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BACKGROUND: Magnetic Resonance Imaging is used for evaluation of bone in Gaucher disease (GD), but a widely available quantitative scoring method remains elusive. AIMS: The study purpose was to assess the reproducibility of the LiverLab tool for assessing bone marrow fat fraction (FF) and determine whether it could differentiate GD patients from healthy subjects. METHODS: Ten healthy volunteers and 18 GD patients were prospectively recruited. FF was calculated at L3, L4 and L5. GD patient bone marrow burden (BMB) score assessed by one observer. Inter and intra-rater agreement assessed with Bland-Altman data plots. Differences in FF between healthy volunteers versus GD patients and between subjects treated versus not treated assessed using two-sample t-tests. In GD patients, the relationship between FF, BMB and glucosylsphingosine was determined using the Pearson's correlation coefficient. RESULTS: Healthy volunteer mean FF was 0.36, standard deviation (SD) 0.10 (range 0.20-0.57). Intra and inter-rater SD were both 0.02. GD patient mean FF was 0.40, SD 0.13 (range 0.09-0.57). No statistical difference was shown between healthy volunteers and GD patients (P = 0.447) or between GD patients whether on enzyme replacement therapy or not (P = 0.090). No significant correlation between mean FF and total BMB (r = -0.525, P = 0.253) or between FF and glucosylsphingosine levels (r = 0.287, P = 0.248). CONCLUSION: Excellent reproducibility of LiverLab FF measurements across studies and observers is comparable to Dixon quantitative chemical shift imaging (QCSI). Lack of statistical difference between GD patients and controls may be explained by limited patient numbers, active treatment or mild disease severity in untreated patients.
Assuntos
Medula Óssea , Doença de Gaucher , Humanos , Adulto , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Doença de Gaucher/diagnóstico por imagem , Doença de Gaucher/terapia , Voluntários Saudáveis , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , VoluntáriosRESUMO
ABSTRACT: A 12-year-old boy developed acute headache and vomiting. MRI brain showed a partially cystic suprasellar mass. He underwent cyst fenestration, but the cyst regrew, so he underwent transcranial subtotal resection of the mass. The pathologic diagnosis was adamantinomatous craniopharyngioma. Residual tumor was treated with proton beam radiation therapy, and panhypopituitarism was treated with hormone replacement therapy, including growth hormone. Serial brain MRI scans over several years showed no evidence of tumor recurrence. But at four years after radiation, surveillance MRI showed a new focus of nonenhancing FLAIR hyperintensity in the left basal ganglia attributed to gliosis caused by radiotherapy. Seven months later, he developed progressive right hemiparesis, expressive aphasia, and blurred vision, prompting reevaluation. MRI brain showed new enhancing and T2/FLAIR hyperintense lesions in the midbrain, basal ganglia, thalamus, anterior temporal lobe, and optic tract. The abnormal regions showed low diffusivity and relatively high regional blood flow. Stereotactic biopsy disclosed a WHO Grade 4 astrocytoma, likely radiation-induced. A germline ataxia telangiectasia mutation was found in the tumor tissue. The risk of radiation-induced pediatric brain malignancies is low but may have been increased by the mutation.
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AIM: To evaluate the intraobserver and interobserver agreement for bone marrow burden (BMB) scores for individual examinations and for the change in BMB score over time in the same patient. METHODS: A total of 119 sets of MR images of the lumbar spine and femora from 60 patients with Gaucher disease were included. Each set of MR images was scored using the BMB score independently by two experienced MSK radiologists. One radiologist performed a second read four weeks later. Intraobserver and interobserver agreement was assessed using Bland-Altman analysis and weighted kappa scores. RESULTS: BMB scores (n=119) demonstrated fair intraobserver agreement (weighted kappa=0.53) with a mean difference of -0.20 and 95% limits of agreement (LOA) of (-3.41, 3.01). Inter observer agreement was poor with weighted kappa 0.28 with mean difference of -0.16 and 95% LOA of (-4.45, 4.11). Change in BMB scores over time (n=59) demonstrated poor/fair intraobserver agreement (weighted kappa 0.41, mean difference-0.20 and 95% LOA (-4.35, 3.94)). Interobserver agreement was poor (weighted kappa 0.25, mean difference -0.12 with wide 95% LOA (-6.23, 5.99)). CONCLUSION: Significant interobserver, and to a lesser extent intraobserver, variation occurs with blinded BMB scoring of Gaucher disease.
Assuntos
Medula Óssea/patologia , Fêmur/patologia , Doença de Gaucher/patologia , Vértebras Lombares/patologia , Medula Óssea/diagnóstico por imagem , Feminino , Fêmur/diagnóstico por imagem , Doença de Gaucher/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Variações Dependentes do ObservadorRESUMO
The number of targeted therapies utilized in precision medicine are rapidly increasing. Neuro-oncology offers a unique challenge due to the varying blood brain barrier (BBB) penetration of each agent. Neuro-oncologists face a difficult task weighing the growing number of potential targeted therapies and their likelihood of BBB penetration. We developed the CNS TAP Working Group and performed an extensive literature review for the evidence-based creation of the CNS TAP tool, which was retrospectively validated by analyzing brain tumor patients who underwent therapy targeted based on genomic results from an academic sequencing study (MiOncoseq, n = 17) or private molecular profiling (Foundation One, n = 7). The CNS TAP tool scores relevant targeted agents by applying multiple variables (i.e., pre-clinical data, clinical data, BBB permeability) to patient specific genomic information and clinical trial availability. In the Michigan cohort, the CNS TAP tool predicted the selected agent 85.7% of the time. The CNS TAP tool predicted the agent independently selected by pediatric neuro-oncologists in the Colorado cohort 50% of the time. Patients with recurrent brain tumors treated with agents predicted by the CNS TAP tool demonstrated a median progression-free survival of 4 months and four patients with recurrent high-grade glioma maintained ongoing partial responses of at least 6 months. The CNS TAP tool is a formalized algorithm to assist clinicians select the optimal targeted therapy for neuro-oncology patients. The CNS TAP tool has relatively high concordance with selected therapies and clinical outcomes in patients receiving targeted therapy in this heterogeneous retrospective cohort were promising.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/tratamento farmacológico , Tomada de Decisão Clínica/métodos , Medicina de Precisão/métodos , Adolescente , Adulto , Algoritmos , Barreira Hematoencefálica/metabolismo , Criança , Pré-Escolar , Humanos , Lactente , Oncologia/métodos , Estudos RetrospectivosRESUMO
Bone disease in kidney transplant recipients (KTRs) is characterized by bone mineral density (BMD) loss but bone microarchitecture changes are poorly defined. In this prospective cohort study, we evaluated bone microarchitecture using non-invasive imaging modalities; high-resolution magnetic resonance imaging (MRI), peripheral quantitative computed tomography (pQCT), dual energy X-ray absorptiometry (DXA), and the trabecular bone score (TBS) following kidney transplantation. Eleven KTRs (48.3 ± 11.2 years) underwent MRI (tibia), pQCT (radius) and DXA at baseline and 12 months post-transplantation. Transiliac bone biopsies, performed at transplantation, showed 70% of patients with high/normal bone turnover. Compared with baseline, 12-month MRI showed deterioration in indices of trabecular network integrity-surface to curve ratio (S/C; -15%, P = 0.03) and erosion index (EI; +19%, P = 0.01). However, cortical area increased (+10.3%, P = 0.04), with a non-significant increase in cortical thickness (CtTh; +7.8%, P = 0.06). At 12 months, parathyroid hormone values (median 10.7 pmol/L) correlated with improved S/C (r = 0.75, P = 0.009) and EI (r = -0.71, P = 0.01) while osteocalcin correlated with CtTh (r = 0.72, P = 0.02) and area (r = 0.70, P = 0.02). TBS decreased from baseline (-5.1%, P = 0.01) with no significant changes in BMD or pQCT. These findings highlight a post-transplant deterioration in trabecular bone quality detected by MRI and TBS, independent of changes in BMD, underlining the potential utility of these modalities in evaluating bone microarchitecture in KTRs.
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Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
Pediatric spinal oligodendrogliomas are rare and aggressive tumors. They do not share the same molecular features of adult oligodendroglioma, and no previous reports have examined the molecular features of pediatric spinal oligodendroglioma. We present the case of a child with a recurrent spinal anaplastic oligodendroglioma. We performed whole exome (paired tumor and germline DNA) and transcriptome (tumor RNA) sequencing, which revealed somatic mutations in NF1 and FGFR1. These data allowed us to explore potential personalized therapies for this patient and expose molecular drivers that may be involved in similar cases.
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Deleção de Genes , Proteínas de Neoplasias , Neurofibromina 1 , Oligodendroglioma , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Neoplasias da Coluna Vertebral , Pré-Escolar , Exoma , Feminino , Humanos , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neurofibromina 1/biossíntese , Neurofibromina 1/genética , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/genética , Oligodendroglioma/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/biossíntese , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/metabolismo , TranscriptomaRESUMO
Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant tumor that is commonly associated with biallelic alterations of SMARCB1. Recurrent or refractory AT/RT has not been molecularly characterized as well. We present the case of a child with recurrent AT/RT who underwent clinically integrated molecular profiling (germline DNA and tumor DNA/RNA sequencing). This demonstrated a somatic lesion in CDKN1C alongside hallmark loss of SMARCB1. This data allowed us to explore potential personalized therapies for this patient and expose a molecular driver that may be involved in similar cases.
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Inibidor de Quinase Dependente de Ciclina p57/genética , Mutação , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/genética , Teratoma/diagnóstico , Teratoma/genética , Biópsia , Encéfalo/patologia , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Lactente , Imageamento por Ressonância Magnética , Recidiva , Tumor Rabdoide/terapia , Análise de Sequência de DNA , Teratoma/terapia , Resultado do TratamentoRESUMO
IMPORTANCE: Cancer is caused by a diverse array of somatic and germline genomic aberrations. Advances in genomic sequencing technologies have improved the ability to detect these molecular aberrations with greater sensitivity. However, integrating them into clinical management in an individualized manner has proven challenging. OBJECTIVE: To evaluate the use of integrative clinical sequencing and genetic counseling in the assessment and treatment of children and young adults with cancer. DESIGN, SETTING, AND PARTICIPANTS: Single-site, observational, consecutive case series (May 2012-October 2014) involving 102 children and young adults (mean age, 10.6 years; median age, 11.5 years, range, 0-22 years) with relapsed, refractory, or rare cancer. EXPOSURES: Participants underwent integrative clinical exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing and genetic counseling. Results were discussed by a precision medicine tumor board, which made recommendations to families and their physicians. MAIN OUTCOMES AND MEASURES: Proportion of patients with potentially actionable findings, results of clinical actions based on integrative clinical sequencing, and estimated proportion of patients or their families at risk of future cancer. RESULTS: Of the 104 screened patients, 102 enrolled with 91 (89%) having adequate tumor tissue to complete sequencing. Only the 91 patients were included in all calculations, including 28 (31%) with hematological malignancies and 63 (69%) with solid tumors. Forty-two patients (46%) had actionable findings that changed their cancer management: 15 of 28 (54%) with hematological malignancies and 27 of 63 (43%) with solid tumors. Individualized actions were taken in 23 of the 91 (25%) based on actionable integrative clinical sequencing findings, including change in treatment for 14 patients (15%) and genetic counseling for future risk for 9 patients (10%). Nine of 91 (10%) of the personalized clinical interventions resulted in ongoing partial clinical remission of 8 to 16 months or helped sustain complete clinical remission of 6 to 21 months. All 9 patients and families with actionable incidental genetic findings agreed to genetic counseling and screening. CONCLUSIONS AND RELEVANCE: In this single-center case series involving young patients with relapsed or refractory cancer, incorporation of integrative clinical sequencing data into clinical management was feasible, revealed potentially actionable findings in 46% of patients, and was associated with change in treatment and family genetic counseling for a small proportion of patients. The lack of a control group limited assessing whether better clinical outcomes resulted from this approach than outcomes that would have occurred with standard care.
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Aconselhamento Genético , Neoplasias/genética , Análise de Sequência de DNA/métodos , Adolescente , Criança , Pré-Escolar , Aberrações Cromossômicas , Família , Estudos de Viabilidade , Fusão Gênica , Neoplasias Hematológicas/genética , Humanos , Achados Incidentais , Lactente , Recém-Nascido , Terapia de Alvo Molecular/métodos , Recidiva Local de Neoplasia/genética , Neoplasias/terapia , Avaliação de Resultados em Cuidados de Saúde , Indução de Remissão , Adulto JovemRESUMO
In order to improve outcomes for CNS mixed malignant germ cell tumors (MMGCT) we sought to increase complete responses (CR) to initial therapy, through intensifying neoadjuvant chemotherapy (CHT1) with added ifosfamide, encouraging second-look surgery, and administering dose-intensive, stem cell-supported chemotherapy (CHT2) to patients with residual tumor, all prior to radiation therapy (RT). Diagnosis was confirmed by biopsy or elevated germ cell tumor markers. After tumor staging was completed, patients received four cycles of chemotherapy (cisplatin, etoposide and ifosfamide, "CHT1"). In patients with Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
, Neoplasias do Sistema Nervoso Central/terapia
, Neoplasias Embrionárias de Células Germinativas/terapia
, Adolescente
, Adulto
, Criança
, Pré-Escolar
, Terapia Combinada
, Intervalo Livre de Doença
, Feminino
, Humanos
, Lactente
, Masculino
, Adulto Jovem
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BACKGROUND: Secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) has a significant effect on bone, affecting both trabecular and cortical compartments. Although parathyroidectomy results in biochemical improvement in mineral metabolism, changes in bone microarchitecture as evaluated by high-resolution imaging modalities are not known. Magnetic resonance imaging (MRI) provides in-depth three-dimensional assessment of bone microarchitecture, as well as determination of mechanical bone strength determined by finite element analysis (FEA). METHODS: We conducted a single-centre longitudinal study to evaluate changes in bone microarchitecture with MRI in patients with SHPT undergoing parathyroidectomy. MRI was performed at the distal tibia at baseline (time of parathyroidectomy) and at least 12 months following surgery. Trabecular and cortical topological parameters as well as bone mechanical competence using FEA were assessed. RESULTS: Fifteen patients with CKD (12 male, 3 female) underwent both MRI scans at the time of surgery and at least 12 months post-surgery. At baseline, 13 patients were on dialysis, one had a functioning kidney transplant, and one was pre-dialysis with stage 5 CKD. Seven patients received a kidney transplant following parathyroidectomy prior to follow-up MRI. MRI parameters in patients at follow up were consistent with loss in trabecular and cortical bone thickness (p = 0.006 and 0.03 respectively). Patients who underwent a kidney transplant in the follow-up period had reduction in trabecular thickness (p = 0.05), whereas those who continued on dialysis had reduction in cortical thickness (p = 0.04) and mechanical bone strength on FEA (p = 0.03). CONCLUSION: Patients with severe SHPT requiring parathyroidectomy have persistent changes in bone microarchitecture at least 12 months following surgery with evidence of ongoing decline in trabecular and cortical thickness.
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BACKGROUND: Secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) leads to complex bone disease, affecting both trabecular and cortical bone, and increased fracture risk. Optimal assessment of bone in patients with CKD is yet to be determined. High-resolution magnetic resonance imaging (MRI) can provide three-dimensional assessment of bone microarchitecture, as well as determination of mechanical strength with finite element analysis (FEA). METHODS: We conducted a single-centre, cross-sectional study to determine bone microarchitecture with MRI in CKD patients with SHPT undergoing parathyroidectomy. Within two weeks of surgery, MRI was performed at the distal tibia and biochemical markers of SHPT (parathyroid hormone [PTH] and alkaline phosphatase [ALP]) were collected. Trabecular and cortical topological parameters as well as bone mechanical competence using FEA were assessed. Correlation of MRI findings of bone was made with biochemical markers. RESULTS: Twenty patients with CKD (15 male, 5 female) underwent MRI at the time of parathyroidectomy (16 on dialysis, 3 with functioning kidney transplant, one pre-dialysis with CKD stage 5). Median PTH at the time of surgery was 138.5â¯pmol/L [39.6-186.7â¯pmol/L]. MRI parameters in patients were consistent with trabecular deterioration, with erosion index (EI) 1.01⯱â¯0.3, and trabecular bone volume (BV/TV) 10.8⯱â¯2.9%, as well as poor trabecular network integrity with surface-to-curve ratio (S/C) 5.4⯱â¯2.3. There was also evidence of reduced cortical thickness, with CTh 2.698⯱â¯0.630â¯mm, and FEA demonstrated overall poor bone mechanical strength with mean elastic modulus of 2.07⯱â¯0.44. CONCLUSION: Patients with severe SHPT requiring parathyroidectomy have evidence of significant changes in bone microarchitecture with trabecular deterioration, low trabecular and cortical bone volume, and reduced mechanical competence of bone.
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PURPOSE: Pediatric high-grade glioma (pHGG) diagnosis portends poor prognosis and therapeutic monitoring remains difficult. Tumors release cell-free tumor DNA (cf-tDNA) into cerebrospinal fluid (CSF), allowing for potential detection of tumor-associated mutations by CSF sampling. We hypothesized that direct, electronic analysis of cf-tDNA with a handheld platform (Oxford Nanopore MinION) could quantify patient-specific CSF cf-tDNA variant allele fraction (VAF) with improved speed and limit of detection compared with established methods. EXPERIMENTAL DESIGN: We performed ultra-short fragment (100-200 bp) PCR amplification of cf-tDNA for clinically actionable alterations in CSF and tumor samples from patients with pHGG (n = 12) alongside nontumor CSF (n = 6). PCR products underwent rapid amplicon-based sequencing by Oxford Nanopore Technology (Nanopore) with quantification of VAF. Additional comparison to next-generation sequencing (NGS) and droplet digital PCR (ddPCR) was performed. RESULTS: Nanopore demonstrated 85% sensitivity and 100% specificity in CSF samples (n = 127 replicates) with 0.1 femtomole DNA limit of detection and 12-hour results, all of which compared favorably with NGS. Multiplexed analysis provided concurrent analysis of H3.3A (H3F3A) and H3C2 (HIST1H3B) mutations in a nonbiopsied patient and results were confirmed by ddPCR. Serial CSF cf-tDNA sequencing by Nanopore demonstrated correlation of radiological response on a clinical trial, with one patient showing dramatic multi-gene molecular response that predicted long-term clinical response. CONCLUSIONS: Nanopore sequencing of ultra-short pHGG CSF cf-tDNA fragments is feasible, efficient, and sensitive with low-input samples thus overcoming many of the barriers restricting wider use of CSF cf-tDNA diagnosis and monitoring in this patient population.
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Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , DNA Tumoral Circulante/genética , Eletrônica , Glioma/patologia , Mutação , Adolescente , Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Estudos de Casos e Controles , Criança , Pré-Escolar , DNA Tumoral Circulante/líquido cefalorraquidiano , Feminino , Seguimentos , Glioma/líquido cefalorraquidiano , Glioma/genética , Glioma/cirurgia , Humanos , Masculino , Reação em Cadeia da Polimerase , PrognósticoRESUMO
Pediatric and adult high-grade gliomas (HGGs) frequently harbor PDGFRA alterations. We hypothesized that cotreatment with everolimus may improve the efficacy of dasatinib in PDGFRα-driven glioma through combinatorial synergism and increased tumor accumulation of dasatinib. We performed dose-response, synergism, P-glycoprotein inhibition, and pharmacokinetic studies in in vitro and in vivo human and mouse models of HGG. Six patients with recurrent PDGFRα-driven glioma were treated with dasatinib and everolimus. We found that dasatinib effectively inhibited the proliferation of mouse and human primary HGG cells with a variety of PDGFRA alterations. Dasatinib exhibited synergy with everolimus in the treatment of HGG cells at low nanomolar concentrations of both agents, with a reduction in mTOR signaling that persisted after dasatinib treatment alone. Prolonged exposure to everolimus significantly improved the CNS retention of dasatinib and extended the survival of PPK tumor-bearing mice (mutant TP53, mutant PDGFRA, H3K27M). Six pediatric patients with glioma tolerated this combination without significant adverse events, and 4 patients with recurrent disease (n = 4) had a median overall survival of 8.5 months. Our results show that the efficacy of dasatinib treatment of PDGFRα-driven HGG was enhanced with everolimus and suggest a promising route for improving targeted therapy for this patient population.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Dasatinibe/administração & dosagem , Everolimo/administração & dosagem , Glioma/tratamento farmacológico , Glioma/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adolescente , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias Encefálicas/metabolismo , Proliferação de Células/efeitos dos fármacos , Criança , Pré-Escolar , Dasatinibe/farmacocinética , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Everolimo/farmacocinética , Feminino , Expressão Gênica , Glioma/metabolismo , Humanos , Masculino , Camundongos , Terapia de Alvo Molecular , Gravidez , Células Tumorais CultivadasRESUMO
INTRODUCTION: Common peroneal nerve (CPN) injury occurs in 10-40% of patients following knee dislocation. Is magnetic resonance imaging (MRI) using routine knee protocols able to adequately evaluate CPN injury and predict long-term outcome? METHODS: Trauma patients presenting for knee MRI at a single public hospital, between July 2007 and May 2017, were retrospectively identified using radiology and orthopaedic databases. Medical records were retrieved for clinical scores. MRI images were scored by two independent radiologists blinded to the clinical CPN status and scores correlated with initial clinical scores using the Pearson correlation coefficient. RESULTS: Final cohort included 107 patients (81 males and 26 females) with a mean age of 39 (range 19-81 years). MRI was considered to be adequate for coverage of the CPN in 84 patients. Fourteen patients had CPN injury clinically (seven complete and seven partial). Concordance between MRI scores and initial clinical scores was 0.456 (P = 0.01). MRI sensitivity and specificity for CPN injury on the 84 adequate scans were 54.5% and 93.2% respectively. All seven cases of partial CPN injury and three of seven cases of complete CPN injury recovered fully. High MRI scores of 5 and 8 were given for the two patients with a persisting complete CPN palsy. Highest scores for partial CPN injury subjects were 2 and 4. CONCLUSIONS: Magnetic resonance imaging using a routine knee protocol is not adequate for the assessment of CPN injury in many subjects. More specific MRI neural sequences with complete CPN coverage may be worth trialing.
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Luxação do Joelho/complicações , Luxação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Nervo Fibular/lesões , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Russell diencephalic syndrome is a condition in which infants become emaciated in the setting of a decreased or normal caloric intake as the result of a hypothalamic astrocytoma. The diagnosis may be delayed if providers initially attribute the symptoms to a behavioral disorder. The detection of nystagmus, which is present in many patients, may be a critical diagnostic clue. The authors describe two patients in whom the discovery of nystagmus months after the onset of emaciation led to the diagnosis of Russell diencephalic syndrome. [J Pediatr Ophthalmol Strabismus. 2019;56:e79-e83.].
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Astrocitoma/complicações , Neoplasias Encefálicas/complicações , Nistagmo Patológico/etiologia , Astrocitoma/diagnóstico , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Masculino , Nistagmo Patológico/diagnóstico , SíndromeRESUMO
[This corrects the article DOI: 10.1038/s41698-017-0036-8.].
RESUMO
BACKGROUND: Chronic kidney disease (CKD) adversely affects bone microarchitecture and increases fracture risk. Historically, bone biopsy has been the 'gold standard' for evaluating renal bone disease but is invasive and infrequently performed. High-resolution magnetic resonance imaging (MRI) quantifies bone microarchitecture noninvasively. In patients with CKD, it has not been compared with results derived from bone biopsy or with imaging using dual energy X-ray absorptiometry (DXA). METHODS: Fourteen patients with end-stage kidney disease (ESKD) underwent MRI at the distal tibia, bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA; hip and spine) and transiliac bone biopsies with histomorphometry and microcomputed tomography (micro-CT). All patients had biomarkers of mineral metabolism. Associations were determined by Spearman's or Pearson's rank correlation coefficients. RESULTS: MRI indices of trabecular network integrity, surface to curve ratio (S/C) and erosion index (EI), correlated to histomorphometric trabecular bone volume (S/C râ¯=â¯0.85, pâ¯=â¯0.0003; EI râ¯=â¯-0.82, pâ¯=â¯0.001), separation (S/C râ¯=â¯-0.58, pâ¯=â¯0.039; EI râ¯=â¯0.79, pâ¯=â¯0.0012) and thickness (S/C, râ¯=â¯0.65, pâ¯=â¯0.017). MRI EI and trabecular thickness (TbTh) also correlated to micro-CT trabecular separation (EI râ¯=â¯0.63, pâ¯=â¯0.02; TbTh râ¯=â¯-0.60, pâ¯=â¯0.02). Significant correlations were observed between histomorphometric mineralization and turnover indices and various MRI parameters. MRI-derived trabecular parameters were also significantly related to femoral neck BMD. CONCLUSIONS: This study highlights the heterogeneity of bone microarchitecture at differing skeletal sites. MRI demonstrates significant, relevant associations to important bone biopsy and DXA indices and warrants further investigation to assess its potential to non-invasively evaluate changes in bone structure and quality over time.
Assuntos
Imageamento por Ressonância Magnética/métodos , Insuficiência Renal Crônica/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Microtomografia por Raio-X/métodos , Adulto , Densidade Óssea/fisiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/tendências , Insuficiência Renal Crônica/terapiaRESUMO
OBJECTIVE: The purpose of this study was to evaluate the use of a recently described assessment tool to quantify bone marrow response to enzyme replacement therapy in a cohort of adult patients with type 1 Gaucher's disease. MATERIALS AND METHODS: Serial MR images of the femurs, lumbar spine, or both of 57 subjects with a diagnosis of Gaucher's disease, 44 of whom were being treated with enzyme replacement therapy, were evaluated by two musculoskeletal radiologists using the bone marrow burden (BMB) scoring system. This system gives a score out of a possible 8 for the lumbar spine and a score out of a possible 8 for the femurs, so the total BMB score is out of 16. RESULTS: The mean total BMB scores at baseline and final measurement were 13 (95% CI, 12.0-13.8) and 6.5 (95% CI, 5.2-7.9), respectively. Total BMB scores improved by 2-12 points (mean, 6.3 points) for 15 subjects in whom total BMB scores obtained before enzyme replacement therapy and at least one time point after commencement of therapy were available. In 39 subjects for whom only baseline and final femoral BMB scores were available, 24 subjects (62%, 95% CI, 47-76%) improved by 2 or more points while on enzyme replacement therapy. In 24 subjects for whom only baseline and final lumbar BMB scores were available, the BMB score in 16 subjects (67%, 95% CI, 48-85%) improved by 2 or more points. CONCLUSION: The use of the BMB score enabled semiquantitative assessment of bone marrow response to enzyme replacement therapy in adult patients with type 1 Gaucher's disease in Australia. The ability to assess therapy response will facilitate the tailoring of dosage regimens in the future.
Assuntos
Medula Óssea/patologia , Fêmur/patologia , Doença de Gaucher/diagnóstico , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Avaliação de Resultados em Cuidados de Saúde/métodos , Adulto , Idoso , Estudos de Coortes , Feminino , Doença de Gaucher/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Approximately 1-5% of pediatric intracranial tumors originate in the thalamus. While great strides have been made to identify consistent molecular markers in adult oligodendrogliomas, such as the 1p/19q co-deletion, it is widely recognized that pediatric oligodendrogliomas have a vastly different molecular make-up. While pediatric thalamic or "central oligodendrogliomas" are histologically similar to peripheral pediatric oligodendrogliomas, they are behaviorally distinct and likely represent a cohesive, but entirely different entity. We describe a case of a 10-year-old girl who was diagnosed with an anaplastic glioma with features consistent with the aggressive entity often diagnosed as central or thalamic oligodendroglioma. We performed whole-exome (paired tumor and germline DNA) and transcriptome (tumor RNA) sequencing, which demonstrated an FGFR3-PHGDH fusion. We describe this fusion and our rationale for pursuing personalized, targeted therapy for the patient's tumor that may potentially play a role in the treatment of similar cases.
RESUMO
Safe maximal surgical resection is the initial treatment of choice for pediatric brainstem low-grade gliomas. Optimal therapy for incompletely resected tumors or that progress after surgery is uncertain. We reviewed the clinical characteristics, therapy, and outcomes of all children with nontectal brainstem low-grade gliomas treated at the University of Michigan between 1993 and 2013. Median age at diagnosis was 6 years; histology was confirmed in 23 of 25 tumors, 64% were pilocytic astrocytoma. Nineteen patients underwent initial tumor resection; 14/19 received no upfront adjuvant therapy. Eight patients in the study had progressive disease; 5 initially resected tumors received chemotherapy at tumor relapse, all with partial or complete radiographic responses. Ten-year progression-free survival is 71% and overall survival, 100%. This single-institution retrospective study demonstrates excellent survival rates for children with brainstem low-grade gliomas. The efficacy of the well-tolerated chemotherapy in this series supports its role in the treatment of unresectable or progressive brainstem low-grade gliomas.