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1.
Eur Radiol ; 34(4): 2174-2182, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37740778

RESUMO

OBJECTIVES: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors prioritizes isocitrate dehydrogenase (IDH) mutation to define tumor types in diffuse gliomas, in contrast to the 2016 classification, which prioritized histological features. Our objective was to investigate the influence of this change in the performance of proton MR spectroscopy (1H-MRS) in segregating high-grade diffuse astrocytoma subgroups. METHODS: Patients with CNS WHO grade 3 and 4 diffuse astrocytoma, known IDH mutation status, and available 1H-MRS were retrospectively retrieved and divided into 4 groups based on IDH mutation status and histological grade. Differences in 1H-MRS between groups were analyzed with the Kruskal-Wallis test. The points on the spectrum that showed the greatest differences were chosen to evaluate the performance of 1H-MRS in discriminating between grades 3 and 4 tumors (WHO 2016 defined), and between IDH-mutant and IDH-wildtype tumors (WHO 2021). ROC curves were constructed with these points, and AUC values were calculated and compared. RESULTS: The study included 223 patients with high-grade diffuse astrocytoma. Discrimination between IDH-mutant and IDH-wildtype tumors showed higher AUC values (highest AUC short TE, 0.943; long TE, 0.864) and more noticeable visual differences than the discrimination between grade 3 and 4 tumors (short TE, 0.885; long TE, 0.838). CONCLUSION: Our findings suggest that 1H-MRS is more applicable to classify high-grade astrocytomas defined with the 2021 criteria. Improved metabolomic robustness and more homogeneous groups yielded better tumor type discrimination by 1H-MRS with the new criteria. CLINICAL RELEVANCE STATEMENT: The 2021 World Health Organization classification of brain tumors empowers molecular criteria to improve tumor characterization. This derives in greater segregation of high-grade diffuse astrocytoma subgroups by MR spectroscopy and warrants further development of brain tumor classification tools with spectroscopy. KEY POINTS: • The new 2021 updated World Health Organization classification of central nervous system tumors maximizes the role of molecular diagnosis in the classification of brain tumors. • Proton MR spectroscopy performs better to segregate high-grade astrocytoma subgroups when defined with the new criteria. • The study provides additional evidence of improved metabolic characterization of brain tumor subgroups with the new criteria.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Humanos , Prótons , Estudos Retrospectivos , Astrocitoma/patologia , Neoplasias Encefálicas/genética , Espectroscopia de Ressonância Magnética , Organização Mundial da Saúde , Mutação , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo
2.
Support Care Cancer ; 28(5): 2457-2472, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32056010

RESUMO

OBJECTIVE: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions. CONCLUSIONS: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions.


Assuntos
Mel , Mucosite/tratamento farmacológico , Plantas Medicinais , Probióticos/uso terapêutico , Saliva/metabolismo , Estomatite/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Goma de Mascar , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Saliva/efeitos dos fármacos
3.
Support Care Cancer ; 27(10): 3997-4010, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31286229

RESUMO

PURPOSE: To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions. CONCLUSIONS: Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.


Assuntos
Glutamina/uso terapêutico , Minerais/uso terapêutico , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Estomatite/tratamento farmacológico , Estomatite/prevenção & controle , Vitaminas/uso terapêutico , Suplementos Nutricionais , Glutamina/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Neoplasias/tratamento farmacológico
4.
J Am Acad Dermatol ; 78(6): 1102-1109, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29273489

RESUMO

BACKGROUND: Dermatologic conditions cause morbidity and mortality among hospitalized cancer patients. An improved understanding is critical for implementing clinical and research programs in inpatient oncodermatology. OBJECTIVE: To characterize inpatient dermatology consultations at a large comprehensive cancer center. METHODS: Retrospective database query of new admissions and medical record review of initial inpatient dermatology consultations comparing inpatients consulted and not consulted during January-December 2015. RESULTS: In total, 412 of 11,533 inpatients received 471 dermatology consultations (54% male, median age 59.5 years). Patients with hematologic cancers were 6 times more likely to receive dermatologic consultations compared with nonhematologic cancers (odds ratio 6.56, 95% confidence interval 5.35-8.05, P < .0001). Patients consulted by a dermatologist had a significantly longer length of stay than inpatients not consulted by dermatology (median 11 vs 5 days, P < .0001). Among the 645 dermatologic conditions diagnosed, the most common categories were inflammatory diseases, infections, and drug reactions; the most frequent conditions were contact dermatitis, herpes zoster, and chemotherapy-induced drug eruptions. LIMITATIONS: The study's retrospective nature and single-institution setting are potential limitations. CONCLUSION: Hematologic malignancies are a significant risk factor for dermatology inpatient consultations. A significantly longer length of stay was associated with dermatology consultations, suggesting high comorbidities in these patients. Increased dermatologic care of these inpatients might improve quality of life, dermatologic health, and ability to receive anticancer agents.


Assuntos
Dermatite/epidemiologia , Dermatite/etiologia , Toxidermias/epidemiologia , Hospitalização/estatística & dados numéricos , Neoplasias/complicações , Encaminhamento e Consulta/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Institutos de Câncer , Estudos de Coortes , Bases de Dados Factuais , Dermatite/patologia , Toxidermias/etiologia , Feminino , Humanos , Incidência , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Cidade de Nova Iorque , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/etiologia
5.
Pediatr Dermatol ; 34(5): 547-553, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28804919

RESUMO

BACKGROUND/OBJECTIVES: Mycosis fungoides (MF) in young patients is rare and may have atypical presentations. There are limited data in these patients. The objective was to determine the clinical outcome and prognosis of young patients with MF. METHODS: A search of our institutional cancer registry database was conducted for patients diagnosed with MF at younger than 30 years of age. RESULTS: Our study included 74 patients (median age at diagnosis 25.5 yrs). Sixty-five (88%) presented with early stage disease and variants of MF (n = 44 [59%]), leading to a median delay in diagnosis of 2.5 years. Hypopigmented MF (n = 27 [36.5%]) was the most common variant, affecting predominantly African American (44.4% vs 19%; p = 0.02) and younger (20 vs 26 yrs; p < 0.001) patients. All patients with hypopigmented MF presented with early stage disease and were less likely to develop progressive disease (PD) than those with other variants (11% vs 34%; p = 0.03). Nineteen patients (26%) developed PD during a median follow-up of 3.5 years, which was associated with advanced-stage disease (89% vs 17%; p < 0.001), older age (>20 yrs) (31% vs 13%; p = 0.08), African American race (52.6% vs 20%; p = 0.009), and poikilodermatous presentation (p < 0.01). Overall survival was good (97.2% at 5 yrs, 95.9% at 10 yrs) despite the delay in diagnosis and atypical presentation. CONCLUSIONS: Progressive disease is associated with older age, African American race, the poikilodermatous variant, and advanced-stage disease. The hypopigmented variant is a common presentation in young patients and has an indolent disease course. Our study confirms an overall favorable prognosis in young patients with MF.


Assuntos
Micose Fungoide/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adolescente , Adulto , Criança , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Masculino , Micose Fungoide/mortalidade , Micose Fungoide/terapia , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Pele/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Taxa de Sobrevida , Adulto Jovem
6.
Eur Radiol ; 26(4): 1048-55, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26188660

RESUMO

OBJECTIVES: To evaluate early post-operative magnetic resonance (EPMR) as a prognostic tool after resection of glioblastoma. METHODS: Sixty EPMR examinations were evaluated for perioperative infarct, tumour growth between diagnosis and EPMR, contrast enhancement pattern, and extent of resection (EOR). The EOR was approached with the subjective evaluation of radiologists and by quantifying volumes. These parameters were tested as predictors of survival using the Kaplan-Meier method. RESULTS: Contrast enhancement was found in 59 patients (59/60; 98 %). Showing a thin-linear pattern of enhancement was the most favourable finding. Patients with this pattern survived longer than patients with thick-linear (median overall survival (OS) thin-linear=609 days; thick-linear=432 days; P = .023) or nodular (median OS = 318 days; P = .001) enhancements. The subjective evaluation of the EOR performed better than its quantification. Patients survived longer when resection was total (median OS total resection=609 days; subtotal=371 days; P = .001). When resection was subtotal, patients survived longer if it was superior to 95 % (median OS resection superior to 95 %=559 days; inferior to 95 %=256 days; P = .034). CONCLUSIONS: EPMR provides valuable prognostic information after surgical resection of glioblastomas. A thin-linear pattern of contrast enhancement is the most favourable finding. Further prognostic stratification may be obtained by assessing the EOR. KEY POINTS: • Some kind of contrast enhancement may be found in most EPMR examinations. • Thin-linear enhancements in the EPMR may be considered benign findings. • The EOR evaluated in the EPMR may stratify prognostic groups of patients. • The subjective evaluation of the EOR performs slightly better than its quantification.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Imageamento por Ressonância Magnética/métodos , Complicações Pós-Operatórias/patologia , Adulto , Idoso , Neoplasias Encefálicas/cirurgia , Meios de Contraste , Feminino , Glioblastoma/cirurgia , Humanos , Aumento da Imagem , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
8.
BMC Endocr Disord ; 15: 73, 2015 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-26610707

RESUMO

BACKGROUND: To evaluate the efficacy, safety, pain perception and health-related quality of life (QoL) of percutaneous ethanol injection treatment (PEIT) as an alternative to thyroid surgery in symptomatic thyroid cysts. METHODS: Thirty consecutive patients (46 ± 10 years; 82% women) with symptomatic benign thyroid cysts relapsed after drainage were included. In all cases, cytology prior to treatment, maximum cyst diameter and volume were determined. PEIT was conducted using the established procedure, and the volume of fluid removed and pain perceived by the patient were assessed. In each procedure, the volume of alcohol instilled was <2 ml. After follow-up, final cyst diameter and volume were determined and the persistence of symptoms and QoL were assessed by a questionnaire (SF-36). RESULTS: Mean symptom duration was 10 ± 20 months. A single session of PEIT was required to complete the procedure in 45% of patients, two in 31% and three in 13%. Mean initial maximum cyst diameter was 3.5 ± 1.0 cm and mean extracted liquid volume 61 ± 36 ml. During PEIT, 39% of patients experienced virtually no pain, 43% mild pain and 17% moderate pain. No complications of PEIT were observed. After 12.1 ± 1.4 months of follow-up, cysts were reduced more than 70% in volume in 86.3% of patients, more than 80% in 61.9% and more than 90% in 42%. On the health-related QoL SF-36 questionnaire, patient scores 6 months post-PEIT did not differ significantly from those of the healthy Spanish population. With respect to cosmetic complaints or local symptoms of compression, PEIT-treated patients presented an initial score of 22 ± 8 and 13 ± 5 after treatment (p < 0.05). CONCLUSIONS: In our experience, percutaneous ethanol injection has prove to be an effective, safe and well-tolerated first-line treatment of symptomatic thyroid cysts.


Assuntos
Cistos/terapia , Etanol/administração & dosagem , Qualidade de Vida , Soluções Esclerosantes/administração & dosagem , Escleroterapia , Doenças da Glândula Tireoide/terapia , Glândula Tireoide/patologia , Ultrassonografia de Intervenção , Cistos/diagnóstico por imagem , Relação Dose-Resposta a Droga , Feminino , Nível de Saúde , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Percepção da Dor , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Espanha/epidemiologia , Doenças da Glândula Tireoide/diagnóstico por imagem , Resultado do Tratamento
10.
Neuro Oncol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946469

RESUMO

BACKGROUND: Encorafenib plus binimetinib (EB) is a standard of care treatment for advanced BRAFV600-mutant melanoma. We assessed efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. METHODS: E-BRAIN/GEM1802 was a prospective, multicenter, single arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression.Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. RESULTS: The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After two months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial PFS and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grade 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). CONCLUSION: Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.

11.
Hum Mol Genet ; 20(17): 3415-23, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21642385

RESUMO

Graves' disease (GD) is the paradigm of an anti-receptor autoimmune disease, with agonistic auto-antibodies against the thyrotropin receptor (TSHR-thyroid-stimulating hormone receptor) being the underlying pathogenic effector mechanism. The TSHR belongs to the category of tissue-restricted antigens, which are promiscuously expressed in the thymus and thereby induce central T cell tolerance. In order to understand the association between TSHR gene polymorphisms and GD, we tested the hypothesis that TSHR gene variants affect susceptibility to GD by influencing levels of TSHR transcription in the thymus. We show that thymic glands from non-autoimmune donors homozygous for the rs179247 SNP predisposing allele of TSHR had significantly fewer TSHR mRNA transcripts than carriers of the protective allele. In addition, in heterozygous individuals, the TSHR predisposing allele was expressed at a lower level than the protective one as demonstrated by allele-specific transcript quantification. This unbalanced allelic expression was detectable in both thymic epithelial cells and thymocytes. Since the level of self-antigen expression is known to influence the threshold of central tolerance, these results are compatible with the notion that defective central tolerance contributes to the pathogenesis of GD, a scenario already implicated in type 1 diabetes mellitus, myasthenia gravis and autoimmune myocarditis.


Assuntos
Doença de Graves/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores da Tireotropina/genética , Timo/metabolismo , Idoso de 80 Anos ou mais , Alelos , Feminino , Citometria de Fluxo , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase em Tempo Real
12.
J Am Acad Dermatol ; 69(3): 357-65, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23796549

RESUMO

BACKGROUND: Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. OBJECTIVE: We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. METHODS: Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. RESULTS: Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. LIMITATIONS: This was a case series retrospective study. CONCLUSION: Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients.


Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , Recidiva Local de Neoplasia/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
13.
Cancers (Basel) ; 15(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37046610

RESUMO

BACKGROUND: We examined cognitive, brain MRI, and lumbar infusion test (LIT) features to identify predictors of response to ventriculoperitoneal shunting (VPS) in long-term cancer survivors with suspected normal pressure hydrocephalus (NPH) following cranial radiotherapy (RT). METHODS: Patients who completed cranial RT at least 2 years before with clinically suspected NPH and an Evans' index (EI) ≥ 0.30 underwent a cognitive and a cerebrospinal fluid (CSF) volumetric (MRI) analysis (n = 36). For those in whom VPS was placed (n = 14), we explored whether adding a CSF volumetric analysis to classical MRI and LIT (Tap Test) features would better identify VPS responders. RESULTS: Nearly 80% exhibited cognitive impairment. The CSF volume at NPH diagnoses was significantly larger in the group of VPS responders (p = 0.04). The addition of CSF volume to NPH diagnoses increased accuracy to 93%, with a positive and negative predictive value of 91% and 100%, respectively. CONCLUSION: The addition of a quantitative MRI analysis of CSF volume to classical MRI and LIT NPH criteria, along with a high clinical suspicion of NPH, may help to identify VPS responders, thus improving the clinical management and prognosis of long-term survivors.

14.
Clin Endocrinol (Oxf) ; 77(5): 691-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22182404

RESUMO

OBJECTIVE: The controversial results on the physiopathological role of visfatin led us to examine both circulating visfatin levels and gene expression in visceral (VAT) and subcutaneous fat (SAT) in a homogeneous group of morbidly obese women. DESIGN, PATIENTS AND MEASUREMENTS: We analysed circulating levels of several adipo/cytokines in 133 Spanish women: 40 lean (C) [body mass index (BMI) < 25 kg/m(2) ] and 93 morbidly obese (MO) (BMI > 40 kg/m(2) ). In the MO group, we found 31 diabetic and 62 nondiabetic subjects. We obtained follow-up blood samples at 6 and 12 months after bariatric surgery from 30 MO patients. We determined the circulating levels of visfatin, adiponectin, interleukin-6 (IL6), C-reactive protein (CRP), resistin and tumour necrosis factor-α (TNFα) by ELISA, and visfatin, adiponectin, IL6, resistin and TNFα gene expression in SAT and VAT by real-time RT-PCR. RESULTS: Circulating visfatin levels were higher in MO women compared with lean controls (C = 1·43 ± 0·14 µg/l, MO = 3·60 ± 0·29 µg/l, P < 0·001). After bariatric surgery-induced weight loss, visfatin levels were reduced significantly over 12 months. Visfatin expression in SAT and VAT was similar, but significantly higher in MO compared to C and independent of the presence of diabetes mellitus. Circulating visfatin levels were positively related to IL6 and CRP levels. Visfatin gene expression in VAT and SAT was strongly related to IL6 and TNFα expression. CONCLUSION: In a homogeneous cohort of morbidly obese women, our findings show that visfatin has a strong relationship with pro-inflammatory factors in severe obesity.


Assuntos
Tecido Adiposo/metabolismo , Citocinas/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Obesidade Mórbida/metabolismo , Adulto , Feminino , Humanos , Interleucina-6/metabolismo , Gordura Intra-Abdominal/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Gordura Subcutânea/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
J Clin Invest ; 132(12)2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35503257

RESUMO

Antigen-presenting cells (APCs) integrate signals emanating from local pathology and program appropriate T cell responses. In allogeneic hematopoietic stem cell transplantation (alloHCT), recipient conditioning releases damage-associated molecular patterns (DAMPs) that generate proinflammatory APCs that secrete IL-12, which is a driver of donor Th1 responses, causing graft-versus-host disease (GVHD). Nevertheless, other mechanisms exist to initiate alloreactive T cell responses, as recipients with disrupted DAMP signaling or lacking IL-12 develop GVHD. We established that tissue damage signals are perceived directly by donor CD4+ T cells and promoted T cell expansion and differentiation. Specifically, the fibroblastic reticular cell-derived DAMP IL-33 is increased by recipient conditioning and is critical for the initial activation, proliferation, and differentiation of alloreactive Th1 cells. IL-33 stimulation of CD4+ T cells was not required for lymphopenia-induced expansion, however. IL-33 promoted IL-12-independent expression of Tbet and generation of Th1 cells that infiltrated GVHD target tissues. Mechanistically, IL-33 augmented CD4+ T cell TCR-associated signaling pathways in response to alloantigen. This enhanced T cell expansion and Th1 polarization, but inhibited the expression of regulatory molecules such as IL-10 and Foxp3. These data establish an unappreciated role for IL-33 as a costimulatory signal for donor Th1 generation after alloHCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Animais , Transplante de Medula Óssea/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Interleucina-12 , Interleucina-33/genética , Camundongos , Camundongos Endogâmicos BALB C , Células Th1/patologia
16.
Ann Transl Med ; 9(8): 648, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33987346

RESUMO

BACKGROUND: The significance of upfront systemic therapies as an alternative to whole brain radiotherapy (WBRT) for multiple brain metastases (BM) is debatable. Our purpose is to investigate if peritumoral edema could predict the intracranial response to systemic chemotherapy (chemo) in patients with advanced non-squamous non-small cell lung cancer (non-SQ-NSCLC) and synchronous multiple BM. METHODS: In this observational cohort study, we evaluated the outcome of 28 patients with multiple BM (≥3) treated with chemo based on cisplatin/carboplatin plus pemetrexed (chemo, group A, n=17) or WBRT plus subsequent chemo (group B, n=11). The intracranial response, assessed by the response assessment neuro-oncology (RANO) BM criteria, was correlated with the degree of BM-associated edema estimated by the maximum diameter ratio among fluid attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1WI (T1Gd) per each BM at the baseline brain magnetic resonance imaging (MRI). RESULTS: No differences were observed in baseline characteristics between both groups, except for the number of patients under steroid treatment that was clearly superior in group B (P=0.007). Median OS was similar between groups. Regarding FLAIR/T1Gd ratio (F/Gd), patients treated with chemo alone exhibited significantly higher values (P=0.001) in those who developed intracranial progression disease (PD) (2.80±0.32 mm), compared with those who achieved partial response (PR) (1.30±0.11 mm) or stable disease (SD) (1.35±0.09 mm). In patients treated with WBRT, F/Gd ratio was not predictive of response. CONCLUSIONS: Peritumoral edema estimated by F/Gd ratio appears a promising predictive tool to identify oligosymptomatic patients with multiple BM in whom WBRT can be postponed.

17.
Neuro Oncol ; 23(5): 803-811, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33130890

RESUMO

BACKGROUND: EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning. METHODS: Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time. RESULTS: Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P < 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes. CONCLUSION: In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy.


Assuntos
Neoplasias Encefálicas , Glioma , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Intervalo Livre de Progressão , Temozolomida/uso terapêutico
18.
Rep Pract Oncol Radiother ; 15(4): 107-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-24376934

RESUMO

We present the case of a patient with progressive Langerhans cell sarcoma whose cutaneous lesions and nodal masses were treated with palliative radiotherapy. Response to relatively low doses of radiotherapy was both good and sustained. We recommend a dose of 15-30 Gy depending on treatment intention and volume of the lesions.

19.
Endocrinol Diabetes Nutr (Engl Ed) ; 67(1): 36-42, 2020 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31109823

RESUMO

INTRODUCTION: There is no agreement on the procedures to be used for diagnosis and treatment of gestational thyroid dysfunction. Controversy still exists on the normal range of thyroid-stimulating hormone (TSH) levels and use of gestational hypothyroidism (GH) screening. The aim of this study was to assess diagnosis and treatment of thyroid dysfunction during pregnancy in a group of Spanish hospitals. STUDY DESIGN: This was a retrospective, multicenter study in pregnant females with GH attending Spanish healthcare centers from March 2013 to July 2014. Variables analyzed included diagnosis criteria for GH (availability of universal screening for gestational thyroid disorders and TSH reference values (RVs) by trimester of pregnancy): risk factors for GH, iodine intake from food or supplementation, gestational age (at diagnosis/treatment) and l-thyroxine treatment. RESULTS: Fourteen centers participated in the study. Universal screening was performed in only half of the centers, and only 14% had their own TSH RVs. Overall, 257 pregnant women were enrolled, 53.7% with hypothyroidism (HT) diagnosed before pregnancy (pre-GH) and 46.3% with HT diagnosed during pregnancy (intra-GH). A comparison of intra-GH and pre-GH women showed that intra-GH women made their first visit later (59.7% vs. 75.4% respectively before week 12, p=0.007) and had more frequently high TSH levels (>2.5µIU/ml) during the first trimester (94.4% vs. 67.0% respectively, p<0.001). CONCLUSIONS: Our results suggest that GH may be underdiagnosed or inadequately diagnosed in most healthcare centers. These findings suggest the need of improving the current practice in Spain.


Assuntos
Hipotireoidismo/diagnóstico , Complicações na Gravidez/diagnóstico , Tireotropina/sangue , Aborto Espontâneo/epidemiologia , Adulto , Biomarcadores/sangue , Feminino , Idade Gestacional , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Iodo/administração & dosagem , Programas de Rastreamento/estatística & dados numéricos , Gravidez , Complicações na Gravidez/sangue , Trimestres da Gravidez/sangue , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Espanha , Tiroxina/uso terapêutico
20.
Endocrinol Diabetes Nutr (Engl Ed) ; 67(1): 61-69, 2020 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30962160

RESUMO

Although iodine nutrition in Spain has improved in recent years, the problem is not completely resolved. It is necessary that health institutions establish measures to ensure an adequate iodine nutrition of the population, especially among the highest risk groups (children and adolescents, women of childbearing age, pregnant women and nursing mothers). A low salt intake should be advised, but it should be iodized. It is also imperative that food control agencies establish effective control over adequate iodization of salt. Indicators on iodine nutrition should be included in future health surveys. The EUthyroid study and the Krakow Declaration on iodine nutrition provide an opportunity to set up a pan-European plan for the prevention of iodine deficiency that should be considered and used by health authorities.


Assuntos
Iodo/administração & dosagem , Iodo/deficiência , Cloreto de Sódio na Dieta/administração & dosagem , Adolescente , Fatores Etários , Animais , Criança , Pré-Escolar , Europa (Continente) , Feminino , Humanos , Lactente , Recém-Nascido , Lactação , Leite/química , Gravidez , Recomendações Nutricionais/legislação & jurisprudência , Espanha/epidemiologia
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