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BACKGROUND: Image-defined risk factors (IDRFs) were promulgated for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). There is limited understanding of the impact of individual IDRFs on resectability of the primary tumor or patient outcomes. A multicenter database of patients with high-risk NB was interrogated to answer this question. DESIGN/METHODS: Patients with high-risk NB (age <20 years) were eligible if cross-sectional imaging was performed at least twice prior to resection. IDRFs and primary tumor measurements were recorded for each imaging study. Extent of resection was determined from operative reports. RESULTS: There were 211 of 229 patients with IDRFs at diagnosis, and 171 patients with IDRFs present pre-surgery. A ≥90% resection was significantly more likely in the absence of tumor invading or encasing the porta hepatis, hepatoduodenal ligament, superior mesenteric artery (SMA), renal pedicles, abdominal aorta/inferior vena cava (IVC), iliac vessels, and/or diaphragm at diagnosis or an overlapping subset of IDRFs (except diaphragm) at pre-surgery. There were no significant differences in event-free survival (EFS) and overall survival (OS) when patients were stratified by the presence versus absence of any IDRF either at diagnosis or pre-surgery. CONCLUSION: Two distinct but overlapping subsets of IDRFs present either at diagnosis or after induction chemotherapy significantly influence the probability of a complete resection in children with high-risk NB. The presence of IDRFs was not associated with significant differences in OS or EFS in this cohort.
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OBJECTIVES: To develop an intuitive and generally applicable system for the reporting, assessment, and documentation of ADC to complement standard BI-RADS criteria. METHODS: This was a multicentric, retrospective analysis of 11 independently conducted institutional review board-approved studies from seven institutions performed between 2007 and 2019. Breast Apparent Diffusion coefficient (ADC-B) categories comprised ADC-B0 (ADC non-diagnostic), ADC-B1 (no enhancing lesion), and ADC-B2-5. The latter was defined by plotting ADC versus cumulative malignancy rates. Statistics comprised ANOVA with post hoc testing and ROC analysis. p values ≤ 0.05 were considered statistically significant. RESULTS: A total of 1625 patients (age: 55.9 years (± 13.8)) with 1736 pathologically verified breast lesions were included. The mean ADC (× 10-3 mm2/s) differed significantly between benign (1.45, SD .40) and malignant lesions (.95, SD .39), and between invasive (.92, SD .22) and in situ carcinomas (1.18, SD .30) (p < .001). The following ADC-B categories were identified: ADC-B0-ADC cannot be assessed; ADC-B1-no contrast-enhancing lesion; ADC-B2-ADC ≥ 1.9 (cumulative malignancy rate < 0.1%); ADC-B3-ADC 1.5 to < 1.9 (0.1-1.7%); ADC-B4-ADC 1.0 to < 1.5 (10-24.5%); and ADC-B5-ADC < 1.0 (> 24.5%). At the latter threshold, a positive predictive value of 95.8% (95% CI 0.94-0.97) for invasive versus non-invasive breast carcinomas was reached. CONCLUSIONS: The breast apparent diffusion coefficient system (ADC-B) provides a simple and widely applicable categorization scheme for assessment, documentation, and reporting of apparent diffusion coefficient values in contrast-enhancing breast lesions on MRI. CLINICAL RELEVANCE STATEMENT: The ADC-B system, based on diverse MRI examinations, is clinically relevant for stratifying breast cancer risk via apparent diffusion coefficient measurements, and complements BI-RADS for improved clinical decision-making and patient outcomes. KEY POINTS: ⢠The breast apparent diffusion coefficient category system (ADC-B) is a simple tool for the assessment, documentation, and reporting of ADC values in contrast-enhancing breast lesions on MRI. ⢠The categories comprise ADC-B0 for non-diagnostic examinations, ADC-B1 for examinations without an enhancing lesion, and ADC-B2-5 for enhancing lesions with an increasing malignancy rate. ⢠The breast apparent diffusion coefficient category system may be used to complement BI-RADS in clinical decision-making.
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Neoplasias da Mama , Meios de Contraste , Humanos , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Diagnóstico Diferencial , Mama/diagnóstico por imagem , Mama/patologia , Imagem de Difusão por Ressonância Magnética , Imageamento por Ressonância Magnética , Neoplasias da Mama/patologia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The pretreatment International Neuroblastoma Risk Group Staging System (INRGSS) discriminates localized tumors L1/L2 depending on the absence/presence of image-defined risk factors (IDRFs) at diagnosis. Referring to this new staging system, we assessed initial imaging of localized thoracic neuroblastoma (NB) and ganglioneuroma (GN) and the extent of initial tumor resection. METHODS: Patients with localized thoracic NB/GN from the German clinical trials NB97 and NB2004 were included. Imaging at diagnosis and operative reports were reviewed retrospectively. IDRFs were assessed centrally and correlated to International Neuroblastoma Staging System (INSS) stage and extent of tumor resection. Additionally, we analyzed data on surgery-related complications. RESULTS: Imaging series of 88 patients were available for central review. In 18 children, no IDRF was present, 28 exhibited one IDRF, 42 two or more IDRFs, resulting in 70 patients with L2 disease. The most frequently observed IDRF was encasement of any vessel (n = 38). Initial surgical resection was aimed for in 45 patients (L1: n = 11; L2: n = 34). Complete and gross total resection rates were higher children with L2 NB (n = 8/25 L1, n = 17/25 L2 vs. n = 2/15 L1, n = 13/15 L2, respectively). The proportion of surgical complications was very similar between INRGSS L1 and L2 (n = 4/11 vs. n = 17/34). All complications were manageable, and no surgery-related deaths were observed. CONCLUSION: In this retrospective cohort, the extent of resection and the rate of surgical complications did not differ substantially between patients classified as L1/L2, indicating that INRGSS L2 does not equate unresectability. It appeared that individual IDRFs differ in value. Larger studies are needed to assess the significance and therapeutic/prognostic impact of such findings.
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Ganglioneuroma , Neuroblastoma , Criança , Humanos , Lactente , Estudos Retrospectivos , Ganglioneuroma/diagnóstico por imagem , Ganglioneuroma/cirurgia , Ganglioneuroma/patologia , Estadiamento de Neoplasias , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/cirurgia , Fatores de RiscoRESUMO
BACKGROUND: The current methods for calculating the ideal implant volume for breast reconstruction are based on pre- or intraoperative volume measurements of the existing breast volume and do not take into account the individual breast density of the woman. This study aims is to identify objective parameters that can help to improve the optimal implant selection. MATERIALS AND METHODS: This retrospective analysis includes 198 breast cancer patients who underwent mastectomy. Breast densities (ACR) measured in mammography and MRI were compared with the removed breast tissue weight and volume of the implants used. In addition, the resected weight was compared directly with the implant volume to calculate a mathematical function. RESULTS: There was no significant correlation between the ACR values and the resected weights [correlation coefficient: mammography:- 0.117 (p = 0.176), MRI - 0.033 (p = 0.756)]. A negative correlation between the implant volumes and both imaging methods could be demonstrated [correlation coefficient: mammography - 0.268; p = 0.002; MRI was - 0.200 (p = 0.055)]. A highly significant correlation between the resected weights and the implant volumes (correlation coefficient 0.744; p < 0.001) was observed. This correlation corresponds to a power function (y = 34.71 x0.39), in which any resected weight can be used for the variable x to calculate the implant volume. CONCLUSION: We were able to show that there is a significant correlation between the resected breast tissue and the implant volume. With our novel potency function, the appropriate implant volume can be calculated for any resected weight making it easier for the surgeon to choose a fitting implant in a simple and more objective manner.
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Implantes de Mama , Neoplasias da Mama , Mamoplastia , Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/métodos , Mastectomia/métodos , Estudos RetrospectivosRESUMO
PURPOSE: To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). METHODS: A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. RESULTS: A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9-93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6-85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6-91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5 (95% CI 29.8-62.9) for the first screening round in BRCA2 carriers to 2.9 (95% CI 1.3-6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years. CONCLUSIONS: High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Detecção Precoce de Câncer , Feminino , Genes BRCA1 , Genes BRCA2 , Alemanha/epidemiologia , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico por imagem , Síndrome Hereditária de Câncer de Mama e Ovário/epidemiologia , Síndrome Hereditária de Câncer de Mama e Ovário/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Programas de Rastreamento , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Vigilância em Saúde Pública , Reprodutibilidade dos Testes , Risco , Adulto JovemRESUMO
Background Otherwise healthy women at high risk for breast cancer undergo annual contrast agent-enhanced breast MRI screening examinations, resulting in high cumulative doses of gadolinium-based contrast agents (GBCAs). Whereas the majority of studies showed no T1 signal ratio increase in deep brain nuclei after more than six doses of macrocyclic GBCA, this has not been explored in a healthy study population. Purpose To assess whether women who are administered large cumulative doses of macrocyclic GBCA with breast MRI at high-risk breast cancer screening exhibit T1 alterations in deep brain nuclei. Materials and Methods In this prospective study from November 2017 to March 2018, healthy women who were either exposed (because of high-risk breast cancer screening) or unexposed to only gadoterate meglumine underwent 3.0-T brain MRI with a dedicated head coil, including T1 mapping and magnetization-prepared rapid gradient-echo sequences. T1 times and T1 signal intensities were measured in the dentate nucleus (DN), globus pallidus (GP), crus anterior of capsula interna (CA), and pons. Ratios of DN to pons and GP to CA were calculated, and univariable Pearson correlation coefficients were calculated. Multivariable analysis included partial regression analysis. Results This study evaluated 25 women (mean age, 51 years ± 11 [standard deviation]) who were exposed to a mean GBCA dose of 129 mL (median 112 mL; range, 70-302 mL) and 16 women (mean age, 37 years ± 10) who were never exposed to any GBCA. Infratentorially, no correlation between cumulative GBCA dose and T1 times or signal intensity ratios was detected (P = .66 and .55, respectively). In partial correlation analysis by considering age as a confounder, there was a moderate negative correlation between GP-to-CA ratio and GBCA dose (r = -0.40; P = .01) but not for GP T1 times (r = 0.19; P = .24). Conclusion After administration of relatively large cumulative doses of gadoterate dimeglumine, healthy women at high risk for breast cancer who underwent annual contrast-enhanced breast MRI screening did not exhibit T1 signal increase in deep brain nuclei at 3.0-T MRI. © RSNA, 2019.
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Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Meglumina/administração & dosagem , Compostos Organometálicos/administração & dosagem , Adulto , Idoso , Meios de Contraste/farmacocinética , Feminino , Humanos , Meglumina/farmacocinética , Pessoa de Meia-Idade , Compostos Organometálicos/farmacocinética , Estudos ProspectivosRESUMO
We aimed to test the potential of phantomless volumetric bone mineral density (PLvBMD) measurements for the determination of volumetric bone mineral density (vBMD) in routine contrast-enhanced computed tomography (CECT). We evaluated 56 tri-phasic abdominal computed tomography scans, including an unenhanced scan as well as defined CECT scans in the arterial and portalvenous phase. PLvBMD analysis was performed by 4 radiologists using an FDA-approved tool for phantomless evaluation of bone density (IntelliSpace, Philips, The Netherlands). Mean vBMD of the first 3 lumbar vertebrae in each contrast phase was determined and interobserver variance of vBMD independent of contrast phase was analyzed using intraclass correlation, Bland-Altman plots, and Student's t test. CECT scans were associated with a significantly higher PLvBMD compared with unenhanced scans (unenhanced computed tomography: 97.8 mg/cc; arterial CECT: 106.3 mg/cc, portalvenous CECT: 106.3 mg/cc). Overall, there was no significant difference of PLvBMD between data acquisition in arterial and portalvenous phases (increase of 8.6% each, standard deviation ratio 37.7%-38.3%). In Bland-Altman analysis, there was no evidence of a relevant reader-related bias or an increase in standard deviation of PLvBMD measurements in contrast-enhanced scans compared with unenhanced scans. The following conversion formulas for unenhanced PLvBMD were determined: unenhancedPLvBMD=0.89×arterialPLvBMD+3,74mg/cc(r2 = 0.94) and unenhancedPLvBMD=0.88×venousPLvBMD+4,56mg/cc(r2 = 0.93). Compared with the results of phantom-based quantitative computed tomography measurements reported in the literature, the PLvBMD changes associated with contrast enhancement were relatively moderate with an increase of 8.6% in average. The time-point of the contrast-enhanced PLvBMD measurements after injection of contrast media did not appear to affect the results. With the adjustment formulas provided in this study, the method can improve osteoporosis screening through detection of reduced bone mass of the vertebrae in routinely conducted CECT.
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Densidade Óssea , Tomografia Computadorizada por Raios X/métodos , Idoso , Calibragem , Meios de Contraste , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Imagens de Fantasmas , Estudos RetrospectivosRESUMO
The clinical course of neuroblastoma is more heterogeneous than any other malignant disease. Most low-risk patients experience regression after limited or even no chemotherapy. However, more than half of high-risk patients die from disease despite intensive multimodal treatment. Precise patient characterization at diagnosis is key for risk-adapted treatment. The guidelines presented here incorporate results from national and international clinical trials to produce recommendations for diagnosing and treating neuroblastoma patients in German hospitals outside of clinical trials.
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Ganglioneuroma/diagnóstico , Ganglioneuroma/terapia , Neuroblastoma/diagnóstico , Neuroblastoma/terapia , Criança , Ensaios Clínicos como Assunto , Terapia Combinada , Ganglioneuroma/mortalidade , Alemanha , Hospitais Pediátricos , Humanos , Neuroblastoma/mortalidade , Prognóstico , Risco Ajustado , Taxa de SobrevidaRESUMO
BACKGROUND: Ganglioneuroma (GN) and ganglioneuroblastoma intermixed (GNBI) are mature variants of neuroblastic tumors (NT). It is still discussed whether incomplete resection of GN/GNBI impairs the outcome of patients. METHODS: Clinical characteristics and outcome of localized GN/GNBI were retrospectively compared to localized neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) registered in the German neuroblastoma trials between 2000 and 2010. RESULTS: Of 808 consecutive localized NT, 162 (20 %) were classified as GN and 55 (7 %) as GNBI. GN/GNBI patients presented more often with stage 1 disease (68 % vs. 37 %, p < 0.001), less frequently with adrenal tumors (31 % vs. 43 %, p = 0.001) and positive mIBG-uptake (34 % vs. 90 %, p < 0.001), and had less often elevated urine catecholamine metabolites (homovanillic acid 39 % vs. 62 %, p < 0.001, vanillylmandelic acid 27 % vs. 64 %, p < 0.001). Median age at diagnosis increased with grade of differentiation (NB/GNBN: 9; GNBI: 61; GN-maturing: 71; GN-mature: 125 months, p < 0.001). Complete tumor resection was achieved at diagnosis in 70 % of 162 GN and 67 % of 55 GNBI, and after 4 to 32 months of observation in 4 GN (2 %) and 5 GNBI (9 %). Eleven patients received chemotherapy without substantial effect. Fifty-five residual tumors (42 GN, 13 GNBI) are currently under observation (median: 44 months). Five patients (3 GN, 2 GNBI) showed local progression; all had tumor residuals > 2 cm. No progression occurred after subtotal resection. Two patients died of treatment, none of tumor progression. CONCLUSIONS: GN/GNBI account for one quarter of localized NT and differ from immature tumors in their clinical features. Chemotherapy is not effective. Subtotal resection appears to be a sufficient treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifiers - NB97 (NCT00017225; registered June 6, 2001); NB2004 (NCT00410631; registered December 11, 2006).
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Tratamento Farmacológico/métodos , Procedimentos Cirúrgicos Endócrinos/métodos , Ganglioneuroblastoma/terapia , Ganglioneuroma/terapia , Adolescente , Idade de Início , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Tempo para o Tratamento , Resultado do TratamentoRESUMO
OBJECTIVES: This study aimed to evaluate the cost-effectiveness of the onasemnogene abeparvovec in relation to nusinersen and risdiplam in the treatment of spinal muscular atrophy type 1 from the perspective of the Brazilian Unified Health System. METHODS: A Markov model was built on a lifetime horizon. Short-term data were obtained from clinical trials of the technologies and from published cohort survival curves (long term). Costs were measured in current 2022 local currency (R$) values and benefits in quality-adjusted life-years (QALYs). Utility values were derived from type 1 spinal muscular atrophy literature, whereas costs related to technologies and maintenance care in each health state were obtained from official sources of reimbursement in Brazil. Deterministic and probabilistic, as well as scenario, sensitivity analyses were performed. RESULTS: Compared with the less costly strategy (nusinersen), the use of onasemnogene abeparvovec resulted in an incremental cost of R$2.468.448,06 ($975 671.169 - purchasing power parity [PPP]) and a 3-QALY increment and incremental cost-effectiveness ratio of R$742.890,92 ($293 632.774 - PPP)/QALY. Risdiplam had an extended dominance from other strategies, resulting in an incremental cost-effectiveness ratio of R$926.586,22 ($366 239.612 - PPP)/QALY compared with nusinersen. Sensitivity analysis showed a significant impact of the follow-up time of the cohort and the cost of acquiring onasemnogene abeparvovec. CONCLUSIONS: Over a lifetime horizon, onasemnogene abeparvovec seems to be a potentially more effective option than nusinersen and risdiplam, albeit with an incremental cost. Such a trade-off should be weighed in efficiency criteria during decision making and outcome monitoring from the perspective of the Brazilian Unified Health System.
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Compostos Azo , Produtos Biológicos , Atrofia Muscular Espinal , Oligonucleotídeos , Pirimidinas , Proteínas Recombinantes de Fusão , Humanos , Brasil , Análise Custo-Benefício , Atrofia Muscular Espinal/tratamento farmacológicoRESUMO
BACKGROUND: Onasemnogene abeparvovec has been approved for the treatment of spinal muscular atrophy 5q type 1 in several countries, which calls for an independent assessment of the evidence regarding efficacy and safety. OBJECTIVE: Conduct a meta-analysis to assess the efficacy and safety of onasemnogene abeparvovec in patients diagnosed with SMA type 1, based on the available evidence. METHODS: This article results from searches conducted on databases up to November 2022. Outcomes of interest were global survival and event-free survival, improvement in motor function and treatment-related adverse events. Risk of bias assessment and certainty of evidence were performed for each outcome. Proportional meta-analysis models were performed when applicable. RESULTS: Four reports of three open-label, non-comparative clinical trials covering 67 patients were included. Meta-analyses of data available in a 12-month follow-up estimate a global survival of 97.56% (95%CI: 92.55 to 99.86, I2 = 0%, n = 67), an event-free survival of 96.5% (95%CI: 90.76 to 99.54, I2 = 32%, n = 66) and a CHOP-INTEND score ≥ 40 points proportion of 87.28% (95%CI: 69.81 to 97.83, I2 = 69%, n = 67). Proportion of 52.64% (95%CI: 27.11 to 77.45, I2 = 78%, n = 67) of treatment-related adverse events was estimated. CONCLUSION: The results indicate a potential change in the natural history of type 1 SMA, but the methodological limitations of the studies make the real extent of the technology's long-term benefits uncertain.
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Proteínas Recombinantes de Fusão , Atrofias Musculares Espinais da Infância , Humanos , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Resultado do TratamentoRESUMO
Structural disconnectivity has been hypothesized as being accountable for the pathophysiology of schizophrenia. Morphometric variables suitable for the empirical study of disconnectivity were studied aiming at the research question whether empirical indicators for disconnectivity are already informative in subjects at risk (SAR) and in young matched patients diagnosed with schizophrenia (SZ). In MRI data of subjects of the two diagnostic groups SZ and SAR, the size of the corpus callosum (CC) as indicator for interhemispherical long distance connections and the gyrification index (GI) as indicator for cortico-cortical connections were analyzed compared to a healthy controls (HC). Each subgroup consists of 21 subjects matched for sex and age. Measurements of the CC and GI were estimated in manually performed tracing procedures. GI data revealed significant differences between the diagnostic groups of both SAR and SZ as compared to HC in the frontal and parietal cortices. Measurements of total CC yielded no significant differences between diagnostic groups. The results are suggestive for impaired cortico-cortical connections as indicated by gyrification changes in SZ and also in SAR, whereas interhemispherical connectivity at the same time appears to be unaffected.
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Mapeamento Encefálico , Corpo Caloso/patologia , Esquizofrenia/patologia , Adulto , Estudos de Casos e Controles , Córtex Cerebral/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Análise Multivariada , Rede Nervosa/patologia , Vias Neurais/patologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
Alzheimer's disease (AD) treatment is freely available in the Brazilian public health system. However, the prescription pattern and its associated factors have been poorly studied in our country. We reviewed all granted requests for AD treatment in the public health system in October 2021 in the Rio Grande do Sul (RS) state, Southern Brazil. We performed a spatial autocorrelation analysis with the population-adjusted patients receiving any AD medication as the outcome and correlated it with several socioeconomic variables. 2382 patients with AD were being treated during the period analyzed. The distribution of the outcome variable was not random (Moran's I 0.17562, P <.0001), with the most developed regions having a higher number of patients/100,000 receiving any AD medication. We show that although AD medications are available through the public health system, there is a clear disparity between regions of RS state. Factors related to socioeconomic development partly explain this finding.
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Doença de Alzheimer , Humanos , Brasil , Prescrições , Saúde Pública , Análise EspacialRESUMO
The specific treatment available for Fabry disease (FD) is enzyme replacement therapy (ERT) with agalsidase alfa or beta. A systematic review and meta-analysis was conducted to assess the efficacy and safety of ERT for FD. Only double-blind, randomized clinical trials (RCTs) comparing agalsidase alfa or beta and placebo were included. ERT with either agalsidase alfa or beta was considered similar for the purposes of analysis. Ten RCTs were identified, which showed improvements in neuropathic pain, in heart abnormalities and in globotriaosylceramide (GL-3) levels. A meta-analysis showed increased odds for fever, rigors, development of IgG antibodies to agalsidase, and no significant association with development of hypertension or reduction in the QRS complex duration on electrocardiogram. The RCTs included in this comparison enrolled few patients, were highly heterogeneous, and were focused mainly on surrogate endpoints, limiting any conclusions as to the real effect of ERT for FD. The available evidence suggests that response to ERT is variable across patient subgroups and that agalsidase may slow progression of FD, with slight improvement of existing changes. Nevertheless, many uncertainties remain, and further studies are necessary.
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BACKGROUND/AIM: The combination of pre-surgical clip placement and hook-wire guided surgery is considered the gold standard for adequately locating non-palpable lesions during breast conserving surgery. After surgical removal of the segment, radiography is required to confirm clip removal, increasing surgical time, post-surgical complication rates, and cost. PATIENTS AND METHODS: We performed a retrospective analysis, using the Faxitron® in-theater specimen radiography system, of the following primary endpoints: surgical time and complication rates. The secondary endpoints were cost effectiveness and clip-location rates. The Control cohort included breast conserving surgery patients prior to May 2019 (n=150) and the Validation cohort included breast conserving surgery patients after May 2019 (n=53). RESULTS: The analysis showed an improvement in surgical time when using the Faxitron® system, which is directly linked to a benefit in cost effectiveness. A numerical benefit in complication rates was also shown. A subgroup analysis showed a significant advantage in surgical time for breast conserving surgery plus sentinel node biopsy and open breast biopsies. CONCLUSION: Use of the Faxitron® system significantly reduces surgical time, which increases cost efficiency while maintaining a low complication rate.
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Mastectomia Segmentar , Biópsia de Linfonodo Sentinela , Custos e Análise de Custo , Humanos , Mastectomia Segmentar/efeitos adversos , Radiografia , Estudos RetrospectivosRESUMO
Cortical thickness (CT) changes possibly contribute to the complex symptomatology of autism. The aberrant developmental trajectories underlying such differences in certain brain regions and their continuation in adulthood are a matter of intense debate. We studied 28 adults with high-functioning autism (HFA) and 28 control subjects matched for age, gender, IQ and handedness. A surface-based whole brain analysis utilizing FreeSurfer was employed to detect CT differences between the two diagnostic groups and to investigate the time course of age-related changes. Direct comparison with control subjects revealed thinner cortex in HFA in the posterior superior temporal sulcus (pSTS) of the left hemisphere. Considering the time course of CT development we found clusters around the pSTS and cuneus in the left and the paracentral lobule in the right hemisphere to be thinner in HFA with comparable age-related slopes in patients and controls. Conversely, we found clusters around the supramarginal gyrus and inferior parietal lobule (IPL) in the left and the precentral and postcentral gyrus in the right hemisphere to be thinner in HFA, but with different age-related slopes in patients and controls. In the latter regions CT showed a steady decrease in controls but no analogous thinning in HFA. CT analyses contribute in characterizing neuroanatomical correlates of HFA. Reduced CT is present in brain regions involved in social cognition. Furthermore, our results demonstrate that aberrant brain development leading to such differences is proceeding throughout adulthood. Discrepancies in prior morphometric studies may be induced by the complex time course of cortical changes.
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Transtorno Autístico/patologia , Córtex Cerebral/patologia , Lobo Temporal/patologia , Adulto , Idade de Início , Envelhecimento/fisiologia , Anatomia Transversal , Encéfalo/anatomia & histologia , Córtex Cerebral/crescimento & desenvolvimento , Análise por Conglomerados , Interpretação Estatística de Dados , Feminino , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Inteligência , Testes de Inteligência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Temporal/crescimento & desenvolvimento , Adulto JovemRESUMO
BACKGROUND/AIMS: Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disorder treated with bone marrow transplantation or enzyme replacement therapy with laronidase, a high-cost orphan drug. Laronidase was approved by the US Food and Drug Administration and the European Medicines Agency in 2003 and by the Brazilian National Health Surveillance Agency in 2005. Many Brazilian MPS I patients have been receiving laronidase despite the absence of a governmental policy regulating access to the drug. Epidemiological and treatment data concerning MPS I are scarce. This study aims to present a demographic profile of Brazilian patients with MPS I, describe the routes of access to laronidase in Brazil, and discuss associated ethical issues relating to public funding of orphan drugs. METHODS: In this cross-sectional observational study, data were collected nationwide between January and September 2008 from physicians, public institutions and non-governmental organisations involved with diagnosis and treatment of MPS I, using two data collection instruments specifically designed for this purpose. RESULTS: The minimum prevalence of MPS I in Brazil was estimated at 1/2,700,000. Most patients (69.8%) were younger than 15 years; 60 (88.2%) received laronidase. The most common route of access to the drug was through lawsuits (86.6%). CONCLUSIONS: In Brazil, MPS I is predominantly a paediatric illness. Even though the cost of laronidase treatment is not officially covered by the Brazilian government, most MPS I patients receive the drug, usually through litigation. This gives rise to major ethical conflicts concerning drug access in a low-resource context. The Brazilian health policy framework lacks evidence-based clinical protocols for the distribution of orphan drugs.
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Custos de Medicamentos/legislação & jurisprudência , Iduronidase/uso terapêutico , Mucopolissacaridose I/tratamento farmacológico , Produção de Droga sem Interesse Comercial/economia , Adolescente , Adulto , Fatores Etários , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Custos de Medicamentos/ética , Feminino , Política de Saúde/economia , Humanos , Iduronidase/economia , Iduronidase/provisão & distribuição , Lactente , Masculino , Pessoa de Meia-Idade , Mucopolissacaridose I/economia , Produção de Droga sem Interesse Comercial/ética , Produção de Droga sem Interesse Comercial/legislação & jurisprudência , Adulto JovemRESUMO
MATERIALS AND METHODS: In this multicentric study, individual patient data from 3 different centers were analyzed. Consecutive patients receiving standardized multiparametric breast magnetic resonance imaging for standard nonscreening indications were included. At each center, 2 experienced radiologists with more than 5 years of experience retrospectively interpreted the examinations in consensus and applied the KS to every histologically verified lesion. The corresponding mean ADC of each lesion was measured using a Wielema type 4 region of interest. According to established methods, the KS and ADC were combined, yielding the KS+ score. Diagnostic accuracy was evaluated by the area under the receiver operating characteristics curve (AUROC) and compared between the KS, ADC, and KS+ (DeLong test). Likewise, the potential to help avoid unnecessary biopsies was compared between the KS, ADC, and KS+ based on established high sensitivity thresholds (McNemar test). RESULTS: A total of 450 lesions in 414 patients (mean age, 51.5 years; interquartile range, 42-60.8 years) were included, with 219 lesions being malignant (48.7%; 95% confidence interval [CI], 44%-53.4%). The performance of the KS (AUROC, 0.915; CI, 0.886-0.939) was significantly better than that of the ADC (AUROC, 0.848; CI, 0.811-0.880; P < 0.001). The largest difference between these parameters was observed when assessing subcentimeter lesions (AUROC, 0.909 for KS; CI, 0.849-0.950 vs 0.811 for ADC; CI, 0.737-0.871; P = 0.02).The use of the KS+ (AUROC, 0.918; CI, 0.889-0.942) improved the performance slightly, but without any significant difference relative to a single KS or ADC reading (P = 0.64).When applying high sensitivity thresholds for avoiding unnecessary biopsies, the KS and ADC achieved equal sensitivity (97.7% for both; cutoff values, >4 for KS and ≤1.4 × 10-3 mm2/s for ADC). However, the rate of potentially avoidable biopsies was higher when using the KS (specificity: 65.4% for KS vs 32.9% for ADC; P < 0.0001). The KS was superior to the KS+ in avoiding unnecessary biopsies. CONCLUSIONS: Both the KS and ADC may be used to distinguish benign from malignant breast lesions. However, KS proved superior in this task including, most of all, when assessing small lesions less than 1 cm. Using the KS may avoid twice as many unnecessary biopsies, and the combination of both the KS and ADS does not improve diagnostic performance.
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Neoplasias da Mama , Imagem de Difusão por Ressonância Magnética , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Pompe disease (PD) is a glycogen storage disorder caused by deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset PD (LOPD). METHODS: We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes. A meta-analysis was also performed. RESULTS: Of 1601 articles identified, 22 were included. Studies were heterogeneous and with very low certainty of evidence for most outcomes. The following outcomes showed improvements associated with GAA ERT, over a mean follow-up of 32.5 months: distance walked in the 6-min walking test (6MWT) (mean change 35.7 m (95% confidence interval [CI] 7.78, 63.75)), physical domain of the SF-36 quality of life (QOL) questionnaire (mean change 1.96 (95% CI 0.33, 3.59)), and time on ventilation (TOV) (mean change -2.64 h (95% CI -5.28, 0.00)). There were no differences between the pre- and post-ERT period for functional vital capacity (FVC), Walton and Gardner-Medwin Scale score, upper-limb strength, or total SF-36 QOL score. Adverse events (AEs) after ERT were mild in most cases. CONCLUSION: Considering the limitations imposed by the rarity of PD, our data suggest that GAA ERT improves 6MWT, physical QOL, and TOV in LOPD patients. ERT was safe in the studied population. PROSPERO register: 135102.
RESUMO
OBJECTIVE: The aim of this study was to evaluate the frequency of hypoglycemia and the treatment satisfaction in patients with type 1 diabetes (T1D) using insulin analogues. METHODS: This observational retrospective study included 516 adult patients with T1D from 38 cities in Southern Brazil. Demographics and clinical data were collected using a self-report questionnaire. Hypoglycemia was defined as an event based on either symptoms or self-monitored blood glucose < 70 mg/dL. Treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and with a specific question with scores ranging from 0-10. Common mental disorders were assessed using the General Health Questionnaire (GHQ-12). RESULTS: Overall, the mean age was 38 ± 14 years and 52% of the participants were women. The median diabetes duration was 18 years. The scores for insulin analogue treatment satisfaction were higher than those for previous treatments. DTSQ scores had a median value of 32 (interquartile range 29-35) and remained unchanged over time. The percentage of patients with hypoglycemia (including severe and nocturnal) was comparable across groups divided according to duration of use of insulin analogues. Most patients (n=395, 77%) screened positive for common mental disorders. CONCLUSION: Patient satisfaction with insulin analogue treatment was high and remained unchanged with time. Episodes of hypoglycemia also remained unchanged over time among patients using insulin analogues.