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1.
Eur J Endocrinol ; 182(5): D1-D16, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32197235

RESUMO

Each year, the proportion of thyroid cancer patients presenting with low-risk disease is increasing. The shift in the landscape of thyroid cancer presentation is forcing clinicians to re-evaluate not only management but also surveillance paradigms. During the follow-up, patients are stratified considering their response to treatment and classified into one of the following response categories: excellent, biochemical incomplete, structural incomplete, or indeterminate. These categories reflect a real-time prognosis and thereby substantially influence and personalise disease management. Although at present, no guideline recommends stopping differentiated thyroid carcinoma (DTC) surveillance at any particular time point, the relatively low prevalence of treatment failures in low-risk patients may prompt early discontinuation of surveillance in this subgroup. Therefore, this debate will present an overview of the controversies surrounding the surveillance of low-risk patients with DTC.


Assuntos
Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Intervalo Livre de Doença , Seguimentos , Humanos , Indução de Remissão/métodos , Medição de Risco/métodos , Medição de Risco/tendências , Neoplasias da Glândula Tireoide/epidemiologia , Fatores de Tempo
2.
Medicine (Baltimore) ; 99(8): e19116, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080085

RESUMO

INTRODUCTION: Transitional drainage, which is followed by cholecystectomy plays a key role in the management of acute cholecystitis, especially in high-risk surgical patients. Endoscopic naso-gallbladder drainage (ENGBD) is an alternative to percutaneous transhepatic gallbladder drainage (PTGBD) for patients who need temporary drainage. There is a lack of prospective comparison on the relevant outcomes of the two drainage methods during the period of drainage, especially the subsequent cholecystectomy. METHODS: This is a randomized controlled two-arm non-blind single center trial. Patients with acute cholecystitis undergo emergent or early cholecystectomy and need drainage will be randomly assigned to group PTGBD or ENGBD. Pain score is defined as the primary endpoint, whereas several secondary endpoints, such as the rates of technical success, clinical remission, open conversion of cholecystectomy will be determined to elucidate more detailed differences between two groups. The general feasibility, safety, and quality checks required for high-quality evidence will be adhered to. DISCUSSION: This study would provide the first type A evidence concerning the comparison of ENGBD versus PTGBD in surgically high-risk patients with acute cholecystitis, it will be the first trial designed to determine the impact of two drainage methods on not only peri-drainage but also peri-LC. TRIAL REGISTRATION: NCT03701464. Registered on October 10, 2018.


Assuntos
Colecistectomia/métodos , Colecistite Aguda/cirurgia , Endoscopia/métodos , Vesícula Biliar/cirurgia , Adulto , Idoso , Colecistite Aguda/microbiologia , Colecistite Aguda/patologia , Colecistostomia/métodos , Drenagem/métodos , Estudos de Viabilidade , Feminino , Vesícula Biliar/microbiologia , Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/fisiopatologia , Estudos Prospectivos , Indução de Remissão/métodos , Resultado do Tratamento
3.
N Engl J Med ; 382(6): 545-553, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32023374

RESUMO

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations. METHODS: In this phase 1 and 2 trial, we administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkin's lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1×105, 1×106, or 1×107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. RESULTS: The administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline. The maximum tolerated dose was not reached. Of the 11 patients who were treated, 8 (73%) had a response; of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission, and 1 had remission of the Richter's transformation component but had persistent CLL. Responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. CONCLUSIONS: Among 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects. (Funded by the M.D. Anderson Cancer Center CLL and Lymphoma Moonshot and the National Institutes of Health; ClinicalTrials.gov number, NCT03056339.).


Assuntos
Antígenos CD19 , Células Matadoras Naturais/transplante , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma não Hodgkin/terapia , Receptores de Antígenos Quiméricos/antagonistas & inibidores , Idoso , Aloenxertos , Terapia Baseada em Transplante de Células e Tecidos , Feminino , Sangue Fetal , Vetores Genéticos , Humanos , Células Matadoras Naturais/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Retroviridae/genética , Condicionamento Pré-Transplante
4.
Mayo Clin Proc ; 95(1): 157-163, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31902411

RESUMO

With improvement in the cure rates for diffuse large B cell lymphoma, the question of surveillance imaging in patients who achieve complete remission after the initial therapy has become relevant. Some of the clinical practice guidelines recommend surveillance scanning. However, several studies have reported no benefit in overall survival with scans. Moreover, studies have highlighted an increased risk for developing secondary malignancies because of exposure to ionizing radiation from the scans. Different international societies have contrasting guidelines for the role of surveillance computerized tomography scans in patients who achieve complete remission after first-line therapy. Any benefit of surveillance imaging must be balanced by the costs, risk of radiation exposure, and lack of survival benefit. The PubMed platform was searched using relevant keywords for English-language articles with no date restrictions. Search terms were cross-referenced with review articles, and additional articles were identified by manually searching reference lists. Results were reviewed by the authors and selected for inclusion based on relevance. We present a review of this current data available for surveillance imaging in patients with diffuse large B cell lymphoma.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Humanos , Linfoma Difuso de Grandes Células B/terapia , Tomografia por Emissão de Pósitrons/efeitos adversos , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Indução de Remissão/métodos , Medição de Risco , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/métodos
5.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(1): 1-9, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-31958923

RESUMO

Patients with clinical complete response(cCR) after neoadjuvant treatment receiving the Watch and Wait('W&W') policy can achieve similar survival of those with yeild pathological complete response (ypCR), and have significantly improved quality of life compared to those undergoing radical operation. Based on thoroughly reviewing the literatures and guidelines at home and abroad, and referring associated clinical experiences from a lot of domestic medical centers, the present version of Chinese Consensus on W&W was established by a panel of many experts of gastrointestinal surgery, medical oncology, radiation oncology, pathology, endoscopy, radiology. This consensus mainly elucidates important conceptions of the W&W policy, current key evidences, risks and benefits for patients, conditions to carry out W&W, criteria of cCR diagnosis, timing of evaluation, follow - up plan, salvage treatment for local relapse and distant metastasis, associated problems of local resection, and is expected to facilitate the clinical practice and research of W&W policy in China.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais/terapia , Conduta Expectante , China , Consenso , Humanos , Guias de Prática Clínica como Assunto , Qualidade de Vida , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Indução de Remissão/métodos , Resultado do Tratamento
6.
Cancer Immunol Immunother ; 69(5): 867-877, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31970440

RESUMO

Acute lymphoblastic leukaemia (ALL) in adults is a rare and difficult-to-treat cancer that is characterised by excess lymphoblasts in the bone marrow. Although many patients achieve remission with chemotherapy, relapse rates are high and the associated impact on survival devastating. Most patients receive chemotherapy and for those whose overall fitness supports it, the most effective treatment to date is allogeneic stem cell transplant that can improve overall survival rates in part due to a 'graft-versus-leukaemia' effect. However, due to the rarity of this disease, and the availability of mature B-cell antigens on the cell surface, few new cancer antigens have been identified in adult B-ALL that could act as targets to remove residual disease in first remission or provide alternative targets for escape variants if and when current immunotherapy strategies fail. We have used RT-PCR analysis, literature searches, antibody-specific profiling and gene expression microarray analysis to identify and prioritise antigens as novel targets for the treatment of adult B-ALL.


Assuntos
Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/farmacologia , Imunoterapia/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Evasão Tumoral/efeitos dos fármacos , Adulto , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/isolamento & purificação , Antígenos de Neoplasias/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Terapia de Alvo Molecular/métodos , Análise de Sequência com Séries de Oligonucleotídeos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Indução de Remissão/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento , Evasão Tumoral/imunologia
7.
Int J Cancer ; 146(5): 1457-1467, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31344264

RESUMO

It remains unclear whether there is a relationship between therapeutic effects of hypomethylating agents (HMAs) and epigenetic modifier gene mutations (EMMs) in patients with cytogenetically intermediate-risk acute myeloid leukemia (IR-AML). Based on targeted-capture sequencing, we retrospectively analyzed the correlation between EMMs and prognosis in 83 IR-AML patients treated with decitabine in combination with cytarabine, aclarubicin hydrochloride and granulocyte colony-stimulating factor (DCAG, n = 35) or "7 + 3" induction regimens (n = 48). In the multivariate analyses, EMM (+) patients did not show any statistically significant difference in remission rates from EMM (-) patients in the DCAG group (p > 0.05), but achieved inferior complete remission (CR; p = 0.03) and overall remission rates (ORR; p = 0.04) after the first course of standard induction regimens (p < 0.05). In the EMM (-) cohort, the DCAG group showed the tendency of adverse total CR (p = 0.06). Besides, DCAG group with EMMs achieved the best survival outcome independent of baseline characteristics, whereas it was opposite in EMM (+) patients receiving standard induction regimens (p < 0.05). Additionally, in the EMM (+) cohort, the survival rate of isolated DCAG group was statistically similar to that of the combination of standard chemotherapies and allogeneic hematopoietic stem cell transplantation (allo-HSCT) (p > 0.40), whereas patients who received only standard regimens had the worst survival rate (0.0%, p < 0.01). It can be concluded that the EMMs might be regarded as the potentially predictive biomarkers of better response to DCAG in IR-AML patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Epigênese Genética/genética , Genes Modificadores/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Aclarubicina/farmacologia , Aclarubicina/uso terapêutico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/farmacologia , Citarabina/uso terapêutico , Metilação de DNA/efeitos dos fármacos , Decitabina/farmacologia , Decitabina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Cariotipagem , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Indução de Remissão/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
8.
Nat Rev Neurol ; 16(1): 56-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31649335

RESUMO

New so-called immune reconstitution therapies (IRTs) have the potential to induce long-term or even permanent drug-free remission in people with multiple sclerosis (MS). These therapies deplete components of the immune system with the aim of allowing the immune system to renew itself. Haematopoietic stem cell transplantation, the oral formulation cladribine and the monoclonal antibodies alemtuzumab, rituximab and ocrelizumab are frequently categorized as IRTs. However, the evidence that IRTs indeed renew adaptive immune cell repertoires and rebuild a healthy immune system in people with MS is variable. Instead, IRTs might foster the expansion of those cells that survive immunosuppression, and this expansion could be associated with acquisition of new functional phenotypes. Understanding immunological changes induced by IRTs and how they correlate with clinical outcomes will be instrumental in guiding the optimal use of immune reconstitution as a durable therapeutic strategy. This Perspectives article critically discusses the efficacy and potential mechanisms of IRTs in the context of immune system renewal and durable disease remission in MS.


Assuntos
Reconstituição Imune/imunologia , Imunoterapia/tendências , Esclerose Múltipla/imunologia , Esclerose Múltipla/terapia , Humanos , Imunoterapia/métodos , Indução de Remissão/métodos
9.
J Oncol Pharm Pract ; 26(1): 99-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30924740

RESUMO

OBJECTIVE: This study was conducted with the aim of making the contribution to a decision for treatment and determination of the modalities in patients diagnosed with non-Hodgkin lymphoma which increasingly become widespread in the geriatric population. MATERIALS AND METHODS: Ninety-one patients aged over 65 years diagnosed with lymphoma and treated in Bezmialem Vakif University Medical Faculty Hospital and Haseki Training and Research Hospital between 2008 and 2013 were retrospectively evaluated. Finally, 63 patients for whom data could be reached were included in the study. RESULTS: Examining the results, histological diagnoses of our patients were as follows: diffuse large B-cell lymphoma (50.8%), follicular lymphoma (23.8%), marginal zone lymphoma (12.7%), mantle cell lymphoma (4.8%), T-cell lymphoma (4.8%), lymphoplasmacytic lymphoma (1.6%) and small lymphocytic lymphoma (1.6%). Stages at the time of diagnosis were early stage by 33.3% and late stage by 66.7%. Of the patients, 36.5% had a low-intermediate and 63.5% a high-intermediate International Prognostic Index score. According to the Eastern Cooperative Oncology Group scoring, 34.9% of the patients have an Eastern Cooperative Oncology Group score of 2-4. Activities of daily living score of 33.3% patients was under 5. Looking at the responses to treatment, the complete response was found in 50.8%, partial response in 4.8%, stable disease in 1.6% and progressive disease in 9.5% of the patients. The mean follow-up duration of patients was found as 25.2 months and disease-free survival after remission as 20.2 months. CONCLUSION: We found that we have achieved a complete remission in more than half of our patients (50.8%). Based on this, treatment should aim remission in elderly patients.


Assuntos
Atividades Cotidianas , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Masculino , Indução de Remissão/métodos , Estudos Retrospectivos
10.
Rheumatology (Oxford) ; 59(1): 153-164, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31257453

RESUMO

OBJECTIVES: The structural consequences of flare after dose reduction/discontinuation of biologic DMARDs in patients with RA who achieve remission are unclear. We compared the incidence of radiographic progression in patients with RA who did and did not experience flare after etanercept (ETN) reduction/withdrawal. METHODS: Eligible adults with moderately active RA despite MTX received ETN 50 mg plus MTX weekly in a 36-week, open-label induction period; patients achieving sustained low disease activity by week 36 were randomized to ETN 50 mg plus MTX, ETN 25 mg plus MTX, or placebo plus MTX in a 52-week, double-blind maintenance period. In post hoc analyses, radiographic progression (Δ modified total Sharp score ⩾0.5 units/year) was compared in patients with and without flare [based on DAS28 relapse (main analysis), and clinical disease activity index and simplified disease activity index relapse (sensitivity analyses)]. Findings from patients receiving full- and reduced-dose combination therapy were pooled for comparison with those from patients receiving MTX only. RESULTS: Significantly more patients receiving MTX monotherapy experienced flare, defined as DAS28 relapse (62% vs 21%; P < 0.0001) and radiographic progression (17% vs 9%; P < 0.001), than patients receiving full-/reduced-dose combination therapy in the double-blind period. Patients with flare defined as clinical disease activity index and simplified disease activity index relapse had higher rates of radiographic progression than those without flare in the full-/reduced-dose combination therapy group (P < 0.01). CONCLUSION: Radiographic progression may be a consequence of flare after biologic DMARD dose reduction/withdrawal in patients with RA. If these approaches are taken, careful monitoring for signs/symptoms of relapse is needed. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00565409.


Assuntos
Artrite Reumatoide/diagnóstico , Etanercepte/uso terapêutico , Radiografia/métodos , Indução de Remissão/métodos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Suspensão de Tratamento
11.
Rheumatology (Oxford) ; 59(1): 205-212, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302705

RESUMO

OBJECTIVES: The aim of this study of patients with RA in Sweden was to investigate secular trends in achieving sustained remission (SR), i.e. DAS28 <2.6 on at least two consecutive occasions and lasting for at least 6 months. METHODS: All adult RA patients registered in the Swedish Rheumatology Quality register through 2012, with at least three registered visits were eligible, a total of 29 084 patients. Year of symptom onset ranged from 1955, but for parts of the analysis only patients with symptom onset between 1994 and 2009 were studied. In total, 95% of patients fulfilled the ACR 1987 classification criteria for RA. Odds of reaching SR for each decade compared with the one before were calculated with logistic regression and individual years of symptom onset were compared with life table analysis. RESULTS: Of patients with symptom onset in the 1980s, 1990s and 2000s, 35.0, 43.0 and 45.6% reached SR, respectively (P < 0.001 for each increment), and the odds of SR were higher in every decade compared with the one before. The hazard ratio for reaching SR was 1.15 (95% CI 1.14, 1.15) for each year from 1994 to 2009 compared with the year before. Five years after symptom onset in 2009, 45.3% of patients had reached SR compared with 15.9% in 1999. CONCLUSION: There is a clear secular trend towards increased incidence of SR in patients with RA in Sweden. This trend most likely reflects earlier diagnosis and treatment start, and adherence to national and international guidelines recommending the treat to target approach.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Diagnóstico Precoce , Sistema de Registros , Indução de Remissão/métodos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Suécia/epidemiologia , Fatores de Tempo
12.
Am J Hematol ; 95(1): 97-115, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31736132

RESUMO

DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15% over 3-5 years). DIAGNOSIS: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109 /L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ~ 30% of patients, while >90% have gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and the oncogenic RAS pathway (~30%) are frequent; while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact over-all survival. RISK STRATIFICATION: Molecularly integrated prognostic models include; the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS-Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift ASXL1 mutations, absolute monocyte count>10 × 109 /L, hemoglobin <10 g/dL, platelet count <100 × 109 /L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97 months, respectively. RISK-ADAPTED THERAPY: Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of ~40%-50% and complete remission rates of ~7%-17%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.


Assuntos
Gerenciamento Clínico , Leucemia Mielomonocítica Crônica/diagnóstico , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Feminino , Humanos , Leucemia Mielomonocítica Crônica/mortalidade , Leucemia Mielomonocítica Crônica/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Medição de Risco , Transplante de Células-Tronco/métodos , Análise de Sobrevida , Transplante Homólogo
13.
Medicine (Baltimore) ; 98(50): e18196, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852076

RESUMO

This study aimed at investigating the prevalence of anxiety and depression, and their risk factors as well as their correlation with prognosis in refractory or relapsed (R/R) acute myeloid leukemia (AML) patients.A total of 180 R/R AML patients were enrolled and their anxiety and depression were assessed by Hospital Anxiety and Depression Scale (HADS) before treatment. Besides, HADS was also evaluated in 180 de novo AML patients prior treatment and 180 healthy controls (HCs), respectively.Both the HADS-Anxiety and HADS-Depression scores were increased in R/R AML patients compared with de novo AML patients and HCs (all P < .001). Meanwhile, the prevalence of anxiety and depression was 53.9% and 45.6% in R/R AML patients, which were also greatly higher compared with de novo AML patients and HCs (all P < .01). Regarding risk factors, higher Eastern Cooperative Oncology Group score and lines of salvage therapy were correlated with anxiety and depression in R/R AML patients (all P < .05). Furthermore, anxiety and depression were associated with shorter overall survival (OS) in R/R AML patients (all P < .05), while no association of different degrees of anxiety and depression with OS was observed (all P > .05).Anxiety and depression are highly prevalent and implicated in the management and prognosis of R/R AML.


Assuntos
Ansiedade/etiologia , Depressão/epidemiologia , Leucemia Mieloide Aguda/complicações , Indução de Remissão/métodos , Medição de Risco/métodos , Ansiedade/epidemiologia , China/epidemiologia , Terapia Combinada , Depressão/etiologia , Feminino , Seguimentos , Humanos , Incidência , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco
14.
PLoS Med ; 16(11): e1002985, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31747392

RESUMO

BACKGROUND: Although bariatric surgery is an effective treatment for type 2 diabetes (T2D) in patients with morbid obesity, further studies are needed to evaluate factors influencing the chance of achieving diabetes remission. The objective of the present study was to investigate the association between T2D duration and the chance of achieving remission of T2D after bariatric surgery. METHODS AND FINDINGS: We conducted a nationwide register-based cohort study including all adult patients with T2D and BMI ≥ 35 kg/m2 who received primary bariatric surgery in Sweden between 2007 and 2015 identified through the Scandinavian Obesity Surgery Registry. The main outcome was remission of T2D, defined as being free from diabetes medication or as complete remission (HbA1c < 42 mmol/mol without medication). In all, 8,546 patients with T2D were included. Mean age was 47.8 ± 10.1 years, mean BMI was 42.2 ± 5.8 kg/m2, 5,277 (61.7%) were women, and mean HbA1c was 58.9 ± 17.4 mmol/mol. The proportion of patients free from diabetes medication 2 years after surgery was 76.6% (n = 6,499), and 69.9% at 5 years (n = 3,765). The chance of being free from T2D medication was less in patients with longer preoperative duration of diabetes both at 2 years (odds ratio [OR] 0.80/year, 95% CI 0.79-0.81, p < 0.001) and 5 years after surgery (OR 0.76/year, 95% CI 0.75-0.78, p < 0.001). Complete remission of T2D was achieved in 58.2% (n = 2,090) at 2 years, and 46.6% at 5 years (n = 681). The chance of achieving complete remission correlated negatively with the duration of diabetes (adjusted OR 0.87/year, 95% CI 0.85-0.89, p < 0.001), insulin treatment (adjusted OR 0.25, 95% CI 0.20-0.31, p < 0.001), age (adjusted OR 0.94/year, 95% CI 0.93-0.95, p < 0.001), and HbA1c at baseline (adjusted OR 0.98/mmol/mol, 95% CI 0.97-0.98, p < 0.001), but was greater among males (adjusted OR 1.57, 95% CI 1.29-1.90, p < 0.001) and patients with higher BMI at baseline (adjusted OR 1.07/kg/m2, 95% CI 1.05-1.09, p < 0.001). The main limitations of the study lie in its retrospective nature and the low availability of HbA1c values at long-term follow-up. CONCLUSIONS: In this study, we found that remission of T2D after bariatric surgery was inversely associated with duration of diabetes and was highest among patients with recent onset and those without insulin treatment.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/cirurgia , Indução de Remissão/métodos , Adulto , Cirurgia Bariátrica/tendências , Glicemia , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Feminino , Hemoglobina A Glicada , Humanos , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Sistema de Registros , Estudos Retrospectivos , Suécia/epidemiologia , Resultado do Tratamento , Perda de Peso
15.
World J Gastroenterol ; 25(39): 6025-6040, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660038

RESUMO

BACKGROUND: Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester, diallyl thiosulfinate) extracted from garlic, has proven activity against Helicobacter pylori (H. Pylori) infection. In recent years, clinical trials have explored its utility as an add-on therapy with variable outcomes reported. AIM: To perform a systemic review of allicin as an add-on treatment for H. Pylori infection and assess its efficacy in randomized controlled trials (RCTs). METHODS: Electronic databases including MEDLINE, EMBASE, the Web of Science, the Cochrane Database, the China National Knowledge Infrastructure Database, Chinese VIP Information Databases, Chinese Medical Databases, and the Wan-Fang Database were searched for keywords including "allicin", "Helicobacter pylori", "randomized clinical trials", and their synonyms. A meta-analysis was performed using the fixed-effects model for low heterogeneity and the random-effects model for high heterogeneity with sensitivity analysis. Bias was evaluated using Egger's tests. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the level of quality, and studies were classed as "high quality", "moderate quality", "low quality", and "very low quality". RESULTS: A total of eight RCTs consisting of 867 participants (435 from the allicin group and 432 from the control group) were included. Eradication rate in the allicin group (93.33%, 406/435) was significantly higher than that of the control group (83.56%, 361/432) [I 2 = 0%, odds ratio (OR) = 2.75, 95% confidence interval (CI): 1.74-4.35, P < 0.001]. The healing rate of ulcers following H. pylori therapy in the allicin group (86.17%, 349/405) was significantly higher than that of the control group (75.87%, 305/402) [I 2 = 0%, OR = 2.05, 95%CI: 1.39-3.03, P < 0.001]. The total remission rate of peptic ulcers across all allicin groups was 97.16%, which was significantly higher than that of controls [96.05% (389/405) vs 86.55% (360/402), I 2 = 0, OR = 3.04, 95%CI: 1.51-6.12, P = 0.015]. No significant differences in side effects were observed. TSA suggested that the trials were of sufficient standard to draw reliable conclusions. The quality of outcomes including eradication rates and side effects was graded as "very low" due to downgrades for "risk of bias" and "indirectness". Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as "low" due to downgrades for "risk of bias". CONCLUSION: Allicin as an add-on therapy improves H. pylori eradication, healing of ulcers, and remission of symptoms. These results are suggested to be treated with caution due to limited quality.


Assuntos
Anti-Infecciosos/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Úlcera Gástrica/tratamento farmacológico , Ácidos Sulfínicos/administração & dosagem , Antiácidos/administração & dosagem , Antiácidos/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Anti-Infecciosos/efeitos adversos , Ensaios Clínicos como Assunto , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Indução de Remissão/métodos , Úlcera Gástrica/microbiologia , Úlcera Gástrica/patologia , Ácidos Sulfínicos/efeitos adversos , Resultado do Tratamento
16.
N Engl J Med ; 381(13): 1201-1214, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553833

RESUMO

BACKGROUND: The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown. METHODS: We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). RESULTS: The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo. CONCLUSIONS: Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Ustekinumab/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Quimioterapia de Indução , Infusões Intravenosas , Injeções Subcutâneas , Quimioterapia de Manutenção , Masculino , Gravidade do Paciente , Indução de Remissão/métodos , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos
17.
N Engl J Med ; 381(13): 1215-1226, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553834

RESUMO

BACKGROUND: Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking. METHODS: In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52. RESULTS: A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P = 0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years. CONCLUSIONS: In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. (Funded by Takeda; VARSITY ClinicalTrials.gov number, NCT02497469; EudraCT number, 2015-000939-33.).


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Adalimumab/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Indução de Remissão/métodos
18.
World J Gastroenterol ; 25(35): 5388-5402, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31558881

RESUMO

BACKGROUND: Abnormal liver chemistry is a common problem in human immunodeficiency virus (HIV)-infected patients. Common causes of abnormal liver enzymes in this population include viral hepatitis B/C or opportunistic infection, drug toxicity, and neoplasm. Autoimmune hepatitis is a rare cause of hepatitis in HIV-infected individuals; however, this condition has been increasingly reported over the past few years. CASE SUMMARY: We present 13 HIV-infected patients (5 males and 8 females) who developed autoimmune hepatitis (AIH) after their immune status was restored, i.e. all patients had stable viral suppression with undetectable HIV viral loads, and median CD4+ counts of 557 cells/× 106 L. Eleven patients presented with chronic persistent elevation of aminotransferase enzyme levels. One patient presented with acute hepatitis and the other patient presented with jaundice. The median levels of aspartate aminotransferase and alanine aminotransferase enzymes were 178 and 177 U/mL, respectively. Elevation of immunoglobulin G levels was present in 11 (85%) patients. Antinuclear antibody and anti-smooth muscle antibody were positive in 11 (85%) and 5 (38%) patients. Liver biopsy was performed in all patients. They had histopathological findings compatible with AIH. The patients were started on prednisolone for remission induction, with good response. After improvement of the liver chemistry, the dose of prednisolone was tapered, and azathioprine was added as life-long maintenance therapy. At the last follow-up visit, all were doing well, without HIV viral rebound or infectious complications. CONCLUSION: This report underscores the emergence of autoimmune hepatitis in the context of HIV infection.


Assuntos
Carga Global da Doença , Infecções por HIV/complicações , Hepatite Autoimune/epidemiologia , Adulto , Alanina Transaminase/sangue , Fármacos Anti-HIV/uso terapêutico , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Aspartato Aminotransferases/sangue , Biópsia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Diagnóstico Diferencial , Feminino , Glucocorticoides/uso terapêutico , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Hepatite Alcoólica/diagnóstico , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Incidência , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Prevalência , Indução de Remissão/métodos , Resultado do Tratamento
19.
J Cancer Res Clin Oncol ; 145(12): 3089-3097, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31559495

RESUMO

PURPOSE: Myelodysplastic syndromes (MDSs) refractory or relapsed after hypomethylating agents (HMAs) remain a therapeutic challenge. The CHG regimen has been demonstrated to be effective in initially treating higher risk MDS. The current study evaluated the efficacy and toxicity of the CHG regimen in patients who were resistant to decitabine. METHODS: Patients with higher risk MDS relapsed or refractory to decitabine were enrolled in this study. Each patient received the CHG regimen (cytarabine (25 mg/day, days 1-14) and homoharringtonine (1 mg/day, days 1-14) intravenously with G-CSF (300 µg/day) subcutaneously from day 0 until neutrophil count recovery to 2.0 × 109 cells/L). Next gene sequencing with a 31-gene panel was carried out in patients. RESULTS: Thirty-three patients were enrolled, including 12 relapsed and 21 refractory cases. The overall response rate (ORR) was 39.4% (13 of 33), with 9 (27.3%) achieving complete remission (CR), 2 having marrow CR (mCR), and 2 achieving partial remission (PR). The CR rate was higher in patients harboring fewer gene mutations (0-1) (55.6%) than in those with more gene mutations (> 1) (12.5%) (p = 0.021). The median overall survival (OS) of the 33 patients was 7.0 months. Patients who achieved a response had significantly longer survival times than were found in those without a response (21.0 M vs. 4.0 M, p < 0.0001). The regimen was endurable for most of the patients. CONCLUSIONS: The CHG priming regimen provided a safe and effective salvage regimen for higher risk MDS patients who were resistant to decitabine. Further studies involving larger samples will be needed. Clinical trial No. ChiCTR-ONC-11001501.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/uso terapêutico , Decitabina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mepesuccinato de Omacetaxina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Citarabina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Mepesuccinato de Omacetaxina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Indução de Remissão/métodos , Terapia de Salvação/métodos , Resultado do Tratamento
20.
BMC Musculoskelet Disord ; 20(1): 420, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506089

RESUMO

BACKGROUND: We aimed to evaluate the prevalence of foot and/or ankle arthritis (FAA) and its impact on clinical indices in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study used data from the Korean College of Rheumatology Biologics & Targeted therapy registry to observe clinical outcomes of patients undergoing biologics therapy and conventional therapy. FAA was defined as ≥1 tender or swollen joint in the ankle and/or 1st-5th metatarsophalangeal (MTP) joints. Disease Activity Score 28 (DAS28), Routine Assessment of Patient Index Data 3 (RAPID3), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) were assessed. RESULTS: Among 2046 patients, 598 had FAA. The ankle joint was the most commonly involved joint in FAA (tender joint, 71.4%; swollen joint, 59.5%), followed by the third and second MTP joints. Patients with FAA showed higher DAS28, RAPID3, SDAI, and CDAI scores. FAA presence was significantly associated with non-remission as per DAS28-ESR (odds ratio, 3.4; 95% confidence interval, 2.0-5.8), DAS28-CRP (3.6, 2.4-5.3), SDAI (6.3, 2.8-14.6), CDAI (7.6, 2.4-24.3), and RAPID3 (5.6, 2.7-11.5) indices on adjusting for age, sex, disease duration, presence of rheumatoid factor, presence of anti-cyclic citrullinated peptide antibody, lung disease, use of methotrexate, and previous use of biological disease-modifying anti-rheumatic drugs. Patients with FAA were less likely to achieve remission of SDAI (n = 6, 1.0%) and CDAI (n = 3, 0.5%) than that of DAS28-ESR (n = 21, 3.5%), DAS28-CRP (n = 38, 6.4%), and RAPID3 (n = 12, 2.0%). CONCLUSIONS: FAA represents a severe disease activity and is an independent risk factor for non-remission in patients with RA.


Assuntos
Articulação do Tornozelo/patologia , Artrite Reumatoide/epidemiologia , Articulação Metatarsofalângica/patologia , Índice de Gravidade de Doença , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Indução de Remissão/métodos , Fatores de Risco , Inquéritos e Questionários , Falha de Tratamento
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