RESUMEN
BACKGROUND: The prognostic value of the extent of resection in the management of Glioblastoma is a long-debated topic, recently widened by the 2022 RANO-Resect Classification, which advocates for the resection of the non-enhancing disease surrounding the main core of tumors (supramaximal resection, SUPR) to achieve additional survival benefits. We conducted a retrospective analysis to corroborate the role of SUPR by the RANO-Resect Classification in a single center, homogenous cohort of patients. METHODS: Records of patients operated for WHO-2021 Glioblastomas at our institution between 2007 and 2018 were retrospectively reviewed; volumetric data of resected lesions were computed and classified by RANO-Resect criteria. Survival and correlation analyses were conducted excluding patients below near-total resection. RESULTS: 117 patients met the inclusion criteria, encompassing 45 near-total resections (NTR), 31 complete resections (CR), and 41 SUPR. Median progression-free and overall survival were 11 and 15 months for NTR, 13 and 17 months or CR, 20 and 24 months for SUPR, respectively (p < 0.001), with inverse correlation observed between survival and FLAIR residual volume (r -0.28). SUPR was not significantly associated with larger preoperative volumes or higher rates of postoperative deficits, although it was less associated with preoperative neurological deficits (OR 3.37, p = 0.003). The impact of SUPR on OS varied between MGMT unmethylated (HR 0.606, p = 0.044) and methylated (HR 0.273, p = 0.002) patient groups. CONCLUSIONS: Results of the present study support the validity of supramaximal resection by the new RANO-Resect classification, also highlighting a possible surgical difference between tumors with methylated and unmethylated MGMT promoter.
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Neoplasias Encefálicas , Glioblastoma , Isocitrato Deshidrogenasa , Humanos , Glioblastoma/cirugía , Glioblastoma/patología , Glioblastoma/genética , Glioblastoma/mortalidad , Estudios Retrospectivos , Persona de Mediana Edad , Masculino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/diagnóstico por imagen , Femenino , Anciano , Adulto , Isocitrato Deshidrogenasa/genética , Procedimientos Neuroquirúrgicos/métodosRESUMEN
BACKGROUND: Although there are reports of otolaryngological symptoms and manifestations of CoronaVirus Disease 19 (COVID-19), there have been no documented cases of sudden neck swelling with rash in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection described in literature. CASE PRESENTATION: We report a case of a sudden neck swelling and rash likely due to late SARS-CoV-2 in a 64-year-old woman. The patient reported COVID-19 symptoms over the previous three weeks. Computed Tomography (CT) revealed a diffuse soft-tissue swelling and edema of subcutaneous tissue, hypodermis, and muscular and deep fascial planes. All the differential diagnoses were ruled out. Both the anamnestic history of the patient's husband who had died of COVID-19 with and the collateral findings of pneumonia and esophageal wall edema suggested the association with COVID-19. This was confirmed by nasopharyngeal swab polymerase chain reaction. The patient was treated with lopinavir/ritonavir, hydroxychloroquine and piperacillin/tazobactam for 7 days. The neck swelling resolved in less than 24 h, while the erythema was still present up to two days later. The patient was discharged after seven days in good clinical condition and with a negative swab. CONCLUSION: Sudden neck swelling with rash may be a coincidental presentation, but, in the pandemic context, it is most likely a direct or indirect complication of COVID-19.
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COVID-19/complicaciones , Exantema/etiología , SARS-CoV-2 , COVID-19/diagnóstico por imagen , Edema/etiología , Femenino , Humanos , Persona de Mediana Edad , Cuello/patología , Tomografía Computarizada por Rayos X , Tratamiento Farmacológico de COVID-19RESUMEN
PURPOSE: We describe the reorganization carried out during the COVID-19 outbreak at one of the stroke centers in Italy and report on the clinical features and procedural variables of stroke patients in need of endovascular treatment. METHODS: From 1 March to 10 May 2020, we retrospectively analyzed data from stroke patients in need of urgent neurointerventional treatment. Clinical presentation, demographics, and clinical history were collected along with procedural variables (door-to-needle time, needle-to-mTiCi time). Each patient underwent a nasal swab (polymerase chain reaction test), clinical screening, and chest CT scan to assess the risk of SARS-CoV-2 infection. Technical success, procedural safety (including staff SARS-CoV-2 infection), and clinical outcome at discharge were retrieved. A comparison was made with the same patient population treated between 1 March and 10 May 2019 to highlight possible differences in the characteristics or outcomes of the patients. RESULTS: One hundred thirty-six ischemic stroke patients were admitted to our facility from 1 March to 10 May 2020. Of these, 12 patients (9%) were classified as "high risk" for SARS-CoV-2 infection. Radiological suspicion of COVID-19 was confirmed in all cases by pharyngeal swab. Five SARS-CoV-2 patients (42%) needed endovascular therapy. None of the staff members tested positive for IgG against SARS-CoV-2. Compared to the same period in 2019, an increase in the mean interval from the first symptoms to hospital arrival was observed (p < 0.05). CONCLUSION: Endovascular treatment of stroke presented several challenges during the COVID-19 outbreak. Within the hospital, special pathways can be used to maintain both procedural safety and procedural times.
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COVID-19/epidemiología , Procedimientos Endovasculares , Planificación de Instituciones de Salud , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Anciano , COVID-19/diagnóstico , Prueba de COVID-19 , Diagnóstico por Imagen , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Italia/epidemiología , Masculino , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/virología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
OBJECTIVES: To compare the outcome of US-guided percutaneous irrigation of calcific tendinopathy (US-PICT) of the rotator cuff in patients with or without previous external shockwave therapy (ESWT). METHODS: We analyzed all patients treated with US-PICT from March 1, 2016, to October 1, 2019, with shoulder pain refractory to conservative management for rotator cuff calcific tendinopathy, diagnosed with ultrasound. Each patient was examined using the Constant-Murley Score (CMS) questionnaire (score 0-100) before and after treatment. We tested CMS differences using the Mann-Whitney U (Wilcoxon rank-sum) test in the two groups. US-PICT was performed placing two or multiple 14G needles, according to the calcification size, inserted under US guidance to create a circuit of irrigation in the calcified tendon. NaCl solution at 38 °C was then injected from the entry needle in a variable amount to hydrate and fragment the calcification, finally allowing for its expulsion through the exit needle. All patients also received an intrabursal steroid injection. RESULTS: From 2016 to 2019, 72 US-PICT treatments were performed on 70 patients (females = 46; males = 26) with a mean age of 49.7 years (SD = 8.7. Thirty-three (47%) underwent previous ESWT, while thirty-seven (53%) had no previous treatments. No treatment-related complications were observed. Follow-up was averagely 14.4 months (median = 11.6, SD = 11.9, range 1-45); 37 patients had a follow-up shorter than 12 months (1-11.6); 35 patients were visited after more than 1 year (12.2-45.6, Table W). Before treatment, the mean CMS was 35 (SD = 21); after treatment, it reached 75.4, with an average CMS improvement of 40.3 points (SD = 23.7, p < 0.001). The comparison of improvement between the ESWT and non-ESWT group yielded no significant difference (p = 0.3). CONCLUSIONS: US-PICT of the rotator cuff is an effective procedure to reduce shoulder pain and increase mobility in patients with calcific tendinopathy, both in short- and long-term time intervals. Previous unsuccessful ESWT does not affect the outcome of US-PICT.
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Calcinosis/terapia , Lesiones del Manguito de los Rotadores/terapia , Dolor de Hombro/terapia , Irrigación Terapéutica/métodos , Ultrasonografía Intervencional/métodos , Terapia Combinada , Femenino , Ondas de Choque de Alta Energía , Humanos , Inyecciones Intraarticulares , Masculino , Persona de Mediana Edad , Esteroides/uso terapéutico , Encuestas y CuestionariosRESUMEN
Glioblastoma (GBM) is the most malignant brain tumor of adults and is characterized by extensive cell dissemination within the brain parenchyma and enhanced angiogenesis. Effective preclinical modeling of these key features suffers from several shortcomings. Aim of this study was to determine whether modulating the expression of extracellular matrix (ECM) modifiers in proneural (PN) and mesenchymal (MES) cancer stem cells (CSCs) and in conventional glioma cell lines (GCLs) might improve tumor invasion and vascularization. To this end, we selected secreted, acidic and rich in cysteine-like 1 (SPARCL1) as a potential mediator of ECM remodeling in GBM. SPARCL1 transcript and protein expression was assessed in PN and MES CSCs as well as GCLs, in their xenografts and in patient-derived specimens by qPCR, WB and IHC. SPARCL1 expression was then enforced in both CSCs and GCLs by lentiviral-based transduction. The effect of SPARCL1 gain-of-function on microvascular proliferation, microglia activation and advanced imaging features was tested in intracranial xenografts by IHC and MRI and validated by chorioallantoic membrane (CAM) assays. SPARCL1 expression significantly enhanced the infiltrative and neoangiogenic features of PN and MES CSC/GCL-induced tumors, with the concomitant activation of inflammatory responses associated with the tumor microenvironment, thus resulting in experimental GBMs that reproduced both the parenchymal infiltration and the increased microvascular density, typical of GBM. Overall, these results indicate that SPARCL1 overexpression might be instrumental for the generation of CSC-derived preclinical models of GBM in which the main pathognomonic hallmarks of GBMs are retrievable, making them suitable for effective preclinical testing of therapeutics.
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Neoplasias Encefálicas/metabolismo , Proteínas de Unión al Calcio/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Glioblastoma/metabolismo , Células Madre Neoplásicas/metabolismo , Neovascularización Patológica/metabolismo , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Femenino , Xenoinjertos , Humanos , Ratones , Microglía/metabolismoRESUMEN
OBJECTIVE: Lombardy (Italy) was the epicentre of the COVID-19 pandemic in March 2020. The healthcare system suffered from a shortage of ICU beds and oxygenation support devices. In our Institution, most patients received chest CT at admission, only interpreted visually. Given the proven value of quantitative CT analysis (QCT) in the setting of ARDS, we tested QCT as an outcome predictor for COVID-19. METHODS: We performed a single-centre retrospective study on COVID-19 patients hospitalised from January 25, 2020, to April 28, 2020, who received CT at admission prompted by respiratory symptoms such as dyspnea or desaturation. QCT was performed using a semi-automated method (3D Slicer). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient's clinical data including oxygenation support throughout hospitalisation. RESULTS: Two hundred twenty-two patients (163 males, median age 66, IQR 54-6) were included; 75% received oxygenation support (20% intubation rate). Compromised lung volume was the most accurate outcome predictor (logistic regression, p < 0.001). %CL values in the 6-23% range increased risk of oxygenation support; values above 23% were at risk for intubation. %CL showed a negative correlation with PaO2/FiO2 ratio (p < 0.001) and was a risk factor for in-hospital mortality (p < 0.001). CONCLUSIONS: QCT provides new metrics of COVID-19. The compromised lung volume is accurate in predicting the need for oxygenation support and intubation and is a significant risk factor for in-hospital death. QCT may serve as a tool for the triaging process of COVID-19. KEY POINTS: ⢠Quantitative computer-aided analysis of chest CT (QCT) provides new metrics of COVID-19. ⢠The compromised lung volume measured in the - 500, 100 HU interval predicts oxygenation support and intubation and is a risk factor for in-hospital death. ⢠Compromised lung values in the 6-23% range prompt oxygenation therapy; values above 23% increase the need for intubation.
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Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Intubación Intratraqueal/métodos , Pulmón/diagnóstico por imagen , Terapia por Inhalación de Oxígeno/métodos , Neumonía Viral/diagnóstico , Tomografía Computarizada por Rayos X/métodos , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Pronóstico , Estudios Retrospectivos , SARS-CoV-2RESUMEN
OBJECTIVE: Coronavirus disease 2019 (COVID-19) has changed the way in which cancer is treated. Patients with high-grade glioma (HGG) are believed to be in a vulnerable category. The aim of this study was to describe the experience of a hub cancer center and the measures that were put in place for treatment of patients with newly diagnosed and recurrent glioma. METHODS: To prevent in-hospital contagion and preserve the safety of health professionals and patients, specific protocols and strict regulations were introduced. Physical distancing, use of surgical masks, and diligent hand hygiene were adopted. Each case was discussed in a multidisciplinary board meeting before treatment. All patient candidates for surgical procedures were tested for SARS-CoV-2 with a nasopharyngeal swab and a chest CT scan. Indications for surgery were the radiological suspicion of HGG in patients with a good performance status and/or the rapid and progressive occurrence of neurological deficits. Adjuvant treatments were performed only in cases of HGG. This therapy consisted of conventional fractional radiotherapy (RT; 60 Gy/30 fractions) with concomitant and adjuvant temozolomide chemotherapy (TMZCHT) in younger patients; in elderly patients, a short course of RT was employed (40.5 Gy/15 fractions). For recurrent HGG, treatments were assessed after a careful evaluation of the patient's general condition, neurological status, and risk of early impairment in neurological status if not treated. During simulation CT for the RT plan, each patient underwent a chest CT study. In cases in which an imaging study was suspicious for COVID-19 pneumonia, the patient was immediately isolated and rapidly underwent nasopharyngeal swab testing. RESULTS: Between March 1 and April 30, 2020, 23 HGGs were treated, and these cases are included in the present evaluation. Fifteen patients harboring newly diagnosed glioblastoma (GBM) underwent resection followed by a regimen of chemotherapy and RT, and 3 patients with newly diagnosed anaplastic oligodendroglioma underwent surgery followed by adjuvant RT. Five patients were treated for recurrent GBM, and they received surgery plus adjuvant RT. One patient in whom the simulation CT study was suspicious for COVID pneumonia was tested with a nasopharyngeal swab, which proved positive for SARS-CoV-2 infection. No patients contracted COVID-19 during hospitalization for surgery or during RT treatment. Corticosteroid therapy was administered to all patients beginning on the 1st day of RT. CONCLUSIONS: The authors' experience during the COVID-19 pandemic showed that patients with HGG can be treated in the most effective manner without a compromise in safety. Careful selection criteria and a multidisciplinary evaluation are pivotal to assessing the optimal therapeutic strategy.
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Neoplasias Encefálicas/cirugía , COVID-19/epidemiología , Glioma/cirugía , Control de Infecciones/organización & administración , SARS-CoV-2 , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/prevención & control , COVID-19/transmisión , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Procedimientos NeuroquirúrgicosRESUMEN
BACKGROUND: Positron emission tomography (PET) using translocator protein (TSPO) ligands has been used to detect neuroinflammatory processes in neurological disorders, including multiple sclerosis (MS). The aim of this study was to evaluate neuroinflammation in a mouse MS model (EAE) using TSPO-PET with 18F-VC701, in combination with magnetic resonance imaging (MRI). METHODS: MOG35-55/CFA and pertussis toxin protocol was used to induce EAE in C57BL/6 mice. Disease progression was monitored daily, whereas MRI evaluation was performed at 1, 2, and 4 weeks post-induction. Microglia activation was assessed in vivo by 18F-VC701 PET at the time of maximum disease score and validated by radioligand ex vivo distribution and immunohistochemistry at 2 and 4 weeks post-immunization. RESULTS: In vivo and ex vivo analyses show that 18F-VC701 significantly accumulates within the central nervous system (CNS), particularly in the cortex, striatum, hippocampus, cerebellum, and cervical spinal cord of EAE compared to control mice, at 2 weeks post-immunization. MRI confirmed the presence of focal brain lesions at 2 weeks post-immunization in both T1-weighted and T2 images. Of note, MRI abnormalities attenuated in later post-immunization phase. Neuropathological analysis confirmed the presence of microglial activation in EAE mice, consistent with the in vivo increase of 18F-VC701 uptake. CONCLUSION: Increase of 18F-VC701 uptake in EAE mice is strongly associated with the presence of microglia activation in the acute phase of the disease. The combined use of TSPO-PET and MRI provided complementary evidence on the ongoing disease process, thus representing an attractive new tool to investigate neuronal damage and neuroinflammation at preclinical levels.
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Radioisótopos de Flúor/metabolismo , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/metabolismo , Tomografía de Emisión de Positrones/métodos , Quinolinas/metabolismo , Secuencia de Aminoácidos , Animales , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/diagnóstico por imagen , Encefalomielitis Autoinmune Experimental/metabolismo , Femenino , Ratones , Ratones Endogámicos C57BLRESUMEN
Ischemic stroke is the leading cause of disability, but effective therapies are currently widely lacking. Recovery from stroke is very much dependent on the possibility to develop treatments able to both halt the neurodegenerative process as well as to foster adaptive tissue plasticity. Here we show that ischemic mice treated with neural precursor cell (NPC) transplantation had on neurophysiological analysis, early after treatment, reduced presynaptic release of glutamate within the ipsilesional corticospinal tract (CST), and an enhanced NMDA-mediated excitatory transmission in the contralesional CST. Concurrently, NPC-treated mice displayed a reduced CST degeneration, increased axonal rewiring, and augmented dendritic arborization, resulting in long-term functional amelioration persisting up to 60 d after ischemia. The enhanced functional and structural plasticity relied on the capacity of transplanted NPCs to localize in the peri-ischemic and ischemic area, to promote the upregulation of the glial glutamate transporter 1 (GLT-1) on astrocytes and to reduce peri-ischemic extracellular glutamate. The upregulation of GLT-1 induced by transplanted NPCs was found to rely on the secretion of VEGF by NPCs. Blocking VEGF during the first week after stroke reduced GLT-1 upregulation as well as long-term behavioral recovery in NPC-treated mice. Our results show that NPC transplantation, by modulating the excitatory-inhibitory balance and stroke microenvironment, is a promising therapy to ameliorate disability, to promote tissue recovery and plasticity processes after stroke. SIGNIFICANCE STATEMENT: Tissue damage and loss of function occurring after stroke can be constrained by fostering plasticity processes of the brain. Over the past years, stem cell transplantation for repair of the CNS has received increasing interest, although underlying mechanism remain elusive. We here show that neural stem/precursor cell transplantation after ischemic stroke is able to foster axonal rewiring and dendritic plasticity and to induce long-term functional recovery. The observed therapeutic effect of neural precursor cells seems to underlie their capacity to upregulate the glial glutamate transporter on astrocytes through the vascular endothelial growth factor inducing favorable changes in the electrical and molecular stroke microenvironment. Cell-based approaches able to influence plasticity seem particularly suited to favor poststroke recovery.
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Astrocitos/metabolismo , Transportador 2 de Aminoácidos Excitadores/biosíntesis , Células-Madre Neurales/trasplante , Trasplante de Células Madre/métodos , Accidente Cerebrovascular/terapia , Animales , Conducta Animal , Isquemia Encefálica/metabolismo , Infarto Cerebral/patología , Transportador 2 de Aminoácidos Excitadores/genética , Ácido Glutámico/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Plasticidad Neuronal , Técnicas de Placa-Clamp , Recuperación de la Función , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/psicología , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Neuroferritinopathy is a rare genetic disease with a dominant autosomal transmission caused by mutations of the ferritin light chain gene (FTL). It belongs to Neurodegeneration with Brain Iron Accumulation, a group of disorders where iron dysregulation is tightly associated with neurodegeneration. We studied the 498-499InsTC mutation which causes the substitution of the last 9 amino acids and an elongation of extra 16 amino acids at the C-terminus of L-ferritin peptide. An analysis with cyclic voltammetry on the purified protein showed that this structural modification severely reduces the ability of the protein to store iron. In order to analyze the impact of the mutation in vivo, we generated mouse models for the some pathogenic human FTL gene in FVB and C57BL/6J strains. Transgenic mice in the FVB background showed high accumulation of the mutated ferritin in brain where it correlated with increased iron deposition with age, as scored by magnetic resonance imaging. Notably, the accumulation of iron-ferritin bodies was accompanied by signs of oxidative damage. In the C57BL/6 background, both the expression of the mutant ferritin and the iron levels were lower than in the FVB strain. Nevertheless, also these mice showed oxidative alterations in the brain. Furthermore, post-natal hippocampal neurons obtained from these mice experienced a marked increased cell death in response to chronic iron overload and/or acute oxidative stress, in comparison to wild-type neurons. Ultrastructural analyses revealed an accumulation of lipofuscin granules associated with iron deposits, particularly enriched in the cerebellum and striatum of our transgenic mice. Finally, experimental subjects were tested throughout development and aging at 2-, 8- and 18-months for behavioral phenotype. Rotarod test revealed a progressive impaired motor coordination building up with age, FTL mutant old mice showing a shorter latency to fall from the apparatus, according to higher accumulation of iron aggregates in the striatum. Our data show that our 498-499InsTC mouse models recapitulate early pathological and clinical traits of the human neuroferritinopathy, thus providing a valuable model for the study of the disease. Finally, we propose a mechanistic model of lipofuscine formation that can account for the etiopathogenesis of human neuroferritinopathy.
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Apoferritinas/genética , Encéfalo/patología , Trastornos del Metabolismo del Hierro/etiología , Distrofias Neuroaxonales , Enfermedades Neurodegenerativas/etiología , Trastornos Psicomotores/etiología , Factores de Edad , Animales , Apoferritinas/metabolismo , Encéfalo/metabolismo , Muerte Celular/genética , Células Cultivadas , Daño del ADN/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Hipocampo/citología , Humanos , Trastornos del Metabolismo del Hierro/complicaciones , Trastornos del Metabolismo del Hierro/genética , Trastornos del Metabolismo del Hierro/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Modelos Moleculares , Distrofias Neuroaxonales/complicaciones , Distrofias Neuroaxonales/genética , Distrofias Neuroaxonales/patología , Neuronas/efectos de los fármacos , Neuronas/metabolismoRESUMEN
Positron emission tomography (PET) can be used to monitor in vivo translocator protein (TSPO) expression by using specific radioligands. Recently, several [11C]PK11195 analogues have been synthesized to improve binding stability and brain availability. [18F]VC701 was synthesized and validated in CD healthy rats by biodistribution and inhibition analysis. Imaging studies were also conducted on animals injected unilaterally in the striatum with quinolinic acid (QA) to evaluate the TSPO ligand uptake in a neuroinflammation/neurodegenerative model. [18F]VC701 was synthesized with a good chemical and radiochemical purity and specific activity higher than 37 GBq/µmol. Kinetic studies performed on healthy animals showed the highest tracer biodistribution in TSPO-rich organs, and preadministration of cold PK11195 caused an overall radioactivity reduction. Metabolism studies showed the absence of radiometabolites in the rat brain of QA lesioned rats, and biodistribution analysis revealed a progressive increase in radioactivity ratios (lesioned to nonlesioned striatum) during time, reaching an approximate value of 5 4 hours after tracer injection. These results encourage further evaluation of this TSPO radioligand in other models of central and peripheral diseases.
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Proteínas Portadoras/metabolismo , Isoquinolinas/síntesis química , Isoquinolinas/metabolismo , Quinolinas/síntesis química , Quinolinas/metabolismo , Radiofármacos/síntesis química , Radiofármacos/metabolismo , Animales , Autorradiografía , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Radioisótopos de Flúor , Ligandos , Masculino , Metaboloma , Tomografía de Emisión de Positrones , Ratas , Distribución TisularRESUMEN
The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs), for which hematopoietic cell transplantation (HCT) is applied to repopulate the recipient myeloid compartment, including microglia, with cells expressing the defective functional hydrolase. By studying wild-type and LSD mice at diverse time-points after HCT, we showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. However, only the use of a conditioning regimen capable of ablating functionally defined brain-resident myeloid precursors allowed turnover of microglia with the donor, mediated by local proliferation of early immigrants rather than entrance of mature cells from the circulation.
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Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedades por Almacenamiento Lisosomal del Sistema Nervioso/terapia , Microglía/citología , Acondicionamiento Pretrasplante/métodos , Análisis de Varianza , Animales , Diferenciación Celular/fisiología , Movimiento Celular/fisiología , Citometría de Flujo , Proteínas Fluorescentes Verdes/metabolismo , Etiquetado Corte-Fin in Situ , Ratones , Ratones NoqueadosRESUMEN
OBJECTIVES: To compare extraocular muscles (EOMs) T2, post-contrast T1 (T1Gad) signal intensity ratios (SIRs) and normalized-apparent diffusion coefficient (n-ADC) values in patients with thyroid-associated orbitopathy (TAO) at different phases of activity and severity and correlate MRI modifications to clinical evolution during follow-up. METHODS: A total of 74 TAO patients were classified as active or inactive on the basis of the clinical activity score (CAS). Severity of EOM impairment was evaluated by assigning a functional score to each rectus. T2, T1Gad SIRs and n-ADC of EOMs were compared in patients with active inflammation, those with inactive disease and 26 healthy controls, and correlated with clinical scores. MRI parameter variation was correlated with clinical modifications during follow-up. RESULTS: All MRI parameters in TAO EOMs were significantly higher than in healthy subjects and correlated with muscle dysfunction and CAS. EOMs of active patients showed higher T2 and T1Gad SIRs than those with inactive disease. The T2 SIR and n-ADC of normally functioning TAO EOMs were higher than those of healthy controls. SIRs decreased in clinically improved and clinically stable EOMs after therapy. CONCLUSIONS: T2 SIR, T1Gad SIR and n-ADC are objective measures of activity and severity of EOMs in TAO patients. MRI shows clinically silent muscle involvement and modifications. KEY POINTS: ⢠MRI and DWI measures are objective, quantitative parameters of TAO activity and severity ⢠MRI and DWI measures significantly correlate with clinical scores in TAO patients ⢠MRI and DWI can identify clinically silent inflammation of deep orbital structures ⢠MRI and DWI can depict subclinical modifications during follow-up ⢠MRI and DWI may aid clinicians in choosing the most appropriate treatment.
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Imagen de Difusión por Resonancia Magnética , Oftalmopatía de Graves/diagnóstico , Músculos Oculomotores/patología , Adulto , Anciano , Estudios de Casos y Controles , Medios de Contraste , Femenino , Humanos , Masculino , Meglumina/análogos & derivados , Persona de Mediana Edad , Compuestos OrganometálicosRESUMEN
PURPOSE: This multicentric study aims to characterize and assess the occurrence of neuroradiological findings among patients with SARS-CoV-2 infection during the first Italian wave of the pandemic outbreak. MATERIALS AND METHODS: Patients' data were collected between May 2020 and June 2020. Clinical and laboratory data, chest imaging, brain CT, and MRI imaging were included. Acquired data were centralized and analyzed in two hospitals: ASST Spedali Civili, Brescia, and IRRCS San Raffaele Research Hospital, Milan, Italy. COVID-19 patients were classified into two different subgroups, vascular and nonvascular. The vascular pattern was further divided into ischemic and hemorrhagic stroke groups. RESULTS: Four hundred and fifteen patients from 20 different Italian Centers were enrolled in the study. The most frequent symptom was focal neurological deficit, found in 143 patients (34.5%). The most frequent neuroradiological finding was ischemic stroke in 122 (29.4%) patients. Forty-four (10.6%) patients presented a cerebral hemorrhage. Forty-seven patients had non-stroke neuroimaging lesions (11.3%). The most common was PRES-like syndrome (28%), SWI hypointensities (22%), and encephalitis (19%). The stroke group had higher CAD risk (37.5% vs 20%, p = .016) and higher D-dimer levels (1875 ng/mL vs 451 ng/mL, p < .001) compared to the negative group. CONCLUSION: Our study describes the biggest cohort study in Italy on brain imaging of COVID-19 patients and confirms that COVID-19 patients are at risk of strokes, possibly due to a pro-thrombotic microenvironment. Moreover, apart from stroke, the other neuroradiological patterns described align with the ones reported worldwide.
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Artificial intelligence (AI) is expected to have a major effect on radiology as it demonstrated remarkable progress in many clinical tasks, mostly regarding the detection, segmentation, classification, monitoring, and prediction of diseases. Generative Adversarial Networks have been proposed as one of the most exciting applications of deep learning in radiology. GANs are a new approach to deep learning that leverages adversarial learning to tackle a wide array of computer vision challenges. Brain radiology was one of the first fields where GANs found their application. In neuroradiology, indeed, GANs open unexplored scenarios, allowing new processes such as image-to-image and cross-modality synthesis, image reconstruction, image segmentation, image synthesis, data augmentation, disease progression models, and brain decoding. In this narrative review, we will provide an introduction to GANs in brain imaging, discussing the clinical potential of GANs, future clinical applications, as well as pitfalls that radiologists should be aware of.
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BACKGROUND AND PURPOSE: Standard of care for recurrent high grade glioma (HGG) is missing. Several treatment options have been investigated including re-irradiation (re-RT). Results are promising but provided by retrospective studies. We designed a single arm prospective phase II study aiming to evaluate efficacy, and toxicity of re-irradiation. MATERIALS AND METHODS: Adults patients with good performance status, HGG diagnosis reclassified according to the new 2021 fifth edition WHO CNS classification, an interval time (IT) from previous RT ≥ 6 months were included. Outcome was evaluated by MRI imaging at 1 month, and every 3 months thereafter. Toxicities were evaluated in terms of radionecrosis occurrence, and neurocognitive status. RESULTS: Ninety recurrent HGG patients were treated, 11 oligodendroglioma grade 3, 18 astrocytoma grade 3 and 4, and 61 glioblastoma grade 4. The median age was 54 years, and majority had KPS 90-100. The median IT between first-RT and re-RT was 24 months. Re-surgery has been performed in 56.6%, and chemotherapy in 53.3%. The median follow up time was 64 months; median overall survival (OS) time,1,2,3-year OS rates were 17 months (95%CI 14-19), 66.7%±4.9, 32.6%±5.0, and 22.2 ± 4.7. Prognostic factors impacting on survival were age (p = 0.0154), IT between first RT and re-RT (p = 0.0051), glioma grade (p = 0.0090), and IDH status (p = 0.0001). Radionecrosis grade 2-3 occurred in 9 (10%) patients; neurocognitive functions remained stable until disease progression. CONCLUSION: Re-RT proved to be a safe and feasible treatment option with low toxicity. Younger patients with grade 3 IDH mutated gliomas, and a longer IT had the better outcome. TRIAL REGISTRATION NUMBER: NCT02567539.
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Neoplasias Encefálicas , Glioma , Traumatismos por Radiación , Reirradiación , Adulto , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/terapia , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Prospectivos , Reirradiación/efectos adversos , Estudios RetrospectivosRESUMEN
Mutations in isocitrate dehydrogenase (IDH)1 and its homolog IDH2 are considered an earliest "driver" genetic event during gliomagenesis, representing now the molecular hallmark of lower-grade gliomas (LGGs). IDH-mutated genes encode for a neomorphic enzyme that converts α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (2-HG), which accumulates to high concentrations and alters cellular epigenetics and metabolism. Targeting IDH mutations is the first attempt to apply "precision oncology" in LGGs. Two distinct strategies have been proposed so far and are under intense clinical investigation: (i) reducing the amount of intratumoral 2-HG by directly blocking the function of mutant IDH enzyme; (ii) exploiting the selective epigenetic and metabolic cellular vulnerabilities as a consequence of 2-HG accumulation. The present review describes the physiopathological mechanisms by which IDH mutations lead to tumorigenesis, discussing their prognostic significance and pivotal role in the gliomas diagnostic classification system. We critically review preclinical evidence and available clinical data of first-generation mutant-selective IDH inhibitors and novel IDH-targeted vaccines. Finally, as an alternative and attractive approach, we present the rationale to take advantage of selective 2-HG related epigenetic and metabolic weaknesses. The results of ongoing clinical trials will help us clarify the complex scenario of IDH-targeted therapeutic approaches in gliomas.
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Non-invasive diagnosis of chemotherapy-associated liver injuries (CALI) is still an unmet need. The present study aims to elucidate the contribution of radiomics to the diagnosis of sinusoidal dilatation (SinDil), nodular regenerative hyperplasia (NRH), and non-alcoholic steatohepatitis (NASH). Patients undergoing hepatectomy for colorectal metastases after chemotherapy (January 2018-February 2020) were retrospectively analyzed. Radiomic features were extracted from a standardized volume of non-tumoral liver parenchyma outlined in the portal phase of preoperative post-chemotherapy computed tomography. Seventy-eight patients were analyzed: 25 had grade 2-3 SinDil, 27 NRH, and 14 NASH. Three radiomic fingerprints independently predicted SinDil: GLRLM_f3 (OR = 12.25), NGLDM_f1 (OR = 7.77), and GLZLM_f2 (OR = 0.53). Combining clinical, laboratory, and radiomic data, the predictive model had accuracy = 82%, sensitivity = 64%, and specificity = 91% (AUC = 0.87 vs. AUC = 0.77 of the model without radiomics). Three radiomic parameters predicted NRH: conventional_HUQ2 (OR = 0.76), GLZLM_f2 (OR = 0.05), and GLZLM_f3 (OR = 7.97). The combined clinical/laboratory/radiomic model had accuracy = 85%, sensitivity = 81%, and specificity = 86% (AUC = 0.91 vs. AUC = 0.85 without radiomics). NASH was predicted by conventional_HUQ2 (OR = 0.79) with accuracy = 91%, sensitivity = 86%, and specificity = 92% (AUC = 0.93 vs. AUC = 0.83 without radiomics). In the validation set, accuracy was 72%, 71%, and 91% for SinDil, NRH, and NASH. Radiomic analysis of liver parenchyma may provide a signature that, in combination with clinical and laboratory data, improves the diagnosis of CALI.
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BACKGROUND: Desmoid-Type Fibromatosis (DTF) is a rare mesenchymal neoplasm with a locally invasive pattern and high risk of local recurrence after surgery. Historically, the standard treatment for DTF was surgical resection. However, considering the difficulty of achieving surgical eradication, the possible unnecessary morbidity and the unpredictability of the natural history, a wait-and-see approach has been proposed for asymptomatic DTF. METHODS: We analyzed 87 consecutive patients with histologically-proven sporadic primary DTF, first recurrence or residual disease managed at our institution between 2000 and 2018. Patients and tumor-related variables were reviewed and analyzed. Two different treatment strategies were adopted according to different time periods: in the "early period" (2000-2010) patients underwent surgical treatment irrespective of the clinical presentation, whereas in the "late period" (2012-2018) asymptomatic patients used to undergo a wait-and-see strategy. The event-free survival (EFS) was compared trough a pre-post comparison. RESULTS: In the early period, surgery was performed in 51 (94.4%) patients and watchful waiting in 3 (5.6%). In the late period, the watchful waiting group accounted for 24 (72.7%) patients and the surgical group for 9 (27.3%). No statistically independent prognostic factors were found. EFS did not show statistically significant differences between early and late period groups. CONCLUSION: Wait-and-see policy has shown to be equivalent to upfront surgery in terms of EFS; therefore, a conservative approach is recommended in asymptomatic patients diagnosed with DTF that can be followed through watchful waiting.
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Fibromatosis Agresiva/mortalidad , Fibromatosis Agresiva/cirugía , Espera Vigilante , Adulto , Anciano , Femenino , Fibromatosis Agresiva/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
Rhabdomyosarcoma (RMS) represents more than 50% of paediatric soft tissue tumours. Conversely, it is extremely rare among adults, where it shows peculiar biological and clinical features that are still poorly investigated. RMS patients should be referred to a Sarcoma Centre, where the contribution of experienced radiologists plays a relevant role in the diagnostic assessment of the disease, including precise localisation, staging, image-guided biopsy, response evaluation after treatment and follow-up. Besides CT and MRI, hybrid imaging including positron emission tomography (PET)/CT and PET/MRI are giving an increasing contribution to provide functional insights about tumour biology and to improve the diagnostic accuracy of the imaging work-up. This review paper provides a revision of the pathology, clinical and radiological features of adult RMS, with a particular focus on the growing role of hybrid PET-based imaging.