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1.
Autops. Case Rep ; 9(4): e2019112, Oct.-Dec. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1024207

RESUMO

Renal transplant patients are treated with immunosuppressive drugs that decrease the effectiveness of the immune system, making them more prone to developing cancer. Skin and lip carcinomas are common malignancies encountered after transplantation, whereas oral carcinomas are rare. We report the case of a 51-year-old female Caucasian patient, with no history of smoking, who presented white lesions on the tongue and an ulcerated lesion on the lower lip beginning 4 months prior. Diagnosis of squamous cell carcinoma for both lesions was made following incisional biopsies. Interestingly, the patient reported a renal transplantation 23 years prior, and was maintained on a combination of cyclosporine, mycophenolate sodium and prednisone. The patient also presented a history of several basal and squamous cell carcinomas on sun-exposed areas of the skin. Both lesions were surgically excised. No sign of recurrence or new lesions in the oral cavity have been observed; however, new skin lesions are frequently diagnosed. This case report highlights that oral cancers may occur in transplant patients in the absence of classical risk factors. Thus, clinicians must be aware of the importance of thorough oral examination in transplant patients in routine follow-up.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Bucais/etiologia , Neoplasias Bucais/patologia , Neoplasias Bucais/prevenção & controle , Carcinoma de Células Escamosas/patologia , Transplante de Rim/efeitos adversos , Imunossupressores/efeitos adversos
3.
BMC Complement Altern Med ; 19(1): 322, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752816

RESUMO

BACKGROUND: Platycodon grandiflorum is a flowering plant that is used in traditional medicine for treating pulmonary and respiratory disorders. It exerts various pharmacological effects, including immunomodulatory and anti-cancer activities. The purpose of this study was to confirm the in vitro and in vivo immune-enhancing effects of P. grandiflorum extract (PGE) on splenocytes isolated from cyclophosphamide (CP)-induced immunosuppressed rats. METHODS: For in vitro analysis, splenocytes were treated with PGE at various doses along with CP. Cell viability was measured by a WST-1 assay, and NK cell activity and cytotoxic T lymphocyte (CTL) activity was also examined. In addition, immunoglobulin A (IgA), IgG, and cytokine levels were measured. For in vivo analysis, Sprague Dawley rats were treated with various doses of PGE along with CP. Complete blood count (CBC) was performed, and plasma levels of IgA, IgG, TNF-α, IFN-γ, IL-2, and IL-12 were quantified. Additionally, tissue damage was assessed through histological analyses of the thymus and spleen. RESULTS: PGE treatment enhanced cell viability and natural killer cell and cytotoxic T lymphocyte activity, and increased the production of CP-induced inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA) in splenocytes. In addition, in CP-treated rats, PGE treatment induced the recovery of white blood cell, neutrophil, and lymphocyte counts, along with mid-range absolute counts, and increased the serum levels of inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA). Moreover, PGE attenuated CP-induced spleen and thymic damage. CONCLUSIONS: Our results confirmed that PGE exerts an immune-enhancing effect both in vitro and in vivo, suggesting that PGE may have applications as a component of immunostimulatory agents or as an ingredient in functional foods.


Assuntos
Adjuvantes Imunológicos/farmacologia , Ciclofosfamida/efeitos adversos , Extratos Vegetais/farmacologia , Platycodon , Baço , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Tolerância Imunológica/efeitos dos fármacos , Imunossupressão , Imunossupressores/efeitos adversos , Ratos , Baço/citologia , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
4.
BMC Neurol ; 19(1): 263, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672142

RESUMO

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rapidly developing demyelinating disease in the cerebral white matter and is often caused by JC polyomavirus (JCV). PML after lung transplantation is rare and has a poor prognosis, with no established therapies. Reducing the patient's immunosuppressant doses, thereby restoring immunity, could be used to treat PML. However, some patients develop immune reconstitution inflammatory syndrome (IRIS) with this treatment, an immune-induced inflammatory response to JCV that results in serious neuronal damage. We herein report a case of a 60-year-old female who suffered from PML 5 years after lung transplantation, had worsened brain lesions thought to be related to PML-IRIS at the time of immunosuppressant reduction, and missed treatment opportunities. CASE PRESENTATION: A 60-year-old female developed PML 5 years after lung transplantation. Fluid-attenuated inversion recovery and diffusion-weighted brain magnetic resonance imaging (MRI) revealed multiple high-signal lesions, mainly in the cerebral white matter. Polymerase chain reaction found 0.32 million copies/mL of JCV in the cerebrospinal fluid. Thus, she was given a diagnosis of PML. Mycophenolate mofetil and tacrolimus dosages were reduced, and CD4-positive cell counts and the blood concentration of each immunosuppressant were monitored. Mefloquine was also orally administered at a daily dose of 275 mg for 3 days and was then administered at a dose of 275 mg per week. Although the patient's CD4-positive cell counts increased and her immune system recovered, her symptoms and brain MRI findings worsened. We suspected PML progression or a transition to PML-IRIS. Steroid pulse therapy to suppress the inflammatory lesions was not possible but was retrospectively indicated. The patient rapidly began to exhibit akinetic mutism and died 4 months after the onset of neurologic symptoms. CONCLUSIONS: When neurologic symptoms and abnormal brain MRI findings are noted during immune recovery, it is often difficult to distinguish between progressed PML and PML-IRIS. However, the pathogenesis of brain lesions usually involves inflammation and immune-reactive mechanisms for JCV. Steroid pulse therapy, which can reduce inflammation, should thus be administered in organ transplantation cases with differential diagnoses including PML-IRIS.


Assuntos
Síndrome Inflamatória da Reconstituição Imune , Leucoencefalopatia Multifocal Progressiva , Transplante de Pulmão , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Vírus JC , Pessoa de Meia-Idade
5.
Hautarzt ; 70(12): 975-988, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31720719

RESUMO

In the context of supportive therapy, possible complaints which may be caused by the cancer itself, by the antitumoral therapy or by psychosocial concerns are considered. Due to the introduction of new anticancer drugs in dermato-oncology, clinicians are confronted with a novel spectrum of adverse events. There are a number of inflammatory, immune-mediated side effects caused by immunotherapies, which can affect virtually any organ. Targeted therapies also have specific side effects. Basically, the management of adverse events depends on their severity. Besides treatment breaks and dosage modifications, immunotherapy-related adverse events are treated with systemic immunosuppressants. Supportive symptomatic therapy is offered. The additional consideration of psychosocial problems can improve quality of life of cancer patients.


Assuntos
Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunossupressores , Imunoterapia , Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Humanos , Imunossupressores/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Qualidade de Vida
6.
Transplant Proc ; 51(9): 2936-2938, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31711578

RESUMO

BACKGROUND: BK virus (BKV) infection represents a potentially dreadful complication after kidney transplantation (KT). When BK viremia is detected, the best therapeutic approach remains not entirely clarified. Critical elements of BK viremia treatment are immunosuppression minimization and introduction of drugs like leflunomide, everolimus, and fluoroquinolones. The study aimed to analyze the results of the BK viremia management in 2 collaborative Italian centers. METHODS: Ten patients undergoing KT in the 2 collaborative Italian centers of Sapienza University of Rome and University of L'Aquila from January 2013 to December 2017 and showing a post-KT diagnosis of BK viremia were retrospectively investigated. RESULTS: Mean time from KT to BKV positivity was 7 months (range: 1-19 months). At diagnosis, the mean viral load was 683,842 copies/mL (range: 5800-4,052,415 copies/mL), with an average zenith of 2,428,410 copies/mL (range: 6762-18,022,500 copies/mL). In the 5 patients with BKV nephropathy, we observed a switch from antimetabolite to leflunomide (n = 5), a switch from tacrolimus to everolimus (n = 3), or an introduction of fluoroquinolones (n = 3). BKV clearance was achieved in 3 patients. CONCLUSIONS: Early BKV diagnosis and stepwise minimization of immunosuppression remain the first-line approach in patients with BK viremia. In the presence of BKV nephropathy, a combination of antiviral drugs like leflunomide and fluoroquinolones/everolimus should favor viremia clearance.


Assuntos
Transplante de Rim , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/imunologia , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/imunologia , Adulto , Antivirais/uso terapêutico , Vírus BK , Feminino , Humanos , Imunossupressão/métodos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/tratamento farmacológico , Estudos Retrospectivos , Infecções Tumorais por Vírus/tratamento farmacológico , Viremia/complicações , Viremia/tratamento farmacológico , Viremia/imunologia
7.
BMC Neurol ; 19(1): 287, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729968

RESUMO

BACKGROUND: Fingolimod (Gilenya®) is approved for relapsing forms of multiple sclerosis in the USA. Owing to transient heart-rate effects when initiating fingolimod, eligible patients undergo precautionary baseline assessment and first-dose observation (FDO) for ≥6 h. Prior to 2014, FDO was undertaken only in clinics. As the FDO period is short, and fingolimod has accumulated evidence of a positive benefit:risk ratio, an in-home treatment-initiation program, Gilenya@Home, was developed to offer a convenient alternative. METHODS: Cardiac parameters and adverse events (AEs) were recorded by healthcare professionals performing fingolimod FDOs in the US Gilenya@Home program or in US Gilenya Assessment Network clinics. Anonymized data were collated retrospectively from the first 34 months in the home setting and from 78 months in clinics; data are reported descriptively. Satisfaction with Gilenya@Home was rated by patients using a 7-item questionnaire that considered aspects such as ease of scheduling, courtesy, and competency. RESULTS: Data were captured as part of standard care from 5573 patients initiating fingolimod in-home (October 2014 to July 2017) and from 15,025 patients initiating in-clinic (July 2010 to December 2016). In the Gilenya@Home questionnaire, 91.7% of 1848 respondents rated their overall satisfaction as "very good," and 7.6% rated their satisfaction as "good." AEs were reported for 30.7 and 32.6% of in-home and in-clinic patients, respectively. In total, 557 in-home (10.0%) and 398 in-clinic (2.6%) patients were monitored for > 6 h; 15 (0.3%) in-home and 129 (0.9%) in-clinic patients were transferred to an emergency room for overnight monitoring. The mean (standard deviation) heart rate (HR; bpm) pre-FDO was 74.8 (12.2) in-home and 74.2 (11.3) in-clinic; reduction in HR at 6 h postdose was 10.6 (12.0) and 6.3 (9.6), respectively. New-onset first-degree atrioventricular block was experienced by 132 (2.4%) in-home and 74 (0.5%) in-clinic patients, and Wenckebach (Mobitz type I) second-degree atrioventricular block by four (0.07%) and nine (0.1%) patients, with no cases of third-degree atrioventricular block. CONCLUSIONS: A substantial number of patients have initiated fingolimod at home, reporting very high levels of satisfaction. Gilenya@Home was as rigorous as the clinic setting in detecting cardiovascular events. Overall, FDO safety outcomes were similar with Gilenya@Home and in-clinic.


Assuntos
Bloqueio Atrioventricular/induzido quimicamente , Cloridrato de Fingolimode/efeitos adversos , Serviços Hospitalares de Assistência Domiciliar , Imunossupressores/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Bloqueio Atrioventricular/diagnóstico , Eletroencefalografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos
8.
Medicine (Baltimore) ; 98(48): e18142, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770250

RESUMO

RATIONALE: Mucormycosis is a rare opportunistic fungal infection with poor prognosis. The incidence of mucormycosis has been increasing, and it is a threat to immunocompromised hosts. We present a case of gastric mucormycosis complicated by a gastropleural fistula during immunosuppressive treatment for adult-onset Still disease (AOSD). PATIENT CONCERNS: An 82-year-old woman diagnosed with AOSD who developed gastric ulcers during the administration of an immunosuppressive therapy with corticosteroids, cyclosporine, and tocilizumab complained of melena and epigastralgia. Esophagogastroduodenoscopy showed multiple ulcers covered with grayish or greenish exudates. DIAGNOSES: The patient diagnosed with mucormycosis based on culture and biopsy of the ulcers, which showed nonseptate hyphae branching at wide angles. Mucor indicus was identified using polymerase chain reaction. INTERVENTIONS AND OUTCOMES: Although liposomal amphotericin B was administered, gastric mucormycosis was found to be complicated by a gastropleural fistula. The patient died because of pneumonia due to cytomegalovirus infection, and autopsy revealed the presence of Mucorales around the fistula connecting the stomach and diaphragm. LESSONS: Gastric mucormycosis is refractory to treatment and fatal. Surgical resection, if possible, along with antifungal drugs can result in better outcomes.


Assuntos
Fístula Gástrica/microbiologia , Mucormicose/complicações , Infecções Oportunistas/complicações , Fístula do Sistema Respiratório/microbiologia , Úlcera Gástrica/microbiologia , Idoso de 80 Anos ou mais , Feminino , Fístula Gástrica/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Mucormicose/induzido quimicamente , Mucormicose/microbiologia , Infecções Oportunistas/induzido quimicamente , Infecções Oportunistas/microbiologia , Pleura/microbiologia , Fístula do Sistema Respiratório/induzido quimicamente , Doença de Still de Início Tardio/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente
9.
Expert Opin Drug Saf ; 18(12): 1133-1144, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31657965

RESUMO

Introduction: Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease with extensive clinical variability. In 2011, the anti-BAFF monoclonal antibody, belimumab, became the first FDA-approved drug for SLE in 50+ years. As with all immunomodulating medications, the benefits must be weighed against the adverse side effects. This is especially pertinent for SLE patients, given the chronic nature of their disease and their need for long-term treatment. The focus of the present review is the safety of belimumab, including data gleaned from clinical trials, their open-label extensions, and 'real-world' clinical settings.Areas covered: Safety data from phase I, phase II, phase III, extension open-label trials, and 'real-world' observational studies of belimumab are reviewed and discussed.Expert opinion: As the only FDA-approved treatment for SLE in the past 60+ years, belimumab has demonstrated significant, albeit modest, efficacy and a reassuring safety profile. Long-term data to date show that it is well-tolerated with a low risk of side effects, even when administered for up to 13 years. Given that belimumab allows providers to decrease daily corticosteroid doses over time (and, thereby, decrease the serious risks associated with chronic corticosteroid use), it should be seen as a valuable tool in the rheumatologist's arsenal.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Corticosteroides/administração & dosagem , Animais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/imunologia , Humanos , Imunossupressores/efeitos adversos , Fatores de Tempo
10.
Ann Hematol ; 98(11): 2579-2591, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31628517

RESUMO

Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores de Calcineurina/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , /etiologia , Japão/epidemiologia , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Neutrófilos , Contagem de Plaquetas , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Expert Opin Drug Metab Toxicol ; 15(10): 803-811, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31595800

RESUMO

Introduction: Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplantation (HSCT); therefore, the prevention of GVHD is important for a successful treatment. Tacrolimus (Tac), a calcineurin inhibitor, has been widely used for the prophylaxis of GVHD in HSCT recipients. Areas covered: This review introduces phase II/III of clinical trials related with Tac's roles in the prevention of GVHD in HSCT. Furthermore, we discuss the normal ranges of Tac concentrations, pharmacogenetics, and drug interactions of Tac, as well as its side effects in adult HSCT recipients. Expert opinion: A series of studies has established the efficacy and safety of Tac alone or in combination with other agents in HSCT. However, successful administration of Tac is complicated by its narrow therapeutic window, inter-patient pharmacokinetic variability, and a spectrum of undesirable side effects. It is necessary to maintain concentrations of Tac within the desired ranges for GVHD prophylaxis. Moreover, various factors contribute to significant variability in Tac pharmacokinetics, including drug interactions and genomic variation.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Tacrolimo/administração & dosagem , Adulto , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacocinética , Interações de Medicamentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Farmacogenética , Tacrolimo/efeitos adversos , Tacrolimo/farmacocinética
12.
Transplant Proc ; 51(9): 3163-3166, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619339

RESUMO

Posttransplant lymphoproliferative disorder (PTLD) is caused by uncontrolled proliferation of lymphoid cells after a hematopoietic stem cell or solid organ transplant procedure related to the Epstein-Barr virus (EBV) infection. A primary central nervous system (CNS) PTLD (CNS-PTLD) is rare and important to distinguish from an intracranial lesion after transplantation. A 66-year-old man with pulmonary arterial hypertension who underwent living-donor lung transplantation 9 years prior noticed disorientation regarding route and dates. Brain magnetic resonance imaging revealed multiple white matter lesions and fluorodeoxyglucose (FDG) positron emission tomography showed FDG uptake in the brain and skin. CNS-PTLD was diagnosed by craniotomy biopsy and EBV-encoded RNA was positive in in situ hybridization findings and elevated in brain tissue. The treatment was started with immunosuppressant reduction and whole brain radiotherapy. But the condition progressed rapidly over 2 months after the first symptom and the patient was passed away 25 days after hospitalization. CNS-PTLD can occur several years after transplantation and it is necessary to keep in mind to distinguish brain disease because early diagnosis and treatment are important.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Pulmão , Transtornos Linfoproliferativos/imunologia , Complicações Pós-Operatórias/imunologia , Idoso , Encéfalo/patologia , Infecções por Vírus Epstein-Barr/imunologia , Humanos , Masculino
13.
Transplant Proc ; 51(9): 3092-3098, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31623898

RESUMO

Gastrointestinal bleeding after kidney transplantation is a complication that can occur from immunosuppressant use. We present a case of refractory small bowel bleeding treated successfully with thalidomide after multiple failed attempts of conventional treatment. A 65-year-old male patient with diabetic nephropathy underwent living donor kidney transplantation. The surgery was uneventful, however, he developed immunosuppressant-induced melena with unstable vital signs 11 days later. There were a total of 4 bleeding episodes until the 90th postoperative day, and he received a total of 290 units of red blood cell transfusion during this period. Endoscopic clipping, transarterial embolization, and 2 surgical interventions failed to stop the bleeding. A trial of thalidomide 100 mg per day finally stopped the bleeding and the patient was discharged on the 110th postoperative day with a functioning renal graft. This case shows that thalidomide can be a safe option to treat immunosuppressant-induced refractory gastrointestinal bleeding in the setting of kidney transplantation. Additionally, this is the first case that reports the survival of a renal graft after more than 3000 mL of transfusion.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Hemorragia Gastrointestinal/tratamento farmacológico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Talidomida/uso terapêutico , Idoso , Humanos , Imunossupressores/efeitos adversos , Doadores Vivos , Masculino , Melena/imunologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Tacrolimo/efeitos adversos
15.
Expert Rev Clin Pharmacol ; 12(11): 1047-1057, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31575290

RESUMO

Introduction: The clinical use of tacrolimus is characterized by many side effects which include neurotoxicity. In contrast, tacrolimus has also shown to have neuroregenerative properties. On a molecular level, the mechanisms of action could provide us more insight into understanding the neurobiological effects. The aim of this article is to review current evidence regarding the use of tacrolimus in peripheral nerve injuries.Areas covered: Available data on tacrolimus' indications were summarized and molecular mechanisms were elucidated to possibly understand the conflicting neurotoxic and neuroregenerative effects. The potential clinical applications of tacrolimus, as immunosuppressant and enhancer of nerve regeneration in peripheral nerve injuries, are discussed. Finally, concepts of delivery are explored.Expert opinion: It is unclear what the exact neurobiological effects of tacrolimus are. Besides its known calcineurin inhibiting properties, the mechanism of action of tacrolimus is mediated by its binding to FK506-binding protein-52, resulting in a bimodal dose response. Experimental models found that tacrolimus administration is preferred up to three days prior to or within 10 days post-nerve reconstruction. Moreover, the indication for the use of tacrolimus has been expanding to fields of dermatology, ophthalmology, orthopedic surgery and rheumatology to improve outcomes after various indications.


Assuntos
Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Tacrolimo/administração & dosagem , Animais , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacologia , Esquema de Medicação , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Tacrolimo/efeitos adversos , Tacrolimo/farmacologia
16.
J Cancer Res Clin Oncol ; 145(12): 3125-3135, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31587105

RESUMO

PURPOSE: Solid organ (SOT) and allogeneic haematopoietic stem cell (HSCT) transplant recipients have elevated risks of de novo or secondary cancer. We explored risk factors hereof. METHODS: Among SOT and HSCT between January 2004 and December 2014, standardised incidence ratio (SIR) of de novo/secondary cancer compared with the Danish population was determined and risk factors were identified using Poisson regression. RESULTS: During a median of 3.4 (IQR 1.3-6.4) and 2.6 (0.8-5.4) person-years (PY) after SOT and HSCT, a total of 212/1656 (13%) and 75/992 (8%) persons developed cancer; SIR 3.61 (3.0-4.3) and 2.2 (1.6-3.0), resp.). SIR correlated with younger age and was highest for skin and haematological cancers for both types of transplantation. Within the cohort, cancer was associated with older age (adjusted incidence rate ratio > 50 vs ≤ 19 years, among SOT and HSCT: 9.4 (3.4-25.7) and 25.4 (5.1-126.0), resp.) and current elevated C-reactive protein (CRP) (≥ 10 vs < 10 mg/L: 2.5 (1.8-3.4) and 2.3 (1.4-3.9), resp.), but neither with prior cancer nor type of immunosuppressants. CONCLUSION: Rates of de novo or secondary cancers are elevated in both SOT and HSCT compared with the general population and mainly for skin and haematological cancers. Among transplant recipients, older age and current elevated CRP are risk factors.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Segunda Neoplasia Primária/etiologia , Neoplasias/etiologia , Transplante de Órgãos/efeitos adversos , Adulto , Estudos de Coortes , Feminino , Humanos , Imunossupressores/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transplantados , Adulto Jovem
17.
Expert Rev Clin Pharmacol ; 12(10): 973-980, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31550941

RESUMO

Introduction: Pemphigus, an autoimmune disease group characterized by blisters and erosions of the skin and/or mucosal membranes has been treated with systemic corticosteroids (CS) and immunosuppressive therapies for the past few decades. Areas Covered: However, common adverse effects and complications of long-term CS and immunosuppressive drugs are limiting their long-term use. The disease results in death if not treated. Thus, currently, researchers are trying to develop new and safer therapeutic approaches. Specifically, targeted therapies to pathogenic immune pathways are under investigation. The B cell inhibitors which block CD20 and CD19 are the main new drugs investigated in clinical trials as alternatives to systemic steroids. Expert Opinion: Randomized controlled trial (RCT) Level evidence shows that rituximab and short course CSs are more effective and safer than standard CS treatment. Specific BTK inhibitors have shown promise in data from a phase II international open-label study. Further studies are ongoing.


Assuntos
Corticosteroides/administração & dosagem , Imunossupressores/administração & dosagem , Pênfigo/tratamento farmacológico , Corticosteroides/efeitos adversos , Corticosteroides/farmacologia , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Animais , Desenvolvimento de Medicamentos/métodos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Terapia de Alvo Molecular , Pênfigo/imunologia , Pênfigo/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Fatores de Tempo
18.
J Drugs Dermatol ; 18(9): 947-949, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524994

RESUMO

Bullous pemphigoid (BP) is a rare blistering skin disease that is commonly treated with corticosteroids and immunosuppressive agents. Here, we present a 74-year-old woman with severe BP following a leg fracture who was successfully treated with omalizumab. We started her on a regimen of omalizumab 300 mg subcutaneously every 4 weeks, and within a week she reported significantly decreased pain and faster healing time of lesions. Incidentally, bilateral erythematous, non-blistering dermatitis developed 5 centimeters distal to the injection sites within a week of her first injection and resolved spontaneously in 2 days. She continues to tolerate the omalizumab injections well after 28 months of treatment and has not developed the injection site dermatitis since the first administration. Omalizumab appears to be a promising treatment modality for BP even when associated with transient injection site reactions, but further studies investigating the mechanisms by which omalizumab reduces bullae in BP are needed. J Drugs Dermatol. 2019;18(9):947-949.


Assuntos
Imunossupressores/administração & dosagem , Reação no Local da Injeção/etiologia , Omalizumab/administração & dosagem , Penfigoide Bolhoso/tratamento farmacológico , Idoso , Feminino , Humanos , Imunossupressores/efeitos adversos , Injeções Subcutâneas , Omalizumab/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
19.
Medicine (Baltimore) ; 98(36): e16992, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490380

RESUMO

RATIONALE: Immunosuppressive agents such as tacrolimus (TAC) and cyclosporin might cause glycemic disorders by suppressing insulin production. However, only a few cases of diabetic ketoacidosis (DKA) with longitudinal evaluation of endogenous insulin secretion related to TAC administration have been reported. PATIENT CONCERNS: A 59-year-old Asian woman, who received prednisolone and TAC 4.0 mg for the treatment of anti-aminoacyl-tRNA synthetase antibody-positive interstitial pneumonia, was admitted to our hospital due to impaired consciousness and general malaise. DIAGNOSES: She had metabolic acidosis; her plasma glucose, fasting serum C-peptide immunoreactivity (CPR), and urinary CPR levels were 989 mg/dL (54.9 mmol/L), 0.62 ng/mL, and 13.4 µg/d, respectively. No islet-related autoantibodies were detected. Therefore, she was diagnosed with TAC-induced DKA. INTERVENTION: Intravenous continuous insulin infusion and rapid saline infusion were administered. TAC was discontinued because of its diabetogenic potential. OUTCOMES: Sixteen weeks after cessation of TAC administration, she showed good glycemic control without administration of insulin or any oral hypoglycemic agents; her serum CPR level also improved dramatically. These findings suggested that TAC-induced pancreatic beta cell toxicity is reversible. LESSONS: We reported a case of TAC-induced DKA with subsequent recovery of pancreatic beta cell function after cessation of TAC, resulting in good glycemic control. As TAC is widely used, we should pay attention to patients' glucose levels even though the TAC concentrations used are within the target range. Furthermore, dose reduction or cessation of TAC should be considered if hyperglycemia is detected during administration of this agent.


Assuntos
Cetoacidose Diabética/induzido quimicamente , Imunossupressores/efeitos adversos , Secreção de Insulina/efeitos dos fármacos , Tacrolimo/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
20.
JAMA ; 322(10): 936-945, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503307

RESUMO

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01829295.


Assuntos
Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Uveíte/tratamento farmacológico , Adulto , Anti-Inflamatórios/administração & dosagem , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Testes de Função Hepática , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Prednisolona/administração & dosagem
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