Sensitivity of multiparametric MRI and targeted biopsy for detection of adverse pathologies (Cribriform gleason pattern 4 and intraductal carcinoma): Correlation of detected and missed prostate cancer foci with whole mount histopathology.

PURPOSE: Accurate preoperative detection of prostate cancer (PCa) exhibiting "cribriform" morphology (intraductal carcinoma [IDC-P] or cribriform Gleason pattern 4 [CrP4]) is important as it is independently associated with a variety of adverse clinical outcomes. The sensitivity of multiparametric magnetic resonance imaging (mpMRI) in the detection of PCa exhibiting "cribriform" morphology remains controversial. MATERIALS AND METHODS: A total of 117 eligible men with prospectively reported mpMRI who underwent in-bore MRI targeted biopsy followed by whole-mount radical prostatectomy (RP) were analyzed for lesion-level imaging-pathology correlation. RESULTS: Of the 206 PCa foci at RP (117 index and 89 non-index), 74% (152/206) were detected by mpMRI. Of the 54 tumors missed by mpMRI, most were non-index (98%, 53/54), grade group (GG) 1 (68%, 37/54) or GG 2 (26%, 14/54), with a median size of 1.0 cm (range, 0.7-1.5 cm), and non-cribriform morphology (96%, 52/54). Cribriform morphology was detected in 26% (53/206) of all tumors, and although targeted biopsies identified 96% (51/53) of these cancers, the cribriform component was depicted in only 45% (24/53). Of these, mpMRI detected all (100%, 44/44) index and 78% (7/9) of the non-index tumors. At univariable analysis, tumor size greater than 5 mm, % pattern 4 > 5%, cribriform morphology, zone (transition versus peripheral zone), and region (apex versus mid/base) were significantly associated with tumor visibility at mpMRI. At multivariable analysis, only tumor size, presence of any pattern 4, and peripheral zone remained significant predictors for visibility by mpMRI. CONCLUSION: At a lesion level, mpMRI offers high sensitivity for the detection of cribriform morphologies, however, the cribriform component is frequently missed by targeted biopsies. The MRI visibility is significantly associated with larger tumor size, presence of Gleason pattern 4, and peripheral zone location.

Whole brain 3D MR fingerprinting in multiple sclerosis: a pilot study.

BACKGROUND: MR fingerprinting (MRF) is a novel imaging method proposed for the diagnosis of Multiple Sclerosis (MS). This study aims to determine if MR Fingerprinting (MRF) relaxometry can differentiate frontal normal appearing white matter (F-NAWM) and splenium in patients diagnosed with MS as compared to controls and to characterize the relaxometry of demyelinating plaques relative to the time of diagnosis. METHODS: Three-dimensional (3D) MRF data were acquired on a 3.0T MRI system resulting in isotropic voxels (1 × 1 × 1 mm3) and a total acquisition time of 4 min 38 s. Data were collected on 18 subjects paired with 18 controls. Regions of interest were drawn over MRF-derived T1 relaxometry maps encompassing selected MS lesions, F-NAWM and splenium. T1 and T2 relaxometry features from those segmented areas were used to classify MS lesions from F-NAWM and splenium with T-distributed stochastic neighbor embedding algorithms. Partial least squares discriminant analysis was performed to discriminate NAWM and Splenium in MS compared with controls. RESULTS: Mean out-of-fold machine learning prediction accuracy for discriminant results between MS patients and controls for F-NAWM was 65 % (p = 0.21) and approached 90 % (p < 0.01) for the splenium. There was significant positive correlation between time since diagnosis and MS lesions mean T2 (p = 0.015), minimum T1 (p = 0.03) and negative correlation with splenium uniformity (p = 0.04). Perfect discrimination (AUC = 1) was achieved between selected features from MS lesions and F-NAWM. CONCLUSIONS: 3D-MRF has the ability to differentiate between MS and controls based on relaxometry properties from the F-NAWM and splenium. Whole brain coverage allows the assessment of quantitative properties within lesions that provide chronological assessment of the time from MS diagnosis.

Whole-brain 3D MR fingerprinting brain imaging: clinical validation and feasibility to patients with meningioma.

PURPOSE: MR fingerprinting (MRF) is a MR technique that allows assessment of tissue relaxation times. The purpose of this study is to evaluate the clinical application of this technique in patients with meningioma. MATERIALS AND METHODS: A whole-brain 3D isotropic 1mm3 acquisition under a 3.0T field strength was used to obtain MRF T1 and T2-based relaxometry values in 4:38 s. The accuracy of values was quantified by scanning a quantitative MR relaxometry phantom. In vivo evaluation was performed by applying the sequence to 20 subjects with 25 meningiomas. Regions of interest included the meningioma, caudate head, centrum semiovale, contralateral white matter and thalamus. For both phantom and subjects, mean values of both T1 and T2 estimates were obtained. Statistical significance of differences in mean values between the meningioma and other brain structures was tested using a Friedman's ANOVA test. RESULTS: MR fingerprinting phantom data demonstrated a linear relationship between measured and reference relaxometry estimates for both T1 (r2 = 0.99) and T2 (r2 = 0.97). MRF T1 relaxation times were longer in meningioma (mean ± SD 1429 ± 202 ms) compared to thalamus (mean ± SD 1054 ± 58 ms; p = 0.004), centrum semiovale (mean ± SD 825 ± 42 ms; p < 0.001) and contralateral white matter (mean ± SD 799 ± 40 ms; p < 0.001). MRF T2 relaxation times were longer for meningioma (mean ± SD 69 ± 27 ms) as compared to thalamus (mean ± SD 27 ± 3 ms; p < 0.001), caudate head (mean ± SD 39 ± 5 ms; p < 0.001) and contralateral white matter (mean ± SD 35 ± 4 ms; p < 0.001) CONCLUSIONS: Phantom measurements indicate that the proposed 3D-MRF sequence relaxometry estimations are valid and reproducible. For in vivo, entire brain coverage was obtained in clinically feasible time and allows quantitative assessment of meningioma in clinical practice.

Bond-Breaking Efficiency of High-Energy Ions in Ultrathin Polymer Films.

Thin films of poly(methyl methacrylate) and poly(vinyl chloride) of different thickness are used to investigate the effect of spatial confinement on the efficiency of bond breaking induced by 2 MeV H^{+} and 2.1 GeV Bi ions. Effective cross sections for oxygen and chlorine loss are extracted for films down to a thickness of about 5 nm and are compared to theoretical estimations based on radial energy density profiles simulated with geant-dna. The cross sections are to a large extent thickness independent, indicating that bond breaking is dominated by short-range processes. This is in contrast to the strongly reduced efficiencies found recently for cratering induced by high-energy ions in similar ultrathin polymer films [Phys. Rev. Lett. 114, 118302 (2015)PRLTAO0031-900710.1103/PhysRevLett.114.118302].

Accuracy and Interobserver Agreement for Prostate Imaging Reporting and Data System, Version 2, for the Characterization of Lesions Identified on Multiparametric MRI of the Prostate.

OBJECTIVE: The objective of this study was to measure the accuracy and interobserver agreement of the Prostate Imaging Reporting and Data System, version 2 (PI-RADSv2), for the characterization of prostate lesions on multiparametric MRI. MATERIALS AND METHODS: This retrospective study included 170 men examined at a single institution between August 2014 and February 2015 on a 3-T MRI scanner. Study patients were found to have lesions concerning for prostate cancer that were targeted for MRI/transrectal ultrasound fusion biopsy. Two experienced readers independently assigned a PI-RADSv2 assessment category to the dominant lesion in each patient. The AUC was calculated to determine reader accuracy for the detection of clinically significant prostate cancer (Gleason score ≥ 3 + 4). The Cohen kappa statistic was used to quantify interobserver agreement. RESULTS: The prevalence of clinically significant prostate cancer was 0.36 (61/170 patients). The AUCs for readers 1 and 2 were 0.871 and 0.882, respectively. The AUCs were greater for peripheral zone lesions than for transition zone lesions. When a PI-RADSv2 assessment category ≥ 3 was considered positive, the agreement between readers was good overall (κ = 0.63) and was fair for transition zone lesions (κ = 0.53). When a PI-RADSv2 assessment category ≥ 4 was considered positive, the agreement was excellent overall (κ = 0.91) and was excellent for both peripheral zone lesions (κ = 0.91) and transition zone lesions (κ = 0.87). CONCLUSION: Two experienced readers were able to accurately identify patients with clinically significant prostate cancer using PI-RADSv2 with good interobserver agreement overall.

Confinement effects of ion tracks in ultrathin polymer films.

We show direct experimental evidence that radiation effects produced by single MeV heavy ions on a polymer surface are weakened when the length of the ion track in the material is confined into layers of a few tens of nanometers. Deviation from the bulk (thick film) behavior of ion-induced craters starts at a critical thickness as large as ∼40 nm, due to suppression of long-range additive effects of excited atoms along the track. Good agreement was found between the experimental results, molecular dynamic simulations, and an analytical model.

Early treatment of multiple sclerosis: a Latin American experts meeting.

Patients with clinically isolated syndrome (CIS) by definition do not have multiple sclerosis (MS) but are at risk of developing it. While studies show earlier immunomodulating drug use is effective, treatment must consider likely patient prognosis. In this paper we review current diagnosis, prognosis, and treatment literature for patients with CIS within Latin American clinical settings. Latin American MS experts, convened by ACINDES (The Civil Association for Research and Development in Health), reviewed current CIS (and early MS) literature and drew consensus conclusions. Three subgroups addressed separate questionnaires on CIS issues: prognosis, diagnosis, and treatment. MRI can contribute to predicting MS risk in patients with CIS; in Latin America, investigation of haplotype presence associated with CIS would be appropriate. McDonald's criteria and subsequent revisions enable earlier, more accurate MS diagnosis. Type A evidence exists supporting all leading immunomodulating MS drugs for effective treatment of CIS with a high risk of conversion to MS. In conclusion, patients with CIS are usually young, with often-limited symptomatic manifestations, and must be adequately prepared to receive preventive treatment. This consensus review should contribute to the dialogue between physicians and patients.

Stem cells from umbilical cord blood do have myogenic potential, with and without differentiation induction in vitro.

The dystrophin gene, located at Xp21, codifies dystrophin, which is part of a protein complex responsible for the membrane stability of muscle cells. Its absence on muscle causes Duchenne Muscular Dystrophy (DMD), a severe disorder, while a defect of muscle dystrophin causes Becker Muscular Dystrophy (DMB), a milder disease. The replacement of the defective muscle through stem cells transplantation is a possible future treatment for these patients. Our objective was to analyze the potential of CD34+ stem cells from umbilical cord blood to differentiate in muscle cells and express dystrophin, in vitro. Protein expression was analyzed by Immunofluorescence, Western Blotting (WB) and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). CD34+ stem cells and myoblasts from a DMD affected patient started to fuse with muscle cells immediately after co-cultures establishment. Differentiation in mature myotubes was observed after 15 days and dystrophin-positive regions were detected through Immunofluorescence analysis. However, WB or RT-PCR analysis did not detect the presence of normal dystrophin in co-cultures of CD34+ and DMD or DMB affected patients' muscle cells. In contrast, some CD34+ stem cells differentiated in dystrophin producers' muscle cells, what was observed by WB, reinforcing that this progenitor cell has the potential to originate muscle dystrophin in vitro, and not just in vivo like reported before.

Cintilografia de perfusão miocárdica em pacientes diabeticos tipo 2 com dor torácica atípica / Myocardial perfusion scintigraphy in type 2 diabetic patients with atypical chest pain

Foram avaliados através de cintilografia miocárdica de perfusão, 67 pacientes com diabetes tipo 2 (DM2) com dor torácica atípica e com eletrocardiograma de repouso normal ou com alterações inespecíficas da repolarização ventricular, com o objetivo de se verificar a prevalência de alterações miocárdicas isquêmicas. A idade média ± DP dos pacientes foi de 63,5 ± 9 anos. Vinte e um (31,3 por cento) homens e 46 (68,7 por cento) mulheres. Grande parte da amostra (62,7 por cento) apresentou exame normal, enquanto em 37,3 por cento a cintilografia apresentou-se positiva para isquemia. O teste ergométrico foi realizado em 91 por cento (n = 61) e em 31,1 por cento foi positivo para isquemia. A concordância entre a cintilografia miocárdica e o teste ergométrico mostrou baixa correlação entre os dois testes (Kappa = 0,49; P = 0,0001). Concluímos que a cintilografia de perfusão miocárdica comprovou-se de elevado valor clínico na avaliação e diagnóstico da doença coronariana em pacientes com DM2 com dor precordial atípica.

[Myocardial perfusion scintigraphy in type 2 diabetic patients with atypical chest pain]. / Cintilografia de perfusão miocárdica em pacientes diabeticos tipo 2 com dor torácica atípica.

To verify the prevalence of ischemic myocardial abnormalities, 67 patients with type 2 diabetes mellitus (DM2) with normal basal electrocardiogram (EKG) or with ventricular repolarization abnormalities were evaluated by a perfusional myocardial scintigraphy. The average age was 63.5 +/- 9 years. Twenty-one (31.3%) were male and 46 (68.7%) female. A significant part of the sample (62.7%) had a normal myocardial scan, 37.3% were positive for ischemia. The majority of the sample (91%; n = 61) was submitted to an EKG during exercise which was positive for ischemia in 31.1%. The concordance between myocardial scintigraphy and the EKG during exercise demonstrated a low correlation between the two procedures (Kappa = 0.49; P = 0.0001). We conclude that perfusional myocardial scan is a highly valuable tool for evaluation and diagnosis of coronary artery disease in DM2 patients with atypical angina.

X-linked hypohidrotic ectodermal dysplasia mutations in Brazilian families.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by severe hypohidrosis, hypotrichosis, and hypodontia. The gene responsible for this pleiotropic syndrome (ED1) consists of 12 exons, 8 of them coding for a transmembrane protein (ectodysplasin-A; EDA-A) involved in the developmental process of epithelial-mesenchymal interaction. ED1 mutations that cause alterations in this protein lead to the XLHED phenotype. The major objective of the present study was to detect ED1 mutations in four Brazilian families with the XLHED phenotype and to compare them to the more than 60 different mutations already reported. DNA of the EDA-A coding exons was amplified by PCR, and single strand conformation analysis (SSCA) of the electrophoretic bands was carried out in polyacrylamide gel stained with silver nitrate. Two of these four families showed altered DNA band patterns. Subsequent DNA sequencing of the two mutated exons showed: (1) a 36 nucleotide deletion at exon 5 responsible for the loss of four Gly-X-Y repeats of the collagen subdomain of EDA-A; (2) a guanine deletion at exon 6 (966 or 967 sites) that alters EDA-A after amino acid 241 and leads to a premature ending at amino acid 279. This mutation at exon 6 seems not to have been reported previously and determines a truncated EDA-A without a part of its extracellular domain that contains the whole TNF homologue subdomain. These two DNA mutations are compatible with the XLHED phenotype. In the other two families the PCR-SSCA methodology was unable to detect any mutation responsible for the XLHED phenotype.

Prevalência de doença tireoideana em pacientes com diabetes tipo 1 / Prevalence of thyroid disease in patients with type 1 diabetes

INTRODUÇÄO: O diabetes mellitus tipo 1 (DM1) freqüentemente se acompanha de outras doenças autoimunes, principalmente doença autoimune da tireóide (DAT). OBJETIVO: Determinar a prevalência de DAT em pacientes com DM1 e investigar possível relacionamento com outros fatores. MÉTODOS: Em 126 pessoas com DM1, foram mensurados TSH, T4 livre, anticorpo anti-peroxidase e hemoglobina A1c. RESULTADOS: DAT foi encontrada em 26 pacientes (20,6 por cento), sendo 11 (8,7 por cento) com hipotireoidismo clínico, 6 (4,8 por cento) com hipotireoidismo subclínico e 9 (7,1 por cento) com tireoidite sem disfunçäo tireoideana. Em um paciente (0,8 por cento), a DAT (hipertireoidismo) precedeu o DM1. Houve relaçäo entre DAT e idade atual e no diagnóstico do DM1. Näo foram encontradas significâncias para sexo, grupo racial, duraçäo do DM, paridade e local de moradia. CONCLUSÖES: A prevalência de DAT é bastante alta para justificar seu rastreamento e está relacionada com a idade atual e a idade do diagnóstico do DM1

Tratamento do diabetes mellitus do tipo 2: novas Opçöes / Treatment of diabetes mellitus type II: new options

O diabetes mellitus do tipo 2 (DM2) resulta de defeitos na secreçäo e açäo da insulina. Ele está frequentemente associado à resistência à insulina, obesidade andróide, dislipidemia e hipertensäo arterial, constituindo a síndrome metabólica. O tratemento atual visa diminuir a resistência à insulina e melhorar a funçäo da célula beta pancreática com dieta, exercícios, hipoglicemiantes orais, anti-hiperglicemiantes e/ou drogas anti-obesidade. Novas drogas no tratamento do DM estäo surgindo, tornando possíveis multiplas opçöes terapêuticas. Este artigo apresenta uma revisäo sobre o assunto.

[Temporal lobe epilepsy with aura of pleasure. Case report]. / Epilepsia do lobo temporal com aura de prazer: relato de caso.

We report on a woman with temporal lobe epilepsy and "orgasm sensation" like an epileptic aura. Literature is controversial about pleasure and ecstasy as an epileptic aura. Aura of pleasure in this case is confirmed, by clinical investigation, electroencephalogram and seizures remission with treatment (phenytoin).

Parvovirose congênita: relato de caso / Congenital parvovirus infection: case report

Apresentamos um caso de regressao espontânea de hidropisia fetal provavelmente causada por infecçao materno-fetal pelo paravirus B 19. Além de hidropisia, observamos anemia e hipocontratilidade cardíaca no feto. O diagnóstico foi estabelecido pela soma dos achados ultra-sonográficos, detecçao do vírus no soro materno, hemograma fetal e dosagem de enzimas hepáticas fetais.

Anomalias cromossômicas em casais com aborto habitual / Chromosomal abnormalities in couples with recurrent spontaneus abortions

Há uma enorme dificuldade em identificar as causas do aborto habitual (ou aborto espontâneo recorrente). Sabe-se que em uma pequena porcentagem de casais com este problema pelo menos um dos cônjuges é portador de uma cromossomopatia. Estudamos 301 casais com dois ou mais abortos espontâneos para verificar a porcentagem de portadores de rearranjos cromossômicos equilibrados. Dos 301 casais, 17 (3,6 por cento) mostraram-se portadores de translocaçoes recíprocas ou inversoes que justificam as perdas gestacionais e outros 2 por cento possuem anomalias de significado duvidoso. Perdas gestacionais ocorreram preferencialmente no primeiro trimestre de gestaçao. Estes dados mostram a importância da cariotipagem dos casais com aborto habitual para diagnóstico e aconselhamento genético em futuras gestaçoes.

O mosaicismo cromossômico em amostra de vilo corial / Chromosome mosaicism in chorionic villus sampling

Este trabalho relata o estudo cromossômico de 1752 AVC realizadas pelo método direto modificado (cultura de 24 horas). O mosaicismo cromossômico representou 1,9 por cento da amostra total (34/1752). Mosaicismo envolvendo cromossomos autossômicos foi observado em 64,7 por cento (22/34), mosaicismo envolvendo cromossomos sexuais em 23,5 por cento dos casos (8/34), mosaicismo envolvendo poliploidia em 5,9 por cento (2/34); um caso (2,9 por cento) envolveu um cromossomo marcador e outro, um rearranjo entre um autossomo e um cromossomo sexual. O mosaicismo placentário confinado representou 58,8 por cento dos casos de mosaicismo (20/34) enquanto que o mosaicismo verdadeiro esteve presente em 14,7 por cento dos casos (5/34). Nós perdemos contato com uma paciente e uma outra abortou antes da realizaçao da amniocentese. Os seguimentos citogenéticos em 7 casos nao foram realizados porque 5 das 7 (l4,7 por cento) decidiram interromper a gestaçao após o resultado da AVC e duas pacientes (5,9 por cento) prosseguiram a gestaçao e relataram que as crianças, ao nascerem, eram clinicamente normais.

Prenatal ultrasound diagnosis of Roberts syndrome at 21 weeks

Descrevemos o primeiro caso no Brasil e síndrome de Roberts identificada em gestaçäo de 21 semanas através de ultra-sonografia. Além de tetrafocomelia, notamos líquido amniótico em volume normal, rins e bexiga sem anomalias, retromicrognatia acentuada sem fissuras lábio-palatinas ou protuberâncias pré-maxilares. Os achados säo confirmados pelos dados de autópsia. Sugerimos que os genes envolvidos na determinaçäo da Síndrome de Roberts interfiram na segmentaçäo normal dos ossos longos e de outros órgäos como o útero