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1.
J Sex Med ; 18(2): 315-326, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33454205

RESUMO

BACKGROUND: Arteriogenic erectile dysfunction is a common disease oftentimes not satisfactory treatable with medical therapy. AIM: To assess the safety and clinical success rate of endovascular revascularization of erection-related arteries with the angiolite BTK stent in patients with arteriogenic erectile dysfunction. METHODS: A total of 100 consecutive men (61.8 ± 10 years) with atherosclerotic lesions in erection-related arteries agreed to participate and were included into a single-center all-comers registry. Endovascular therapy with angiolite BTK drug-eluting stents was performed on a total of 211 lesions. Patients received a baseline International Index of Erectile Function (IIEF)-15 questionnaire at first presentation and 3 and 12 months after stenting. An improvement by 4 points in the erectile function domain consisting of 6 questions (IIEF-6) was defined as minimal clinically important difference. A total of 24 patients with 52 stented arterial lesions underwent angiographic follow-up of the initially treated arterial side during secondary revascularization of the contralateral side (angiographic sub-study). OUTCOME: Clinical improvement of erections in 100 patients undergoing endovascular revascularization of erection-related arteries. RESULTS: No major adverse events occurred during endovascular revascularization or within 30 days thereafter. Technical success was achieved in all lesions and procedural success in all patients. At 1 year, 55 of 97 patients (56.7%) improved by at least 4 points in IIEF-6 score and thus achieved a clinically relevant improvement of erectile function.In the angiographic sub-study, arterial patency and binary restenosis were observed in 46 of 52 (88.5%) and in 8 of 52 (15.4%), respectively, after a mean follow-up of 9.6 ± 5.8 months. CLINICAL IMPLICATIONS: In patients with arteriogenic erectile dysfunction, endovascular therapy with a novel thin-strut sirolimus eluting stent is a safe and feasible treatment option. STRENGTHS & LIMITATIONS: This real-world arterial revascularization registry included patients with a multitude of risk factors for ED, thereby representing the heterogeneity in patients in the clinical practice, which is one of its strengths but also one of its weaknesses. Another strength was the focus being laid on analyzing outcomes of patients with arteriogenic ED using only a single endovascular device. Further studies are warranted to better define subgroups of patients with impaired clinical outcomes. CONCLUSION: Within the present all-comers registry, endovascular therapy of erectile dysfunction with the angiolite BTK stent was shown to be a safe and feasible treatment option resulting in clinical improvement rates comparable to earlier clinical trials although also showing that further research is warranted to define patient subgroups with particular benefits of endovascular therapy. Schönhofen J, Räber L, Knöchel J, et al. Endovascular Therapy for Arteriogenic Erectile Dysfunction With a Novel Sirolimus-Eluting Stent. J Sex Med 2021;18:315-326.


Assuntos
Stents Farmacológicos , Procedimentos Endovasculares , Disfunção Erétil , Stents Farmacológicos/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Disfunção Erétil/terapia , Humanos , Masculino , Sirolimo/efeitos adversos , Stents , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(50): e23291, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327255

RESUMO

BACKGROUND: Interleukin 6 (IL-6) inhibitors are the first-line treatment for idiopathic multicentric Castleman disease (iMCD); however, there is no established treatment for cases that are resistant to IL-6 inhibitors. Although sirolimus, a mammalian target of rapamycin inhibitor, has been suggested to be effective in patients with iMCD, the long-term safety and efficacy of sirolimus on individuals with IL-6 inhibitor-resistant iMCD have not been evaluated. METHODS/DESIGN: In this investigator-initiated, multicenter, open-label trial, the long-term safety of sirolimus will be evaluated in patients participating in a placebo-controlled, randomized, double-blind, parallel-group trial on tocilizumab (TCZ)-resistant iMCD. The study will be conducted in 7 centers in Japan. This trial will be promptly started after the evaluation and examination for 16 weeks in the preceding study. The trial will be completed by the time the drug is approved for iMCD treatment in Japan. The primary endpoint is the incidence of adverse events. The secondary endpoints include the following: the levels of hemoglobin, albumin, and C-reactive protein; change in CHAP score; physician global assessment (100-mm visual analog scale); patient global assessment (100-mm visual analog scale); and lymph node changes in subjects with lymphadenopathy. DISCUSSION: This clinical trial will provide evidence regarding the long-term safety of sirolimus as a potential novel therapeutic agent for patients with tocilizumab-resistant iMCD. TRIAL REGISTRATION NUMBER: jRCT2051200050.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Imunossupressores/uso terapêutico , Sirolimo/uso terapêutico , Método Duplo-Cego , Humanos , Imunossupressores/efeitos adversos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Sirolimo/efeitos adversos , Falha de Tratamento , Resultado do Tratamento
3.
Medicine (Baltimore) ; 99(40): e22596, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019479

RESUMO

BACKGROUND: The pathophysiologic of vascular malformations is still unclear, and the treatment of vascular malformations is a challenge. With improvement in the understanding of pathogenesis of vascular malformations, sirolimus has been a promising and effective treatment. As so far, there is absent convincing evidence to confirm the efficacy of sirolimus for vascular malformations. The purpose of this study was to evaluate the effectiveness and safety of sirolimus in the treatment of vascular malformations. METHODS: The literatures about the management of vascular malformations with sirolimus would be searched from databases of MEDLINE, EMBASE, PubMed, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine Database (CBM), Wan Fang Database, China National Knowledge Infrastructure Database (CNKI), and VIP Science Technology Periodical Database. We will search each database from inception or 1995 to August 20, 2020. Two researchers worked independently on literature selection, data extraction and quality assessment. The efficacy and safety of sirolimus in the treatment of vascular malformations were the main outcomes. Adverse events after sirolimus were evaluated as the secondary outcomes. The included studies will be analyzed by Review Manager 5.3. If the results are applicable, meta-analysis would also be performed. RESULTS: The study will evaluate the efficacy and safety of sirolimus in the treatment of vascular malformations based on current evidence. CONCLUSION: The conclusion of this study will provide more reliable, evidence-based data for the use of sirolimus in the treatment of vascular malformations. PROSPERO REGISTRATION NUMBER: CRD42020167881.


Assuntos
Imunossupressores/uso terapêutico , Sirolimo/uso terapêutico , Malformações Vasculares/tratamento farmacológico , Gerenciamento de Dados , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Projetos de Pesquisa , Segurança , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento , Malformações Vasculares/fisiopatologia
4.
Cochrane Database Syst Rev ; 10: CD012796, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33058158

RESUMO

BACKGROUND: Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors since the publication of a Cochrane Review on targeted therapy for metastatic renal cell carcinoma (mRCC) in 2008. This review represents an update of that original review. OBJECTIVES: To assess the effects of targeted therapies for clear cell mRCC in patients naïve to systemic therapy. SEARCH METHODS: We performed a comprehensive search with no restrictions on language or publication status. The date of the latest search was 18 June 2020. SELECTION CRITERIA: We included randomised controlled trials, recruiting patients with clear cell mRCC naïve to previous systemic treatment. The index intervention was any TKI-based targeted therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the included studies and extracted data for the primary outcomes: progression-free survival (PFS), overall survival (OS) and serious adverse events (SAEs); and the secondary outcomes: health-related quality of life (QoL), response rate and minor adverse events (AEs). We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: We included 18 RCTs reporting on 11,590 participants randomised across 18 comparisons. This abstract focuses on the primary outcomes of select comparisons. 1. Pazopanib versus sunitinib Pazopanib may result in little to no difference in PFS as compared to sunitinib (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.90 to 1.23; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 420 per 1000 in this trial at 12 months, this corresponds to 18 fewer participants experiencing PFS (95% CI 76 fewer to 38 more) per 1000 participants. Pazopanib may result in little to no difference in OS compared to sunitinib (HR 0.92, 95% CI 0.80 to 1.06; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 27 more OSs (95% CI 19 fewer to 70 more) per 1000 participants. Pazopanib may result in little to no difference in SAEs as compared to sunitinib (risk ratio (RR) 1.01, 95% CI 0.94 to 1.09; 1 study, 1102 participants; low-certainty evidence). Based on the control event risk of 734 per 1000 in this trial, this corresponds to 7 more participants experiencing SAEs (95% CI 44 fewer to 66 more) per 1000 participants. 2. Sunitinib versus avelumab and axitinib Sunitinib probably reduces PFS as compared to avelumab plus axitinib (HR 1.45, 95% CI 1.17 to 1.80; 1 study, 886 participants; moderate-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 130 fewer participants experiencing PFS (95% CI 209 fewer to 53 fewer) per 1000 participants. Sunitinib may result in little to no difference in OS (HR 1.28, 95% CI 0.92 to 1.79; 1 study, 886 participants; low-certainty evidence). Based on the control event risk of 890 per 1000 in this trial at 12 months, this would result in 29 fewer OSs (95% CI 78 fewer to 8 more) per 1000 participants. Sunitinib may result in little to no difference in SAEs (RR 1.01, 95% CI 0.93 to 1.10; 1 study, 873 participants; low-certainty evidence). Based on the control event risk of 705 per 1000 in this trial, this corresponds to 7 more SAEs (95% CI 49 fewer to 71 more) per 1000 participants.  3. Sunitinib versus pembrolizumab and axitinib Sunitinib probably reduces PFS as compared to pembrolizumab plus axitinib (HR 1.45, 95% CI 1.19 to 1.76; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 590 per 1000 in this trial at 12 months, this corresponds to 125 fewer participants experiencing PFS (95% CI 195 fewer to 56 fewer) per 1000 participants. Sunitinib probably reduces OS (HR 1.90, 95% CI 1.36 to 2.65; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 880 per 1000 in this trial at 12 months, this would result in 96 fewer OSs (95% CI 167 fewer to 40 fewer) per 1000 participants. Sunitinib may reduce SAEs as compared to pembrolizumab plus axitinib (RR 0.90, 95% CI 0.81 to 1.02; 1 study, 854 participants; low-certainty evidence) although the CI includes the possibility of no effect. Based on the control event risk of 604 per 1000 in this trial, this corresponds to 60 fewer SAEs (95% CI 115 fewer to 12 more) per 1000 participants.  4. Sunitinib versus nivolumab and ipilimumab Sunitinib may reduce PFS as compared to nivolumab plus ipilimumab (HR 1.30, 95% CI 1.11 to 1.52; 1 study, 847 participants; low-certainty evidence). Based on the control event risk of 280 per 1000 in this trial at 30 months' follow-up, this corresponds to 89 fewer PFSs (95% CI 136 fewer to 37 fewer) per 1000 participants. Sunitinib reduces OS (HR 1.52, 95% CI 1.23 to 1.89; 1 study, 847 participants; high-certainty evidence). Based on the control event risk 600 per 1000 in this trial at 30 months, this would result in 140 fewer OSs (95% CI 219 fewer to 67 fewer) per 1000 participants. Sunitinib probably increases SAEs (RR 1.37, 95% CI 1.22 to 1.53; 1 study, 1082 participants; moderate-certainty evidence). Based on the control event risk of 457 per 1000 in this trial, this corresponds to 169 more SAEs (95% CI 101 more to 242 more) per 1000 participants. AUTHORS' CONCLUSIONS: Based on the low to high certainty of evidence, several combinations of immune checkpoint inhibitors appear to be superior to single-agent targeted therapy in terms of PFS and OS, and with a favourable AE profile. Some single-agent targeted therapies demonstrated a similar or improved oncological outcome compared to others; minor differences were observed for AE within this group. The certainty of evidence was variable ranging from high to very low and all comparisons were based on single trials.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Axitinibe/efeitos adversos , Axitinibe/uso terapêutico , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Viés , Carcinoma de Células Renais/mortalidade , Everolimo/efeitos adversos , Everolimo/uso terapêutico , Humanos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Qualidade de Vida , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Sorafenibe/efeitos adversos , Sorafenibe/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Sunitinibe/efeitos adversos , Sunitinibe/uso terapêutico
5.
Transplantation ; 104(8): 1686-1694, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732848

RESUMO

BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). RESULTS: Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.


Assuntos
Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Imunossupressores/efeitos adversos , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR/imunologia , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Resultado do Tratamento
6.
Ann Hematol ; 99(8): 1771-1778, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32601796

RESUMO

Mantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T3 phase Ib clinical trial, we investigated the recommended dose of temsirolimus in association with R-CHOP (R-CHOP-T), or high-dose cytarabine plus rituximab (R-DHA-T), or fludarabine, cyclophosphamide plus rituximab (R-FC-T). From November 11, 2011 to February 26, 2015, forty-one patients were enrolled. Patients presented with high MIPI (47.5%) at relapse and a median number of treatments of 1 (1-3). Patients were treated by R-CHOP-T (n = 10), R-FC-T (n = 14), or R-DHA-T (n = 17) according to the choice of local investigators. The maximum tolerated dose (MTD) was 15 mg in the R-CHOP-T arm and has not been determined in other treatment arms because of toxicities. All patients experienced ≥ Grade 3 adverse events, mainly thrombocytopenia (76%). Twenty-six patients discontinued prematurely the treatment, mostly for toxicity (n = 12) and progression of the disease (n = 8). Of note, 6 patients of the R-DHA-T arm reached complete remission (35%). Temsirolimus with immuno-chemotherapy is associated with a high rate of toxicities. Determination of MTD could only be achieved for R-CHOP-T arm. Associations between temsirolimus and other targeted therapies may be warranted for R/R MCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia , Linfoma de Célula do Manto/terapia , Sirolimo/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Trombocitopenia/mortalidade , Vincristina/administração & dosagem , Vincristina/efeitos adversos
7.
J Endovasc Ther ; 27(5): 683-690, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32666871

RESUMO

Purpose: To evaluate the safety and efficacy of the novel SELUTION sustained-limus-release (SLR) drug-eluting balloon (DEB) in the treatment of femoropopliteal lesions. Materials and Methods: Between October 2016 and May 2017, 50 subjects (mean age 69.6±10.4 years; 29 men) with symptomatic moderate to severe lower limb ischemia (Rutherford categories 2 or 3) were enrolled at 4 German centers for the SELUTION SLR first-in-human trial (ClinicalTrials.gov NCT02941224). The SELUTION SLR utilizes micro-reservoirs (biodegradable polymer spheres containing sirolimus) embedded within an amphipathic membrane coated onto an angioplasty balloon. The biodegradable reservoirs are transferred to the target vessel lumen during brief balloon inflation. The primary trial objective was comparison of angiographic late lumen loss at 6 months against an objective performance criterion (OPC) value of 1.04 mm for uncoated balloon angioplasty. Secondary endpoints included device, procedural, and clinical success; clinical and imaging assessments of primary patency and restenosis; functional assessments including Rutherford category and ankle-brachial index (ABI); and major adverse events [composite of cardiovascular mortality, index limb amputation, target limb thrombosis, and clinically-driven target lesion revascularization (CD-TLR)]. Results: At 6 months, median angiographic late lumen loss following SELUTION SLR treatment was 0.19 mm (range -1.16 to 3.07). Mean angiographic late lumen loss (n=34) was 0.29±0.84 mm (95% CI -0.01 to 0.58), significantly lower than the 1.04-mm OPC value (p<0.001). The rate of primary patency by duplex ultrasound was 88.4%, and freedom from angiographic binary restenosis was 91.2%. Through 6 months, there was significant improvement over baseline in Rutherford categories (p<0.001) and in ABI measurements (p<0.001). A single case (2%) of CD-TLR occurred at 5 months. There were no other major adverse events. Conclusion: Through 6 months, the SELUTION SLR DEB appears to inhibit restenosis effectively and safely, improving outcomes in subjects with symptomatic femoropopliteal disease.


Assuntos
Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Artéria Femoral , Isquemia/terapia , Doença Arterial Periférica/terapia , Artéria Poplítea , Sirolimo/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Constrição Patológica , Preparações de Ação Retardada , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Alemanha , Humanos , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
8.
Gastroenterol Hepatol ; 43(8): 457-463, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32646657

RESUMO

SARS-CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS-CoV-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on SARS-CoV-2 infection, and suggests guidelines for the management of immunosuppression.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Fígado , Pandemias , Pneumonia Viral/epidemiologia , Imunidade Adaptativa , Antivirais/farmacologia , Betacoronavirus/imunologia , Betacoronavirus/fisiologia , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacologia , Inibidores de Calcineurina/uso terapêutico , Contraindicações de Medicamentos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças , Interações Medicamentosas , Everolimo/efeitos adversos , Everolimo/farmacologia , Everolimo/uso terapêutico , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Imunidade Inata , Hospedeiro Imunocomprometido , Imunossupressão/métodos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/farmacologia , Ácido Micofenólico/uso terapêutico , Pneumonia Viral/imunologia , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/prevenção & controle , Sirolimo/efeitos adversos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores
9.
JACC Cardiovasc Interv ; 13(9): 1100-1109, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32381186

RESUMO

OBJECTIVES: The aim of this study was to assess 2-year safety and efficacy of the current-generation thin composite-wire-strut durable-polymer Resolute Onyx zotarolimus-eluting stent (ZES), compared with the ultrathin-strut biodegradable-polymer Orsiro sirolimus-eluting stent (SES) in all-comers and a pre-specified small-vessel subgroup analysis. BACKGROUND: The Resolute Onyx ZES is widely used in clinical practice, but no follow-up data beyond 1 year have been published. The randomized BIONYX (Bioresorbable Polymer-Coated Orsiro Versus Durable Polymer-Coated Resolute Onyx Stents) trial (NCT02508714) established the noninferiority of ZES versus SES regarding target vessel failure (TVF) rates. METHODS: A total of 2,488 all-comer patients were treated at 7 coronary intervention centers in Belgium, Israel, and the Netherlands. The main endpoint, TVF, was a composite of safety (cardiac death or target vessel-related myocardial infarction) and efficacy (clinically indicated target vessel revascularization). Two-year follow-up data were analyzed using Kaplan-Meier methods. RESULTS: Two-year follow-up data were available for 2,460 of 2,488 patients (98.9%). TVF occurred in 93 of 1,243 patients (7.6%) assigned to ZES versus 87 of 1,245 patients (7.1%) assigned to SES (log-rank p = 0.66). There was no significant between-stent difference in individual components of this endpoint. The incidence of definite-or-probable stent thrombosis was low for both treatment arms (0.4% vs. 1.1%; log-rank p = 0.057). In patients stented in small vessels, there was no between-stent difference (TVF 8.2% vs. 8.7% [log-rank p = 0.75], target lesion revascularization 4.0% vs. 4.4% [log-rank p = 0.77]). CONCLUSIONS: At 2-year follow-up, the novel thin composite-wire-strut durable-polymer Resolute Onyx ZES showed in all-comers similar safety and efficacy compared with the ultrathin cobalt-chromium-strut biodegradable-polymer Orsiro SES. The analysis of patients who were treated in small vessels also suggested no advantage for either stent.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Sirolimo/análogos & derivados , Idoso , Bélgica , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Trombose Coronária/etiologia , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Países Baixos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Desenho de Prótese , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
10.
Transplant Proc ; 52(6): 1950-1952, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32444121

RESUMO

OBJECTIVE: Thrombocytopenia is a common condition in patients undergoing liver transplantation (LT). Thrombocytopenia is prevalent in early postoperative phase, and it gradually improves after several weeks. Delayed severe thrombocytopenia occurring after the initial recovery of platelets is rare. We report a case of a patient with delayed severe thrombocytopenia 59 weeks after LT. CASE PRESENTATION: Our patient was a 61-year-old man who presented to our institution 59 weeks after undergoing LT. He presented for removal of a bile duct stent that was inserted 3 months prior. Tacrolimus replaced sirolimus for immunosuppression during the seventh week after transplantation due to sirolimus-induced nephrotoxicity. On admission, the patient's vital signs were normal and his physical examination was unremarkable. Laboratory parameters demonstrated that the platelet (PLT) level was significantly decreased to 18 × 109/L. PLTs reached a nadir of 3 × 109/L even after utilization of interleukin-11, thrombopoietin, and low-dose prednisone. Although rare, sirolimus toxicity was suspected. Therefore, sirolimus was gradually replaced by cyclosporin A in combination with low-dose prednisone. Subsequently, a normal PLT level was gradually recovered. This study was approved by the ethical committee of the First Hospital of Jilin University and was performed in accordance with the ethical standards of the Helsinki Congress and Istanbul Declaration. CONCLUSIONS: Recurrent delayed severe thrombocytopenia is rare after LT. Sirolimus toxicity might be a reason for its occurrence if other possible factors are excluded. After diagnosis, sirolimus therapy should be discontinued and patients should be treated with an alternative immunosuppressive regimen.


Assuntos
Imunossupressores/efeitos adversos , Transplante de Fígado , Complicações Pós-Operatórias/induzido quimicamente , Sirolimo/efeitos adversos , Trombocitopenia/induzido quimicamente , Ciclosporina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Tacrolimo/uso terapêutico
11.
Jpn J Clin Oncol ; 50(8): 940-947, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32458996

RESUMO

OBJECTIVE: A prospective, observational, post-marketing surveillance was conducted to assess the safety and effectiveness of temsirolimus in patients with renal cell carcinoma in Japan. METHODS: Patients prescribed temsirolimus for advanced renal cell carcinoma were registered and received temsirolimus (25 mg weekly, intravenous infusion for 30-60 minutes) in routine clinical settings (observation period: 96 weeks). RESULTS: Among 1001 patients included in the safety analysis data set (median age, 65.0 years; men, 74.8%; Eastern Cooperative Oncology Group performance status 0 or 1, 69.6%), 778 (77.7%) reported adverse drug reactions. The most common (≥10%) all-grade adverse drug reactions were stomatitis (26.7%), interstitial lung disease (17.3%) and platelet count decreased (11.1%). The incidence rate of grade ≥3 interstitial lung disease was 4.5%. The onset of interstitial lung disease was more frequent after 4-8 weeks of treatment or in patients with lower Eastern Cooperative Oncology Group performance status (21.6% for score 0 vs 8.3% for score 4, P < 0.001). Among 654 patients in the effectiveness analysis data set, the response and clinical benefit rates were 6.7% (95% confidence interval 4.9-8.9) and 53.2% (95% confidence interval 49.3-57.1), respectively. The median progression-free survival was 18.3 weeks (95% confidence interval 16.9-21.1). CONCLUSIONS: The safety and effectiveness profile of temsirolimus observed in this study was similar to that observed in the multinational phase 3 study. The results are generalizable to the real-world scenario at the time of this research, and safety and effectiveness of temsirolimus as a subsequent anticancer therapy for renal cell carcinoma warrants further investigation. (ClinicalTrials.gov identifier NCT01210482, NCT01420601).


Assuntos
Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Vigilância de Produtos Comercializados , Sirolimo/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Japão , Neoplasias Renais/patologia , Doenças Pulmonares Intersticiais/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Resultado do Tratamento
12.
JACC Cardiovasc Interv ; 13(7): 820-830, 2020 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-32273094

RESUMO

OBJECTIVES: The aim of this study was to determine 1-year safety and efficacy after treatment with the COMBO and Orsiro stents. BACKGROUND: The COMBO stainless-steel stent has an anti-CD34+ antibody coating to capture endothelial progenitor cells, thereby promoting faster endothelialization. The Orsiro is an ultrathin-strut cobalt-chromium stent, covered by an extremely thin layer of amorphous silicon carbide to minimize ion leakage. Both devices elute sirolimus from biodegradable polymers. METHODS: For this analysis we included European patients from the COMBO collaboration, a patient-level pooling of 2 prospective all-comers registries of COMBO stent implantation (n = 2,775), and all patients randomized to the Orsiro stent (n = 1,169) from the Dutch BIO-RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population) randomized trial. The main outcome of interest was 1-year target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization evaluated using propensity score-matched analysis. RESULTS: At baseline, COMBO patients were older and had more insulin-treated diabetes, renal insufficiency, and other comorbidities. However, Orsiro patients included more current smokers and more acute coronary syndrome presentations. Orsiro patients also received longer stents and had more complex target lesions. After propensity score-matched analysis (n = 862/arm), 1-year target lesion failure occurred in 4.1% of COMBO-treated and 2.7% of Orsiro-treated patients (hazard ratio: 1.55; 95% confidence interval: 0.92 to 2.62; p = 0.10). Definite stent thrombosis occurred in 0.5% of COMBO-treated and 0.5% of Orsiro-treated patients (p = 0.99). CONCLUSIONS: A propensity score-matched comparison of all comers treated with the COMBO or Orsiro stent showed no statistically significant differences. Stent thrombosis risk was low and similar between the stents. (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population [BIO-RESORT], NCT01674803; MASCOT-Post Marketing Registry [MASCOT], NCT02183454; Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE Reg], NCT01874002).


Assuntos
Implantes Absorvíveis , Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Polímeros/química , Sirolimo/administração & dosagem , Idoso , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/etiologia , Bases de Dados Factuais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Pontuação de Propensão , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Medição de Risco , Fatores de Risco , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Transplant Proc ; 52(3): 767-774, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32192743

RESUMO

BACKGROUND: Sirolimus is approved for prophylaxis of organ rejection following renal transplantation. Rates of treatment-emergent adverse events (TEAEs) leading to sirolimus discontinuation differ geographically. METHODS: Rates of TEAEs, serious AEs (SAEs), and discontinuations were evaluated in 3 clinical trials of conversion from calcineurin inhibitors to sirolimus. Posttransplantation, patients were treated over 4 years (study 1), over 1 year (study 2), and over 2 years (study 3). TEAEs, SAEs, and discontinuation rates were compared between Latin America (LATAM) vs North America (NA) and Europe/rest of world (EU/ROW). Data from studies 2 and 3, with similar times to conversion, were pooled. RESULTS: Study 1 comprised 551 patients (LATAM, n=189); studies 2/3 comprised 395 (LATAM, n=111). LATAM patients were significantly younger than NA or EU/ROW patients in study 1 and studies 2/3 (P < .0001), with a lower proportion of white patients and higher proportion of patients of other races in LATAM vs NA (P < .0001) and EU/ROW (P = .02) groups. Almost all patients reported TEAEs. Discontinuation because of medical events was significantly lower (P < .05) in LATAM vs NA or EU/ROW. Hypercholesterolemia and hypertriglyceridemia were more common, and anemia and peripheral edema less common in LATAM; diarrhea and proteinuria did not differ by region. Types of AEs leading to discontinuation did not differ by region. CONCLUSION: LATAM renal transplant recipients converted to sirolimus were more likely to remain on therapy than patients in other regions.


Assuntos
Imunossupressores/efeitos adversos , Sirolimo/efeitos adversos , Adulto , Europa (Continente) , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Transplante de Rim , América Latina , Masculino , Pessoa de Meia-Idade , América do Norte , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos
15.
Expert Rev Med Devices ; 17(4): 257-265, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32154750

RESUMO

Introduction: The increasing complexity of patients undergoing percutaneous coronary intervention (PCI) regarding both coronary anatomy and comorbidities requires dedicated devices. The Resolute Onyx (R-Onyx, Medtronic, CA, USA) stent is a novel durable polymer zotarolimus-eluting stent (ZES) promising better deliverability, increased radiopacity and lower thrombogenicity.Areas covered: In this review, we discuss device features, preclinical evidence, and clinical studies including patients treated with R-Onyx. The BIONYX and Onyx ONE studies were two major landmark trials demonstrating non-inferiority of R-Onyx as compared to other latest generation devices. We also elaborate on alternative innovations in drug-eluting stent (DES) technology and how R-Onyx fits into this field.Expert opinion: R-Onyx is designed to address the challenges of contemporary PCI, but evidence on its clinical performance is largely derived from studies on older generation devices from the ZES family. Nonetheless, all clinical studies on R-Onyx consistently show excellent outcomes, with particularly low rates of stent thrombosis, making it a promising candidate for short dual antiplatelet regimens. In addition, R-Onyx is available with a wide range of stent diameters allowing accurate sizing for both very small and very large coronary vessels.


Assuntos
Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Sirolimo/análogos & derivados , Ensaios Clínicos como Assunto , Humanos , Desenho de Prótese , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Resultado do Tratamento
16.
Circ Cardiovasc Interv ; 13(3): e008525, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32160779

RESUMO

BACKGROUND: There is limited data comparing the Xience everolimus-eluting stent (EES) and the Resolute zotarolimus-eluting stent (ZES) with the BioMatrix biolimus-eluting stent (BES). METHODS: This open-label, randomized, noninferiority trial enrolled all-comer patients to be randomly treated with either BES, EES, or ZES in a 1:1:1 ratio in 15 centers across South Korea. The primary end point was a device-oriented composite outcome consisting of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization at 24 months. The BES was compared with the EES and the ZES by intention-to-treat analyses with a noninferiority margin of 3.8%, respectively. RESULTS: Because of slow recruitment and low event rates, this trial was prematurely terminated after enrollment of 1935 (75%) of the intended 2580 patients. Of the 1911 patients randomized to either EES (n=638), BES (n=634), or ZES (n =639), the rate of device-oriented composite outcome was 3.6%, 2.2%, and 3.9%, respectively, at 24 months (BES versus EES: absolute risk difference -1.4% [upper limit of 1-sided 95% CI: -3.2%]; P for noninferiority <0.001; BES versus ZES: absolute risk difference -1.7% [upper limit of 1-sided 95% CI: -3.6%]; P for noninferiority <0.001). CONCLUSIONS: The BES was noninferior to either the EES or the ZES in all-comer patients for device-oriented composite outcome at the 24-month follow-up. However, caution is advised regarding interpretation of these results due to the premature termination of this study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01397175.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Stents Farmacológicos , Everolimo/administração & dosagem , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea/instrumentação , Sirolimo/análogos & derivados , Idoso , Fármacos Cardiovasculares/efeitos adversos , Término Precoce de Ensaios Clínicos , Everolimo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Desenho de Prótese , Recidiva , República da Coreia , Fatores de Risco , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Resultado do Tratamento
17.
Cardiovasc Drugs Ther ; 34(3): 335-344, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32212061

RESUMO

OBJECTIVES: The objective of this post hoc analysis was to analyze real-world dual antiplatelet therapy (DAPT) regimens following polymer-free sirolimus-eluting stent (PF-SES) implantations in an unselected patient population. METHODS: Patient-level data from two all-comers observational studies (ClinicalTrials.gov Identifiers: NCT02629575 and NCT02905214) were pooled and analyzed in terms of their primary endpoint. During the data verification process, we observed substantial deviations from DAPT guideline recommendations. To illuminate this gap between clinical practice and guideline recommendations, we conducted a post hoc analysis of DAPT regimens and clinical event rates for which we defined the net adverse event rate (NACE) consisting of target lesion revascularization (TLR, primary endpoint of all-comers observational studies) all-cause death, myocardial infarction (MI), stent thrombosis (ST), and bleeding events. A logistic regression was utilized to determine predictors why ticagrelor was used in stable coronary artery disease (CAD) patients instead of the guideline-recommended clopidogrel. RESULTS: For stable CAD, the composite endpoint of clinical, bleeding, and stent thrombosis, i.e., NACE, between the clopidogrel and ticagrelor treatment groups was not different (5.4% vs. 5.1%, p = 0.745). Likewise, in the acute coronary syndrome (ACS) cohort, the NACE rates were not different between both DAPT strategies (9.2% vs. 9.3%, p = 0.927). There were also no differences in the accumulated rates for TLR, myocardial infarction ([MI], mortality, bleeding events, and stent thrombosis in elective and ACS patients. The main predictors for ticagrelor use in stable CAD patients were age < 65 years, smaller vessels, treatment of ostial and calcified lesions, and in-stent restenosis. CONCLUSION: Within the framework of a post hoc analysis based on a real-world, large cohort study, there were no differences in the combined endpoint of major adverse cardiac events (MACE), bleeding and thrombotic events for clopidogrel and ticagrelor in stable CAD or ACS patients. Despite the recommendation for clopidogrel by the European Society of Cardiology (ESC), real-world ticagrelor use was observed in subgroups of stable CAD patients that ought to be explored in future trials.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/administração & dosagem , Sirolimo/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/etiologia , Trombose Coronária/prevenção & controle , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/mortalidade , Feminino , Fidelidade a Diretrizes , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Desenho de Prótese , Medição de Risco , Fatores de Risco , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
18.
Respir Res ; 21(1): 55, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059669

RESUMO

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare, low-grade multisystem neoplastic disease. Most LAM patients are at a high risk of losing lung function at an accelerated rate and developing progressive dyspnea. Recently, several studies have reported their experience with pharmacological treatments for LAM. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy and safety of these therapies. METHODS: PubMed (Medline), EMBASE, Cochrane Library, Web of Science and EBSCO Host were searched (until March 31, 2019) for eligible prospective studies regarding LAM patients treated with pharmacological treatments. Random effect models were used for quantitative analysis. RESULTS: Fourteen prospective studies regarding five pharmacological treatments (including sirolimus, everolimus, doxycycline, triptorelin, and a combination therapy of sirolimus and hydroxychloroquine) were enrolled in our systematic review, and ten of them were used for the meta-analysis. Seven prospective studies reported that sirolimus was effective at improving or stabilizing lung function and alleviating renal angiomyolipoma (AML) in LAM patients. Subsequent quantitative analyses showed that during sirolimus treatment, the pooled values of lung function and 6-min walk distance (6MWD) were not significantly changed (P > 0.05), with the pooled response rate of AML being 0.62 (95% confidence intervals [CIs]: 0.43 to 0.82, I2 = 65%). Regarding everolimus, three prospective studies reported similar effects to those of sirolimus with regard to preserving lung function and reducing AMLs. The meta-analysis showed that the changes in lung function during everolimus treatment were not statistically significant (P > 0.05), while the pooled response rate of AML was 0.78 (95% CI: 0.68 to 0.88, I2 = 8%). Neither the qualitative nor the quantitative results confirmed the benefits of doxycycline or triptorelin treatment, and the effects of the combination therapy were unclear in LAM patients. Most of the adverse events during pharmacological treatments were low or moderate grade and tolerable. CONCLUSIONS: Overall, sirolimus and everolimus were recommended for the treatment of LAM because they could stabilize lung function and alleviate renal AML. Doxycycline and triptorelin were not recommended for the treatment of LAM because no beneficial outcomes were consistently observed. The efficacy and safety of combination therapy remain to be further explored.


Assuntos
Antineoplásicos/administração & dosagem , Everolimo/administração & dosagem , Linfangioleiomiomatose/diagnóstico , Linfangioleiomiomatose/tratamento farmacológico , Sirolimo/administração & dosagem , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto/métodos , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Everolimo/efeitos adversos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Hiperlipidemias/induzido quimicamente , Linfangioleiomiomatose/epidemiologia , Estudos Prospectivos , Sirolimo/efeitos adversos , Estomatite/induzido quimicamente , Resultado do Tratamento
19.
Ann Hematol ; 99(4): 737-741, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32030447

RESUMO

For patients with pure red cell aplasia (PRCA), cyclosporine (CsA) is the first line therapy. Occasionally, some patients who suffer from renal insufficiency cannot tolerate CsA. To explore the efficacy and tolerance of sirolimus treatment for those patients, twelve PRCA patients with renal insufficiency from May 2014 to May 2018 in Peking Union Medical College Hospital were enrolled, treated with sirolimus, and followed up at the median time of 16 (10-50) months. Eleven patients (91.7%) responded to sirolimus, with 58.3% complete response (CR) and 41.7% partial response (PR). The median time to achieve the optimum effect was 4 (1-7) months. The serum creatinine level remained stable or even reduced during the treatment period for eleven patients. Seven patients (58.3%) reported adverse events during sirolimus therapy, including increased blood glucose, infection, skin rash, elevated triglyceride or total cholesterol, and elevated serum creatinine compared with baseline. No treatment-related death was noticed during the follow-up time. Three patients relapsed with an overall response rate of 75.0% at 1 year. These results suggested that sirolimus was effective and tolerable for patients with PRCA complicated with renal insufficiency.


Assuntos
Imunossupressores/uso terapêutico , Aplasia Pura de Série Vermelha/tratamento farmacológico , Insuficiência Renal/etiologia , Sirolimo/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/sangue , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Erupção por Droga/etiologia , Avaliação de Medicamentos , Substituição de Medicamentos , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Hipertrigliceridemia/induzido quimicamente , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Aplasia Pura de Série Vermelha/complicações , Indução de Remissão , Insuficiência Renal/sangue , Estudos Retrospectivos , Sirolimo/efeitos adversos , Resultado do Tratamento
20.
Cardiovasc Revasc Med ; 21(4): 540-548, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31952919

RESUMO

Advances in stent design and the development of bioresorbable polymers have allowed the development of novel stent technologies such as the Orsiro bioresorbable-polymer sirolimus eluting stent (BP-SES). Over several noninferiority trials, the BP-SES has demonstrated itself to be a safe and effective therapy for obstructive coronary artery disease. This article reviews the current evidence of the efficacy of the BP-SES and examines its performance in high-risk populations, such as patients presenting with ST-segment myocardial infarction, chronic total occlusions, diabetes, and small vessel disease.


Assuntos
Implantes Absorvíveis , Síndrome Coronariana Aguda/terapia , Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Sirolimo/administração & dosagem , Síndrome Coronariana Aguda/diagnóstico por imagem , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Desenho de Prótese , Fatores de Risco , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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