RESUMO
MOTIVATION: Online assessment of tumor characteristics during surgery is important and has the potential to establish an intra-operative surgeon feedback mechanism. With the availability of such feedback, surgeons could decide to be more liberal or conservative regarding the resection of the tumor. While there are methods to perform metabolomics-based tumor pathology prediction, their model complexity predictive performance is limited by the small dataset sizes. Furthermore, the information conveyed by the feedback provided on the tumor tissue could be improved both in terms of content and accuracy. RESULTS: In this study, we propose a metabolic pathway-informed deep learning model (PiDeeL) to perform survival analysis and pathology assessment based on metabolite concentrations. We show that incorporating pathway information into the model architecture substantially reduces parameter complexity and achieves better survival analysis and pathological classification performance. With these design decisions, we show that PiDeeL improves tumor pathology prediction performance of the state-of-the-art in terms of the Area Under the ROC Curve by 3.38% and the Area Under the Precision-Recall Curve by 4.06%. Similarly, with respect to the time-dependent concordance index (c-index), PiDeeL achieves better survival analysis performance (improvement of 4.3%) when compared to the state-of-the-art. Moreover, we show that importance analyses performed on input metabolite features as well as pathway-specific neurons of PiDeeL provide insights into tumor metabolism. We foresee that the use of this model in the surgery room will help surgeons adjust the surgery plan on the fly and will result in better prognosis estimates tailored to surgical procedures. AVAILABILITY AND IMPLEMENTATION: The code is released at https://github.com/ciceklab/PiDeeL. The data used in this study are released at https://zenodo.org/record/7228791.
Assuntos
Aprendizado Profundo , Glioma , Humanos , Redes e Vias Metabólicas , Análise de Sobrevida , Área Sob a CurvaRESUMO
MOTIVATION: Identification and removal of micro-scale residual tumor tissue during brain tumor surgery are key for survival in glioma patients. For this goal, High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) spectroscopy-based assessment of tumor margins during surgery has been an effective method. However, the time required for metabolite quantification and the need for human experts such as a pathologist to be present during surgery are major bottlenecks of this technique. While machine learning techniques that analyze the NMR spectrum in an untargeted manner (i.e. using the full raw signal) have been shown to effectively automate this feedback mechanism, high dimensional and noisy structure of the NMR signal limits the attained performance. RESULTS: In this study, we show that identifying informative regions in the HRMAS NMR spectrum and using them for tumor margin assessment improves the prediction power. We use the spectra normalized with the ERETIC (electronic reference to access in vivo concentrations) method which uses an external reference signal to calibrate the HRMAS NMR spectrum. We train models to predict quantities of metabolites from annotated regions of this spectrum. Using these predictions for tumor margin assessment provides performance improvements up to 4.6% the Area Under the ROC Curve (AUC-ROC) and 2.8% the Area Under the Precision-Recall Curve (AUC-PR). We validate the importance of various tumor biomarkers and identify a novel region between 7.97 ppm and 8.09 ppm as a new candidate for a glioma biomarker. AVAILABILITY AND IMPLEMENTATION: The code is released at https://github.com/ciceklab/targeted_brain_tumor_margin_assessment. The data underlying this article are available in Zenodo, at https://doi.org/10.5281/zenodo.5781769. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Metabolômica/métodos , Espectroscopia de Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/cirurgia , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Heterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B-MIM:620174). Whether they represent a common cause of sporadic late-onset cerebellar ataxia (SLOCA) remains to be established. OBJECTIVES: To estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients. METHODS: FGF14 expansions screening combined with longitudinal deep-phenotyping in a prospective cohort of 118 SLOCA patients (onset >40 years of age, no family history of cerebellar ataxia) without a definite diagnosis. RESULTS: Prevalence of SCA27B was 12.7% (15/118). Higher age of onset, higher Spinocerebellar Degeneration Functional Score, presence of vertigo, diplopia, nystagmus, orthostatic hypotension absence, and sensorimotor neuropathy were significantly associated with SCA27B. Ataxia progression was ≈0.4 points per year on the Scale for Assessment and Rating of Ataxia. CONCLUSIONS: FGF14 expansion is a major cause of SLOCA. Our natural history data will inform future FGF14 clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Assuntos
Ataxia Cerebelar , Ataxias Espinocerebelares , Degenerações Espinocerebelares , Humanos , Ataxia/complicações , Ataxia Cerebelar/epidemiologia , Ataxia Cerebelar/genética , Ataxia Cerebelar/complicações , Estudos Prospectivos , Ataxias Espinocerebelares/genética , Degenerações Espinocerebelares/epidemiologia , Degenerações Espinocerebelares/genética , Degenerações Espinocerebelares/complicaçõesRESUMO
The use of 13C-labeled molecular probes is essential to explore altered metabolic pathways in human pathologies. The analysis of the different 13C isotopologues resulting from these changes in metabolic pathways is essential to understand the different biological processes involved. We propose an NMR methodology consisting of eight different NMR experiments performed under HRMAS conditions to explore metabolic pathways in unprocessed pathological cells and tissues. This methodology has the potential to study human pathologies in the medical field and to enable the analysis of the mode of action of therapeutic treatments.
Assuntos
Imageamento por Ressonância Magnética , Sondas Moleculares , Humanos , Espectroscopia de Ressonância Magnética/métodos , Redes e Vias MetabólicasRESUMO
BACKGROUND AND PURPOSE: Stroke-related restless legs syndrome (sRLS) secondary to ischemic lesions is an emerging entity and an interesting condition, but there are limited available data to help us further understand its underlying pathways. In this study, we characterized sRLS clinically, neuroanatomically and functionally. METHODS: Consecutive patients hospitalized in the Stroke Unit of the University Hospital of Strasbourg were assessed clinically and electrophysiologically for sRLS characteristics. They underwent brain magnetic resonance imaging for the neuroanatomical study of involved structures, and received functional evaluations with 18 F-FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose) positron emission tomography (PET) for glucose consumption, 123 I-FP-CIT ([123]I-2beta-carbometoxy-3beta-[4-iodophenyl]-N-[3-fluoropropyl]nortropane) single-photon emission computed tomography for dopamine reuptake and PET with 18 F-FDOPA ((3,4-dihydroxy-6-[18]F-fluoro-l-phenylalanine) for presynaptic dopaminergic synthesis. RESULTS: Sixteen patients with sRLS, eight women and eight men, aged 41-81 years, were included. The clinical characteristics of sRLS and idiopathic RLS were similar. Most patients presented with bilateral and symmetric de novo RLS. Eight patients had infarction in the lenticulostriate area (middle cerebral artery and internal carotid arteria). The body of the caudate nucleus was most commonly affected. Seven patients had sRLS secondary to ventral brainstem infarction (perforating branches of the basilar arteria) affecting the pons in six patients and the medulla oblongata in one patient. Both the corticospinal tract and the cortico-pontocerebellar fibres were lesioned in all patients with brainstem stroke. One patient had infarction in the left posterior cerebellar vermis and occipital area (posterior cerebral artery and superior cerebellar artery). Isotopic explorations showed a significantly increased dopaminergic tone in the striatum ipsilateral to lenticulostriate infarction. Dopamine fixation was normal in patients with stroke outside of the lenticulostriate area. CONCLUSIONS: Clinicians should be aware of the characteristics of sRLS for the appropriate diagnosis and treatment of this condition.
Assuntos
Síndrome das Pernas Inquietas , Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Complete resection of the tumor is important for survival in glioma patients. Even if the gross total resection was achieved, left-over micro-scale tissue in the excision cavity risks recurrence. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) technique can distinguish healthy and malign tissue efficiently using peak intensities of biomarker metabolites. The method is fast, sensitive and can work with small and unprocessed samples, which makes it a good fit for real-time analysis during surgery. However, only a targeted analysis for the existence of known tumor biomarkers can be made and this requires a technician with chemistry background, and a pathologist with knowledge on tumor metabolism to be present during surgery. Here, we show that we can accurately perform this analysis in real-time and can analyze the full spectrum in an untargeted fashion using machine learning. We work on a new and large HRMAS NMR dataset of glioma and control samples (n = 565), which are also labeled with a quantitative pathology analysis. Our results show that a random forest based approach can distinguish samples with tumor cells and controls accurately and effectively with a median AUC of 85.6% and AUPR of 93.4%. We also show that we can further distinguish benign and malignant samples with a median AUC of 87.1% and AUPR of 96.1%. We analyze the feature (peak) importance for classification to interpret the results of the classifier. We validate that known malignancy biomarkers such as creatine and 2-hydroxyglutarate play an important role in distinguishing tumor and normal cells and suggest new biomarker regions. The code is released at http://github.com/ciceklab/HRMAS_NC.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Aprendizado de Máquina , Espectroscopia de Ressonância Magnética/métodos , Margens de Excisão , Algoritmos , Biópsia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Estudos de Coortes , Glioma/patologia , Glioma/cirurgia , Humanos , Período IntraoperatórioRESUMO
Background. Pneumoperitoneum insufflation with warmed and humidified carbon dioxide (WH-CO2) can prevent heat loss and increase tissue oxygenation. We evaluated the impact of localized WH-CO2 insufflation on the anastomotic healing process. Methods. Sixty male Wistar rats were randomized: Group 1 (control, n = 12), Group 2 (cold and dry CO2, CD-CO2, n = 24), and Group 3 (WH-CO2, n = 24). A magnetic compression side-to-side colonic anastomosis was performed under 60-minute local abdominal CO2 flow insufflation. Animal temperature was recorded. IL-1, IL-6, and CRP levels were assessed before and after insufflation and on postoperative day (POD) 7 and POD 10. Endoscopic follow-up was performed on POD 7 and POD 10. A burst pressure (BP) test of the specimen was performed on POD 10, and histopathological analysis was then performed. Metabolomics of the anastomotic site was determined. Results. Seven rats (5 CD-CO2 group, 1 WH-CO2 group, and 1 control group) died during the survival period. Necropsies revealed intestinal occlusions (n = 2). One additional rat from the CD-CO2 group was sacrificed on POD 7 due to intestinal perforation. The postoperative course was uneventful in the remaining cases. There was no difference in BP among the groups. Thermal monitoring confirmed that WH-CO2 insufflation was effective to reduce heat loss. IL-1 levels were statistically and significantly lower on POD 10 in the WH-CO2 group than the CD-CO2 group but not lower than the control group. CRP levels, histopathology, and metabolomics did not show any difference between the 3 groups. Conclusions. WH-CO2 was effective to preserve core temperature. However, it did not improve anastomotic healing.
Assuntos
Insuflação , Anastomose Cirúrgica , Animais , Dióxido de Carbono , Fenômenos Magnéticos , Masculino , Modelos Teóricos , Ratos , Ratos WistarRESUMO
Meningiomas are in most cases benign brain tumors. The WHO 2016 classification defines three grades of meningiomas. This classification had a prognosis value because grade III meningiomas have a worse prognosis value compared to grades I and II meningiomas. However, some benign or atypical meningiomas can have a clinical aggressive behavior. There are currently no reliable markers which allow distinguishing between the meningiomas with a good prognosis and those which may recur. High-resolution magic angle spinning (HRMAS) spectrometry is a noninvasive method able to determine the metabolite profile of a tissue sample. We retrospectively analyzed 62 meningioma samples by using HRMAS spectrometry (43 metabolites). We described a metabolic profile defined by a high concentration for acetate, threonine, N-acetyl-lysine, hydroxybutyrate, myoinositol, ascorbate, scylloinositol, and total choline and a low concentration for aspartate, glucose, isoleucine, valine, adenosine, arginine, and alanine. This metabolomic signature was associated with poor prognosis histological markers [Ki-67 ≥ 40%, high histological grade and negative progesterone receptor (PR) expression]. We also described a similar metabolomic spectrum between grade III and grade I meningiomas. Moreover, all grade I meningiomas with a low Ki-67 expression and a positive PR expression did not have the same metabolomic profile. Metabolomic analysis could be used to determine an aggressive meningioma in order to discuss a personalized treatment. Further studies are needed to confirm these results and to correlate this metabolic profile with survival data.
Assuntos
Neoplasias Encefálicas/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Meningioma/metabolismo , Aminoácidos/análise , Aminoácidos/metabolismo , Biópsia , Neoplasias Encefálicas/cirurgia , Proliferação de Células , Humanos , Antígeno Ki-67/metabolismo , Meningioma/patologia , Meningioma/cirurgia , Metabolômica/métodosRESUMO
BACKGROUND: In neurodegenerative diseases, alongside genetic factors, the possible intervention of environmental factors in the pathogenesis is increasingly being considered. In particular, recent evidence suggests the intervention of a pesticide-like xenobiotic in the initiation of disease with Lewy bodies (DLB). OBJECTIVES: To test for the presence of pesticides or other xenobiotics in the cerebrospinal fluid (CSF) of patients with DLB. METHODS: A total of 45 patients were included in this study: 16 patients with DLB at the prodromal stage, 8 patients with DLB at the demented stage, 8 patients with Alzheimer's disease (AD) at the prodromal stage and 13 patients with AD at the demented stage. CSF was obtained by lumbar puncture and analysed by liquid chromatography-mass spectrometry. RESULTS: Among the compounds detected in greater abundance in the CSF of patients with DLB compared with patients with AD, only one had a xenobiotic profile potentially related to the pathophysiology of DLB. After normalisation and scaling, bis(2-ethylhexyl) phthalate was more abundant in the CSF of patients with DLB (whole cohort: 2.7-fold abundant in DLB, p=0.031; patients with dementia: 3.8-fold abundant in DLB, p=0.001). CONCLUSIONS: This study is the first reported presence of a phthalate in the CSF of patients with DLB. This molecule, which is widely distributed in the environment and enters the body orally, nasally and transdermally, was first introduced in the 1920s as a plasticizer. Thereafter, the first cases of DLB were described in the 1960s and 1970s. These observations suggest that phthalates may be involved in the pathophysiology of DLB.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Dietilexilftalato/efeitos adversos , Dietilexilftalato/líquido cefalorraquidiano , Exposição Ambiental , Doença por Corpos de Lewy/líquido cefalorraquidiano , Metabolômica , Idoso , Doença de Alzheimer/diagnóstico , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico , Masculino , Pessoa de Meia-Idade , Sintomas Prodrômicos , Xenobióticos/efeitos adversosRESUMO
PURPOSE: The aim of this study is to generate a metabolic database for biomedical studies of biopsy specimens by high-resolution magic angle spinning (HRMAS) nuclear MR (NMR). METHODS: Seventy-six metabolites, classically found in human biopsy samples, were prepared in aqueous solution at a known concentration and analyzed by HRMAS NMR. The spectra were recorded under the same conditions as the ones used for the analysis of biopsy specimens routinely performed in our hospital. RESULTS: For each metabolite, a complete set of NMR spectra (1D 1 H, 1D 1 H-CPMG, 2D J-Resolved, 2D TOCSY, and 2D 1 H-13 C HSQC) was recorded at 500 MHz and 277 K. All spectra were manually assigned using the information contained in the different spectra and existing databases. Experiments to measure the T1 and the T2 of the different protons present in the 76 metabolites were also recorded. CONCLUSION: This new HRMAS metabolic database is a useful tool for all scientists working on human biopsy specimens, particularly in the field of oncology. It will make the identification of metabolites in biopsy specimens faster and more reliable. Additionally, the knowledge of the T1 and T2 values will allow to obtain a more accurate quantification of the metabolites present in biopsy specimens.
Assuntos
Biópsia , Bases de Dados Factuais , Imageamento por Ressonância Magnética , Metabolômica , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Sistemas de Gerenciamento de Base de Dados , Humanos , Metaboloma/fisiologiaRESUMO
OBJECTIVE: To devise a simple PET-CT score for measurement of muscle disease activity in patients with inflammatory myopathies (IMs) and to assess its validity. METHODS: A total of 44 PET-CT examinations in 34 IM patients (performed during cancer screening) and 20 PET-CT examinations in matched controls (investigated for pulmonary nodules with a conclusion of benignity) were analysed. Maximal standardized uptake values (SUVmax) were recorded bilaterally in eight proximal muscles. The muscle SUVmax (mSUVmax) was defined as the average of the 16 muscle SUVmax values, normalized on the liver mean SUV. Reliability, validity and responsiveness were evaluated. RESULTS: The mSUVmax was increased in IM patients compared with controls. This index allowed the identification of patients with high vs low muscle disease activity using the myositis intention to treat activity index as the gold standard. In patients with subsequent examinations, our method showed good accuracy to detect changes in muscle disease activity [area under the curve 0.96 (95% CI 0.84, 1)]. Responsiveness was strong. Interrater reliability was excellent. CONCLUSION: PET-CT, a non-invasive tool useful for cancer screening, is also valuable to measure muscle disease activity and its evolution in IM patients.
RESUMO
INTRODUCTION: The identification of frequent acquired mutations shows that patients with oligodendrogliomas have divergent biology with differing prognoses regardless of histological classification. A better understanding of molecular features as well as their metabolic pathways is essential. OBJECTIVES: The aim of this study was to examine the relationship between the tumor metabolome, six genomic aberrations (isocitrate dehydrogenase1 [IDH1] mutation, 1p/19q codeletion, tumor protein p53 [TP53] mutation, O6-methylguanin-DNA methyltransferase [MGMT] promoter methylation, epidermal growth factor receptor [EGFR] amplification, phosphate and tensin homolog [PTEN] methylation), and the patients' survival time. METHODS: We applied 1H high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy to 72 resected oligodendrogliomas. RESULTS: The presence of IDH1, TP53, 1p19q codeletion, MGMT promoter methylation reduced the relative risk of death, whereas PTEN methylation and EGFR amplification were associated with poor prognosis. Increased concentration of 2-hydroxyglutarate (2HG), N-acetyl-aspartate (NAA), myo-inositol and the glycerophosphocholine/phosphocholine (GPC/PC) ratio were good prognostic factors. Increasing the concentration of serine, glycine, glutamate and alanine led to an increased relative risk of death. CONCLUSION: HRMAS NMR spectroscopy provides accurate information on the metabolomics of oligodendrogliomas, making it possible to find new biomarkers indicative of survival. It enables rapid characterization of intact tissue and could be used as an intraoperative method.
Assuntos
Metabolômica , Oligodendroglioma/genética , Oligodendroglioma/metabolismo , Adulto , Humanos , Espectroscopia de Ressonância Magnética , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: Posthepatectomy liver failure (PHLF) is the main limitation to extending liver resection but its pathophysiology is not yet fully understood. The aim of the study was to describe the metabolic adaptations that occur with PHLF. METHODS: A retrospective study of 82 patients using nuclear magnetic resonance metabolomics to identify and quantify intra-hepatic metabolites was performed. The metabolite levels were compared using metabolic network analysis ADEMA between fatal PHLF (FLF) and non fatal PHLF and according to PHLF/ACLF grading. RESULTS: Metabolomic profiles were significantly different between patients presenting FLF and non FLF or grade 3 ACLF versus < grade 3 ACLF. In the patients undergoing hepatectomy, valine, alanine and glycerophosphocholine were identified as powerful biomarkers to predict FLF (AUROC 0.806, 0.802 and 0.856 respectively). Network analysis showed an activation of aerobic glycolysis with glutaminolysis as observed in highly proliferating systems. Inversely, ACLF3 showed deprivation of glucose and lactate compared to lower ACLF grade. CONCLUSION: Clinical andbiological severity of ACLF and PHLF correlate with specific metabolic adaptations. Metabolomics can predict fatal liver failure after hepatectomy and underline significant differences in the metabolic patterns of ACLF and PHLF.
Assuntos
Insuficiência Hepática Crônica Agudizada/metabolismo , Biomarcadores/metabolismo , Hepatectomia/efeitos adversos , Fígado/metabolismo , Metabolômica/métodos , Complicações Pós-Operatórias , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/etiologia , Idoso , Alanina/metabolismo , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Fígado/patologia , Neoplasias Hepáticas/cirurgia , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Diester Fosfórico Hidrolases/metabolismo , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Valina/metabolismoRESUMO
BACKGROUND & AIMS: There is an emerging need to assess the metabolic state of liver allografts especially in the novel setting of machine perfusion preservation and donor in cardiac death (DCD) grafts. High-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS-NMR) could be a useful tool in this setting as it can extemporaneously provide untargeted metabolic profiling. The purpose of this study was to evaluate the potential value of HR-MAS-NMR metabolomic analysis of back-table biopsies for the prediction of early allograft dysfunction (EAD) and donor-recipient matching. METHOD: The metabolic profiles of back-table biopsies obtained by HR-MAS-NMR, were compared according to the presence of EAD using partial least squares discriminant analysis. Network analysis was used to identify metabolites which changed significantly. The profiles were compared to native livers to identify metabolites for donor-recipient matching. RESULTS: The metabolic profiles were significantly different in grafts that caused EAD compared to those that did not. The constructed model can be used to predict the graft outcome with excellent accuracy. The metabolites showing the most significant differences were lactate level >8.3â¯mmol/g and phosphocholine content >0.646â¯mmol/g, which were significantly associated with graft dysfunction with an excellent accuracy (AUROClactatesâ¯=â¯0.906; AUROCphosphocholineâ¯=â¯0.816). Native livers from patients with sarcopenia had low lactate and glycerophosphocholine content. In patients with sarcopenia, the risk of EAD was significantly higher when transplanting a graft with a high-risk graft metabolic score. CONCLUSION: This study underlines the cost of metabolic adaptation, identifying lactate and choline-derived metabolites as predictors of poor graft function in both native livers and liver grafts. HR-MAS-NMR seems a valid technique to evaluate graft quality and the consequences of cold ischemia on the graft. It could be used to assess the efficiency of graft resuscitation on machine perfusion in future studies. LAY SUMMARY: Real-time metabolomic profiles of human grafts during back-table can accurately predict graft dysfunction. High lactate and phosphocholine content are highly predictive of graft dysfunction whereas low lactate and phosphocholine content characterize patients with sarcopenia. In these patients, the cost of metabolic adaptation may explain the poor outcomes.
Assuntos
Transplante de Fígado , Metabolômica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glutamina/metabolismo , Humanos , Ácido Láctico/metabolismo , Transplante de Fígado/efeitos adversos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fosfolipídeos/metabolismo , Doadores de Tecidos , Transplante HomólogoRESUMO
OBJECTIVE: Within a complex systems biology perspective, we wished to assess whether hippocampi with established neuropathological features have distinct metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2). Hippocampus metabolome from patients with epilepsy-associated neuroepithelial tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs), was also compared to noHS epileptiform tissue. METHODS: All patients underwent standardized temporal lobectomy. We applied 1 H high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy to 48 resected human hippocampi. NMR spectra allowed quantification of 21 metabolites. Data were analyzed using multivariate analysis based on mutual information. RESULTS: Clear distinct metabolomic profiles were observed between all studied groups. Sixteen and 18 expected metabolite levels out of 21 were significantly different for HS1 and HS2, respectively, when compared to noHS. Distinct concentration variations for glutamine, glutamate, and N-acetylaspartate (NAA) were observed between HS1 and HS2. Hippocampi from GG and DNT patients showed 7 and 11 significant differences in metabolite concentrations when compared to the same group, respectively. GG and DNT had a clear distinct metabolomic profile, notably regarding choline compounds, glutamine, glutamate, aspartate, and taurine. Lactate and acetate underwent similar variations in both groups. SIGNIFICANCE: HRMAS NMR metabolomic analysis was able to disentangle metabolic profiles between HS, noHS, and epileptic hippocampi associated with EANT. HRMAS NMR metabolomic analysis may contribute to a better identification of abnormal biochemical processes and neuropathogenic combinations underlying mesial temporal lobe epilepsy.
Assuntos
Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Metabolômica/métodos , Adolescente , Adulto , Criança , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/cirurgia , Feminino , Hipocampo/cirurgia , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Lobo Temporal/metabolismo , Lobo Temporal/patologia , Lobo Temporal/cirurgia , Adulto JovemRESUMO
BACKGROUND AND AIMS: Ischemia-reperfusion injury impacts early liver graft function. Interleukin 6 (IL-6) as early as at reperfusion has shown to predict in-hospital complications, but its impact on vascular complications and long-term outcomes is not ascertained. METHODS: A retrospective study was conducted on all consecutive patients transplanted during a 6-year period to define significant early systemic inflammatory response (ESIR). The main end-point was 3-year graft survival. Significant ESIR was defined according to IL-6 level at reperfusion on an exploratory set of 121 patients and validated on an independent cohort (n = 153). RESULTS: Significant ESIR was defined as IL-6 at reperfusion >1000 ng/mL in the exploratory cohort. Three-year graft and overall survival were lower in patients with ESIR in the determination set (P = 0.001 and 0.045, respectively). This was confirmed in the validation set (P = 0.045 and 0.027). In patients with high cytolysis, IL-6 identified patients at risk for arterial thrombosis. The main determinants for IL-6 level were intragraft lactate level, cold ischemia time, and anhepatic phase duration (P = 0.005). IL-6 level independently predicted graft survival (P = 0.0003). CONCLUSIONS: IL-6 at reperfusion is a valid biomarker to predict long-term survival. Furthermore, it helps the interpretation of cytolysis in the prediction of early vascular complications.
Assuntos
Biomarcadores/sangue , Rejeição de Enxerto/diagnóstico , Inflamação/diagnóstico , Interleucina-6/sangue , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Traumatismo por Reperfusão/diagnóstico , Adulto , Idoso , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Inflamação/sangue , Inflamação/etiologia , Inflamação/patologia , Circulação Hepática , Masculino , Pessoa de Meia-Idade , Prognóstico , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
An 84-year-old man, who presented lower limbs limb-shaking syndrome at orthostatism lasting a few seconds, was referred in our stroke unit. Magnetic resonance imaging showed an acute infarction in the right thalamus and the insular cortex, left extracranial carotid stenosis at 80%, and low flow in the right middle cerebral artery but did not explain limb-shaking syndrome symptomatology. We performed comparative positional brain perfusion single-photon emission computed tomography (SPECT), in the upright and in the supine position, to explore and localize hypoperfusion-endangered brain structures that may be involved in the presenting symptoms. Brain perfusion SPECT showed deep hypoperfusion in bilateral carotid territories in the upright position in favor of a hemodynamic mechanism, on which blood pressure was maintained higher to avoid hypoperfusion and the patient remained supine for a longer period of time than in the usual support. Late postoperative brain perfusion SPECT after left endarterectomy did not show significant abnormalities. Limb-shaking syndrome may be related to a transient decrease in blood pressure and cerebral blood flow caused by postural changes. Positional brain perfusion SPECT seems to be helpful to improve clinical care. Positional brain perfusion SPECT should be discussed in the acute phase of stroke and if there are involuntary movements.
Assuntos
Infarto Encefálico/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Posicionamento do Paciente , Tomografia Computadorizada de Emissão de Fóton Único , Tremor/etiologia , Idoso de 80 Anos ou mais , Pressão Sanguínea , Infarto Encefálico/etiologia , Infarto Encefálico/fisiopatologia , Estenose das Carótidas/complicações , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/cirurgia , Circulação Cerebrovascular , Imagem de Difusão por Ressonância Magnética , Endarterectomia das Carótidas , Humanos , Angiografia por Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Decúbito Dorsal , Resultado do Tratamento , Tremor/fisiopatologiaRESUMO
Positron emission tomography/computed tomography (PET/CT) represents an emerging imaging guidance modality that has been applied to successfully guide percutaneous procedures such as biopsies and tumour ablations. The aim of the present narrative review is to report the indications, advantages and disadvantages of PET/CT-guided procedures in the field of interventional oncology and to briefly describe the experience gained with this new emerging technique while performing biopsies and tumor ablations.
Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radiografia Intervencionista/métodos , Técnicas de Ablação/métodos , Humanos , Biópsia Guiada por Imagem , Neoplasias/patologia , Compostos RadiofarmacêuticosRESUMO
PURPOSE: Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of 18F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up. METHODS: Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated. Patients underwent both 18F-FDOPA PET/CT and MRA (15 patents) or CTA (1 patent). Both methods were first assessed under blinded conditions and afterwards correlated. Head and neck imaging abnormalities without histological confirmation were considered true-positive results based on a consensus between radiologists and nuclear physicians and on further 18F-FDOPA PET/CT and/or MRA. RESULTS: 18F-FDOPA PET/CT and MRA/CTA were concordant in 14 patients and in disagreement in 2 patients. 18F-FDOPA PET/CT and MRA/CTA identified, respectively, 12 and 10 presumed recurrent HNPGLs in 12 patients. The two lesions diagnosed by PET/CT only were confirmed during follow-up by otoscopic examination and MRA performed 29 and 17 months later. 18F-FDOPA PET/CT images were only slightly influenced by the posttreatment sequelae, showing a better interobserver reproducibility than MRA/CTA. Finally, in 2 of the 16 studied patients, 18F-FDOPA PET/CT detected two additional synchronous primary HNPGLs. CONCLUSION: 18F-FDOPA PET/CT is highly sensitive in posttreatment evaluation of patients with HNPGLs, and also offers better interobserver reproducibility than MRA/CTA and whole-body examination. We therefore suggest that 18F-FDOPA PET/CT is performed as the first diagnostic imaging modality in symptomatic patients with suspicion of HNPGL relapse after primary treatment when 68Ga-labeled somatostatin analogues are not available.
Assuntos
Angiografia por Tomografia Computadorizada , Di-Hidroxifenilalanina/análogos & derivados , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imageamento por Ressonância Magnética , Paraganglioma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Di-Hidroxifenilalanina/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Paraganglioma/metabolismo , Recidiva , Estudos RetrospectivosRESUMO
BACKGROUND: Protection against acute skeletal muscle metabolic dysfunction and oxidative stress could be a therapeutic target in volume expansion for severely bleeding patients. OBJECTIVES: This experimental pilot study in swine aims at comparing 130/0.4 hydroxyethyl starch (HES) with 4% albumin along with crystalloid perfusion for first-line volume expansion in haemorrhagic shock with a particular emphasis on oxidative stress and muscular mitochondrial function. DESIGN: Randomised experimental study. SETTING: Digestive Cancer Research Institute Preclinical Laboratory, Strasbourg University Hospital, France, from February 2012 to June 2013. ANIMALS: Twenty large white pigs. INTERVENTION: Pressure-controlled haemorrhagic shock and volume resuscitation using either 4% human serum albumin or 130/0.4 HES along with crystalloid perfusion were performed in 20 large white pigs. MAIN OUTCOME MEASURES: Muscular biopsy of gastrocnemius muscle was performed for metabolomics screening, mitochondrial respiratory chain assessment and electron spin resonance reactive oxygen species production along with arterial and venous reactive oxygen species production at baseline, at the completion of shock, at 90âmin and at 180âmin after volume expansion. RESULTS: There was no difference between the two groups in measurements of skeletal muscle superoxide production. In a pooled analysis, there was a statistically significant decrease in gastrocnemius muscle creatine content from baseline to 90âmin (Pâ<â0.05) and 180âmin (Pâ<â0.05). Muscular lactate content and mitochondrial respiratory chain oxidative capacity remained constant at the respective time points. CONCLUSION: In this pilot experimental study in swine, during pressure-controlled haemorrhagic shock treated with either albumin or 130/0.4 HES in conjunction with crystalloid perfusion, skeletal muscle metabolic profile was unaltered. ETHICAL APPROVAL NUMBER: 38.2012.01.031.