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Article ; Online: Histiocitosis.

Rocamora-Blanch, Gemma / Climent, Fina / Solanich, Xavier

2023 Volume 161, Issue 4, Page(s) 166–175

Abstract: Histiocytosis is a group of rare diseases characterized by inflammation and accumulation of cells derived from monocytes and macrophages in different tissues. The symptoms are highly variable, from mild forms with involvement of a single organ to severe ... ...

Title translation	Histiocytosis.
Abstract	Histiocytosis is a group of rare diseases characterized by inflammation and accumulation of cells derived from monocytes and macrophages in different tissues. The symptoms are highly variable, from mild forms with involvement of a single organ to severe multisystem forms that can be life compromising. The diagnosis of histiocytosis is based on the clinic, radiological findings and pathological anatomy. A biopsy of the affected tissue is recommended in all cases as it may have therapeutic implications. During the last decade, some mutations have been identified in the affected tissue that condition activation of the MAPK/ERK and PI3K/AKT pathway, in a variable proportion depending on the type of histiocytosis. In this review we mainly focus on Langerhans Cell Histiocytosis, Erdheim-Chester Disease and Rosai-Dorfman Disease.
MeSH term(s)	Humans ; Phosphatidylinositol 3-Kinases ; Histiocytosis, Langerhans-Cell/diagnosis ; Histiocytosis, Langerhans-Cell/therapy ; Erdheim-Chester Disease/diagnosis ; Erdheim-Chester Disease/therapy ; Histiocytosis, Sinus ; Mutation
Chemical Substances	Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
Language	Spanish
Publishing date	2023-05-30
Publishing country	Spain
Document type	Journal Article ; Review
ZDB-ID	411607-0
ISSN	1578-8989 ; 0025-7753
ISSN (online)	1578-8989
ISSN	0025-7753
DOI	10.1016/j.medcli.2023.05.001
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Article: Clinical Significance of Indeterminate QuantiFERON-TB Gold Plus Assay Results in Hospitalized COVID-19 Patients with Severe Hyperinflammatory Syndrome.

Solanich, Xavier / Fernández-Huerta, Miguel / Basaez, Celeste / Antolí, Arnau / Rocamora-Blanch, Gemma / Corbella, Xavier / Santin, Miguel / Alcaide, Fernando

Journal of clinical medicine

2021 Volume 10, Issue 5

Abstract: Performance of the QuantiFERON-TB Gold Plus (QFT-Plus) assay could be affected by conditions of immune dysregulation. Little is known about the reliability of QTF-Plus in COVID-19 patients. Our aim was to determine the prevalence and the factors related ... ...

Abstract	Performance of the QuantiFERON-TB Gold Plus (QFT-Plus) assay could be affected by conditions of immune dysregulation. Little is known about the reliability of QTF-Plus in COVID-19 patients. Our aim was to determine the prevalence and the factors related to an indeterminate QFT-Plus test in COVID-19 hospitalized patients, and to analyze its relationship with in-hospital mortality. A retrospective analysis of all hospitalized COVID-19 patients on whom a QTF-Plus assay was performed in a tertiary care public hospital during the first epidemic wave in Spain (March-April 2020). Out of a total of 96 patients included, 34 (35.4%) had an indeterminate result, in all cases due to a lack of response in the mitogen control. Factors related to COVID-19 severity, such as higher lactate dehydrogenase (LDH) (odds ratio [OR] 1.005 [95% confidence interval [CI] 1.002-1.008]) and previous administration of corticosteroids (OR 4.477 [95% CI 1.397-14.345]), were independent predictors for indeterminate QFT-Plus assay. Furthermore, indeterminate results were more frequent among COVID-19 patients who died during hospitalization (29.1% vs. 64.7%;
Language	English
Publishing date	2021-02-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10050918
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Article ; Online: Multiple Drug Regimen-Refractory Rosai-Dorfman-Destombes Disease Mimicking Relapsing Polychondritis Successfully Treated with Cobimetinib.

López-Aldabe, Kima / Escrihuela-Vidal, Francesc / Tuells-Morales, Manel / Llobera-Ris, Clàudia / Bauer-Alonso, Andrea / Cortes-Romera, Montserrat / Gràcia-Sànchez, Laura / Tormo-Ratera, Marian / Juanola Roura, Xavier / Penin-Mosquera, Rosa Maria / Corbella, Xavier / Solanich, Xavier

European journal of case reports in internal medicine

2022 Volume 9, Issue 2, Page(s) 3076

Abstract: Rosai-Dorfman-Destombes disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare non-Langerhans cell histiocytosis of unknown cause. The disease often manifests as painless bilateral cervical lymphadenopathy associated with systemic ... ...

Abstract	Rosai-Dorfman-Destombes disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare non-Langerhans cell histiocytosis of unknown cause. The disease often manifests as painless bilateral cervical lymphadenopathy associated with systemic symptoms such as fever and weight loss. Extranodal disease is also frequent and can involve any organ, mostly the skin, nasal cavity, bone, and retro-orbital tissue. Swelling of cartilaginous tissues, such as the helix of the ear or laryngeal structures, may mimic the entity known as relapsing polychondritis. Although spontaneous remission is the most expected evolution, some cases require systemic treatment with prednisone, methotrexate or cytotoxic agents, with variable rates of success. In this respect, since somatic variants in the genes involved in the mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK) pathway have been observed to play a pathogenic role in RDD. Therefore, the use of therapies targeting these pathogenic variants appears to be a reasonable strategy. Here we present the case of a 37-year-old woman with RDD and extensive extranodal involvement that showed a rapid and complete response to the MEK inhibitor cobimetinib. Learning points: Rosai-Dorfman-Destombes disease (RDD) may mimic the entity known as relapsing polychondritis but should be treated with drug therapy for the underlying disease.Mutations in MAPK/ERK pathway components should be determined in RDD with systemic involvement, although testing to determine every somatic mutation responsible for the disease is not available in all healthcare centres.MEK inhibitors like cobimetinib could be effective in RDD cases with severe and refractory systemic disease, even if molecular analysis has not been possible.
Language	English
Publishing date	2022-02-04
Publishing country	Italy
Document type	Journal Article
ISSN	2284-2594
ISSN (online)	2284-2594
DOI	10.12890/2022_003076
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Article ; Online: Clinical Significance of Indeterminate QuantiFERON-TB Gold Plus Assay Results in Hospitalized COVID-19 Patients with Severe Hyperinflammatory Syndrome

Xavier Solanich / Miguel Fernández-Huerta / Celeste Basaez / Arnau Antolí / Gemma Rocamora-Blanch / Xavier Corbella / Miguel Santin / Fernando Alcaide

Journal of Clinical Medicine, Vol 10, Iss 5, p

2021 Volume 918

Abstract	Performance of the QuantiFERON-TB Gold Plus (QFT-Plus) assay could be affected by conditions of immune dysregulation. Little is known about the reliability of QTF-Plus in COVID-19 patients. Our aim was to determine the prevalence and the factors related to an indeterminate QFT-Plus test in COVID-19 hospitalized patients, and to analyze its relationship with in-hospital mortality. A retrospective analysis of all hospitalized COVID-19 patients on whom a QTF-Plus assay was performed in a tertiary care public hospital during the first epidemic wave in Spain (March–April 2020). Out of a total of 96 patients included, 34 (35.4%) had an indeterminate result, in all cases due to a lack of response in the mitogen control. Factors related to COVID-19 severity, such as higher lactate dehydrogenase (LDH) (odds ratio [OR] 1.005 [95% confidence interval [CI] 1.002–1.008]) and previous administration of corticosteroids (OR 4.477 [95% CI 1.397–14.345]), were independent predictors for indeterminate QFT-Plus assay. Furthermore, indeterminate results were more frequent among COVID-19 patients who died during hospitalization (29.1% vs. 64.7%; p = 0.005). We conclude that QFT-Plus assay yielded an unexpected, high prevalence of indeterminate results in severe COVID-19 patients. Factors related to worse COVID-19 outcome, such as LDH, as well as corticosteroid use before the QFT-Plus assay, seem to be predictors for an indeterminate result. The role of an indeterminate QFT-Plus result in predicting COVID-19 severity and mortality should be evaluated.
Keywords	QuantiFERON-TB Gold Plus ; indeterminate ; COVID-19 ; SARS-CoV-2 ; corticosteroids ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial.

Malchair, Pierre / Giol, Jordi / García, Vanesa / Rodríguez, Orlando / Ruibal, José Carlos / Zarauza, Alvaro / Llopis, Ferrán / Matellán, Leire / Bernal, Tania / Solís, Beatriz / Otero, Aurema / Carnaval, Thiago / Jofre, Hector / Jacob, Javier / Solanich, Xavier / Antolí, Arnau / Rocamora, Gemma / Videla, Sebastián

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2023 Volume 76, Issue 10, Page(s) 1784–1792

Abstract: Background: We aimed to evaluate icatibant, a competitive antagonist of the bradykinin B2 receptors, for the treatment of inpatients with coronavirus disease 2019 (COVID-19) pneumonia admitted in the early hypoxemic stage.: Methods: The randomized, ... ...

Abstract	Background: We aimed to evaluate icatibant, a competitive antagonist of the bradykinin B2 receptors, for the treatment of inpatients with coronavirus disease 2019 (COVID-19) pneumonia admitted in the early hypoxemic stage. Methods: The randomized, open-label clinical trial of icatibant for COVID-19 pneumonia (ICAT·COVID, registered as NCT04978051 at ClinicalTrials.gov) was conducted in Barcelona. Inpatients requiring supplemental but not high-flow oxygen or mechanical ventilation were allocated (1:1) to treatment with either three 30-mg icatibant doses/d for 3 consecutive days plus standard care or standard care alone, and followed for up to 28 days after initial discharge. The primary and key secondary outcomes were clinical response on study day 10/discharge and clinical efficacy at 28 days from initial discharge, respectively. Results: Clinical response occurred in 27 of 37 patients (73.0%) in the icatibant group and 20 of 36 patients (55.6%) in the control group (rate difference, 17.42; 95% confidence interval [CI], -4.22 to 39.06; P = .115). Clinical efficacy ensued in 37 patients (100.0%) in the icatibant group and 30 patients (83.3%) in the control group (rate difference, 16.67; 95% CI, 4.49-28.84; P = .011). No patient died in the icatibant group, compared with 6 patients (16.7%) in the control group (P = .011). All patients but 1 had adverse events, which were evenly distributed between study arms. No patient withdrew because of adverse events. Conclusions: Adding icatibant to standard care was safe and improved both COVID-19 pneumonia and mortality in this proof-of-concept study. A larger, phase 3 trial is warranted to establish the clinical value of this treatment. Clinical trials registration: NCT04978051.
MeSH term(s)	Humans ; COVID-19 ; Hospitalization ; Inpatients ; SARS-CoV-2 ; Treatment Outcome ; Proof of Concept Study
Chemical Substances	icatibant (7PG89G35Q7)
Language	English
Publishing date	2023-01-05
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciac984
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Article ; Online: Dermatologic and Dermatopathologic Features of Monogenic Autoinflammatory Diseases.

Figueras-Nart, Ignasi / Mascaró, José M / Solanich, Xavier / Hernández-Rodríguez, José

Frontiers in immunology

2019 Volume 10, Page(s) 2448

Abstract: Autoinflammatory diseases include disorders with a monogenic cause and also complex conditions associated to polygenic or multifactorial factors. An increased number of both monogenic and polygenic autoinflammatory conditions have been identified during ... ...

Abstract	Autoinflammatory diseases include disorders with a monogenic cause and also complex conditions associated to polygenic or multifactorial factors. An increased number of both monogenic and polygenic autoinflammatory conditions have been identified during the last years. Although skin manifestations are often predominant in monogenic autoinflammatory diseases, clinical and histopathological information regarding their dermatological involvement is still scarce. Monogenic autoinflammatory diseases with cutaneous expression can be classified based on the predominant lesion: (1) maculopapular rashes or inflammatory plaques; (2) urticarial rashes; (3) pustular, pyogenic or neutrophilic dermatosis-like rashes; (4) panniculitis or subcutaneous nodules; (5) vasculitis or vasculopathy; (6) hyperkeratotic lesions; (7) hyperpigmented lesions; (8) bullous lesions; and (9) aphthous lesions. By using this classification, this review intends to provide clinical and histopathological knowledge about cutaneous involvement in monogenic autoinflammatory diseases.
MeSH term(s)	Autoimmune Diseases/diagnosis ; Autoimmune Diseases/etiology ; Autoimmune Diseases/therapy ; Autoimmunity ; Biomarkers ; Biopsy ; Dermatitis/diagnosis ; Dermatitis/etiology ; Dermatitis/therapy ; Diagnosis, Differential ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Phenotype ; Skin/pathology ; Symptom Assessment
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-10-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.02448
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Article ; Online: Multiple Drug Regimen-Refractory Rosai–Dorfman–Destombes Disease Mimicking Relapsing Polychondritis Successfully Treated with Cobimetinib

Kima López-Aldabe / Francesc Escrihuela-Vidal / Manel Tuells-Morales / Clàudia Llobera-Ris / Andrea Bauer-Alonso / Montserrat Cortes-Romera / Laura Gràcia-Sànchez / Marian Tormo-Ratera / Xavier Juanola Roura / Rosa Maria Penin-Mosquera / Xavier Corbella / Xavier Solanich

European Journal of Case Reports in Internal Medicine (2022)

2022

Abstract: Rosai-Dorfman-Destombes disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare non-Langerhans cell histiocytosis of unknown cause. The disease often manifests as bilateral painless cervical lymphadenopathy associated with systemic ... ...

Abstract	Rosai-Dorfman-Destombes disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare non-Langerhans cell histiocytosis of unknown cause. The disease often manifests as bilateral painless cervical lymphadenopathy associated with systemic symptoms such as fever and weight loss. Extranodal disease is also frequent and can involve any organ, mostly skin, nasal cavity, bone, and retro-orbital tissue. Swelling of cartilaginous tissues such as ear helix or laryngeal structures may mimic the entity known as relapsing polychondritis. Although spontaneous remission is the most expected evolution, some cases require systemic treatment with prednisone, methotrexate or cytotoxic agents, with variable success rates. In this respect, since somatic variants in genes involved in the mitogen-activated protein kinase (MAPK) pathway have been observed to play a pathogenic role in RDD, the use of therapies targeting these pathogenic variants seems to be a reasonable strategy. Here we present a case of RDD with extensive extranodal involvement that showed a rapid and complete response to the MEK inhibitor cobimetinib
Keywords	rosai–dorfman–destombes disease ; rosai–dorfman disease ; relapsing polychondritis ; mapk/erk pathway ; cobimetinib ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	SMC MEDIA SRL
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study protocol (ICAT-COVID).

Malchair, Pierre / Otero, Aurema / Giol, Jordi / Solanich, Xavier / Carnaval, Thiago / Fernández-Nistal, Alonso / Sánchez-Gabriel, Ana / Montoto, Carmen / Lleonart, Ramon / Videla, Sebastián

Trials

2022 Volume 23, Issue 1, Page(s) 303

Abstract: Background: COVID-19 has quickly become a global pandemic with a substantial number of deaths and is a considerable burden for healthcare systems worldwide. Although most cases are paucisymptomatic and limited to the viral infection-related symptoms, ... ...

Abstract	Background: COVID-19 has quickly become a global pandemic with a substantial number of deaths and is a considerable burden for healthcare systems worldwide. Although most cases are paucisymptomatic and limited to the viral infection-related symptoms, some patients evolve to a second phase, with an impaired inflammatory response (cytokine storm) that may lead to acute respiratory distress syndrome and death. This is thought to be caused by increased bradykinin synthesis. Methods: ICAT-COVID is a multicenter, randomized, open-label, proof-of-concept phase II clinical trial assessing the clinical efficacy and safety of adding icatibant to the standard of care in patients hospitalized with COVID-19 without invasive mechanical ventilation. Patients hospitalized with a confirmed COVID-19 pneumonia diagnosis (RT-PCR or antigen test ≤ 10 days prior to randomization, and radiographic evidence of pulmonary infiltrates), rated "4" or "5" on the WHO's clinical status scale, are eligible. Patients will be randomized on a 1:1 ratio to either standard of care-plus-icatibant (experimental group) or to standard of care alone (control group). The experimental group will receive 30 mg of icatibant subcutaneously 3 times a day for 3 days (for a total of 9 doses). The expected sample size is 120 patients (60 per group) from 2 sites in Spain. Primary outcomes are the efficacy and safety of Icatibant. The main efficacy outcome is the number of patients reaching grades "2" or "1" on the WHO scale within 10 days of starting treatment. Secondary outcomes include "long-term efficacy": number of patients discharged who do not present COVID-19-related relapse or comorbidity up until 28 days after discharge, and mortality. Discussion: Icatibant, a bradykinin type 2 receptor antagonist with proven effectiveness and safety against hereditary angioedema attacks, may be beneficial for COVID-19 patients by inhibiting bradykinin's action on endothelial cells and by inhibiting the SARS-CoV-2 M protease. Our working hypothesis is that treatment with standard of care-plus-icatibant is effective and safe to treat patients infected with SARS-CoV-2 admitted to hospital for pneumonia without invasive mechanical ventilation. Trial registration: EudraCT 2020-002166-13. Clinicaltrials: gov NCT04978051.
MeSH term(s)	Bradykinin/adverse effects ; Bradykinin/analogs & derivatives ; COVID-19 ; Clinical Trials, Phase II as Topic ; Endothelial Cells ; Hospital Units ; Humans ; Multicenter Studies as Topic ; Neoplasm Recurrence, Local ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; SARS-CoV-2 ; Treatment Outcome
Chemical Substances	icatibant (7PG89G35Q7) ; Bradykinin (S8TIM42R2W)
Language	English
Publishing date	2022-04-12
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article
ZDB-ID	2040523-6
ISSN	1745-6215 ; 1468-6694 ; 1745-6215
ISSN (online)	1745-6215
ISSN	1468-6694 ; 1745-6215
DOI	10.1186/s13063-022-06219-7
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Article: Clinical features and outcomes in a cohort of patients with immunoglobulin G4-related disease at a university hospital in Spain.

Quero, Maria / Draibe, Juliana / Solanich, Xavier / Rama, Inés / Gomà, Montserrat / Martínez-Valenzuela, Laura / Fulladosa, Xavier / Cruzado, Josep M / Torras, Joan

Clinical kidney journal

2019 Volume 12, Issue 6, Page(s) 829–835

Abstract: Background: Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory, immune-mediated disorder, which characteristically affects the glandular tissue but has the potential to affect any organ.: Methods: We retrospectively reviewed clinical, ...

Abstract	Background: Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory, immune-mediated disorder, which characteristically affects the glandular tissue but has the potential to affect any organ. Methods: We retrospectively reviewed clinical, laboratory, histological characteristics and treatment response during 12 months of follow-up of a cohort of patients with IgG4-RD diagnosed at a tertiary public hospital. Disease activity was assessed by means of the IgG4-RD responder index (IgG4-RD RI). Results: In all, 15 patients have been diagnosed at our Institution and herein studied (80% men), with a median age of 60.7 years and a mean affectation of 2.8 organs per patient. We identified six patients with definitive diagnosis and nine with possible IgG4-RD, according to the Japanese diagnostic algorithm. IgG4-RD RI decreased from a median of 11.3 at baseline to 4.0 after 6 months and 6.2 after 12 months. Relapse occurred in five patients and was associated with lower cumulative steroid doses. Five patients (33.3%) required additional immunosuppressive (IS) drugs. Five adverse events were seen during follow-up: three infections, one deep vein thrombosis and one gastrointestinal bleeding. One patient died of pneumonia. Conclusions: IgG4-RD is an inflammatory disease that can affect any organ. Glucocorticoids were an effective first line of treatment; however, this treatment is associated with important adverse events and relapses occurred in patients with low cumulative doses. As an alternative, IS treatment with rituximab could be an interesting option in those patients.
Language	English
Publishing date	2019-04-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2655800-2
ISSN	2048-8513 ; 2048-8505
ISSN (online)	2048-8513
ISSN	2048-8505
DOI	10.1093/ckj/sfz031
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Zs.A 6587: Show issues

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Article ; Online: Diagnosis and clinical management of thrombotic thrombocytopenic purpura (TTP): a consensus statement from the TTP Catalan group.

Blood transfusion = Trasfusione del sangue

2023 Volume 22, Issue 2, Page(s) 176–184

Abstract: Thrombotic thrombocytopenic purpura (TTP) is a low prevalence disease characterized by severe deficiency of the enzyme ADAMTS13, leading to the development of thrombotic microangiopathy (TMA) and often resulting in severe organ disfunction. TTP is an ... ...

Abstract	Thrombotic thrombocytopenic purpura (TTP) is a low prevalence disease characterized by severe deficiency of the enzyme ADAMTS13, leading to the development of thrombotic microangiopathy (TMA) and often resulting in severe organ disfunction. TTP is an extremely serious condition and, therefore, timely and appropriate treatment is critical to prevent life-threatening complications.Over the past 25 years, significant advances in the understanding of the pathophysiology of immune TTP have led to the development of readily available techniques for measuring ADAMTS13 levels, as well as new drugs that are particularly effective in the acute phase and in preventing relapses. These developments have improved the course of the disease.Given the complexity of the disease and its various clinical and laboratory manifestations, early diagnosis and treatment can be challenging.To address this challenge, a group of experienced professionals from the Catalan TTP group have developed this consensus statement to standardize terminology, diagnosis, treatment and follow up for immune TTP, based on currently available scientific evidence in the field. This guidance document aims to provide healthcare professionals with a comprehensive tool to make more accurate and timely diagnosis of TTP and improve patient outcomes.
MeSH term(s)	Humans ; Purpura, Thrombotic Thrombocytopenic/diagnosis ; Purpura, Thrombotic Thrombocytopenic/therapy ; Purpura, Thrombotic Thrombocytopenic/etiology ; Purpura, Thrombocytopenic, Idiopathic ; ADAMTS13 Protein ; Consensus ; von Willebrand Factor ; Recurrence
Chemical Substances	ADAMTS13 Protein (EC 3.4.24.87) ; von Willebrand Factor
Language	English
Publishing date	2023-09-04
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2135732-8
ISSN	2385-2070 ; 0041-1787 ; 1723-2007
ISSN (online)	2385-2070
ISSN	0041-1787 ; 1723-2007
DOI	10.2450/BloodTransfus.522
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