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1.
Clin Transplant ; 37(12): e15132, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37705362

RESUMO

In this project, we describe proteasome inhibitor (PI) treatment of antibody-mediated rejection (AMR) in heart transplantation (HTX). From January 2018 to September 2021, 10 patients were treated with PI for AMR: carfilzomib (CFZ) n = 8; bortezomib (BTZ) n = 2. Patients received 1-3 cycles of PI. All patients had ≥1 strong donor-specific antibody (DSA) (mean fluorescence intensity [MFI] > 8000) in undiluted serum. Most DSAs (20/21) had HLA class II specificity. The MFI of strong DSAs had a median reduction of 56% (IQR = 13%-89%) in undiluted serum and 92% (IQR = 53%-95%) at 1:16 dilution. Seventeen DSAs in seven patients were reduced > 50% at 1:16 dilution after treatment. Four DSAs from three patients did not respond. DSA with MFI > 8000 at 1:16 dilution was less responsive to treatment. 60% (6/10) patients presented with graft dysfunction; 4/6 recovered ejection fraction > 40% after treatment. Pathologic AMR was resolved in 5/7 (71.4%) of patients within 1 year after treatment. 9/10 (90%) patients survived to 1 year after AMR diagnosis. Using PI in AMR resulted in significant DSA reduction with some resolution of graft dysfunction. Larger studies are needed to evaluate PI for AMR.


Assuntos
Transplante de Coração , Transplante de Rim , Humanos , Inibidores de Proteassoma/uso terapêutico , Isoanticorpos , Transplante de Rim/efeitos adversos , Antígenos HLA , Doadores de Tecidos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Estudos Retrospectivos
2.
Artif Organs ; 47(2): 361-369, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36271639

RESUMO

BACKGROUND: Impella 5.5 (Abiomed; Danvers, MA) (IMP5) is a commonly used, surgically implanted, tMCS device that requires systemic anticoagulation and purge solution to avoid pump failure. To avoid heparin-induced thrombocytopenia (HIT) from unfractionated heparin (UFH) use, our program has explored the utility of bivalirudin (BIV) for systemic anticoagulation and sodium bicarbonate-dextrose purge solution (SBPS) in IMP5.5. METHODS: This single center, retrospective study included 34 patients supported on IMP5.5 with BIV based AC and SBPS between December 1st 2020 to December 1st 2021.The efficacy and safety end points were incidence of development of HIT, Tissue Plasminogen Activator (tPA) use for suspected pump thrombosis, stroke, and device failure as well as clinically significant bleeding. RESULTS: The median duration of IMP5.5 support was 9.8 days (IQR: 6-15). Most patients were bridged to HTX (58%) followed by recovery (27%) and LVAD implantation (15%). Patients were therapeutic on bivalirudin for 64% of their IMP5.5 support. One patient (2.9%) suffered from ischemic stroke and 26.5% (9) patients developed clinically significant bleeding. tPA was administered to 7(21%) patients. One patient in the entire cohort developed HIT. CONCLUSIONS: Our experience supports the use of systemic BIV and SBPS as a method to avoid heparin exposure in a patient population predisposed to the development of HIT.


Assuntos
Heparina , Trombocitopenia , Humanos , Heparina/efeitos adversos , Anticoagulantes/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Bicarbonato de Sódio , Estudos Retrospectivos , Hirudinas/efeitos adversos , Fragmentos de Peptídeos/efeitos adversos , Hemorragia/induzido quimicamente , Proteínas Recombinantes/efeitos adversos , Resultado do Tratamento
3.
Ann Pharmacother ; 50(1): 47-59, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26416949

RESUMO

OBJECTIVE: To evaluate the place in therapy of fresh frozen plasma (FFP), C1 esterase concentrate (C1-INH), ecallantide, and icatibant in the management of angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-IA). DATA SOURCES: A literature search was performed using PubMed (1946 through August 2015) and Embase (<1966 through August 2015). References from identified articles were reviewed. STUDY SELECTION AND DATA EXTRACTION: Consensus papers, practice guidelines, case reports/series, clinical trials, and meeting abstracts published in English and involving humans were included. DATA SYNTHESIS: No medications are currently Food and Drug Administration-approved for managing ACEI-IA. Emerging evidence suggests that FFP and medications approved for management of acute attacks of hereditary angioedema, another bradykinin-mediated event, may be effective for use in ACEI-IA. Positive efficacy results were reported with FFP and C1-INH while mixed results have been seen with ecallantide. Off-label icatibant has the most evidence supporting its use in ACEI-IA with rapid symptom resolution (10 minutes to 6 hours) and avoidance of intubation and tracheotomy in several cases. These agents were well-tolerated in ACEI-IA. CONCLUSION: ACEI-IA is typically a self-limiting event. First-line therapies include ACEI discontinuation, observation, and supportive medications (eg, corticosteroids, antihistamines, and epinephrine). Symptom progression can be life-threatening and may require interventions such as tracheotomy and intubation. Off-label use of FFP and medications approved for hereditary angioedema have resulted in rapid resolution of symptoms and avoidance of intubation. Among these agents, icatibant has the most supporting evidence and has been incorporated into practice guidelines and algorithms as a second-line agent for serious life-threatening ACE-IA.


Assuntos
Angioedema/induzido quimicamente , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Angioedema/terapia , Angioedemas Hereditários/tratamento farmacológico , Bradicinina/análogos & derivados , Bradicinina/uso terapêutico , Complemento C1s/uso terapêutico , Humanos , Uso Off-Label , Peptídeos/uso terapêutico , Plasma , Estados Unidos
4.
J Crit Care ; 66: 166-172, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34301439

RESUMO

PURPOSE: Three continuous dosing strategies of cisatracurium (CIS) for acute respiratory distress syndrome (ARDS) have been described in the literature. After implementation of a ventilator synchrony protocol (VSP), we sought to determine which continuous CIS dosing strategy utilized the least amount of drug without compromising efficacy. METHODS: We retrospectively reviewed patients with ARDS receiving continuous CIS from January 1, 2013 to December 31, 2018. We categorized patients into one of three dosing strategies: fixed dose (FD), titration based solely on train-of-four (TOF), or the VSP. We documented drug consumption and determined efficacy by comparing the change in PaO2/FiO2 ratio (P/F) and oxygenation index (OI) from baseline up to 48 h. RESULTS: A total of 1047 patients were screened, and 189 met inclusion criteria (VSP = 69, TOF = 99, FD = 21). Drug consumption (mg) was significantly lower in the VSP arm: 415 [IQR 318-528] compared to both the TOF: 665 [IQR 472-927] and the FD arms: 1730 [IQR 1695-1800], p < 0.001 for each. The change in P/F and OI from baseline were statistically equivalent at all time points. CONCLUSION: Without impacting efficacy of gas exchange, a protocol using ventilator synchrony for CIS titration required significantly less drug compared to TOF-based titration and a fixed dosing regimen.


Assuntos
Síndrome do Desconforto Respiratório , Atracúrio/análogos & derivados , Uso de Medicamentos , Humanos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Estudos Retrospectivos
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