RESUMO
PURPOSE: Peripheral neuropathy (PN) is common in patients with multiple myeloma (MM). We hypothesized that the relationship between hypovitaminosis D and PN described in diabetes mellitus patients may also be present in MM patients. METHODS: To study this potential association, we assessed the incidence of hypovitaminosis D (vitamin D < 75 nmol/L [= 30 ng/mL]) in smouldering and active MM patients in two Dutch hospitals. Furthermore, a validated questionnaire was used to distinguish different PN grades. RESULTS: Of the 120 patients included between January 2017 and August 2018, 84% had an inadequate vitamin D level (median vitamin D level 49.5 nmol/L [IQR 34-65 nmol/L]; mean age: 68 years [SD ± 7.7]; males: 58%). PN was reported by 69% of patients (n = 83); however, of these 83 patients, PN was not documented in the medical records of 52%. An association was found between lower vitamin D levels and higher incidence of PN in the total population (P = 0.035), and in the active MM patients (P = 0.016). CONCLUSION: This multi-centre cohort study showed that PN and hypovitaminosis D are common in MM patients, and addressing low vitamin D levels in the treatment of MM patients might be beneficial in reducing the risk of PN. More attention for PN is warranted, as PN is underreported by clinicians. Further research is needed to fully understand the implications of vitamin D in the development of PN in patients with MM. CLINICAL TRIAL REGISTRATION: Netherland Trial Register NL5835, date of registration July 28, 2016.
Assuntos
Mieloma Múltiplo , Doenças do Sistema Nervoso Periférico , Deficiência de Vitamina D , Idoso , Estudos de Coortes , Estudos Transversais , Humanos , Masculino , Mieloma Múltiplo/epidemiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/etiologia , Prevalência , Vitamina D , Deficiência de Vitamina D/epidemiologiaRESUMO
PURPOSE: This prospective, observational population-based cohort study was performed to determine overall survival (OS) in multiple myeloma (MM) patients in Friesland, the Netherlands, in the era of novel agents and to analyse the influence of first-line treatment, MM-related end-organ damage and comorbidities at initial presentation on OS. METHODS: Detailed clinical information was obtained from the population-based registry 'HemoBase' during the period January 2005 to January 2013, with a follow-up to January 2014. RESULTS: Overall, the symptomatic MM patients (n = 225) had a median OS of 40 months. In the age categories <65, 65-75 and ≥75 years, 99, 94 and 87% of the patients received treatment, with a median OS of 92, 42 and 31 months, respectively. OS for patients with or without treatment was 43 and 3 months, respectively. In multivariable analysis, risk factors for worse OS were increasing age (<65: reference; 65-75: HRadj. = 2.2 (95% CI 1.3-3.7) and ≥75: HRadj. = 2.8 (95% CI 1.7-4.8); P < 0.001), not receiving initial treatment (HRadj. = 4.0 (95% CI 2.1-7.7); P < 0.001), hypercalcaemia (P < 0.001, HRadj. = 1.7 (95% CI 1.2-2.6), P = 0.006) and impaired renal function (HRadj. = 2.6 (95% CI 1.7-4.0); P < 0.001). CONCLUSIONS: Increasing age, not receiving initial treatment, hypercalcaemia and impaired renal function at initial presentation were independent risk factors for worse OS. Comorbidity according to Charlson comorbidity index score was not an independent variable predicting OS.
Assuntos
Antineoplásicos/uso terapêutico , Hipercalcemia/epidemiologia , Nefropatias/epidemiologia , Mieloma Múltiplo/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipercalcemia/complicações , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Análise Multivariada , Países Baixos , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Taxa de SobrevidaRESUMO
Kikuchi disease is a rare disorder with an unknown pathogenesis and a typically self-limiting natural course in predominantly previously healthy young women. Here we present a 54-year-old woman suffering from an overwhelming presentation of Kikuchi disease, associated with haemophagocytic syndrome, liver cell necrosis and nephrotic syndrome. She recovered fully without immunosuppressive treatment. This case report adds to the already broad clinical spectrum of Kikuchi disease described in literature. Awareness among physicians of the full clinical spectrum of Kikuchi disease and the self-limiting nature of this syndrome leads to a good diagnostic approach and may prevent initiation of longstanding immunosuppressive therapy.
Assuntos
Linfadenite Histiocítica Necrosante/complicações , Fígado/patologia , Linfo-Histiocitose Hemofagocítica/etiologia , Insuficiência de Múltiplos Órgãos/etiologia , Síndrome Nefrótica/etiologia , Análise Química do Sangue , Feminino , Linfadenite Histiocítica Necrosante/diagnóstico , Humanos , Pessoa de Meia-Idade , Necrose/etiologia , Remissão EspontâneaRESUMO
Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials.
Assuntos
Mineração de Dados/métodos , Registros Eletrônicos de Saúde , Medicina Baseada em Evidências/métodos , Hematologia/métodos , Oncologia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Sistema de Registros , Coleta de Dados , Humanos , Registro Médico CoordenadoRESUMO
BACKGROUND: Associations of Hodgkin's lymphoma with HLA have been reported for many years. In 20-40% of patients with this disorder, Epstein-Barr virus (EBV) is present in the neoplastic cells. Because presentation of EBV antigenic peptides can elicit vigorous immune responses, we investigated associations of the HLA region with EBV-positive and EBV-negative Hodgkin's lymphoma. METHODS: In a retrospective, population-based study, patients with Hodgkin's lymphoma were reclassified according to the WHO classification, and EBV status was assessed by in-situ hybridisation of EBV-encoded small RNAs. Germline DNA was isolated from 200 patients diagnosed between 1987 and 2000 and from their first-degree relatives. Genotyping was done with 33 microsatellite markers spanning the entire HLA region and two single-nucleotide polymorphisms in the genes for tumour necrosis factor alpha and beta. Classic association analysis and the haplotype sharing statistic were used to compare patients with controls. FINDINGS: Classic association analysis (but not the haplotype sharing statistic) showed an association of consecutive markers D6S265 and D6S510 (p=0.0002 and 0.0003), located in the HLA class I region, with EBV-positive lymphomas. The haplotype sharing statistic (but not classic association analysis) showed a significant difference in mean haplotype sharing between patients and controls surrounding marker D6S273 (p=0.00003), located in HLA class III. INTERPRETATION: Areas within the HLA class I and class III regions are associated with susceptibility to Hodgkin's lymphoma, the association with class I being specific for EBV-positive disease. This finding strongly suggests that antigenic presentation of EBV-derived peptides is involved in the pathogenesis of EBV-involved Hodgkin's lymphoma. RELEVANCE TO PRACTICE: Polymorphisms in the HLA region could explain ethnic variation in the incidence of Hodgkin's lymphoma. The association of EBV-positive Hodgkin's lymphoma with HLA class I suggests that this polymorphism might affect the proper presentation of EBV antigens to cytotoxic T lymphocytes.
Assuntos
Predisposição Genética para Doença , Antígenos HLA/genética , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/genética , Doença de Hodgkin/virologia , Adolescente , Adulto , Idoso , Criança , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Cytogenetic analysis using banding techniques of B-chronic lymphocytic leukemia (CLL) is hampered by the difficult in vitro proliferation of these tumor cells. For detection of specific cytogenetic aberrations these problems can be overcome with non-radioactive in situ hybridization (ISH). ISH may especially be applied for the detection of trisomy 12, which is the most frequent cytogenetic aberration in CLL. Sixty-seven patients with CLL, four normal controls and one lymphoblastoid B-cell line with a trisomy 12 were studied using a chromosome 12 specific probe. To determine the hybridization properties of the CLL cells, all samples were also hybridized with probes specific for chromosomes 1 and 8. All leukemias were analyzed by immunocytochemistry to determine the proportion of tumor cells. Eight cases (11%) showed a trisomy 12. After correction for the number of tumor cells, it was demonstrated that in almost all cases (7 out of 8), the aberration was present in a proportion of the tumor cells (between 30 and 72%). Except for one patient this mosaicism persisted with long-term follow-up. We conclude that the in vivo incidence of trisomy 12 in CLL is approximately 11%, and that trisomy 12 occurs in most instances in only a subpopulation of the leukemic cells. Both findings suggest that trisomy 12 in CLL is a late event.
Assuntos
Cromossomos Humanos Par 12 , Leucemia Linfocítica Crônica de Células B/genética , Trissomia , Sondas de DNA , Humanos , Hibridização in Situ Fluorescente , MosaicismoRESUMO
Malignant cells from 24 cases of hairy cell leukemia were studied by in situ hybridization for evidence of selective aneuploidy using alphoid and satellite probes specific for 16 human chromosomes. Based on these data, hairy cell leukemia appears to be diploid for the chromosomes studied and is a malignancy which displays the phenomenon of pairing of the centromere and p arm of chromosome 15 during interphase.
Assuntos
Leucemia de Células Pilosas/genética , Centrômero , Aberrações Cromossômicas , Cromossomos Humanos Par 15 , Diploide , Humanos , Hibridização In Situ , Interfase , Leucemia de Células Pilosas/patologiaRESUMO
We investigated the expression of the neural cell adhesion molecule (NCAM) in a series of surgically resected lung carcinomas of various histological subtypes by means of a panel of monoclonal antibodies recognising different N-CAM epitopes. In a subgroup of 56 tumours, the results of immunostaining with MAb 123C3--the antibody studied most extensively in our material--were compared to the ultrastructure, and in 231 radically resected non-small cell carcinomas, with histological tumour type and with clinical follow-up data. N-CAM expression was not limited to neuroendocrine tumours, as assessed ultrastructurally. Non-small cell lung carcinomas positive for MAb 123C3 showed post-operative overall and disease-free survival times significantly shorter than 123C3-negative non-small cell carcinomas.
Assuntos
Biomarcadores Tumorais/análise , Moléculas de Adesão Celular Neuronais/análise , Neoplasias Pulmonares/química , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/química , Carcinoma de Células Pequenas/química , Diferenciação Celular , Linhagem Celular , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/ultraestrutura , Testes de Precipitina , PrognósticoRESUMO
AIMS: To investigate the feasibility of non-radioactive in situ hybridisation (ISH) for the identification of sex-mismatched plastic embedded bone marrow biopsy specimens. METHODS: After a suspected accidental transposition of two glycol-methacrylate embedded bone marrow specimens, in situ hybridisation with sex chromosome specific probes was performed. RESULTS: Quantitative analysis of the hybridisation signals established unequivocably the origin of the specimens. CONCLUSIONS: ISH is feasible on GMA embedded bone marrow specimens, and can be used for the identification of accidentally transposed specimens provided that they are of sex-matched origin.
Assuntos
Medula Óssea/ultraestrutura , Cromossomos Sexuais/química , Técnicas Citológicas , Sondas de DNA , Feminino , Humanos , Masculino , Hibridização de Ácido Nucleico , Manejo de EspécimesRESUMO
A new EBV positive human B-cell line, BONNA-12 was established from splenic cells of a patient with a hairy cell leukemia (HCL). BONNA-12 cells grew spontaneously and formed colonies in semisolid media. Although the BONNA-12 cell line was identical with the patient's spleen cells by HLA analysis and Southern blot examination of minisatellite DNA patterns, the immunoglobulin heavy and light chain rearrangement patterns differed from the original HCL. Cytogenetic analysis of the BONNA-12 cell line demonstrated in the major cell clone a 47, X, -Y, +9, +12 karyotype. Trisomy 12 is a characteristic abnormality in chronic lymphocytic leukemia that also rarely occurs in HCL. The BONNA-12 cell line is of potential value in the study of trisomy 12 in chronic B cell malignancies.
RESUMO
Hyperplastic colonic polyps are considered to be benign. We report the case of a man with multiple hyperplastic colon polyps who developed a colonic adenocarcinoma. The literature on the relation between hyperplastic colon polyps and adenocarcinoma is discussed.
Assuntos
Adenocarcinoma/complicações , Neoplasias do Colo/complicações , Pólipos do Colo/complicações , Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Humanos , Hiperplasia , Masculino , Pessoa de Meia-IdadeRESUMO
Three patients are described with giant cell arteritis (GCA) of multiple medium sized and large blood vessels including the temporal artery and the aorta. The patients presented with malaise, myalgias and different symptoms due to decreased local blood flow. Progression of the disease could be blocked with immunosuppressive drugs in all 3 patients. With this report we want to emphasize that GCA is associated with a wide ranging disease spectrum in which temporal arteritis and Takayasu's arteritis represent two subsets.
Assuntos
Arterite de Células Gigantes , Idoso , Aorta Abdominal/fisiopatologia , Feminino , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/fisiopatologia , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Radiografia , Fluxo Sanguíneo Regional , Artéria Subclávia/fisiopatologia , Arterite de Takayasu/classificação , Arterite de Takayasu/diagnóstico , Artérias Temporais/fisiopatologiaRESUMO
Hypereosinophilia can be related to various diseases; when it occurs without an obvious cause it is called idiopathic hypereosinophilic syndrome (IHES). We describe a patient with increasing eosinophilia, which in spite of extensive diagnostic procedures initially remained unexplained. However, during follow-up it became apparent that this patient had a lethal enteropathy-associated T lymphoma (EATL) causing the hypereosinophilia.
Assuntos
Eosinofilia/etiologia , Neoplasias Intestinais/complicações , Linfoma de Células T/complicações , Idoso , Humanos , MasculinoRESUMO
The OEIS complex is an association of fetal malformations including omphalocele, exstrophy of the cloaca, imperforate anus and spinal defects. We present a fetus with the OEIS complex in combination with a cardiac defect. Until now very few cases with this combination have been described.
Assuntos
Anormalidades Múltiplas , Cardiopatias Congênitas , Adulto , Feminino , Humanos , Masculino , SíndromeAssuntos
Aneurisma/diagnóstico por imagem , Ponte de Artéria Coronária , Doenças do Mediastino/diagnóstico por imagem , Veia Safena/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Veia Safena/transplante , Tomografia Computadorizada por Raios XRESUMO
The interdisciplinary field of quantitative microscopy (computer-aided microscopy) and artificial image understanding systems is explored, with an emphasis on the philosophical aspects of pathology and artificial intelligence. Three methodological problems of traditional diagnostic pathology are identified: those of validity, variability and organisation. Quantitative microscopy is a potential research strategy for solving these problems. In practice, however, the quantitative microscopy program is handicapped by the difficulty of building artificial image-understanding systems. We discuss the segmentation problem in image understanding, and four general strategies, three cognitivistic and one connectionistic, are reviewed.
Assuntos
Inteligência Artificial , Diagnóstico por Imagem , Processamento de Imagem Assistida por Computador , Microscopia/métodos , Humanos , Patologia/instrumentação , Filosofia MédicaRESUMO
Paraffin sections of 19 surgically resected small cell lung carcinomas (SCLC), 33 non-small cell lung carcinomas (NSCLC) of various types, and four bronchial carcinoids were immunostained with monoclonal antibodies (MoAbs) 735 and anti-Leu 7, both recognizing some sugar epitopes present on the neural cell adhesion molecule N-CAM. With MoAb 735, all SCLC were stained focally or diffusely, and one carcinoid was stained focally. Only three of the 33 NSCLC were faintly and focally positive with MoAb 735; these three tumours showed relatively small tumour cells and small, oval nuclei. Anti-Leu 7 stained all the carcinoids, only eight SCLC, sometimes focally, and eight NSCLC. MoAb 735 was thus superior to anti-Leu 7 in distinguishing between SCLC and NSCLE. Since MoAb 735 stained all SCLC strongly and is applicable on paraffin sections, it provides a well-needed addition to the immunomarkers used in the diagnostic distinction of SCLC and NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Pequenas/diagnóstico , Adesão Celular , Epitopos/análise , Humanos , Neoplasias Pulmonares/diagnósticoRESUMO
In situ hybridization (ISH) techniques on interphase cells, or interphase cytogenetics, have powerful potential clinical and biological applications, such as detection of minimal residual disease, early relapse, and the study of clonal evolution and expansion in neoplasia. Much attention has been paid to issues related to ISH data acquisition, i.e., the numbers, colors, intensities, and spatial relationships of hybridization signals. The methodology concerning data analysis, which is of prime importance for clinical applications, however, is less well investigated. We have studied the latter for the detection of small monosomic and trisomic cell populations using various mixtures of human female and male cells. With a chromosome X specific probe, the male cells stimulated monosomic subpopulations of 0, 1, 5, 10, 50, 90, 95, 99, and 100%. Analogously, when a (7 + Y) specific probe combination was used, containing a mixture of chromosome No. 7 and Y-specific DNA, the male cells simulated trisomic cell populations. Probes specific for chromosomes Nos. 1, 7, 8, and 9 were used for estimation of ISH artifacts. Three statistical tests, the Kolmogorov-Smirnov test, the multiple-proportion test, and the z'-max test, were applied to the empirical data using the control data as a reference for ISH artifacts. The Kolmogorov-Smirnov test was found to be inferior for discrimination of small monosomic or trisomic cell populations. The other two tests showed that when 400 cells were evaluated, and using selected control probes, monosomy X could be detected at a frequency of 5% aberrant cells, and trisomy 7 + Y at a frequency of 1%.(ABSTRACT TRUNCATED AT 250 WORDS)