known to selectively remove immunoglobulins and immune complexes from plasma and is applied in a variety of autoimmune diseases and for desensitization before, or at acute rejection after organ transplantation. Performance, safety, and clinical effectiveness of immunoadsorption were the aim of this study. This prospective, noninterventional, multicentre cohort study included patients treated with immunoadsorption (Immunosorba or GLOBAFFIN adsorbers) for any indication. Clinical effectiveness was assessed after termination of the patient's individual treatment schedule. Eighty‐one patients were included, 69 were treated with Immunosorba, 11 with GLOBAFFIN, one patient with both adsorbers. A majority of patients was treated for neurological indications, dilated cardiomyopathy, and before or after kidney or heart transplantation. Mean IgG reduction from pre‐ to post‐treatment was 69.9% ± 11.5% for Immunosorba and 74.1% ± 5.0% for GLOBAFFIN, respectively. The overall IgG reduction over a complete treatment block was 68%–93% with Immunosorba and 62%–90% with GLOBAFFIN depending on the duration of the overall treatment. After termination of the immunoadsorption therapy, an improvement of clinical status was observed in 63.0%, stabilization of symptoms in 29.6%, and a deterioration in 4.9% of patients. Changes in fibrinogen, thrombocytes, and albumin were mostly classified as noncritical. Overall, the treatments were well tolerated. Immunoadsorption in routine clinical practice with both GLOBAFFIN and Immunosorba has been safely performed, was well tolerated by patients, and effective in lowering immunoglobulins with an improvement or maintenance of clinical status, thus represents an additional therapeutic option for therapy refractory immune disorders.
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Affiliation(s)
- Kornelius Fuchs
- Department of Neurology, University Hospital, Regensburg, Germany
| | - Silke Rummler
- Institute for Transfusion Medicine, University Hospital, Jena, Germany
| | - Wolfgang Ries
- Internal Medicine, Department of Nephrology, Diakonissenkrankenhaus, Flensburg, Germany
| | | | - Jochen Selbach
- Department of Nephrology, Caritas Hospital, Bad Mergentheim, Germany
| | | | - Christian Morath
- Department for Dialysis, Nierenzentrum Heidelberg, Heidelberg, Germany
| | - Adelheid Gauly
- Fresenius Medical Care, Global Medical Office, Bad Homburg, Germany
| | - Saynab Atiye
- Fresenius Medical Care, Global Medical Office, Bad Homburg, Germany
| | | | - Mareike Giefer
- Fresenius Medical Care, Global Medical Office, Bad Homburg, Germany
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13
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Noble J, Metzger A, Naciri Bennani H, Daligault M, Masson D, Terrec F, Imerzoukene F, Bardy B, Fiard G, Marlu R, Chevallier E, Janbon B, Malvezzi P, Rostaing L, Jouve T. Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation. J Clin Med 2021; 10:jcm10061316. [PMID: 33806743 PMCID: PMC8005077 DOI: 10.3390/jcm10061316] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 03/07/2021] [Accepted: 03/17/2021] [Indexed: 12/23/2022] Open
Abstract
Nearly 18% of patients on a waiting list for kidney transplantation (KT) are highly sensitized, which make access to KT more difficult. We assessed the efficacy and tolerance of different techniques (plasma exchanges [PE], double-filtration plasmapheresis [DFPP], and immunoadsorption [IA]) to remove donor specific antibodies (DSA) in the setting of HLA-incompatible (HLAi) KT. All patients that underwent apheresis for HLAi KT within a single center were included. Intra-session and inter-session Mean Fluorescence Intensity (MFI) decrease in DSA, clinical and biological tolerances were assessed. A total of 881 sessions were performed for 45 patients: 107 DFPP, 54 PE, 720 IA. The procedures led to HLAi KT in 39 patients (87%) after 29 (15–51) days. A higher volume of treated plasma was associated with a greater decrease of inter-session class I and II DSA (p = 0.04, p = 0.02). IA, PE, and a lower maximal DSA MFI were associated with a greater decrease in intra-session class II DSA (p < 0.01). Safety was good: severe adverse events occurred in 17 sessions (1.9%), more frequently with DFPP (6.5%) p < 0.01. Hypotension occurred in 154 sessions (17.5%), more frequently with DFPP (p < 0.01). Apheresis is well tolerated (IA and PE > DFPP) and effective at removing HLA antibodies and allows HLAi KT for sensitized patients.
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Affiliation(s)
- Johan Noble
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
- University Grenoble Alpes, 38000 Grenoble, France
| | - Antoine Metzger
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
| | - Hamza Naciri Bennani
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
| | - Melanie Daligault
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
| | - Dominique Masson
- HLA Laboratory—Établissement Français du Sang-EFS-, 38000 Grenoble, France; (D.M.); (B.B.)
| | - Florian Terrec
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
| | - Farida Imerzoukene
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
| | - Beatrice Bardy
- HLA Laboratory—Établissement Français du Sang-EFS-, 38000 Grenoble, France; (D.M.); (B.B.)
| | - Gaelle Fiard
- Urology Department, University Hospital Grenoble, 38000 Grenoble, France;
- TIMC-IMAG, Grenoble INP, CNRS, University Grenoble Alpes, F-38000 Grenoble, France
| | - Raphael Marlu
- Haemostasis Laboratory, University Hospital Grenoble, 38000 Grenoble, France;
| | - Eloi Chevallier
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
| | - Benedicte Janbon
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
| | - Paolo Malvezzi
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
| | - Lionel Rostaing
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
- University Grenoble Alpes, 38000 Grenoble, France
- Correspondence: ; Tel.: +33-476768945; Fax: +33-476765263
| | - Thomas Jouve
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, 38000 Grenoble, France; (J.N.); (A.M.); (H.N.B.); (M.D.); (F.T.); (F.I.); (E.C.); (B.J.); (P.M.); (T.J.)
- University Grenoble Alpes, 38000 Grenoble, France
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14
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Sanchez AP, Balogun RA. Therapeutic Plasma Exchange in the Critically Ill Patient: Technology and Indications. Adv Chronic Kidney Dis 2021; 28:59-73. [PMID: 34389138 DOI: 10.1053/j.ackd.2021.03.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 01/20/2021] [Accepted: 03/17/2021] [Indexed: 12/17/2022]
Abstract
Therapeutic plasma exchange (TPE) is frequently the most common Apheresis Medicine technique used for extracorporeal therapy of a wide variety of renal, neurological, hematological, and other clinical indications. Many of these clinical indications require intensive care during critical illness. Conventional TPE uses one of two main technical methods to achieve the goal of removing known disease mediators from the plasma: using centrifugal forces to separate and remove components of blood, or a membrane filtration method that separates plasma from the cellular components of blood. The following review discusses the basic principles of TPE, the technological aspects, and relevant clinical scenarios encountered in the intensive care unit, including relevant guidelines and recommendations from the American Society for Apheresis.
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15
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Immunoadsorption enables successful rAAV5-mediated repeated hepatic gene delivery in nonhuman primates. Blood Adv 2020; 3:2632-2641. [PMID: 31501158 DOI: 10.1182/bloodadvances.2019000380] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 07/28/2019] [Indexed: 12/11/2022] Open
Abstract
Adeno-associated virus (AAV)-based liver gene therapy has been shown to be clinically successful. However, the presence of circulating neutralizing antibodies (NABs) against AAV vector capsids remains a major challenge as it may prevent successful transduction of the target cells. Therefore, there is a need to develop strategies that would enable AAV-mediated gene delivery to patients with preexisting anti-AAV NABs. In the current study, the feasibility of using an immunoadsorption (IA) procedure for repeated, liver-targeted gene delivery in nonhuman primates was explored. The animals were administered IV with recombinant AAV5 (rAAV5) carrying the reporter gene human secreted embryonic alkaline phosphatase (hSEAP). Seven weeks after the first rAAV treatment, all of the animals were readministered with rAAV5 carrying the therapeutic hemophilia B gene human factor IX (hFIX). Half of the animals administered with rAAV5-hSEAP underwent IA prior to the second rAAV5 exposure. The transduction efficacies of rAAV5-hSEAP and rAAV5-hFIX were assessed by measuring the levels of hSEAP and hFIX proteins. Although no hFIX was detected after rAAV5-hFIX readministration without prior IA, all animals submitted to IA showed therapeutic levels of hFIX expression, and a threshold of anti-AAV5 NAB levels compatible with successful readministration was demonstrated. In summary, our data demonstrate that the use of a clinically applicable IA procedure enables successful readministration of an rAAV5-based gene transfer in a clinically relevant animal model. Finally, the analysis of anti-AAV NAB levels in human subjects submitted to IA confirmed the safety and efficacy of the procedure to reduce anti-AAV NABs. Furthermore, clinical translation was assessed using an immunoglobulin G assay as surrogate.
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Ahmadpoor P, Aglae C, Cariou S, Pambrun E, Renaud S, Garo F, Darmon R, Schultz C, Prelipcean C, Reboul P, Moranne O. Physiological role of plasma and its components and the clinical implications of different methods of apheresis: A narrative review. Ther Apher Dial 2020; 25:262-272. [PMID: 32710797 DOI: 10.1111/1744-9987.13567] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 06/17/2020] [Accepted: 07/22/2020] [Indexed: 12/23/2022]
Abstract
Nowadays, therapeutic plasmapheresis (TP) is accepted as part of the treatment for specific groups of diseases. The availability of different methods, including double filtration and adsorption, increases selectivity for the removal of substances. However, the use of these techniques requires a thorough understanding of the characteristics and components of plasma. By considering pivotal papers from several databases, the aim of this narrative review is to describe the characteristics of plasma related to apheresis techniques. We have tried to cover the clinical implications including physiology, estimation of plasma volume, viscosity, and a description of its components including the size, volume of distribution, and half-lives of the different substances to be removed or maintained depending on the clinical situation and applied apheresis technique. Applying this knowledge will help us to choose the right method and dosage and improve the efficacy of the procedure by preventing or addressing any complications.
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Affiliation(s)
- Pedram Ahmadpoor
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Cedric Aglae
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Sylvain Cariou
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Emilie Pambrun
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Sophie Renaud
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Florian Garo
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Ruben Darmon
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Celine Schultz
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Camelia Prelipcean
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Pascal Reboul
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France
| | - Olivier Moranne
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France.,EA2415, Université de Montpellier, Montpellier, France
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Giammanco A, Cefalù AB, Noto D, Averna MR. Therapeutic Options for Homozygous Familial Hypercholesterolemia: The Role of Lomitapide. Curr Med Chem 2020; 27:3773-3783. [DOI: 10.2174/0929867326666190121120735] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 10/25/2018] [Accepted: 12/28/2018] [Indexed: 11/22/2022]
Abstract
Background:Lomitapide (Juxtapid® in US and Lojuxta® in Europe) is the first developed inhibitor of the Microsomal Triglyceride Transfer Protein (MTP) approved as a novel drug for the management of Homozygous Familial Hypercholesterolemia (HoFH). It acts by binding directly and selectively to MTP thus decreasing the assembly and secretion of the apo-B containing lipoproteins both in the liver and in the intestine.Aims:The present review aims at summarizing the recent knowledge on lomitapide in the management of HoFH.Results:The efficacy and safety of lomitapide have been evaluated in several trials and it has been shown a reduction of the plasma levels of Low-Density Lipoprotein Cholesterol (LDL-C) by an average of more than 50%. Although the most common side effects are gastrointestinal and liver events, lomitapide presents generally with a good tolerability and satisfactory patients compliance. Recently, in Europe, to evaluate the long-term safety and efficacy of lomitapide, the LOWER registry (ClinicalTrials.gov Identifier: NCT02135705) has been established in order to acquire informations on HoFH lomitapidetreated patients from “real life” clinical practice.:Furthermore, the observation that lomitapide decreases triglyceride levels may be considered for patients affected by severe forms of hypertriglyceridemia who undergo recurrent episodes of pancreatitis and are poor responders to conventional treatment.Conclusion:Lomitapide represents an innovative and efficacious drug for the treatment of HoFH. Longterm safety data, treatment of pediatric and pregnant HoFH patients and management of severe hypertriglyceridemia still require further investigations.
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Affiliation(s)
- Antonina Giammanco
- Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.Mi.S), Policlinico “Paolo Giaccone”, Università di Palermo, Via del Vespro 129, 90127 Palermo, Italy
| | - Angelo B. Cefalù
- Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.Mi.S), Policlinico “Paolo Giaccone”, Università di Palermo, Via del Vespro 129, 90127 Palermo, Italy
| | - Davide Noto
- Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.Mi.S), Policlinico “Paolo Giaccone”, Università di Palermo, Via del Vespro 129, 90127 Palermo, Italy
| | - Maurizio R. Averna
- Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.Mi.S), Policlinico “Paolo Giaccone”, Università di Palermo, Via del Vespro 129, 90127 Palermo, Italy
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18
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Salvadori M, Tsalouchos A. Therapeutic apheresis in kidney transplantation: An updated review. World J Transplant 2019; 9:103-122. [PMID: 31750088 PMCID: PMC6851502 DOI: 10.5500/wjt.v9.i6.103] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 10/02/2019] [Accepted: 10/15/2019] [Indexed: 02/05/2023] Open
Abstract
Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers such as ABO blood group incompatibility and preformed donor-specific antibodies can complicate the outcome of deceased- or living- donor transplantation. Postoperatively, additional problems such as antibody-mediated rejection and a recurrence of primary focal segmental glomerulosclerosis can limit therapeutic success and decrease graft survival. Therapeutic apheresis techniques find application in these issues by separating and selectively removing exchanging or modifying pathogenic material from the patient by an extracorporeal aphaeresis system. The purpose of this review is to describe the available techniques of therapeutic aphaeresis with their specific advantages and disadvantages and examine the evidence supporting the application of therapeutic aphaeresis as an adjunctive therapeutic option to immunosuppressive agents in protocols before and after kidney transplantation.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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19
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Rolfes L, Pfeuffer S, Ruck T, Melzer N, Pawlitzki M, Heming M, Brand M, Wiendl H, Meuth SG. Therapeutic Apheresis in Acute Relapsing Multiple Sclerosis: Current Evidence and Unmet Needs-A Systematic Review. J Clin Med 2019; 8:jcm8101623. [PMID: 31590282 PMCID: PMC6832170 DOI: 10.3390/jcm8101623] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 10/01/2019] [Accepted: 10/02/2019] [Indexed: 12/13/2022] Open
Abstract
Multiple sclerosis (MS) is the most abundant inflammatory demyelinating disorder of the central nervous system. Despite recent advances in its long-term immunomodulatory treatment, MS patients still suffer from relapses, significantly contributing to disability accrual. In recent years, apheresis procedures such as therapeutic plasma exchange (TPE) and immunoadsorption (IA) have been recognized as two options for treating MS relapses, that do not respond to standard treatment with corticosteroids. TPE is already incorporated in most international guidelines, although evidence for its use resulted mostly from either case series or small unblinded and/or non-randomized trials. Data on IA are still sparse, but several studies indicate comparable efficacy between both apheresis procedures. This article gives an overview of the published evidence on TPE and IA in the treatment of acute relapses in MS. Further, we outline current evidence regarding individual outcome predictors, describe technical details of apheresis procedures, and discuss apheresis treatment in children and during pregnancy.
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Affiliation(s)
- Leoni Rolfes
- Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
| | - Steffen Pfeuffer
- Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
| | - Tobias Ruck
- Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
| | - Nico Melzer
- Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
| | - Marc Pawlitzki
- Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
| | - Michael Heming
- Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
| | - Marcus Brand
- Department of Internal Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
| | - Heinz Wiendl
- Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
| | - Sven G Meuth
- Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
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20
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Blackburn KM, Kubiliun M, Harris S, Vernino S. Neurological autoimmune disorders with prominent gastrointestinal manifestations: A review of presentation, evaluation, and treatment. Neurogastroenterol Motil 2019; 31:e13611. [PMID: 31016817 DOI: 10.1111/nmo.13611] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 03/19/2019] [Accepted: 04/10/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND The identification of autoantibodies directed against neuronal antigens has led to the recognition of a wide spectrum of neurological autoimmune disorders (NAD). With timely recognition and treatment, many patients with NAD see rapid improvement. Symptoms associated with NAD can be diverse and are determined by the regions of the nervous system affected. In addition to neurological symptoms, a number of these disorders present with prominent gastrointestinal (GI) manifestations such as nausea, diarrhea, weight loss, and gastroparesis prompting an initial evaluation by gastroenterologists. PURPOSE This review provides a general overview of autoantibodies within the nervous system, focusing on three scenarios in which nervous system autoimmunity may initially present with gut symptoms. A general approach to evaluation and treatment, including antibody testing, will be reviewed.
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Affiliation(s)
- Kyle M Blackburn
- Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Maddie Kubiliun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Samar Harris
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Steven Vernino
- Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas
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21
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Durdu MS, Cakici M, Gumus F, Deniz GC, Bozdag SC, Ozcinar E, Yaman ND, Ilhan O, Ucanok K. Promising utilization areas of therapeutic plasmapheresis in cardiovascular surgery practice. Transfus Apher Sci 2018; 57:762-767. [PMID: 30249533 DOI: 10.1016/j.transci.2018.09.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 09/10/2018] [Accepted: 09/16/2018] [Indexed: 01/07/2023]
Abstract
OBJECTIVE Apheresis is performed for treatment of numerous diseases by removing auto-antibodies, antigen-antibody complexes, allo-antibodies, paraproteins, non-Ig proteins, toxins, exogenous poisons. In current study, we present our experience of using therapeutic plasma exchange (TPE) in patients with different types of clinical scenarios. METHODS Between January 2013 and May 2016, we retrospectively presented the results of 64 patients in whom postoperative TPE was performed in ICU setting after cardiac surgery. Patients were grouped into four as; 1-sepsis (n = 26), 2-hepatorenal syndrome(n = 24), 3-antibody mediated rejection(AMR) following heart transplantation(n = 4) and 4-right heart failure(RHF) after left ventricular asist device(LVAD)(n = 10). Hemodynamic parameters were monitored constantly, pre- and post-procedure peripheral blood tests including renal and liver functions and daily complete blood count (CBC), sedimentation, C-reactive protein and procalcitonin (ng/ml) levels were studied. RESULTS The mean age was 61 ± 17.67 years old and 56.25% (n = 36) were male. Mean Pre TPE left ventricular ejection fraction (LVEF) (%), central venous pressure (CVP)(mmHg) pulmonary capillary wedge pressure (PCWP)(mmHg) and pulmonary arterial pressure (PAP)(mmHg) were measured as 41.8 ± 8.1, 15.5 ± 4.4, 17.3 ± 3.24 and 39.9 ± 5.4, respectively. Procalcitonin (ng/ml) level of patients undergoing TPE due to sepsis was significantly reduced from 873 ± 401 ng/ml to 248 ± 132 ng/ml. Seventeen (26.5%) patients died in hospital during treatment, mean length of intensive care unit (ICU) stay(days) was 13.2 ± 5.1. CONCLUSION This study shows that TEP is a safe and feasible treatment modality in patients with different types of complications after cardiac surgery and hopefully this study will lead to new utilization areas.
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Affiliation(s)
- Mustafa Serkan Durdu
- Department of Cardiovascular Surgery, Heart Center, Cebeci Hospitals, Ankara University School of Medicine, Ankara, Turkey
| | - Mehmet Cakici
- Department of Cardiovascular Surgery, Heart Center, Cebeci Hospitals, Ankara University School of Medicine, Ankara, Turkey.
| | - Fatih Gumus
- Department of Cardiovascular Surgery, Heart Center, Cebeci Hospitals, Ankara University School of Medicine, Ankara, Turkey
| | | | - Sinem Civriz Bozdag
- Department of Hematology, Cebeci Hospitals, Ankara University School of Medicine, Ankara, Turkey
| | - Evren Ozcinar
- Department of Cardiovascular Surgery, Heart Center, Cebeci Hospitals, Ankara University School of Medicine, Ankara, Turkey
| | - Nur Dikmen Yaman
- Department of Cardiovascular Surgery, Heart Center, Cebeci Hospitals, Ankara University School of Medicine, Ankara, Turkey
| | - Osman Ilhan
- Department of Hematology, Cebeci Hospitals, Ankara University School of Medicine, Ankara, Turkey
| | - Kemalettin Ucanok
- Department of Cardiovascular Surgery, Heart Center, Cebeci Hospitals, Ankara University School of Medicine, Ankara, Turkey
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22
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Perondi F, Brovida C, Ceccherini G, Guidi G, Lippi I. Double filtration plasmapheresis in the treatment of hyperproteinemia in dogs affected by Leishmania infantum. J Vet Sci 2018; 19:472-476. [PMID: 29284208 PMCID: PMC5974530 DOI: 10.4142/jvs.2018.19.3.472] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 10/23/2017] [Accepted: 11/24/2017] [Indexed: 11/20/2022] Open
Abstract
Three dogs were evaluated for severe hyperproteinemia and hyperglobulinemia secondary to Leishmania infantum. Double filtration plasmapheresis (DFPP) was performed in two dogs at days 1, 2, and 6 after presentation. The third dog received DFPP at days 1 and 3 after presentation and eleven hemodialysis treatments. Significant reduction in serum total protein (p < 0.0001), alpha-1 (p = 0.023), alpha-2 (p = 0.018), gamma globulins (p = 0.0105), and a significant increase in albumin/globulin ratio (p = 0.0018) were found. DFPP may be a promising therapeutic technique for rapid resolution of signs of hyperproteinemia in dogs affected by L. infantum.
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Affiliation(s)
- Francesca Perondi
- Department of Veterinary Sciences, University of Pisa, 56122 Pisa, Italy
| | | | - Gianila Ceccherini
- Department of Veterinary Sciences, University of Pisa, 56122 Pisa, Italy
| | - Grazia Guidi
- Department of Veterinary Sciences, University of Pisa, 56122 Pisa, Italy
| | - Ilaria Lippi
- Department of Veterinary Sciences, University of Pisa, 56122 Pisa, Italy
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23
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Tiwari AK, Bhardwaj G, Aggarwal G, Arora D, Dara RC, Acharya DP, Gayam S, Choudhuri J. Changing Trends in Therapeutic Plasmapheresis: An Indian Perspective. Ther Apher Dial 2017; 21:500-506. [DOI: 10.1111/1744-9987.12549] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 03/07/2017] [Accepted: 03/21/2017] [Indexed: 12/15/2022]
Affiliation(s)
- Aseem K Tiwari
- Department of Transfusion Medicine; Medanta-The Medicity; Gurgaon India
| | - Gunjan Bhardwaj
- Department of Transfusion Medicine; Medanta-The Medicity; Gurgaon India
| | - Geet Aggarwal
- Department of Transfusion Medicine; Medanta-The Medicity; Gurgaon India
| | - Dinesh Arora
- Department of Transfusion Medicine; Medanta-The Medicity; Gurgaon India
| | - Ravi C Dara
- Department of Transfusion Medicine; Medanta-The Medicity; Gurgaon India
| | - Devi P Acharya
- Department of Transfusion Medicine; Medanta-The Medicity; Gurgaon India
| | - Sangeetha Gayam
- Department of Transfusion Medicine; Kamineni Institute of Medical Sciences; Hyderabad Narketpally India
| | - Jui Choudhuri
- Department of Transfusion Medicine; Medanta-The Medicity; Gurgaon India
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24
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Affiliation(s)
- Nika Kruljec
- Faculty
of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia
| | - Tomaž Bratkovič
- Faculty
of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia
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25
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Ngoune R, Peters A, von Elverfeldt D, Winkler K, Pütz G. Accumulating nanoparticles by EPR: A route of no return. J Control Release 2016; 238:58-70. [PMID: 27448444 DOI: 10.1016/j.jconrel.2016.07.028] [Citation(s) in RCA: 152] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Revised: 07/13/2016] [Accepted: 07/17/2016] [Indexed: 11/26/2022]
Abstract
Nanoparticle-based drug delivery to ease anticancer therapy relies primarily on the enhanced permeability and retention effect (EPR). The leaky vascular structure in tumors allows extravasation of nanoparticles, often termed passive targeting. Long term retention of nanoparticles is attributed to the lack of lymphatic drainage, and unidirectional extravasation has been implied. Fluorescent liposomes with a plasma half-life of 29h were injected into tumor-bearing rats, and biodistribution in tumor, skin, paws and ears was monitored via in vivo fluorescence measurements. To calculate tissue accumulation, an algorithm was developed to subtract the blood signal from the total fluorescence recorded. Accumulation in tumor tissue was much higher than that in other tissues monitored, initially exhibiting very rapid accumulation followed by a long plateau phase with little change. Discontinuous plasmapheresis was established that was as effective as highly sophisticated clinical plasmapheresis. We observed no difference in the tumor tissue's accumulation when plasmapheresis was performed 22h after liposome injection. In contrast, plasmapheresis led to a significant inhibition of further accumulation in other tissues. When the liposomes' blood concentration was rapidly lowered, we detected no drop in tumor fluorescence. Thus extravasation via EPR is most likely a route of no return. These data support the emerging view of a more dynamic model of EPR, where gaps or entire vessels may open and close over time, or accumulated liposomes become entangled within the pores, hampering further accumulation.
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Affiliation(s)
- Romeo Ngoune
- University Freiburg Medical Center, Institute for Clinical Chemistry, Freiburg, Germany.
| | - Annette Peters
- University Freiburg Medical Center, Institute for Clinical Chemistry, Freiburg, Germany.
| | - Dominik von Elverfeldt
- University Freiburg Medical Center, Department of Diagnostic Radiology Medical Physics, Freiburg, Germany.
| | - Karl Winkler
- University Freiburg Medical Center, Institute for Clinical Chemistry, Freiburg, Germany.
| | - Gerhard Pütz
- University Freiburg Medical Center, Institute for Clinical Chemistry, Freiburg, Germany.
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Koefoed-Nielsen P, Bistrup C, Christiansen M. Protein a Immunoadsorption May Hamper the Decision to Transplant Due to Interference With CDC Crossmatch Results. J Clin Apher 2016; 32:163-169. [PMID: 27258774 DOI: 10.1002/jca.21476] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 05/16/2016] [Indexed: 11/10/2022]
Abstract
Transplanting immunized patients requires immunological monitoring in the pretransplant phase to follow reduction of donor specific HLA antibodies (DSA) after Staphylococcus aureus protein A (SPA) immunoadsorption (IA) or therapeutic plasma exchange followed by IVIG and Rituximab administration. Pretreatment aims to significantly reduce DSA strength. The Tissue Typing Lab at Aarhus University Hospital performs immunological monitoring of approximately 150 kidney transplantation patients per year from two transplant centers. From 2012 to 2013, we experienced seven patients desensitized using SPA IA, initially presenting negative cytotoxic complement dependent (CDC) T-cell crossmatches but positive B and T cell flowcytometric crossmatch, who despite significant DSA reduction developed weakly positive CDC T-cell crossmatch shortly prior to transplantation. We hypothesised that leached SPA during IA could be the cause, as the complication was not observed in patients who received plasma exchanges. We found that the positive CDC was not donor specific and SPA column material incubated with control serum reproduced a positive CDC T-cell crossmatch. Finally, we detected leached SPA in one of the patient samples using a highly sensitive time-resolved fluorescent assay. In conclusion, the results emphasize the importance of carefully considering CDC crossmatch results subsequent to IA, before a planned transplantation is either postponed or cancelled. J. Clin. Apheresis 32:163-169, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
| | - Claus Bistrup
- Department of Nephrology, Odense University Hospital, Odense, Denmark
| | - Mette Christiansen
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus N, Denmark
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Dubey D, Blackburn K, Greenberg B, Stuve O, Vernino S. Diagnostic and therapeutic strategies for management of autoimmune encephalopathies. Expert Rev Neurother 2016; 16:937-49. [PMID: 27171736 DOI: 10.1080/14737175.2016.1189328] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
INTRODUCTION The understanding of the etio-pathogenesis of autoimmune encephalopathy syndromes has grown significantly in recent years. These are potentially reversible conditions, with variable clinical presentation and potential dramatic response to immunotherapy. AREAS COVERED In this article we review various diagnostic techniques and therapeutic options for management of autoimmune encephalopathy. We also review medication adverse effects and monitoring strategies. Expert commentary: Early diagnosis and immunomodulatory treatment remains the cornerstone of management, to halt the underlying neuro-inflammatory process and prevent permanent neuronal injury. The availability of serological testing and various imaging modalities has further improved detection of these immune-mediated neurological disorders. Understanding the mechanisms and potential adverse effects of immunomodulatory therapies will help physicians to choose the most favorable therapeutic strategy for each patient.
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Affiliation(s)
- Divyanshu Dubey
- a Department of Neurology and Neurotherapeutics , UT Southwestern Medical Center , Dallas , TX , USA
| | - Kyle Blackburn
- a Department of Neurology and Neurotherapeutics , UT Southwestern Medical Center , Dallas , TX , USA
| | - Benjamin Greenberg
- a Department of Neurology and Neurotherapeutics , UT Southwestern Medical Center , Dallas , TX , USA
| | - Olaf Stuve
- a Department of Neurology and Neurotherapeutics , UT Southwestern Medical Center , Dallas , TX , USA.,b Neurology Section , VA North Texas Health Care System, Medical Service , Dallas , TX , USA
| | - Steven Vernino
- a Department of Neurology and Neurotherapeutics , UT Southwestern Medical Center , Dallas , TX , USA
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Galán Carrillo I, Demelo-Rodriguez P, Rodríguez Ferrero ML, Anaya F. Double filtration plasmapheresis in the treatment of pancreatitis due to severe hypertriglyceridemia. J Clin Lipidol 2015; 9:698-702. [PMID: 26350817 DOI: 10.1016/j.jacl.2015.07.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 06/19/2015] [Accepted: 07/03/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND Severe hypertriglyceridemia (HTG) leads to major complications such as acute pancreatitis. Lipoprotein apheresis has been proposed as a therapeutic tool for decreasing triglyceride levels, although experience is limited. OBJECTIVE To describe our experience with double filtration plasmapheresis (DFPP) in patients with severe HTG and pancreatitis in the plasmapheresis unit of a tertiary hospital in Spain. METHODS We recruited 4 patients with severe HTG (triglycerides [TGs] >1000 mg/dL) and acute pancreatitis. All the patients underwent DFPP as part of their treatment. Epidemiologic and laboratory data were collected before and after each plasmapheresis session. RESULTS The average TG level before plasmapheresis was 3136 mg/dL (35.44 mmol/L; range, 1306-6693 mg/dL, 14.76-75.63 mmol/L), and the average Acute Physiology And Chronic Health Evaluation (APACHE) II level before the first session was 6 (range, 3-8). All patients made a full recovery, with a significant improvement in TG levels after plasmapheresis. The mean number of sessions was 2.1 (range, 1-3), and mean TG level after plasmapheresis was 428 mg/dL (4.84 mmol/L; range, 169-515 mg/dL; 1.91-5.82 mmol/L). After the first session, the mean decrease in TG levels was 69.16% (2169 mg/dL, range, 945-5925 mg/dL; 24.51 mmol/L, range, 10.78-66.95 mmol/L), and after the last session, TG levels fell by 89.09% (2794 mg/dL, range, 945-6198 mg/dL; 31.57 mmol/L, range, 10.68-70.04 mmol/L). None of the patients developed complications related to plasmapheresis. CONCLUSIONS According to available evidence and our own experience, DFPP can be an effective and rapid treatment option in patients with severe HTG and complications. However, further research, including randomized controlled studies, is necessary.
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Affiliation(s)
| | - Pablo Demelo-Rodriguez
- Internal Medicine Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | - Fernando Anaya
- Nephrology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Lionaki S, Vlachopanos G, Georgalis A, Liapis G, Skalioti C, Zavos G, Boletis JN. Individualized scheme of immunoadsorption for the recurrence of idiopathic focal segmental glomerulosclerosis in the graft: a single center experience. Ren Fail 2015; 37:777-83. [PMID: 25715638 DOI: 10.3109/0886022x.2015.1015366] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVES To explore the role of immunoadsorption (IA) for the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) recurrence in the renal allograft, if applied in a personalized manner. METHODS We studied patients with end-stage renal disease (ESRD) due to idiopathic FSGS, transplanted between 2001 and 2010. Patients with FSGS recurrence were treated with daily sessions of IA for the first week, followed by an every other day scheme and then individualized tapering until discontinuation. Complete remission was defined as a reduction of 24-h proteinuria to ≤ 0.5 g/day and partial remission as a reduction of 24-h proteinuria to 50% or more from baseline. RESULTS Of the 18 renal transplant recipients with ESRD due to idiopathic FSGS, 12 (66.7%) experienced disease recurrence in a mean time of 0.75 months post-transplantation (KTx), with a mean proteinuria of 8.9 g/day at the time of recurrence. The mean recipient age was 30.8 years; the mean donor age was 47.4 years, while living related donors provided the allograft in seven cases. Four of the patients received therapy with rituximab in addition to IA. During a mean time of follow-up of 48.3 months, seven patients (58.3%) achieved complete remission, and five (41.7%) partial remission. At the end of follow-up, eight patients (66.7%) had functioning grafts, being in sustained remission, in contrast to four patients (33.3%), who ended up in ESRD because of FSGS recurrence. CONCLUSIONS IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.
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Affiliation(s)
- Sophia Lionaki
- a Department of Nephrology & Transplantation Unit , Laiko Hospital , Athens , Greece
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Comparison between the traditional and a rapid screening test for cryoimmunoglobulins detection. BIOMED RESEARCH INTERNATIONAL 2015; 2015:783063. [PMID: 25692146 PMCID: PMC4321088 DOI: 10.1155/2015/783063] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2014] [Accepted: 01/03/2015] [Indexed: 12/31/2022]
Abstract
OBJECTIVES A new rapid, automatic, and sensitive screening test useful to detect cryoglobulins in serum samples is proposed. DESIGN AND METHODS The increase of turbidity during the cryoglobulin aggregation was monitored spectrophotometrically in sera from 400 patients with clinical evidence of cryoglobulinemia related disorders and 100 controls. Results were correlated to those obtained by the traditional method. RESULTS Kinetics of the aggregation curves were described by their maximum turbidity increase, lag time, and slope. Despite a partial correspondence between the traditional and the rapid test, patients with symptomatic cryoglobulinemia showed turbidity values significantly higher than the determined cutoff. Moreover, a functional classification of cryoglobulins is proposed. CONCLUSIONS Due to its high reproducibility, operator independence, low cost, and results obtained within 2 hours, the rapid test can be used as a "real time" monitoring of cryoglobulinemia related diseases and for the evaluation of plasmapheresis efficacy.
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Anis S, Abbas K, Mubarak M, Ahmed E, Bhatti S, Muzaffar R. Vasculitis with renal involvement in essential mixed cryoglobulinemia: Case report and mini-review. World J Clin Cases 2014; 2:160-166. [PMID: 24868518 PMCID: PMC4023312 DOI: 10.12998/wjcc.v2.i5.160] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Revised: 02/13/2014] [Accepted: 04/11/2014] [Indexed: 02/05/2023] Open
Abstract
The discovery of a strong association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has led to an increasingly rare diagnosis of idiopathic essential MC (EMC). The incidence of EMC is high in regions where there is a comparatively low HCV infection burden and low in areas of high infection prevalence, including HCV. The diagnosis of EMC requires an extensive laboratory investigation to exclude all possible causes of cryoglobulin formation. In addition, although cryoglobulin testing is simple, improper testing conditions will result in false negative results. Here, we present a 46-year-old female patient with a case of EMC with dermatological and renal manifestations, highlighting the importance of extensive investigation to reach a proper diagnosis. We review the need for appropriate laboratory testing, which is often neglected in clinical practice and which can result in false negative results. This review also emphasizes the significance of an extended testing repertoire necessary for better patient management. Despite a strong association of MC with HCV infection and other causes that lead to cryoglobulin formation, EMC remains a separate entity. Correct diagnosis requires proper temperature regulation during sample handling, as well as characterization and quantification of the cryoprecipitate. Inclusion of rheumatoid factor activity and complement levels in the cryoglobulin test-panel promotes better patient management and monitoring. Consensus guidelines should be developed and implemented for cryoglobulin detection and the diagnosis of cryoglobulinemic syndrome, which will reduce variability in inter-laboratory reporting.
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Panno MD, Cefalù AB, Averna MR. Lomitapide: a novel drug for homozygous familial hypercholesterolemia. ACTA ACUST UNITED AC 2014. [DOI: 10.2217/clp.13.74] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Julius U, Fischer S, Schatz U, Hohenstein B, Bornstein SR. Lipoprotein apheresis: an update. ACTA ACUST UNITED AC 2013. [DOI: 10.2217/clp.13.68] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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