Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.826
Filtrar
1.
Anticancer Res ; 41(4): 2171-2175, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813429

RESUMO

BACKGROUND: Although indications of laparoscopic hepatectomy have been expanded, the laparoscopic approach after right hepatic lobectomy has a very high burden. The purpose of this study was to evaluate patients undergoing laparoscopic repeat hepatectomy for recurrent hepatic tumors after open right lobectomy. PATIENTS AND METHODS: Five cases of laparoscopic repeat hepatectomy for recurrent hepatic tumors after open right lobectomy were included in the study. RESULTS: All the tumors in segment 3 were intraoperatively detected and curatively resected by partial hepatectomy. The tumors in segment 2 could not be detected intraoperatively due to hypertrophic liver deformity and adhesion. They were curatively resected by anatomical subsegmental approach. CONCLUSION: For recurrent tumors located in segment 2 after right lobectomy, anatomical subsegmental approach should be preferred, not only from an oncological standpoint, but also for securing curative laparoscopic resection and overcoming anatomical difficulties.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Reoperação/métodos , Idoso , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Indução de Remissão/métodos , Resultado do Tratamento
3.
Lancet Haematol ; 8(4): e299-e304, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33770485

RESUMO

To our knowledge, no study has evaluated the quality of control groups in randomised controlled trials of multiple myeloma. We aimed to do a systematic review of randomised controlled trials of multiple myeloma to ascertain the quality of the control groups used. PubMed (MEDLINE), Embase, Cochrane Controlled Register of Trials, and CinicalTrials.gov were searched for articles of randomised controlled trials of multiple myeloma based in the USA that initiated participant enrolment between Jan 1, 2010, and June 30, 2020. A control group regimen was considered to be inferior if a previous randomised controlled trial had shown an improved progression-free survival versus the control group before enrolment. Of 49 identified randomised controlled trials, seven (14%) began enrolling patients into inferior control groups after an existing superior regimen to the control had already been published. Nine (18%) of the 49 trials continued enrolment on substandard control groups after data emerged during the study enrolment period. The median time that newer data emerged regarding inferiority of the control group from the time a trial first enrolled a patient was 13 months (IQR 8-29 months). 12 (75%) of these 16 randomised controlled trials are published, and nine (75%) of the 12 published trials had overlapping investigators with trials that had previously shown the inferiority of the control group being used. Greater scrutiny on the quality of control groups in randomised controlled trials of multiple myeloma is needed.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Grupos Controle , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Mieloma Múltiplo/epidemiologia , Intervalo Livre de Progressão , Controle de Qualidade , Indução de Remissão/métodos , Estados Unidos/epidemiologia
4.
Medicine (Baltimore) ; 100(7): e24498, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607779

RESUMO

INTRODUCTION: No standard guideline has been established for the treatment of plasmablastic lymphoma (PBL) and prognosis remains extremely poor, given that patients relapse early after chemotherapy and show resistance to commonly used cytostatic drugs. PATIENT CONCERNS: We present the case of a 52-year-old HIV-negative man who presented with a mass at the left sternoclavicular joint. He had no significant comorbidities and no latent immunosuppression. DIAGNOSIS: The largest lymph node measured was 36 × 19 mm. An excisional biopsy showed diffuse proliferation of large lymphoid cells which were positive for CD38 and CD138, but negative for CD20. He was diagnosed with stage IV PBL with a low IPI. INTERVENTIONS: The patient was treated with four cycles of induction therapy with bortezomib, epirubicin and dexamethasone. He achieved complete remission. But 3 months after receiving consolidated autologous hematopoietic stem cell transplantation, he relapsed. Allogeneic hematopoietic stem cell transplantation was performed on the patient. OUTCOMES: The patient achieved remission again and there were no serious complications after allogeneic hematopoietic stem cell transplantation. This patient was followed up once every three months, and to date, he has been disease-free for more than 4 years. CONCLUSION: The survival of recurrent PBL after autologous hematopoietic stem cell transplantation is very poor. Salvage allogeneic hematopoietic stem cell transplantation may bring long-term survival opportunities for those patients. Further clinical studies are needed to explore the role of allogeneic hematopoietic stem cell transplantation in refractory and recurrent PBL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Plasmablástico/terapia , Transplante Homólogo/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Soronegatividade para HIV , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/patologia , Indução de Remissão/métodos , Transplante Homólogo/efeitos adversos
5.
Eur J Endocrinol ; 184(4): 575-585, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33606663

RESUMO

Objective: Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design: Retrospective analysis of the Italian data set of patients with TNDM. Methods: Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results: Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; -2.27 SD) than those with KATP mutations (4.0 weeks; -1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions: If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.


Assuntos
Diabetes Mellitus , Doenças do Recém-Nascido , Conjuntos de Dados como Assunto , Diabetes Mellitus/classificação , Diabetes Mellitus/congênito , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino/normas , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/classificação , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/terapia , Itália , Masculino , Mutação , Canais de Potássio Corretores do Fluxo de Internalização/genética , Indução de Remissão/métodos , Estudos Retrospectivos , Receptores Sulfonilureia/genética
6.
Medicine (Baltimore) ; 100(3): e24273, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546048

RESUMO

ABSTRACT: The exact dose of cytarabine still remain controversial for the management of patients with acute myeloid leukemia (AML) after complete remission (CR), but recent studies favor lower doses. This study aimed to investigate the toxic effects of single-intermediate dose (ID) cytarabine in patients with AML after achieving CR, compared with standard-dose cytarabine.In this retrospective study, AML patients who achieved CR after consolidation therapy before enrollment between 07/2008 and 05/2019 were included. All patients were divided into single-ID cytarabine and standard-dose cytarabine. The Kaplan-Meier method was used to compare overall survival (OS) and relapse-free time (RFS). Cox regression models were used to assess factors independently associated with OS and RFS. The toxic side effects of hematology and non-hematology were observed.52 patients were enrolled. There were 33 in ID group, 19 in Standard dose group. The 3-year RFS rate (40.4% vs 22.2%, P = .031) was better in the ID group than in the standard-dose group, while the 3-year OS rate was not different between the 2 groups (50.2% vs 27.8%, P = .074). Treatment stratage of ID cytarabine chemotherapy significantly improve the prognosis of AML regardless of patient age, risk grade, WBC count. There were no significant differences between the 2 groups in grade 3 to 4 bone marrow suppression, gastrointestinal symptoms, blood transfusion, infections.Patients with AML receiving ID cytarabine showed better survival and similar toxicity profiles compared with patients who received standard-dose cytarabine.


Assuntos
Quimioterapia de Consolidação/normas , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão/métodos , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia de Consolidação/métodos , Quimioterapia de Consolidação/estatística & dados numéricos , Citarabina/farmacologia , Citarabina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
7.
Blood ; 137(1): 20-28, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410896

RESUMO

Legacy data show that ∼40% of children with acute lymphoblastic leukemia (ALL) were cured with limited antimetabolite-based chemotherapy regimens. However, identifying patients with very-low-risk (VLR) ALL remains imprecise. Patients selected based on a combination of presenting features and a minimal residual disease (MRD) level <0.01% on day 19 of induction therapy had excellent outcomes with low-intensity treatment. We investigated the impact of MRD levels between 0.001% and <0.01% early in remission induction on the outcome of VLR ALL treated with a low-intensity regimen. Between October of 2011 and September of 2015, 200 consecutive patients with B-precursor ALL with favorable clinicopathologic features and MRD levels <0.01%, as assessed by flow cytometry in the bone marrow on day 19 and at the end of induction therapy, received reduced-intensity therapy. The 5-year event-free survival was 89.5% (± 2.2% standard error [SE]), and the overall survival was 95.5% (± 1.5% SE). The 5-year cumulative incidence of relapse (CIR) was 7% (95% confidence interval, 4-11%). MRD levels were between 0.001% and <0.01% on day 19 in 29 patients. These patients had a 5-year CIR that was significantly higher than that of patients with undetectable residual leukemia (17.2% ± 7.2% vs 5.3% ± 1.7%, respectively; P = .02). Our study shows that children with VLR ALL can be treated successfully with decreased-intensity therapy, and it suggests that the classification criteria for VLR can be further refined by using a more sensitive MRD assay.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Indução de Remissão/métodos
8.
Nutrients ; 12(12)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33322060

RESUMO

The treatment of Pediatric Crohn's Disease (CD) requires attention both to achieve mucosal healing and to optimize growth, while also maintaining proper bone health. Exclusive Enteral Nutrition (EEN) is recommended as first-line treatment in luminal CD. The therapeutic mechanisms of EEN are being discovered by advances in the study of the gut microbiota. Although the total exclusion of a normal diet during the time of EEN continues to be of high importance, new modalities of dietary treatment suggest a successful future for the nutritional management of CD. In this sense, Crohn's Disease Exclusion Diet (CDED) is a long-term strategy, it apparently acts on the mechanisms that influence the appearance of inflammation (reducing dietary exposure to products negatively affecting the microbiota), but does so using specific available whole foods to achieve this goal, increases the time of clinical remission and promotes healthy lifestyle habits. The development of CDED, which partly minimizes the problems of EEN, has enabled a turnaround in the treatment of pediatric CD. This review highlights the role of enteral nutrition in the treatment of Crohn's disease with special emphasis on newer dietary modalities such as CDED.


Assuntos
Doença de Crohn/terapia , Dieta/tendências , Nutrição Enteral/tendências , Adolescente , Criança , Dieta/métodos , Nutrição Enteral/métodos , Feminino , Humanos , Masculino , Indução de Remissão/métodos
9.
Medicine (Baltimore) ; 99(44): e22894, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126341

RESUMO

BACKGROUND: Positioning infliximab (IFX), cyclosporine and tacrolimus (TAC) for treating ulcerative colitis (UC) is in great debate. METHODS: A literature search identified studies that investigated IFX vs. cyclosporine or IFX vs TAC in UC patients. Short-term remission, short-term, 1-year and 3-year colectomy rate were employed as primary end-points to assess efficacy. Odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed. RESULTS: Overall, 15 studies comprised 596 patients in IFX group and 866 in calcineurin inhibitors group (644 received cyclosporine and 222 received TAC). No significant difference was seen between IFX and calcineurin inhibitors with regard to short-term remission. IFX led to a lower short-term (OR: 0.59, 95% CI: 0.43-0.82, P:.001), 1-year (OR: 0.53, 95% CI: 0.38-0.73, P < .001), 3-year colectomy (OR: 0.41, 95% CI: 0.20-0.84, P:.02) than calcineurin inhibitors. IFX led to a lower short-term (OR: 0.51, 95% CI: 0.36-0.71, P < .001), 1-year (OR: 0.53, 95% CI: 0.37-0.74, P:.003) colectomy and a trend of lower 3-year colectomy (OR: 0.49, 95% CI: 0.22-1.06, P:.07) than cyclosporine while no significant difference was seen between IFX and TAC. Results of network meta-analysis showed that the order was cyclosporine, TAC and IFX from high rate to low with regard to short-term and 1-year colectomy. CONCLUSION: IFX treatment leads to a lower short-term, 1-year colectomy rate and a trend of lower 3-year colectomy rate in UC patients than cyclosporine while no significant difference is seen between IFX and TAC. TAC may be superior than cyclosporine with regard to efficacy based on indirect comparisons. Randomized trials with fixed protocol are warranted to identify the optimal medical strategy in patients with UC.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Ciclosporina/farmacologia , Infliximab/farmacologia , Tacrolimo/farmacologia , Colectomia/estatística & dados numéricos , Colite Ulcerativa/imunologia , Colite Ulcerativa/cirurgia , Humanos , Imunossupressores/farmacologia , Indução de Remissão/métodos , Resultado do Tratamento
10.
Nat Commun ; 11(1): 4458, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895383

RESUMO

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling.


Assuntos
Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fator 1 de Crescimento de Fibroblastos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Hipotálamo/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteína Relacionada com Agouti/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Glicemia/análise , Comunicação Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/administração & dosagem , Sacarose na Dieta/efeitos adversos , Humanos , Hipotálamo/citologia , Hipotálamo/patologia , Injeções Intraventriculares , Leptina/genética , Masculino , Melanocortinas/metabolismo , Hormônios Estimuladores de Melanócitos/administração & dosagem , Camundongos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , RNA-Seq , Receptor Tipo 4 de Melanocortina/genética , Receptores de Melanocortina/antagonistas & inibidores , Receptores de Melanocortina/metabolismo , Indução de Remissão/métodos , Transdução de Sinais/efeitos dos fármacos , Análise de Célula Única , Técnicas Estereotáxicas , Transcriptoma/efeitos dos fármacos
11.
Cochrane Database Syst Rev ; 8: CD000544, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32856298

RESUMO

BACKGROUND: Oral 5-aminosalicylic acid (5-ASA; also known as mesalazine or mesalamine) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. In an earlier version of this review, we found that 5-ASA drugs were more effective than placebo for maintenance of remission of ulcerative colitis (UC), but had a significant therapeutic inferiority relative to SASP. In this version, we have rerun the search to bring the review up to date. OBJECTIVES: To assess the efficacy, dose-responsiveness, and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent UC and to compare the efficacy and safety of once-daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. SEARCH METHODS: We performed a literature search for studies on 11 June 2019 using MEDLINE, Embase, and the Cochrane Library. In addition, we searched review articles and conference proceedings. SELECTION CRITERIA: We included randomized controlled trials with a minimum treatment duration of six months. We considered studies of oral 5-ASA therapy for treatment of participants with quiescent UC compared with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose-ranging studies. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were adherence, adverse events (AE), serious adverse events (SAE), withdrawals due to AEs, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus SASP, once-daily dosing versus conventional dosing, 5-ASA (balsalazide, Pentasa, and olsalazine) versus comparator 5-ASA formulation (Asacol and Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each outcome. We analyzed data on an intention-to-treat basis, and used GRADE to assess the overall certainty of the evidence. MAIN RESULTS: The search identified 44 studies (9967 participants). Most studies were at low risk of bias. Ten studies were at high risk of bias. Seven of these studies were single-blind and three were open-label. 5-ASA is more effective than placebo for maintenance of clinical or endoscopic remission. About 37% (335/907) of 5-ASA participants relapsed at six to 12 months compared to 55% (355/648) of placebo participants (RR 0.68, 95% CI 0.61 to 0.76; 8 studies, 1555 participants; high-certainty evidence). Adherence to study medication was not reported for this comparison. SAEs were reported in 1% (6/550) of participants in the 5-ASA group compared to 2% (5/276) of participants in the placebo group at six to 12 months (RR 0.60, 95% CI 0.19 to 1.84; 3 studies, 826 participants; low-certainty evidence). There is probably little or no difference in AEs at six to 12 months' follow-up (RR 0.93, 95% CI 0.73 to 1.18; 5 studies, 1132 participants; moderate-certainty evidence). SASP is more effective than 5-ASA for maintenance of remission. About 48% (416/871) of 5-ASA participants relapsed at six to 18 months compared to 43% (336/784) of SASP participants (RR 1.14, 95% CI 1.03 to 1.27; 12 studies, 1655 participants; high-certainty evidence). Adherence to study medication and SAEs were not reported for this comparison. There is probably little or no difference in AEs at six to 12 months' follow-up (RR 1.07, 95% CI 0.82 to 1.40; 7 studies, 1138 participants; moderate-certainty evidence). There is little or no difference in clinical or endoscopic remission rates between once-daily and conventionally dosed 5-ASA. About 37% (717/1939) of once-daily participants relapsed over 12 months compared to 39% (770/1971) of conventional-dosing participants (RR 0.94, 95% CI 0.88 to 1.01; 10 studies, 3910 participants; high-certainty evidence). There is probably little or no difference in medication adherence rates. About 10% (106/1152) of participants in the once-daily group failed to adhere to their medication regimen compared to 8% (84/1154) of participants in the conventional-dosing group (RR 1.18, 95% CI 0.72 to 1.93; 9 studies, 2306 participants; moderate-certainty evidence). About 3% (41/1587) of participants in the once-daily group experienced a SAE compared to 2% (35/1609) of participants in the conventional-dose group at six to 12 months (RR 1.20, 95% CI 0.77 to 1.87; moderate-certainty evidence). There is little or no difference in the incidence of AEs at six to 13 months' follow-up (RR 0.98, 95% CI 0.92 to 1.04; 8 studies, 3497 participants; high-certainty evidence). There may be little or no difference in the efficacy of different 5-ASA formulations. About 44% (158/358) of participants in the 5-ASA group relapsed at six to 18 months compared to 41% (142/349) of participants in the 5-ASA comparator group (RR 1.08, 95% CI 0.91 to 1.28; 6 studies, 707 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is high-certainty evidence that 5-ASA is superior to placebo for maintenance therapy in UC. There is high-certainty evidence that 5-ASA is inferior compared to SASP. There is probably little or no difference between 5-ASA and placebo, and 5-ASA and SASP in commonly reported AEs such as flatulence, abdominal pain, nausea, diarrhea, headache, and dyspepsia. Oral 5-ASA administered once daily has a similar benefit and harm profile as conventional dosing for maintenance of remission in quiescent UC.


Assuntos
Ácidos Aminossalicílicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Mesalamina/administração & dosagem , Administração Oral , Anti-Inflamatórios não Esteroides/efeitos adversos , Viés , Colite Ulcerativa/prevenção & controle , Esquema de Medicação , Humanos , Adesão à Medicação/estatística & dados numéricos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Indução de Remissão/métodos , Sulfassalazina/administração & dosagem , Sulfassalazina/efeitos adversos
13.
PLoS One ; 15(8): e0235503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760083

RESUMO

PURPOSE: We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors, including a baseline mini nutritional assessment short form (MNA-SF) score, of response and survival. PATIENTS AND METHODS: Between 2010 and 2018, 96 AML patients aged 65 and above who received decitabine treatment at 6 centers in Korea were retrospectively evaluated. Response rates, hematologic improvements (HI), progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The median age at diagnosis was 73.9 years, and the median number of decitabine treatments administered to the patients was 4 (range, 1-29). Of 85 patients, 15 patients (17.6%) achieved complete remission (CR) or CR with incomplete blood count recovery. Twelve patients (14.1%) showed partial remission (PR), and 18 (21.2%) demonstrated HI without an objective response. The median PFS and OS were 7.0 (95% confidence interval [CI], 4.9-9.0) and 10.6 (95% CI, 7.7-13.5%) months, respectively. In multivariate analyses, MNA-SF score ≥ 8 and the absence of peripheral blood (PB) blasts were significant predictors for improved PFS and OS. CONCLUSIONS: For older patients with newly diagnosed AML, a high MNA-SF score and the absence of PB blasts were independently associated with improved survival.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Decitabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Contagem de Células Sanguíneas , Medula Óssea/patologia , Decitabina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Avaliação Nutricional , Intervalo Livre de Progressão , República da Coreia/epidemiologia , Estudos Retrospectivos , Perda de Peso
14.
Lancet ; 396(10246): 267-276, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711802

RESUMO

BACKGROUND: Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. METHODS: The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5-15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4-6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012. FINDINGS: Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35-0·73) with tapered prednisone and -0·08 (-0·27 to 0·12) with continued prednisone (difference 0·61 [0·35-0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71-0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency. INTERPRETATION: In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. FUNDING: F Hoffmann-La Roche.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Indução de Remissão/métodos , Administração Intravenosa , Administração Oral , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/etnologia , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , França/epidemiologia , Alemanha/epidemiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Injeções Subcutâneas , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Federação Russa/epidemiologia , Sérvia/epidemiologia , Tunísia/epidemiologia
15.
Nat Commun ; 11(1): 3549, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669548

RESUMO

Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias Musculares/terapia , Recidiva Local de Neoplasia/terapia , Receptor ErbB-2/imunologia , Rabdomiossarcoma/terapia , Linfócitos T/transplante , Biópsia , Medula Óssea/patologia , Criança , Ensaios Clínicos Fase I como Assunto , Humanos , Masculino , Neoplasias Musculares/imunologia , Neoplasias Musculares/patologia , Recidiva Local de Neoplasia/imunologia , Receptores de Antígenos Quiméricos/imunologia , Indução de Remissão/métodos , Rabdomiossarcoma/imunologia , Rabdomiossarcoma/secundário , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Autólogo/métodos , Resultado do Tratamento
16.
Inflamm Bowel Dis ; 26(7): 971-973, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32393973

RESUMO

First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.


Assuntos
Aborto Espontâneo , Colite Ulcerativa , Infecções por Coronavirus , Ciclosporina/administração & dosagem , Metilprednisolona/administração & dosagem , Pandemias , Pneumonia Viral , Complicações na Gravidez , Indução de Remissão/métodos , Adulto , Antivirais/administração & dosagem , Betacoronavirus/isolamento & purificação , Proteína C-Reativa/análise , Técnicas de Laboratório Clínico/métodos , Colite Ulcerativa/sangue , Colite Ulcerativa/complicações , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/terapia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Imunossupressores/administração & dosagem , Gravidade do Paciente , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Gravidez , Complicações na Gravidez/fisiopatologia , Complicações na Gravidez/terapia , Sigmoidoscopia/métodos , Resultado do Tratamento
17.
Nat Rev Clin Oncol ; 17(8): 493-503, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32377005

RESUMO

In the past few years, international treatment guidelines for chronic myeloid leukaemia have incorporated recommendations for attempting discontinuation of treatment with tyrosine-kinase inhibitors (TKIs) outside of the setting of a clinical trial with the aim of a treatment-free remission (TFR). Physicians involved in the treatment of chronic myeloid leukaemia need to be sufficiently well informed to guide patients through decision-making about the discontinuation of treatment with TKIs targeting BCR-ABL1 by providing a balanced assessment of the potential risks and benefits of stopping or continuing therapy. These guidelines also seek to ensure that the risks associated with being off treatment are kept to a minimum. In this Review, we summarize the clinical studies of TFR and how their results can guide routine clinical practice with a focus on specific aspects such as molecular monitoring and the pregnancy-specific risks associated with a TFR attempt in female patients. We also address the development of predictors of outcome after TKI discontinuation and present strategies that warrant further consideration to enable more patients to enter TFR.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Indução de Remissão/métodos , Ensaios Clínicos como Assunto , Feminino , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Guias como Assunto , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Gravidez , Resultado do Tratamento
18.
J Oncol Pharm Pract ; 26(5): 1220-1224, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32437235

RESUMO

The advent of BCR-ABL1 tyrosine kinase inhibitors has revolutionized the treatment and prognosis of chronic myeloid leukemia. Life expectancy for patients with chronic phase chronic myeloid leukemia now nears that of the healthy population; however, optimal outcomes require continuous tyrosine kinase inhibitor administration, which can impact patient quality of life. Consequently, the concept of treatment-free remission has been explored in patients achieving and sustaining a deep molecular response. Heterogeneous data exist with multiple tyrosine kinase inhibitors; however, nilotinib is currently the only therapy that has been approved by the US Food and Drug Administration for treatment-free remission. The decision to pursue treatment-free remission is one that relies heavily on both patient- and disease-related factors. Herein, we will discuss relevant considerations to be made when determining an optimal candidate for treatment-free remission.


Assuntos
Proteínas de Fusão bcr-abl/antagonistas & inibidores , Leucemia Mieloide de Fase Crônica/diagnóstico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Leucemia Mieloide de Fase Crônica/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Qualidade de Vida , Indução de Remissão/métodos , Resultado do Tratamento
20.
Gulf J Oncolog ; 1(32): 12-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32342913

RESUMO

INTRODUCTION: A phase II study was conducted in patients, unsuited for surgery, with locally advanced squamous cell carcinoma of oral cavity (stage III or IV) and without distant metastasis. The objectives were to evaluate overall response (OR) rate and safety of subjects treated with induction regimen docetaxel and cisplatin, followed by definitive chemoradiotherapy (CRT) in this setting. METHODS AND MATERIALS: Induction regimen consisted of docetaxel 75mg/m2 and cisplatin 75mg/m2 on day 1; cycles repeated every 21 days for three cycles with supportive G-CSF treatment beginning at first cycle. Definitive CRT consisted of weekly cisplatin 30mg/m2 for four weeks starting concomitantly with 60 Gy/30 fractions of conventional radiotherapy for six weeks. Primary and secondary efficacy criteria were OR rate at three weeks after cycle three and eight weeks after last cycle of CRT respectively. RESULTS: Three centers enrolled 35 patients. Primary efficacy endpoint: OR rate of evaluable patients after induction (n=27) was 88.9% (95% CI:71.9-96.2). Complete response (CR) was not achieved by any patient; partial response (PR) was achieved by 88.9% (24/27). From intent to treat (ITT) analysis OR rate was 68.6% (24/35). Secondary efficacy endpoint: OR rate of evaluable patients after definitive CRT (n=19) was 78.9%(95%CI:56.7-91.5) with CR and PR achieved by 2(10.5%) and 13(68.4%) patients respectively. From ITT analysis CR rate was 5.7% (2/35) and OR rate was 42.9% (15/35). During induction most common hematological toxicity was leukopenia in eight patients, with =Grade 3 leukopenia reported in three patients. During CRT most common adverse events were alopecia, stomatitis and nausea. CONCLUSION: We observed an ITT response rate of 68.6% with induction regimen docetaxel plus cisplatin, with a manageable safety profile. Hence, further investigation in this setting is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Indução de Remissão/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/farmacologia , Docetaxel/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...