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BACKGROUND: Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. METHODS: The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID). RESULTS: 137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. CONCLUSION: HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Fragilidade , Mieloma Múltiplo , Qualidade de Vida , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/psicologia , Idoso , Masculino , Feminino , Estudos Prospectivos , Bortezomib/uso terapêutico , Bortezomib/administração & dosagem , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Melfalan/uso terapêutico , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Prednisona/efeitos adversos , Idoso FragilizadoRESUMO
A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).
Assuntos
Hematínicos , Síndromes Mielodisplásicas , Humanos , Lenalidomida/farmacologia , Hematínicos/farmacologia , Eritropoese , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Fator Estimulador de Colônias de Granulócitos/farmacologia , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Resultado do TratamentoRESUMO
Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).
Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Transporte Ativo do Núcleo Celular , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Humanos , Hidrazinas , TriazóisRESUMO
More effective treatment modalities are urgently needed in patients with acute myeloid leukemia (AML) of older age. We hypothesized that adding lenalidomide to intensive standard chemotherapy might improve their outcome. After establishing a safe lenalidomide, dose elderly patients with AML were randomly assigned in this randomized Phase 2 study (n = 222) to receive standard chemotherapy ("3 + 7") with or without lenalidomide at a dose of 20 mg/day 1-21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without lenalidomide (20 mg/day 1-21). The CR/CRi rates in the two arms were not different (69 vs. 66%). Event-free survival (EFS) at 36 months was 19% for the standard arm versus 21% for the lenalidomide arm and overall survival (OS) 35% vs. 30%, respectively. The frequencies and grade of adverse events were not significantly different between the treatment arms. Cardiovascular toxicities were rare and equally distributed between the arms. The results of the present study show that the addition of lenalidomide to standard remission induction chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR2294 in The NederlandsTrial Register (www.trialregister.nl).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Indução/mortalidade , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Citarabina/administração & dosagem , Feminino , Seguimentos , Humanos , Lenalidomida/administração & dosagem , Leucemia Mieloide Aguda/patologia , Masculino , Síndromes Mielodisplásicas/patologia , Prognóstico , Indução de Remissão , Taxa de SobrevidaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Infection with the human immunodeficiency virus (HIV) is still a major health problem world-wide. HIV infection has changed into a chronic infection with the chance of developing long-term complications. Vascular complications are frequently reported in the current literature. HIV and treatment by highly active antiretroviral therapy (HAART) are associated with many cardiovascular risk factors. An increased risk of arterial cardiovascular complications was found in a number of studies. However, data about the risk of venous thrombotic disease (VTE), including potentially fatal conditions as pulmonary embolism, were limited. In a systematic review of the literature, ten relevant epidemiological studies were identified that investigated the risk of venous thrombotic disease in HIV-infected patients. The incidence was increased two- to tenfold in comparison with a healthy population of the same age. However, these studies were mainly retrospective cohort studies that were prone to selection bias, confounding factors were not always mentioned and in all but three control populations were missing. An increased risk of venous thrombotic disease in HIV-infected patients could be explained by the presence of a hypercoagulable state, characterised by an increase in procoagulant factors, such as endothelial TF expression and thrombogenic properties of microparticles, and a decrease in anticoagulant factors, including AT III, HC II and the protein C pathway. Furthermore, the risk of VTE was associated with an increased risk of infections and autoimmune haemolytic anaemia, and was weakly associated with HAART. All together, quite some evidence pointed towards a relationship between HIV infection and venous thrombotic disease, but the association still needs to be established in properly designed epidemiological studies.
Assuntos
Infecções por HIV/complicações , Trombose Venosa/epidemiologia , Doença Crônica , Estudos de Coortes , Humanos , Incidência , Países Baixos/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa/complicaçõesRESUMO
Daratumumab is an anti-CD38 monoclonal antibody with lytic activity against multiple myeloma (MM) cells, including ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent cytotoxicity). Owing to a marked heterogeneity of response to daratumumab therapy in MM, we investigated determinants of the sensitivity of MM cells toward daratumumab-mediated ADCC and CDC. In bone marrow samples from 144 MM patients, we observed no difference in daratumumab-mediated lysis between newly diagnosed or relapsed/refractory patients. However, we discovered, next to an expected effect of effector (natural killer cells/monocytes) to target (MM cells) ratio on ADCC, a significant association between CD38 expression and daratumumab-mediated ADCC (127 patients), as well as CDC (56 patients). Similarly, experiments with isogenic MM cell lines expressing different levels of CD38 revealed that the level of CD38 expression is an important determinant of daratumumab-mediated ADCC and CDC. Importantly, all-trans retinoic acid (ATRA) increased CD38 expression levels but also reduced expression of the complement-inhibitory proteins CD55 and CD59 in both cell lines and primary MM samples. This resulted in a significant enhancement of the activity of daratumumab in vitro and in a humanized MM mouse model as well. Our results provide the preclinical rationale for further evaluation of daratumumab combined with ATRA in MM patients.
Assuntos
ADP-Ribosil Ciclase 1/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Sinergismo Farmacológico , Glicoproteínas de Membrana/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Monoclonais/administração & dosagem , Citotoxicidade Celular Dependente de Anticorpos , Apoptose/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Proliferação de Células/efeitos dos fármacos , Citotoxicidade Imunológica , Proteínas de Ligação a DNA/fisiologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologia , Terapia de Salvação , Tretinoína/administração & dosagem , Células Tumorais CultivadasRESUMO
This study examined recovery over the first year following traumatic brain injury (TBI) in children 6-12 years of age. Forty-two children with severe TBI and 52 with moderate TBI were compared to 58 children with orthopedic injuries. The children and their families were evaluated at a baseline assessment and at 6- and 12-month follow-ups. Findings documented cognitive, achievement, and behavioral sequelae of TBI, with only limited evidence for recovery over the first year postinjury. Outcomes were predicted by preinjury factors, TBI severity, and measures of the postinjury family environment. Some of the sequelae of severe TBI were more marked in the context of higher compared with lower levels of family burden or dysfunction. The findings confirm the need to consider environmental contributions to outcomes of TBI in children.
Assuntos
Lesões Encefálicas/diagnóstico , Criança , Transtornos Cognitivos/diagnóstico , Estudos de Coortes , Feminino , Seguimentos , Escala de Coma de Glasgow , Humanos , Escala de Gravidade do Ferimento , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Fatores de TempoRESUMO
Previous studies of children with Landau-Kleffner syndrome and related language-epilepsy syndromes have focused on the relationship of seizure control to language recovery. We examined the effect of premorbid language skills and behavior, as well as some characteristics of clinical seizures and electroencephalograms, on language recovery in a retrospective study of 67 children with the severe receptive and expressive language disorder, verbal auditory agnosia. Fifty-eight percent of these children had seizures, 76% were autistic, and 24% had a history of language regression after showing previously normal language skills. The duration of language loss was not influenced by the persistence of clinical seizures. Premorbid language and behavior were more predictive of language recovery in these children. Most children with normal early language (acquired verbal auditory agnosia) had onset of language loss after age 3 years, in contrast to those with abnormal early language. Children with acquired verbal auditory agnosia were more likely to show fluctuations in language skills than those in other groups. Autistic children were more likely to begin having seizures before age 3 years, and had a longer duration of language loss and lower educational placement at time of last follow-up than those with normal behavior. This study emphasizes the importance of assessing premorbid language and behavior in predicting recovery of language skills in children with language-epilepsy syndromes.
Assuntos
Agnosia/diagnóstico , Transtornos da Percepção Auditiva/diagnóstico , Transtorno Autístico/diagnóstico , Epilepsia/diagnóstico , Síndrome de Landau-Kleffner/diagnóstico , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Desenvolvimento da Linguagem , Percepção da Fala , Adolescente , Transtornos da Articulação , Criança , Feminino , Seguimentos , Humanos , MasculinoRESUMO
We compared the course of a preschool child we followed for 4 years with published reports of 24 children with fluent aphasia. Our patient spoke fluently within 3 weeks of the injury. She was severely anomic and made many semantic paraphasic errors. Unlike other children with fluent aphasia, her prosody of speech was impaired initially, and her spontaneous language was dominated by stock phrases. Residual deficits include chronic impairment of auditory comprehension, repetition, and word retrieval. She has more disfluencies in spontaneous speech 4 years after her head injury than acutely. School achievement in reading and mathematics remains below age level. Attention to the timing of recovery of fluent speech and to the characteristics of receptive and expressive language over time will permit more accurate description of fluent aphasia in childhood.
Assuntos
Afasia de Wernicke/diagnóstico , Afasia/diagnóstico , Logro , Afasia/fisiopatologia , Afasia/psicologia , Afasia de Wernicke/fisiopatologia , Afasia de Wernicke/psicologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encefalopatias/fisiopatologia , Pré-Escolar , Feminino , Humanos , Transtornos da Linguagem/diagnóstico , Testes de Linguagem , Testes de Discriminação da Fala , Inteligibilidade da Fala , Tomografia Computadorizada por Raios XRESUMO
When a child is admitted to the hospital with presumed encephalitis, the physician must use clinical criteria to gauge the appropriate level of hospital care and to give a preliminary assessment of outcome to the family because the etiology is unknown. This study attempted to determine which clinical factors gathered on hospital admission would be most helpful to the physician. The records of 106 children (ages 1 month to 20 years), admitted to Rainbow Babies and Childrens Hospital between 1978-1989 who had discharge diagnoses of encephalitis, were reviewed. Seventy-five met the case definition of presumed viral encephalitis, with viral etiology established in 23% of patients. Poor short-term outcome was defined as the presence of an abnormal neurologic examination at hospital discharge, and was present in 32% of patients. Focal signs on neurologic examination (odds risk: 16.30, P < .05) and abnormal neuroimaging studies (odds risk: 5.66, P < .05) were the only 2 factors present at admission that predicted a poor short-term outcome. Glasgow coma scale at admission was predictive of an abnormal neurologic examination at discharge only when profoundly depressed (6 or less); otherwise, this scale was not useful as a prognostic tool. Factors that were not correlated with adverse outcomes included age younger than 1 year, any type of seizure occurrence, status epilepticus, diffuse or focal electroencephalographic abnormalities, or abnormal cerebrospinal fluid findings.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Dano Encefálico Crônico/etiologia , Encefalite/etiologia , Exame Neurológico , Admissão do Paciente , Adolescente , Adulto , Dano Encefálico Crônico/diagnóstico , Criança , Pré-Escolar , Cuidados Críticos , Encefalite/complicações , Encefalite/diagnóstico , Encefalite Viral/complicações , Encefalite Viral/diagnóstico , Encefalite Viral/etiologia , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Convulsões/etiologiaRESUMO
Pediatricians can identify a child with a developmental language disorder by expanding a traditional developmental assessment with special screening tests of language skills. They can direct parents to specialists who can define the nature of the language disturbance in more detail and predict its natural history. They must then support the parents as they learn to use the community resources available for remediation of their child. As more is learned about the biologic bases of normal and abnormal language development in children, pediatricians will undoubtedly have an even more central role in identification of patients with language disorders and education of their families.
Assuntos
Linguagem Infantil , Transtornos da Linguagem/diagnóstico , Pré-Escolar , Humanos , Lactente , Transtornos da Linguagem/complicações , Transtornos da Linguagem/terapiaRESUMO
The present study examined the extent to which verbal auditory agnosia (VAA) is primarily a phonemic decoding disorder, as contrasted to a more global defect in acoustic processing. Subjects were six young adults who presented with VAA in childhood and who, at the time of testing, showed varying degrees of residual auditory discrimination impairment. They were compared to a group of young adults with normal language development matched for age and gender. Cortical event-related potentials (ERPs) were recorded to tones and to consonant-vowel stimuli presented in an "oddball" discrimination paradigm. In addition to cortical ERPs, auditory brainstem responses (ABRs) and middle latency responses (MLRs) were recorded. Cognitive and language assessments were obtained for the VAA subjects. ABRs and MLRs were normal. In comparison with the control group, the cortical ERPs of the VAA subjects showed a delay in the N1 component recorded over lateral temporal cortex both to tones and to speech sounds, despite an N1 of normal latency overlying the frontocentral region of the scalp. These electrophysiologic findings indicate a slowing of processing of both speech and nonspeech auditory stimuli and suggest that the locus of this abnormality is within the secondary auditory cortex in the lateral surface of the temporal lobes.
Assuntos
Agnosia/diagnóstico , Agnosia/fisiopatologia , Percepção da Fala , Lobo Temporal/fisiopatologia , Adolescente , Adulto , Agnosia/complicações , Potenciais Evocados Auditivos , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Humanos , Transtornos da Linguagem/complicações , Tempo de Reação , Testes de Discriminação da FalaRESUMO
Turner's syndrome is associated with congenital heart disease in a third of cases. Several reports of aortic dilatation and of death by dissection or rupture of the aorta have been published. The authors undertook a prospective study to assess the incidence of cardiac malformations and aortic dilatation in genetically confirmed Turner's syndrome. Twenty-six out of 34 patients recalled (76%), aged 7 to 30 years (average 17 +/- 6 years) accepted their inclusion in this study and underwent clinical examination, ECG, chest X-ray and echocardiography. Thirteen patients had a monosomy 45X and 13 a mosaic or structural abnormality. Six had a history of cardiovascular disease (operated coarctation: 2 cases, kinking: 2 cases, Hypertension: 2 cases). Eight patients (30%) had one or several anatomical cardiovascular abnormalities: bicuspid aortic valve (19.2%), abnormalities of the aortic isthmus (kinking or coarctation) (15.4%), aortic regurgitation (7.7%), mitral stenosis (3.8%), partial anomalous venous drainage (3.8%), patent ductus arteriosus (3.8%) and left superior vena cava (11.5%). Systematic evaluation of the aorta resulted in the diagnosis of dilatation of the ascending aorta in 1 case and dilatation of the sinus of Valsalva in 2 other cases. The authors conclude that echocardiographic evaluation is essential after the diagnosis of Turner's syndrome. It should be repeated regularly to detect dilatation of the aorta which carries the risk of serious complications, such as rupture or dissection of the aorta.
Assuntos
Cardiopatias Congênitas/complicações , Síndrome de Turner/complicações , Adolescente , Adulto , Criança , Ecocardiografia , Eletrocardiografia , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Cariotipagem , Imageamento por Ressonância Magnética , Estudos Prospectivos , Radiografia Torácica , Síndrome de Turner/genéticaRESUMO
A 6-month-old girl had been admitted three times due to the sudden onset of respiratory and gastrointestinal symptoms, paleness and a reduced level of consciousness. Various laboratory tests (including allergy tests) as well as microbiological and radiological investigations did not establish the cause. Only when it was noticed that the incidents followed a change of diet, did it became obvious that a reaction to food components was the underlying cause. A provocation test revealed an anaphylactic reaction to rice flour. Food allergy is a widespread problem within paediatrics; rice flour appears to be hypoallergenic, but can lead to immunological responses.
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Anafilaxia/etiologia , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/diagnóstico , Oryza/efeitos adversos , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Testes CutâneosRESUMO
On behalf of the lymphoma and multiple myeloma working parties of the Dutch/Belgian Haemato-Oncology Foundation for Adults in The Netherlands (HOVON), we present a guideline for diagnosis and management of Waldenström's macroglobulinemia (WM). Considering the indolent behaviour and heterogeneous clinical presentation of WM, it is crucial to determine the right indications for treatment, as well as to individualise therapeutic options. There are significant differences from the approach to multiple myeloma or the treatment of other indolent non-Hodkgin lymphomas, and these results cannot always be extrapolated. There is a lack of large clinical trials due to the low incidence of WM. Based on the available data, we provide a practical diagnostic classification, as well as recommendations for first-line therapy and options for treating relapsed disease. Some typical clinical features of WM, such as autoimmune phenomena and 'IgM flare' after rituximab treatment, are highlighted. A more elaborate version of this guideline was published in the 'Nederlands Tijdschrift voor Hematologie' (Dutch Journal for Hematology) September 2012.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores Imunológicos/uso terapêutico , Macroglobulinemia de Waldenstrom/diagnóstico , Medula Óssea/patologia , Humanos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/terapia , Plasmaferese , Macroglobulinemia de Waldenstrom/terapiaRESUMO
Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T(0)). The median age at diagnosis was 58 years, and time from diagnosis to T(0) was 3.3 years. Following T(0), 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T(0) in 94 patients (44%) including ≥ partial response in 69 (32%). The median overall survival and event-free survival from T(0) were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.
Assuntos
Antineoplásicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Progressão da Doença , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Recidiva , Análise de SobrevidaRESUMO
PURPOSE: The aim of this study was to evaluate whether quantitative changes in contrast enhancement (CE) after neoadjuvant chemotherapy (NC) are associated with histological signs of tumor regression and whether quantitative dynamic MRI (dMRI) is capable of accurately assessing preoperative tumor size compared to mammography (MG) and ultrasound (US). METHODS: Thirty-one patients with breast cancer underwent MRI before and after NC. Dynamic CE was measured using a turbo-FLASH sequence and quantified by a two-compartment model, where two parameters, k(ep) (distribution constant rate) and A (amplitude), were calculated and color mapped. RESULTS: When tumors had signs of histological regression in the operative specimen (n=17) decrease of the parameters A and k(ep) was significantly more marked compared to tumors without regression (n=12). The correlation between tumor size measured by dMRI and histopathology was 0.81 when areas of unspecific CE were included; when they were not included the correlation was 0.66 and tumor size was systematically underestimated. In 26 patients dMRI was retrospectively compared with MG (r=0.51; dMRI, r=0.80) and in 22 patients with US (r=0.60; dMRI, r=0.75). CONCLUSION: Changes in dynamic CE are associated with histological tumor regression. Quantitative dMRI enables a valid assessment of tumor residue and is superior to MG and US. Remaining unspecific CE within the original tumor site should be considered as potentially malignant.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Meios de Contraste , Interpretação Estatística de Dados , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia MamáriaRESUMO
Recent literature has revealed different percentages of prenatal detection of congenital heart disease. Therefore we chose to analyse the sensitivity of this screening in Isère county and to scrutinize to which extent factors like severity of the anomaly, extracardiac anomalies and maternal age influence the sensitivity. This retrospective study covers the period from 1989 to 1995. All the pregnancies with congenital heart disease in Isère county in France were reviewed and analysed, which was possible thanks to our registry of congenital anomalies. In this period, 316 cases were registered in the central database. We obtained an overall sensitivity of 34.8 per cent. By splitting the different malformations into two groups we got a detection rate of 53.7 per cent for major malformations and 26.7 per cent for other abnormalities. This difference is significant. Nevertheless, the sensitivity remains quite low. This result stresses the need for better education of investigators in primary care units, particularly because the prenatal diagnosis of congenital heart disease has a major impact on the outcome of pregnancy, which can be seen in the increased number of abortions in this group.