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1.
Ann Oncol ; 33(3): 259-275, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34923107

RESUMO

BACKGROUND: Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, high-grade B-cell lymphoma and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future. DESIGN: The European Society for Blood and Marrow Transplantation (EBMT)-Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association collaborated to draft best practice recommendations based on the current literature to support health care professionals in delivering consistent, high-quality care in this rapidly moving field. RESULTS: Thirty-six CAR-T experts (medical, nursing, pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post-authorisation safety surveillance and regulatory issues. CONCLUSIONS: We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for haematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.


Assuntos
Hematologia , Receptores de Antígenos Quiméricos , Acreditação , Adulto , Medula Óssea , Humanos , Imunoterapia Adotiva , Receptores de Antígenos de Linfócitos T
2.
Mult Scler ; 27(8): 1198-1204, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33565902

RESUMO

BACKGROUND: Autologous haematopoietic stem cell transplantation (AHSCT) is an effective treatment for patients with multiple sclerosis (MS) who have highly active disease, despite the use of standard disease-modifying therapies (DMTs). However, the optimal time for offering AHSCT to patients with 'aggressive' MS is yet to be established. OBJECTIVES: The objective was to explore the safety and efficacy of AHSCT as a first-line DMT in patients with 'aggressive' MS. METHODS: All patients with 'aggressive' MS who received AHSCT as a first-line DMT in five European and North American centres were retrospectively evaluated. RESULTS: Twenty patients were identified. The median interval between diagnosis and AHSCT was 5 (1-20) months. All had multiple poor prognostic markers with a median pre-transplant Expanded Disability Status Scale (EDSS) score of 5.0 (1.5-9.5). After a median follow-up of 30 (12-118) months, the median EDSS score improved to 2.0 (0-6.5, p < 0.0001). No patient had further relapses. Three had residual magnetic resonance imaging (MRI) disease activities in the first 6 months post-transplant, but no further new or enhancing lesions were observed in subsequent scans. CONCLUSION: AHSCT is safe and effective as a first-line DMT in inducing rapid and sustained remission in patients with 'aggressive' MS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla , Humanos , Esclerose Múltipla/terapia , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
3.
Br J Dermatol ; 185(5): 887-898, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34036569

RESUMO

The management of moderate-to-severe psoriasis has been transformed by the introduction of biological therapies. These medicines, particularly those targeting interleukin (IL)-17 and IL-23p19, can offer clear or nearly clear skin for the majority of patients with psoriasis, with good long-term drug survival. However, as currently used, none of these therapies is curative and disconcertingly there is a small but increasing number of patients with severe psoriasis who have failed all currently available therapeutic modalities. A similar scenario has occurred in other immune-mediated inflammatory diseases (IMIDs) where treatment options are limited in severely affected patients. In these cases, cell therapy, including haematopoietic stem cell transplantation (HSCT) and mesenchymal stromal cells (MSC), has been utilized. This review discusses the various forms of cell therapy currently available, their utility in the management of IMIDs and emerging evidence for efficacy in severe psoriasis that is unresponsive to biological therapy. Balancing the risks and benefits of treatment vs. the underlying disease is key; cell therapy carries significant risks, costs, regulation and other complexities, which must be justified by outcomes. Although HSCT has anecdotally been reported to benefit severe psoriasis, sometimes with apparent cure, this has mainly been in the setting of other coincidental 'routine' indications. In psoriasis, cell therapies, such as MSC and regulatory T cells, with a lower risk of complications are likely to be more appropriate. Well-designed controlled trials coupled with mechanistic studies are warranted if advanced cell therapies are to be developed and delivered as a realistic option for severe psoriasis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Psoríase , Terapia Biológica , Humanos , Psoríase/terapia
4.
Z Rheumatol ; 79(5): 419-428, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32356079

RESUMO

The recent introduction of biologic and targeted synthetic disease-modifying drugs has led to more specificity in the treatment of autoimmune diseases; however, they require continuous or intermittent administration, are associated with cumulative risks for side effects, result in high costs and provide no cure. In contrast, high-dose chemotherapy followed by transplantation of autologous hematopoietic stem cells (AHSCT) has been demonstrated to induce clinical remission in various autoimmune diseases that can persist over many years without continued maintenance therapy. The principle behind AHSCT is an elimination of important components of the autoreactive immunological memory with subsequent regeneration of the complete immune system. Several studies have indicated that such an immune reset is associated with fundamental changes in the immune repertoire leading to an induction of tolerance against self-antigens. This article presents the current indications of AHSCT for autoimmune diseases based on the registry data of the European Society of Blood and Marrow Transplantation (EBMT) and discusses the results from mechanistic studies, which provide detailed insights into the mode of action of this treatment.


Assuntos
Doenças Autoimunes , Transplante de Células-Tronco Hematopoéticas , Doenças Autoimunes/terapia , Humanos , Sistema Imunitário , Tolerância Imunológica , Sistema de Registros , Transplante Autólogo
5.
Biol Blood Marrow Transplant ; 25(10): 2079-2085, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31229642

RESUMO

Beyond its impact on bone health, numerous studies have investigated the immune-regulatory properties of vitamin D and shown how its deficiency can affect outcomes in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in acute or chronic graft-versus-host disease. This survey, carried out by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT), describes the current clinical practice discrepancies across the EBMT HSCT programs. We therefore recommend the development of evidence-based guidelines to standardize evaluation criteria and to harmonize the management of vitamin D deficiency in patients undergoing allogeneic HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Deficiência de Vitamina D/terapia , Vitamina D/uso terapêutico , Europa (Continente) , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Inquéritos e Questionários , Transplante Homólogo/métodos , Vitamina D/farmacologia
6.
Neuropathol Appl Neurobiol ; 45(3): 244-261, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29790198

RESUMO

INTRODUCTION: Cell biological and genetic evidence implicate failures in degrading aggregating proteins, such as tau and TDP-43, through the autophagy or lysosomal pathways in the pathogenesis of frontotemporal lobar degeneration (FTLD). METHODS: We investigated changes in the degradative pathways in 60 patients with different pathological or genetic forms of FTLD employing immunohistochemistry for marker proteins such as lysosomal-associated membrane proteins 1 (LAMP-1) and 2 (LAMP-2), cathepsin D (CTSD) and microtubule-associated protein 1 light chain 3 alpha (LC3A). Immunostained sections were qualitatively and semi-quantitatively assessed for the appearance, distribution and intensity of staining in neurones of the dentate gyrus (DG) and CA4 region of the hippocampus, and the temporal cortex (Tcx). RESULTS: Lower levels of neuronal LAMP-1 immunostaining were present in the DG and Tcx in FTLD-tau compared to FTLD-TDP. There was less LAMP-1 immunostaining in FTLD-tau with MAPT mutations, and FTLD-tau with Pick bodies, compared to FTLD-TDP types A and B, and less LAMP-1 immunostaining in FTLD-TDP type C than in FTLD-TDP types A and B. There was greater LAMP-1 immunostaining in GRN mutation which may reflect the underlying type A histology rather than mutation. There were no differences in neuronal LAMP-2, CTSD, EEA-1 or LC3A immunostaining between any of the five FTLD histological or four genetic groups, nor between FTLD-TDP and FTLD-tau. CONCLUSIONS: The underlying pathological mechanism in FTLD-tau may lie with a relative deficiency of lysosomes, or defective vesicular transport, whereas the failure to clear TDP-43 aggregates may lie with lysosomal dysfunction rather than a lack of available lysosomes or degradative enzymes.


Assuntos
Doença de Alzheimer/metabolismo , Autofagossomos/metabolismo , Catepsina D/metabolismo , Degeneração Lobar Frontotemporal/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Lisossomos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
BJOG ; 125(6): 686-692, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28941068

RESUMO

OBJECTIVE: Using a simple simulation, we illustrate why associations estimated from studies restricted to preterm births cannot be interpreted causally. DESIGN, SETTING AND POPULATION: Data simulation involving a hypothetical cohort of fetuses who may be healthy or have one or more of four pathological factors (termed A through D, increasing in severity) with known effects on gestational length and risk of mortality. We focus on babies born at ≤32 weeks of gestation. METHODS: We visually represent the simulated population and compare the association between A (which may represent pre-eclampsia) and neonatal death. We then repeat the exercise with D (standing in for chorioamnionitis) as the exposure of interest. MAIN OUTCOME MEASURES: Odds ratios of neonatal death in the simulated data. RESULTS: In most weeks, and for both A and D, the calculated odds ratios are substantially biased and underestimate the true risk of neonatal death associated with each pathology. For example, factor A has a true causal odds ratio of 1.50, yet it appears protective among births ≤32 weeks (estimated crude odds ratio 0.39; gestational age-adjusted odds ratio 0.71). CONCLUSIONS: Among very preterm births, virtually all babies are born with pathologies that increase the risk of adverse outcomes. Hence, babies exposed to one factor (e.g. pre-eclampsia) are compared with babies who have a mix of other pathologies. Such selection bias affects studies carried out among very preterm births (e.g. where pre-eclampsia appears to reduce risk of adverse neonatal outcomes). TWEETABLE ABSTRACT: Selection bias affects studies of preterm births, complicating interpretation.


Assuntos
Doenças do Prematuro/etiologia , Nascimento Prematuro/etiologia , Viés , Estudos de Coortes , Simulação por Computador , Feminino , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Doenças do Prematuro/mortalidade , Masculino , Razão de Chances , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/mortalidade , Gravidez , Nascimento Prematuro/mortalidade
8.
Eur J Cancer Care (Engl) ; 27(2): e12623, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28026132

RESUMO

An increasing cohort of haematopoietic cell transplantation (HCT) survivors has raised awareness of long-term and late effects. Updated recommendations for HCT late effects screening were published in 2012 [Majhail et al. Biology of Blood and Marrow Transplantation, 18 (2012):348]. We aimed to assess the clinical efficacy of a dedicated screening clinic to identify problems in HCT survivors using the international guidelines. Clinic letters and test results of the first 59 consecutive patients attending the screening clinic were evaluated. 30 females and 29 males (mean age of 49 years, range 22-74) were included. The mean time since transplant was 6 years (0.5-18). 49/65 transplants were allogeneic. Primary indications for HCT were myeloid (56%), lymphoid (37%), solid tumour (5%) and auto-immune diseases (2%). 134 complications were reported (mean 2, range 0-8), with 114 documented further actions/referrals. The most commonly reported concerns were pain 18/59 (31%), fatigue 14/59 (24%), sexual function 14/59 (24%) and sleep disturbance 11/59 (19%). Second primary malignancies were recorded in five cases. Implementation and audit of the international late effect screening guidelines confirm the need for systematic long-term physical and psychological screening and care, thus ensuring timely and efficient identification of problems and the opportunity to minimise morbidity effects and optimise health.


Assuntos
Transplante de Medula Óssea/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Adulto Jovem
9.
Neuropathol Appl Neurobiol ; 42(3): 242-54, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26538301

RESUMO

AIMS: A hexanucleotide expansion in C9orf72 is the major genetic cause of inherited behavioural variant Frontotemporal dementia (bvFTD) and motor neurone disease (MND), although the pathological mechanism(s) underlying disease remains uncertain. METHODS: Using antibodies to poly-GA, poly-GP, poly-GR, poly-AP and poly-PR proteins, we examined sections of cerebral cortex, hippocampus, thalamus, cerebellum and spinal cord, from 20 patients with bvFTD and/or MND bearing an expansion in C9orf72 for aggregated deposits of dipeptide repeat proteins (DPR). RESULTS: Antibodies to poly-GA, poly-GP and poly-GR detected numerous rounded cytoplasmic inclusions (NCI) within granule cells of hippocampal dentate gyrus and those of the cerebellum, as well as 'star-burst' shaped NCI in pyramidal neurones of CA3/4 region of hippocampus. NCI were uncommon in Purkinje cells, and only very rarely seen in anterior horn cells. Poly-PA antibody detected occasional NCI within CA3/4 neurones alone, whereas poly-PR antibody did not identify any NCI but immunostained the nucleus of anterior horn cells, CA3/4 neurones and Purkinje cells, in patients with or without expansion in C9orf72, as well as in normal controls. Poly-GA antibody generally detected more DPR than poly-GP, which in turn was greater than poly-GR. All patients with bvFTD + MND or MND showed plentiful p62/TDP-43 positive inclusions in remaining anterior horn cells. CONCLUSION: Degeneration and loss of anterior horn cells associated with expansions in C9orf72 occurs in the absence of DPR, and implies that changes involving loss of nuclear staining for and a cytoplasmic aggregation of TDP-43 are more likely to be the cause of this.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Degeneração Lobar Frontotemporal/patologia , Doença dos Neurônios Motores/patologia , Degeneração Neural/patologia , Proteínas/genética , Idoso , Proteína C9orf72 , Expansão das Repetições de DNA , Dipeptídeos , Feminino , Degeneração Lobar Frontotemporal/genética , Humanos , Imuno-Histoquímica , Corpos de Inclusão/metabolismo , Corpos de Inclusão/patologia , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/genética , Degeneração Neural/genética , Neurônios/patologia
10.
BJOG ; 123(2): 271-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26840780

RESUMO

OBJECTIVE: To compare perinatal outcomes between elective induction of labour (eIOL) and expectant management in obese women. DESIGN: Retrospective cohort study. SETTING: Deliveries in California in 2007. POPULATION: Term, singleton, vertex, nonanomalous deliveries among obese women (n = 74 725). METHODS: Women who underwent eIOL at 37 weeks were compared with women who were expectantly managed at that gestational age. Similar comparisons were made at 38, 39, and 40 weeks. Results were stratified by parity. Chi-square tests and multivariable logistic regression were used for statistical comparison. MAIN OUTCOME MEASURES: Method of delivery, severe perineal lacerations, postpartum haemorrhage, chorioamnionitis, macrosomia, shoulder dystocia, brachial plexus injury, respiratory distress syndrome. RESULTS: The odds of caesarean delivery were lower among nulliparous women with eIOL at 37 weeks [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.34-0.90] and 39 weeks (OR 0.77, 95% CI 0.63-0.95) compared to expectant management. Among multiparous women with a prior vaginal delivery, eIOL at 37 (OR 0.39, 95% CI 0.24-0.64), 38 (OR 0.65, 95% CI 0.51-0.82), and 39 weeks (OR 0.67, 95% CI 0.56-0.81) was associated with lower odds of caesarean. Additionally, eIOL at 38, 39, and 40 weeks was associated with lower odds of macrosomia. There were no differences in the odds of operative vaginal delivery, lacerations, brachial plexus injury or respiratory distress syndrome. CONCLUSIONS: In obese women, term eIOL may decrease the risk of caesarean delivery, particularly in multiparas, without increasing the risks of other adverse outcomes when compared with expectant management.


Assuntos
Cesárea/estatística & dados numéricos , Distocia/epidemiologia , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Trabalho de Parto Induzido/estatística & dados numéricos , Obesidade/complicações , Complicações do Trabalho de Parto/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , California/epidemiologia , Procedimentos Cirúrgicos Eletivos/psicologia , Feminino , Humanos , Recém-Nascido , Trabalho de Parto Induzido/psicologia , Modelos Logísticos , Obesidade/epidemiologia , Obesidade/psicologia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco
11.
Br J Cancer ; 113(3): 365-71, 2015 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-26151455

RESUMO

Aberrant activation of intracellular signalling pathways confers malignant properties on cancer cells. Targeting intracellular signalling pathways has been a productive strategy for drug development, with several drugs acting on signalling pathways already in use and more continually being developed. The JAK/STAT signalling pathway provides an example of this paradigm in haematological malignancies, with the identification of JAK2 mutations in myeloproliferative neoplasms leading to the development of specific clinically effective JAK2 inhibitors, such as ruxolitinib. It is now clear that many solid tumours also show activation of JAK/STAT signalling. In this review, we focus on the role of JAK/STAT signalling in solid tumours, examining the molecular mechanisms that cause inappropriate pathway activation and their cellular consequences. We also discuss the degree to which activated JAK/STAT signalling contributes to oncogenesis. Studies showing the effect of activation of JAK/STAT signalling upon prognosis in several tumour types are summarised. Finally, we discuss the prospects for treating solid tumours using strategies targeting JAK/STAT signalling, including what can be learned from haematological malignancies and the extent to which results in solid tumours might be expected to differ.


Assuntos
Janus Quinases/fisiologia , Neoplasias , Fatores de Transcrição STAT/fisiologia , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Humanos , Neoplasias/diagnóstico , Neoplasias/etiologia , Neoplasias/terapia , Prognóstico , Transdução de Sinais/fisiologia
12.
AIDS Behav ; 19(12): 2311-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25686574

RESUMO

African American men who have sex with men have been disproportionately affected by the HIV epidemic in the United States and remain to this day one of the groups with highest HIV prevalence and incidence. Our goal was to clarify the current state of HIV risk, sexual behaviors, and structural/network-network level factors that affect black MSM's population risk of HIV, enabling the formulation of targeted and up-to-date public health messages/campaigns directed at this vulnerable population. Our approach maximized the use of local data through a process of synthesis and triangulation of multiple independent and overlapping sources of information that are sometimes separately published and often not examined side-by-side. Among African American MSM, we observed stable HIV incidence despite increases in reported individual risk behavior and STDs. An increasing proportion of African American MSM are reporting HIV testing in the past 6 months and seroadaptive behaviors, which may play a role in this observed decline in HIV among MSM in San Francisco, California. Our analysis suggests that currently the HIV epidemic is stable among African American MSM in San Francisco. However, we suggest that the observed stability is due to factors prohibiting expansion of new infections rather than decreasing risks for HIV infection among African American MSM.


Assuntos
Negro ou Afro-Americano , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , São Francisco/epidemiologia , Minorias Sexuais e de Gênero , Adulto Jovem
13.
Neuropathol Appl Neurobiol ; 40(2): 136-48, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23808763

RESUMO

AIMS: Pathological heterogeneity of Aß deposition in senile plaques (SP) and cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD) has been long noted. The aim of this study was to classify cases of AD according to their pattern of Aß deposition, and to seek factors which might predict, or predispose towards, this heterogeneity. METHODS: The form, distribution and severity of Aß deposition (as SP and/or CAA) was assessed semiquantitatively in immunostained sections of frontal, temporal and occipital cortex from 134 pathologically confirmed cases of AD. RESULTS: Four patterns of Aß deposition were defined. Type 1 describes cases predominantly with SP, with or without CAA within leptomeningeal vessels alone. Type 2 describes cases where, along with many SP, CAA is present in both leptomeningeal and deeper penetrating arteries. Type 3 describes cases where capillary CAA is present along with SP and arterial CAA. Type 4 describes a predominantly vascular phenotype, where Aß deposition is much more prevalent in and around blood vessels, than as SP. As would be anticipated from the group definitions, there were significant differences in the distribution and degree of CAA across the phenotype groups, although Aß deposition as SP did not vary. There were no significant differences between phenotype groups with regard to age of onset, age at death, disease duration and brain weight, or disease presentation. Women were over-represented in the type 1 phenotype and men in type 2. Genetically, type 3 (capillary subtype) cases were strongly associated with possession of the APOE ε4 allele. CONCLUSIONS: This study offers an alternative method of pathologically classifying cases of AD. Further studies may derive additional genetic, environmental or clinical factors which associate with, or may be responsible for, these varying pathological presentations of AD.


Assuntos
Doença de Alzheimer/patologia , Angiopatia Amiloide Cerebral/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/classificação , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Amiloide/patologia
14.
Support Care Cancer ; 22(10): 2615-20, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24733635

RESUMO

PURPOSE: It is recommended that patients with multiple myeloma should be assessed for unmet holistic needs at key times in their disease trajectory. The aim of this exploratory study was to characterise the holistic needs of advanced, intensively treated multiple myeloma using a structured assessment tool. METHODS: Patients with multiple myeloma who had undergone a haematopoietic stem cell transplantation and subsequent treatment for at least one episode of progressive disease but were in stable plateau phase were included in the study. Patients' holistic needs were assessed using the self-reporting tool, Sheffield Profile for Assessment and Referral for Care (SPARC). RESULTS: Thirty-two patients with a median age of 60 years at assessment and a median of 5.5 years from diagnosis were recruited. Using the SPARC, half of the patients reported tiredness as 'quite a bit/very much,' while one third complained that daytime somnolence and insomnia were 'quite a bit/very much.' Forty-four percent of patients reported pain. One third of patients were bothered and distressed by the side effects from their treatment and were worried about long-term effects of their treatment. Thirty-one percent of patients felt that the effect of their condition had an impact on their sexual life, and 40 % were worried about the effect that their illness was having on their family or other people. CONCLUSION: This is the first study to use a self-reported holistic needs assessment tool in multiple myeloma. A multidimensional structured questionnaire like the SPARC could provide a useful first step in the effective delivery of supportive and palliative care for patients with multiple myeloma.


Assuntos
Mieloma Múltiplo/psicologia , Avaliação das Necessidades , Psicometria/instrumentação , Inquéritos e Questionários/normas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia
15.
Eur J Cancer Care (Engl) ; 23(3): 349-62, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24330318

RESUMO

Following haematopoietic stem cell transplant (HSCT) some patients experience long-term physical and psychosocial problems which impact on everyday life. The aim of this service evaluation was to investigate the psychosocial supportive care available for HSCT patients in three UK centres, particularly related to five identified areas of concern: fatigue; psychological distress; vocational and financial issues; sexuality, and fertility. HSCT health professionals were invited to audio-recorded semi-structured interviews. Enquiry was made into supportive care provided routinely (proactive), provided in response to a need (reactive) and missing (gaps in service) from pre-transplant to 18 months post transplant. Information gathered was transcribed and subjected to framework analysis. Interviews were conducted with 84 staff including nurses, doctors, psychologists, social workers, physiotherapists, dieticians and occupational therapists. Support for the five main areas of concern was variable across centres particularly with limitation of services for psychology; sexual dysfunction and fertility. Pro-active interventions such as psychological screening were rare with support being more commonly provided in response to an identified need. Support provided reactively for the areas of concern was comprehensive across professional groups and centres. Further work explores patients' psychosocial issues and other ways of providing adjuvant support.


Assuntos
Transplante de Células-Tronco Hematopoéticas/psicologia , Serviços de Saúde Mental , Apoio Social , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Reino Unido
16.
Biol Blood Marrow Transplant ; 19(4): 666-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23253561

RESUMO

We analyzed the long-term outcomes of pediatric patients registered in the European Group for Blood and Marrow Transplantation database who underwent hematopoietic stem cell transplantation (HSCT) for severe treatment refractory autoimmune cytopenia. With a median follow-up of 100 months, event-free survival was 54% overall, with no significant difference between allogeneic HSCT (n = 15) and autologous HSCT (n = 7) recipients (58% versus 42%; P = .50). Despite a trend toward failure of response or relapse after autologous HSCT compared with allogeneic HSCT, the difference was not significant (43% versus 13%; P = .30). Treatment-related mortality was high in both HSCT groups (29% and 16%; P = .09). Based on the limited numbers of subjects in this retrospective analysis, both allogeneic and autologous HSCT may induce complete and persistent responses in approximately one-half of pediatric patients with severe refractory autoimmune cytopenia, although treatment-related toxicity is high.


Assuntos
Doenças Autoimunes/terapia , Transplante de Células-Tronco Hematopoéticas , Neutropenia/terapia , Trombocitopenia/terapia , Adolescente , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neutropenia/imunologia , Neutropenia/patologia , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Trombocitopenia/imunologia , Trombocitopenia/patologia , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
17.
Ann Oncol ; 24(9): 2430-4, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23712545

RESUMO

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/cirurgia , Recidiva Local de Neoplasia/mortalidade , Transplante de Células-Tronco , Adolescente , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Sobrevida , Transplante Autólogo , Falha de Tratamento , Adulto Jovem
18.
Clin Exp Immunol ; 171(2): 201-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23286947

RESUMO

Serum free light chain (sFLC) measurement has gained widespread acceptance and is incorporated into various diagnostic and response criteria. Non-linearity and antigen excess are the main causes of 'variability' in the measurement of sFLC using immunoassay, but the impact of these on measurement has been unclear. We performed a retrospective evaluation using a dilutional strategy to detect these phenomena. A total of 464 samples in 2009 and 373 samples in 2010 were analysed for sFLC. Non-linearity was detected in both high and apparently normal sFLC. Major non-linearity of more than twofold is common in high kappa (20·2%) and lambda (14·1%). It is less common in samples with apparently normal levels - kappa (6·4%) and lambda (9·5%). 9·4% of kappa and 15·5% of lambda showed antigen excess at screening dilutions. 34·4% of the samples had either non-linearity or antigen excess. We conclude that significant measurement variability is common in the measurement of sFLC. There is currently no reliable technique to detect non-linearity phenomena unless a serial dilution strategy is applied to every analysis. We recommend that laboratories routinely reporting sFLC results for clinical services need appropriate strategies for addressing these issues. Clinicians should be aware of these limitations in interpretation of sFLC assay for individual patients. Future guidelines should adopt action thresholds which are grounded firmly in test performance parameters.


Assuntos
Imunoensaio/estatística & dados numéricos , Imunoensaio/normas , Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo/sangue , Testes Diagnósticos de Rotina , Humanos , Dinâmica não Linear , Variações Dependentes do Observador , Valores de Referência , Estudos Retrospectivos
19.
Neuropathol Appl Neurobiol ; 39(2): 157-65, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22497712

RESUMO

AIMS: We aimed to investigate the role of the nuclear carrier and binding proteins, transportin 1 (TRN1) and transportin 2 (TRN2), TATA-binding protein-associated factor 15 (TAF15) and Ewing's sarcoma protein (EWS) in inclusion body formation in cases of frontotemporal lobar degeneration (FTLD) associated with fused in sarcoma protein (FTLD-FUS). METHODS: Eight cases of FTLD-FUS (five cases of atypical FTLD-U, two of neuronal intermediate filament inclusion body disease and one of basophilic inclusion body disease) were immunostained for FUS, TRN1, TRN2, TAF15 and EWS. Ten cases of FTLD associated with TDP-43 inclusions served as reference cases. RESULTS: The inclusion bodies in FTLD-FUS contained TRN1 and TAF15 and, to a lesser extent, EWS, but not TRN2. The patterns of immunostaining for TRN1 and TAF15 were very similar to that of FUS. None of these proteins was associated with tau or TDP-43 aggregations in FTLD. CONCLUSIONS: Data suggest that FUS, TRN1 and TAF15 may participate in a functional pathway in an interdependent way, and imply that the function of TDP-43 may not necessarily be in parallel with, or complementary to, that of FUS, despite each protein sharing many similar structural elements.


Assuntos
Degeneração Lobar Frontotemporal/metabolismo , Proteína EWS de Ligação a RNA/metabolismo , Proteína FUS de Ligação a RNA/metabolismo , Fatores Associados à Proteína de Ligação a TATA/metabolismo , beta Carioferinas/metabolismo , Adulto , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Corpos de Inclusão/metabolismo , Masculino , Pessoa de Meia-Idade
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