RESUMO
INTRODUCTION: Long regarded as "America's Past Time", over 8.6 million children partake in organized and recreational baseball. Although improved equipment has reduced contemporary injury rates, nearly half of pediatric baseball injuries requiring hospitalization are due to craniofacial trauma. Sideline personnel at the youth levels, often without advanced medical training, frequently act as first-responders in instances of acute craniofacial injury. METHODS: An IRB-approved survey was distributed nationally to target field personnel working at youth, high school, collegiate, and professional baseball levels. Survey items included: comfort in assessing subtypes of acute craniofacial trauma (loss of consciousness (LOC), skull injury, orbital injury, nasal injury, and dental injury) via Likert scale, years of medical training, presence of an emergency action plan (EAP), and access to higher level care from emergency medical services (EMS) or a nearby hospital. RESULTS: When comparing the amateur and professional cohorts, the respondents from professional teams were significantly more confident in assessing LOC (Pâ=â0.001), skull injury (Pâ<â0.001), orbital injury (Pâ<â0.001), nasal injury (Pâ<â0.001), and dental injury (Pâ<â0.001). The professional teams had significantly more years of first aid training (Pâ<â0.0001) and were significantly more likely to have an EAP (Pâ<â0.0001). Professional teams also had a significantly higher average of reported craniofacial incidents (Pâ=â0.0279). CONCLUSION: The authors identified a significant disparity in comfort level between amateur and professional baseball field personnel for identifying and managing acute craniofacial trauma. Based on these findings, the authors were able to develop a rudimentary tool for on-field personnel to effectively assess and manage craniofacial injuries.
Assuntos
Traumatismos em Atletas , Beisebol , Serviços Médicos de Emergência , Traumatismos Faciais , Adolescente , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/terapia , Criança , Emergências , Serviço Hospitalar de Emergência , Traumatismos Faciais/epidemiologia , Traumatismos Faciais/terapia , HumanosRESUMO
PURPOSE: Extent of resection remains a paramount prognostic factor for long-term outcomes for glioblastoma. As such, supramaximal resection or anatomic lobectomy have been offered for non-eloquent glioblastoma in an attempt to improve overall survival. Here, we conduct a propensity-matched analysis of patients with non-eloquent glioblastoma who underwent either lobectomy or gross total resection of lesion to investigate the efficacy of supramaximal resection of glioblastoma. METHODS: Patients who underwent initial surgery for gross total resection or lobectomy for non-eloquent glioblastoma at our tertiary care referral center from 2010 to 2019 were included for this propensity-matched survival analysis. Propensity scores were generated with the following covariates: age, location, preoperative KPS, product of perpendicular maximal tumor diameters, and product of perpendicular FLAIR signal diameters. Inverse probability of treatment weighting (IPTW) with generated propensity scores was used to compare progression-free survival and overall survival. RESULTS: Sixty-nine patients were identified who underwent initial resection of glioblastoma for non-eloquent glioblastoma from 2010 to 2019 (GTR = 37, lobectomy = 32). Using IPTW, overall survival (30.7 vs. 14.1 months) and progression-free survival (17.2 vs. 8.1 months were significantly higher in the lobectomy cohort compared to the GTR group (p < 0.001). There was no significant difference in pre-op or post-op KPS or complication rates between the two groups. CONCLUSION: Our propensity-matched study suggests that lobectomy for non-eloquent glioblastoma confers an added survival benefit compared to GTR alone. For patients with non-eloquent glioblastoma, a supramaximal resection by means of an anatomic lobectomy should be considered as a primary surgical treatment in select patients if feasible.
Assuntos
Neoplasias Encefálicas/mortalidade , Craniotomia/mortalidade , Glioblastoma/mortalidade , Procedimentos Neurocirúrgicos/mortalidade , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Feminino , Seguimentos , Glioblastoma/patologia , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Although mesenchymal stem cells (MSCs) have been implicated as stromal components of several cancers, their ultimate contribution to tumorigenesis and their potential to drive cancer stem cells, particularly in the unique microenvironment of human brain tumors, remain largely undefined. Consequently, using established criteria, we isolated glioma-associated-human MSCs (GA-hMSCs) from fresh human glioma surgical specimens for the first time. We show that these GA-hMSCs are nontumorigenic stromal cells that are phenotypically similar to prototypical bone marrow-MSCs. Low-passage genomic sequencing analyses comparing GA-hMSCs with matched tumor-initiating glioma stem cells (GSCs) suggest that most GA-hMSCs (60%) are normal cells recruited to the tumor (group 1 GA-hMSCs), although, rarely (10%), GA-hMSCs may differentiate directly from GSCs (group 2 GA-hMSCs) or display genetic patterns intermediate between these groups (group 3 GA-hMSCs). Importantly, GA-hMSCs increase proliferation and self-renewal of GSCs in vitro and enhance GSC tumorigenicity and mesenchymal features in vivo, confirming their functional significance within the GSC niche. These effects are mediated by GA-hMSC-secreted interleukin-6, which activates STAT3 in GSCs. Our results establish GA-hMSCs as a potentially new stromal component of gliomas that drives the aggressiveness of GSCs, and point to GA-hMSCs as a novel therapeutic target within gliomas.
Assuntos
Proliferação de Células , Receptor gp130 de Citocina/metabolismo , Glioma/metabolismo , Interleucina-6/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Feminino , Glioma/patologia , Humanos , Masculino , Células-Tronco Mesenquimais/patologiaRESUMO
Recent technological advancements have drastically improved the safety and surgical precision of operative neuro-oncology. These include techniques for avoiding critical functional structures through pre-operative mapping and trajectory planning, as well the development and refinement of minimally invasive surgical approaches. Innovations in intra-operative tumor mapping, and post-resection tumor ablation have further combined to improve surgical outcomes. This review highlights such advancements and discusses future directions within operative neuro-oncology.
Assuntos
Neoplasias Encefálicas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Procedimentos Neurocirúrgicos/tendências , Oncologia Cirúrgica/tendências , Mapeamento Encefálico , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Neuronavegação , Procedimentos Neurocirúrgicos/efeitos adversos , Cuidados Pré-Operatórios/tendências , Resultado do TratamentoRESUMO
BACKGROUND: Determining the appropriate surgical indications for obtunded octogenarians with traumatic acute subdural hematoma (aSDH) has been challenging. We sought to determine which easily available data would be useful adjuncts to assist in early and quick decision-making. METHODS: We performed a single-center, retrospective review of patients aged ≥80 years with confirmed traumatic aSDH who had undergone emergent surgery. The clinical measurements included the Karnofsky performance scale score, Charlson comorbidity index, Glasgow coma scale (GCS), and abbreviated injury score. The radiographic measurements included the Rotterdam computed tomography score, aSDH thickness, midline shift, and optic nerve sheath diameter (ONSD). The neurologic outcomes were defined using the extended Glasgow outcome scale-extended (GOS-E) at hospital discharge and 3-month follow-up. The Pearson correlation coefficient was used to compare the ONSD with all clinical, radiographic, and outcome variables. Multivariate logistic regression was used to assess the relationship between the discharge and 3-month GOS-E scores between all clinical and radiographic variables. RESULTS: A total of 17 patients met the inclusion criteria. The mean age was 82.5 ± 1.6 years (range, 80-85 years), and the mean GCS score was 11.2 ± 4.1 (range, 4-15). The mean discharge and 3-month GOS-E scores were 3.4 ± 2.6 (range, 1-8) and 2.3 ± 2.1 (range, 1-7), respectively. We found significant negative correlations between the ONSD and the GCS score (r = -0.62; P < 0.01) and the ONSD and discharge GOS-E score (r = -0.49; P = 0.05). Multivariate analysis revealed a significant association between the abbreviated injury score and the discharge GOS-E score (P = 0.05). CONCLUSIONS: Octogenarians sustaining aSDH and requiring emergent surgery have poor outcomes. More data are needed to determine whether the ONSD can be a useful adjunct tool to predict the efficacy of emergent surgery.
Assuntos
Hematoma Subdural Agudo , Hematoma Subdural Intracraniano , Idoso de 80 Anos ou mais , Humanos , Hematoma Subdural Agudo/cirurgia , Octogenários , Estudos Retrospectivos , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Resultado do TratamentoRESUMO
Asthma is a complex respiratory disease characterized by chronic inflammation of airways and frequently associated with atopic symptoms. The population from the Canary Islands, which has resulted from a recent admixture of North African and Iberian populations, shows the highest prevalence of asthma and atopic symptoms among the Spanish populations. Although environmental particularities would account for the majority of such disparity, genetic ancestry might play a role in increasing the susceptibility of asthma or atopy, as have been demonstrated in other recently African-admixed populations. Here, we aimed to explore whether genetic ancestry was associated with asthma or related traits in the Canary Islanders. For that, a total of 734 DNA samples from unrelated individuals of the GOA study, self-reporting at least two generations of ancestors from the Canary Islands (391 asthmatics and 343 controls), were successfully genotyped for 83 ancestry informative markers (AIMs), which allowed to precisely distinguishing between North African and Iberian ancestries. No association was found between genetic ancestry and asthma or related traits after adjusting by demographic variables differing among compared groups. Similarly, none of the individual AIMs was associated with asthma when results were considered in the context of the multiple comparisons performed (0.005 ≤ p value ≤ 0.042; 0.221 ≤ q value ≤ 0.443). Our results suggest that if genetic ancestry were involved in the susceptibility to asthma or related traits among Canary Islanders, its effects would be modest. Larger studies, examining more genetic variants, would be needed to explore such possibility.
Assuntos
Asma/genética , Predisposição Genética para Doença/genética , Hipersensibilidade Imediata/genética , Adolescente , Adulto , África/etnologia , Alelos , Asma/etnologia , População Negra/genética , Criança , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Hipersensibilidade Imediata/etnologia , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espanha/epidemiologia , Adulto JovemRESUMO
Patients who present with traumatic brain injury (TBI) combined with blunt cerebrovascular injuries (BCVI) are difficult to manage, in part because treatment for each entity may exacerbate the other. It is necessary to develop a treatment paradigm that ensures maximum benefit while mitigating the opposing risks. A cohort of 150 patients from 2015 to present, with either internal carotid artery (ICA) and/or vertebral artery (VA) dissections or pseudoaneurysms, was cross-referenced with those who had sustained TBI. Of the 38 patients identified with both TBI and BCVI, 25 suffered ICA injuries, 10 had VA injuries and 3 had combined ICA/VA injuries. Unilateral BCVI occurred in 30 patients, while 8 had bilateral BCVI. Two patients required surgical intervention for TBI, and 5 patients required endovascular intervention for BCVI. Positive emboli detection studies (EDS) on transcranial dopplers (TCD) were demonstrated in 19 patients, with 9 patients having radiographic evidence of stroke. Anti-platelet therapy was initiated in 32 patients, and anti-coagulation in 10 patients, without new or worsening intracranial hemorrhages (ICH). Overall, 76% of patients were able to be discharged home or to rehabilitation, with good recovery demonstrated in 73% of the patients who had appropriate follow-up. In the setting of concurrent TBI and BCVI, use of anti-platelet/coagulation to prevent stroke can be safe if monitored closely. Here we describe a treatment paradigm which weighs the risk and benefits of therapies based on severity of ICH and stroke prevention, which tended to result in good disposition and recovery.
Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/terapia , Traumatismo Cerebrovascular/complicações , Traumatismo Cerebrovascular/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Ferimentos não Penetrantes/terapia , Adulto JovemRESUMO
BACKGROUND: The response to the global severe acute respiratory syndrome coronavirus 2 pandemic culminated in mandatory isolation throughout the world, with nationwide confinement orders issued to decrease viral spread. These drastic measures were successful in "flattening the curve" and maintaining the previous rate of coronavirus disease 2019 infections and deaths. To date, the effects of the coronavirus disease 2019 pandemic on neurotrauma has not been reported. METHODS: We retrospectively analyzed hospital admissions from Ryder Trauma Center at Jackson Memorial Hospital, during the months of March and April from 2016 to 2020. Specifically, we identified all patients who had cranial neurotrauma consisting of traumatic brain injury and/or skull fractures, as well as spinal neurotrauma consisting of vertebral fractures and/or spinal cord injury. We then performed chart review to determine mechanism of injury and if emergent surgical intervention was required. RESULTS: Compared with previous years, we saw a significant decline in the number of neurotraumas during the pandemic, with a 62% decline after the lockdown began. The number of emergent neurotrauma surgical cases also significantly decreased by 84% in the month of April. Interestingly, although the number of vehicular traumas decreased by 77%, there was a significant 100% increase in the number of gunshot wounds. CONCLUSIONS: Population seclusion had a direct effect on the frequency of neurotrauma, whereas the change in relative proportion of certain mechanisms may be associated with the psychosocial effects of social distancing and quarantine.
Assuntos
Lesões Encefálicas Traumáticas/epidemiologia , COVID-19/epidemiologia , Admissão do Paciente/tendências , Quarentena/tendências , Traumatismos da Medula Espinal/epidemiologia , Centros de Traumatologia/tendências , Acidentes por Quedas , Lesões Encefálicas Traumáticas/diagnóstico , COVID-19/prevenção & controle , Humanos , Pandemias/prevenção & controle , Estudos Retrospectivos , Traumatismos da Medula Espinal/diagnósticoRESUMO
The aim of this study was to investigate, during the summer of the year 2008, the variation in leaf water and photosynthetic characteristics of Eucryphia cordifolia Cav. (Cunoniaceae) along its broad latitudinal distribution in central south Chile (36 degrees to 42 degrees S). The latitudinal variation in water potential (Psi(w)), water potential at saturation (Psipi(sat)), water potential at the turgor lost point (Psipi(tlp)), stomatal density of the leaves, leaf nitrogen concentrations and photosynthetic light response were studied in eight populations. The populations located in the northern region of the distribution of E. cordifolia had the lowest leaf water potential. Osmotic potential at full turgor was highest in the two southernmost populations and gradually decreased towards the northernmost points. Similarly, osmotic potential at zero turgor was the lowest in the northern population. On the contrary, the symplastic water content was lower in the two southernmost populations. The highest net photosynthesis rate was recorded for plants in the populations of intermediate distributions, and it was dependent on the precipitation and temperature gradient. The northern populations, which are subject to the lowest precipitations, showed the lowest stomatal densities, which were tightly linked with stomatal conductance variation. Therefore, the variability of A(max) was independent of stomatal density and conductance, so that the northern populations, subject to environments with less water availability, presented higher photosynthetic water use efficiency. Photosynthesis variations were also not associated with changes in leaf water potential or in nitrogen content in E. cordifolia leaves, which did not show any consistent latitudinal or altitudinal trend. In conclusion, the results support our hypothesis that the leaf water relations, stomatal characteristics and photosynthetic rates of the leaf would vary along its latitudinal gradient, helping to explain the ability of E. cordifolia trees to inhabit a broad latitudinal and altitudinal range throughout the central south Chile.
Assuntos
Magnoliopsida/fisiologia , Fotossíntese/fisiologia , Água/metabolismo , Altitude , Chile , DemografiaRESUMO
Laser interstitial thermal therapy (LITT) offers a minimally-invasive treatment option for glioblastomas (GBM) which are relatively small or in eloquent areas. While laser ablation for malignant gliomas has been shown to be safe and effective, the role of the subsequent immune response in not well established. In this study we aim to analyze the prognostic potential of edema volume and acute inflammation, quantified as neutrophil-to-lymphocyte ratio (NLR), in predicting overall survival. Twenty-one patients were identified with new or recurrent GBMs that were candidates for LITT. Laser ablation was performed using standard solid tumor protocol for treatment volume, intensity and duration. Edema volume was quantified using MRI imaging, while retrospective chart review was performed to calculate NLR and survival. In patients treated with LITT for GBM, peri-tumoral vasogenic edema volumes did not significantly change post-operatively, p > 0.200, while NLR significantly increased, p = 0.0002. The degree of NLR increase correlated with longer overall survivals, and ROC analysis demonstrated an area under the curve of 0.827, p = 0.0112. A delta-NLR cutoff of 7.0 results in positive and negative predictive values of 78% and 75%, respectively, in predicting overall survival >1 year. Patients with with delta-NLR > 7.0 lived significantly longer that those with delta-NLR < 7.0, median survival 440 days compared to 239 days, p = 0.0297. We demonstrate preliminary data that monitoring the inflammatory response after LITT in GBM patients offers a potential prognostic measurement to assist in predicting treatment efficacy and overall survival.
Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Hipertermia Induzida/métodos , Terapia a Laser/métodos , Linfócitos/metabolismo , Neutrófilos/metabolismo , Adulto , Idoso , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/mortalidade , Feminino , Seguimentos , Glioblastoma/sangue , Glioblastoma/mortalidade , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do TratamentoRESUMO
With a recent trend towards supra-maximal resection for gliomas and minimally invasive techniques, keyhole temporal lobectomies may serve an important role in neurosurgical oncology. Due to their location and proximity to eloquent brain, temporal lobe gliomas offer unique challenges that may limit the extent of resection. Here we describe a modified technique using mini-craniotomies through a keyhole approach for temporal lobectomies in glioma patients. We retrospectively reviewed data from consecutive patients who underwent temporal lobectomies for resection of gliomas from 2012 to 2018. Demographic data, extent of tumor resection, pre and post-op KPS, short term and long term complications, as well as other relevant data were collected. We identified 57 patients who underwent keyhole-mini craniotomy for temporal lobectomies for glioma. Surgical procedures were performed in 12 patients for low-grade glioma (LGG) and 45 patients for high-grade glioma (HGG). Awake craniotomies were performed in 15 of the cases, and 13 cases were for tumor recurrence. Supra-maximal resection (SMR) was achieved in 15 patients, while gross total resection (GTR) and near total resection (NTR) achieved in 32 patients and 10 patients, respectively. Average pre- and post-op KPS were equivalent, and post-operative complications requiring surgical intervention were experienced in 4 patients. Here we show that our modified keyhole craniotomy is both safe and effective in achieving SMR or GTR in glioma patients, with minimal morbidity. This minimally-invasive temporal lobectomy may be an instrumental tool for neurosurgical oncologists transitioning to less invasive techniques.
Assuntos
Neoplasias Encefálicas/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Glioma/cirurgia , Adulto , Idoso , Craniotomia/métodos , Estudos de Viabilidade , Feminino , Glioma/patologia , Hemisferectomia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/cirurgia , Psicocirurgia , Estudos Retrospectivos , Técnicas Estereotáxicas , Lobo Temporal/patologia , VigíliaRESUMO
BACKGROUND: It has been suggested that autonomic nervous system dysfunction may explain all of fibromyalgia (FM) multisystem features. Such proposal is based mostly on the results of diverse heart rate variability analyses. The Composite Autonomic Symptom Scale (COMPASS) is a different validated method to recognize dysautonomia. OBJECTIVES: The main objective of our study was to investigate symptoms of autonomic dysfunction in FM patients by means of COMPASS. A secondary objective was to define whether there is a correlation between COMPASS and Fibromyalgia Impact Questionnaire (FIQ) scores in FM patients. METHODS: Design, analytical cross-sectional study. Our study population included 3 different groups of women: 30 patients with FM, 30 patients with rheumatoid arthritis, and 30 women who considered themselves healthy. All participants filled out COMPASS and FIQ questionnaires. RESULTS: FM patients had significantly higher values in all COMPASS domains. COMPASS total score (54.6 +/- 20.9; mean +/- standard deviation) clearly differentiated FM patients from the other 2 groups (21.6 +/- 16.5 and 9.5 +/- 10.2, respectively). P < 0.0001. The majority of FM patients gave affirmative answers to questions related to orthostatic, digestive, sleep, sudomotor, or mucosal dysfunction. There was a significant correlation between COMPASS and FIQ scores (Spearman r = 0.5, P < 0.005). CONCLUSIONS: Patients with FM have multiple nonpain symptoms related to different expressions of autonomic dysfunction. There is a correlation between a questionnaire that measures FM severity (FIQ) and an autonomic dysfunction questionnaire (COMPASS). Such correlation suggests that autonomic dysfunction is inherent to FM.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Fibromialgia/fisiopatologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto , Artrite Reumatoide/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Avaliação da Deficiência , Feminino , Nível de Saúde , Humanos , Pessoa de Meia-IdadeAssuntos
Asma/genética , Quinases Associadas a Receptores de Interleucina-1/genética , Adolescente , Adulto , Asma/imunologia , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espanha , Adulto JovemRESUMO
The detection of glioblastoma (GBM) in biofluids offers potential advantages over existing paradigms for the diagnosis and therapeutic monitoring of glial tumors. Biofluid-based detection of GBM focuses on detecting tumor-specific biomarkers in the blood and CSF. Current clinical research concentrates on studying 3 distinct tumor-related elements: extracellular macromolecules, extracellular vesicles, and circulating tumor cells. Investigations into these 3 biological classifications span the range of locales for tumor-specific biomarker discovery, and combined, have the potential to significantly impact GBM diagnosis, monitoring for treatment response, and surveillance for recurrence. This review highlights the recent advancements in the development of biomarkers and their efficacy for the detection of GBM.
Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/líquido cefalorraquidiano , Vesículas Extracelulares , Glioblastoma/sangue , Glioblastoma/líquido cefalorraquidiano , Humanos , Células Neoplásicas CirculantesRESUMO
Background: Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM), generated by deletion of exons 2 to 7 of EGFR. The proximal breakpoints occur in variable positions within the 123-kb intron 1, presenting significant challenges in terms of polymerase chain reaction (PCR)-based mapping. Molecular mechanisms underlying these deletions remain unclear. Methods: We determined the presence of EGFRvIII and its breakpoints for 29 GBM samples using quantitative PCR, arrayed PCR mapping, Sanger sequencing, and whole genome sequencing (WGS). Patient-specific breakpoint PCR was performed on tumors, plasma, and cerebrospinal fluid (CSF) samples. The breakpoint sequences and single nucleotide polymorphisms (SNPs) were analyzed to elucidate the underlying biogenic mechanism. Results: PCR mapping and WGS independently unveiled 8 EGFRvIII breakpoints in 6 tumors. Patient-specific primers yielded EGFRvIII PCR amplicons in matched tumors and in cell-free DNA (cfDNA) from a CSF sample, but not in cfDNA or extracellular-vesicle DNA from plasma. The breakpoint analysis revealed nucleotide insertions in 4 samples, an insertion of a region outside of the EGFR locus in 1, microhomologies in 3, as well as a duplication or an inversion accompanied by microhomologies in 2, suggestive of distinct DNA repair mechanisms. In the GBM samples that harbored distinct breakpoints, the SNP compositions of EGFRvIII and amplified non-vIII EGFR were identical, suggesting that these rearrangements arose from amplified non-vIII EGFR. Conclusion: Our approach efficiently "fingerprints" each sample's EGFRvIII breakpoints. Breakpoint sequence analyses suggest that independent breakpoints arose from precursor amplified non-vIII EGFR through different DNA repair mechanisms.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Receptores ErbB/genética , Deleção de Genes , Rearranjo Gênico , Genoma Humano , Glioblastoma/genética , Sequência de Bases , Neoplasias Encefálicas/patologia , Seguimentos , Glioblastoma/patologia , Humanos , Polimorfismo de Nucleotídeo Único , Prognóstico , Homologia de Sequência , Sequenciamento Completo do Genoma/métodosRESUMO
Introduction: Fibromyalgia syndrome (FMS) is characterized by chronic musculoskeletal pain, fatigue, and the sense of waking unrefreshed. Obstructive sleep apnoea syndrome (OSAS) and FMS have symptoms in common and the association of OSAS in these patients could confuse the diagnosis and worsen the severity and prognosis of FMS. The objective of this study was to establish the presence of OSAS in patients with FMS and sleep complaints in a sleep clinic. Methods: A cross-sectional study was conducted in patients aged 18 and above with FMS who were referred by rheumatology to a sleep clinic to confirm OSAS with polysomnography from 2015 to 2018. Descriptive statistics tools were applied. Results: Polysomnographic investigations were performed in 51 patients with FMS. OSAS was detected in 82% of patients. The mean age was 65 years. Of the patients studied, 82% were women and 78% of them had OSAS. All the male patients with FM had OSAS. Of the patients, 27.5% were normal weight and 45% were overweight. Of the patients, 23% had severe OSAS, 31% moderate and 45% mild. Conclusion: We found a high frequency of OSAS in this group of FMS patients. Since the 2 diseases share symptoms, it is interesting to delve deeper into the investigation of common pathophysiological mechanisms. The coexistence of the 2 pathologies poses diagnostic and therapeutic challenges that implies the need for further study at local level.
Introducción: La fibromialgia (FM) se caracteriza por dolor crónico, cansancio y sueno no reparador. El síndrome de apnea hipopnea obstructiva del sueño (SAHOS) tiene síntomas en común con la FM y su presencia puede confundir el diagnóstico y empeorar la gravedad y el pronóstico de la FM. El objetivo de este estudio fue establecer la presencia de SAHOS en pacientes con FM y alteraciones del sueño en una clínica de sueño. Métodos: Estudio observacional, de corte transversal, en pacientes mayores de 18 arios con FM remitidos por Reumatología a una clínica de sueño para confirmar SAHOS por medio de polisomnografía, entre el 2015 y el 2018. Se aplicaron herramientas de estadística descriptiva. Resultados: Se realizó polisomnografía completa a 51 pacientes con FM y se confirmó SAHOS en el 82%. La edad media fue de 65 años. El 82% de los pacientes estudiados fueron mujeres y, de estas, el 78% tuvo SAHOS. Al 100% de los hombres con FM se les diagnosticó SAHOS. El 27,5% tuvo un peso normal y el 45% sobrepeso. El 23% de los pacientes tuvo SAHOS grave, el 31% moderado y el 45% leve. Conclusiones: Encontramos una alta frecuencia de SAHOS en este grupo de pacientes con FM. Las 2 enfermedades comparten síntomas, por lo que es interesante profundizar más en la investigación de mecanismos fisiopatológicos comunes. La coexistencia de las 2 patologías plantea retos diagnósticos y terapéuticos que vislumbran la necesidad de estudios más profundos a escala local.
Assuntos
Humanos , Pessoa de Meia-Idade , Idoso , Doenças Respiratórias , Reumatologia , Fibromialgia , Doenças Musculoesqueléticas , Ocupações em Saúde , Medicina , Doenças MuscularesRESUMO
Priapism is defined as an erection that persists beyond four hours, lasting beyond or unrelated to sexual stimulation (Salonia et al., 2014). Because the risk of ischemic damage and impotence is high with priapism (35%), management guidelines are directed towards rapid treatment of this condition (Salonia et al., 2014). This report describes the rare case of an 18-year-old male who presented to the Emergency Department (ED) three times with recurrent and worsening episodes of sustained penile erections. On the patient's third visit, he presented with priapism of greater than six-hour duration that was found to be the result of chronic myeloid leukemia. Clinician awareness of the diagnostic semantics and differential diagnosis surrounding priapism is pivotal in its urgent management.
RESUMO
Tumor-stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressor NCOR1. Our results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC-derived exosomes in the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma. Cancer Res; 77(21); 5808-19. ©2017 AACR.
Assuntos
Transformação Celular Neoplásica , Exossomos/genética , Glioma/genética , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Animais , Western Blotting , Células Cultivadas , Exossomos/metabolismo , Exossomos/ultraestrutura , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Glioma/patologia , Humanos , Camundongos Nus , Microscopia Eletrônica , Células-Tronco Neoplásicas/transplante , Correpressor 1 de Receptor Nuclear/genética , Correpressor 1 de Receptor Nuclear/metabolismo , Transplante de Células-Tronco/métodos , Transplante HeterólogoRESUMO
PURPOSE: To develop a cerebrospinal fluid (CSF) miRNA diagnostic biomarker for glioblastoma. EXPERIMENTAL DESIGN: Glioblastoma tissue and matched CSF from the same patient (obtained prior to tumor manipulation) were profiled by TaqMan OpenArray® Human MicroRNA Panel. CSF miRNA profiles from glioblastoma patients and controls were created from three discovery cohorts and confirmed in two validation cohorts. RESULTS: miRNA profiles from clinical CSF correlated with those found in glioblastoma tissues. Comparison of CSF miRNA profiles between glioblastoma patients and non-brain tumor patients yielded a tumor "signature" consisting of nine miRNAs. The "signature" correlated with glioblastoma tumor volume (p=0.008). When prospectively applied to cisternal CSF, the sensitivity and specificity of the 'signature' for glioblastoma detection were 67% and 80%, respectively. For lumbar CSF, the sensitivity and specificity of the signature were 28% and 95%, respectively. Comparable results were obtained from analyses of CSF extracellular vesicles (EVs) and crude CSF. CONCLUSION: We report a CSF miRNA signature as a "liquid biopsy" diagnostic platform for glioblastoma.
RESUMO
BACKGROUND: RNAs within extracellular vesicles (EVs) have potential as diagnostic biomarkers for patients with cancer and are identified in a variety of biofluids. Glioblastomas (GBMs) release EVs containing RNA into cerebrospinal fluid (CSF). Here we describe a multi-institutional study of RNA extracted from CSF-derived EVs of GBM patients to detect the presence of tumor-associated amplifications and mutations in epidermal growth factor receptor (EGFR). METHODS: CSF and matching tumor tissue were obtained from patients undergoing resection of GBMs. We determined wild-type (wt)EGFR DNA copy number amplification, as well as wtEGFR and EGFR variant (v)III RNA expression in tumor samples. We also characterized wtEGFR and EGFRvIII RNA expression in CSF-derived EVs. RESULTS: EGFRvIII-positive tumors had significantly greater wtEGFR DNA amplification (P = 0.02) and RNA expression (P = 0.03), and EGFRvIII-positive CSF-derived EVs had significantly more wtEGFR RNA expression (P = 0.004). EGFRvIII was detected in CSF-derived EVs for 14 of the 23 EGFRvIII tissue-positive GBM patients. Conversely, only one of the 48 EGFRvIII tissue-negative patients had the EGFRvIII mutation detected in their CSF-derived EVs. These results yield a sensitivity of 61% and a specificity of 98% for the utility of CSF-derived EVs to detect an EGFRvIII-positive GBM. CONCLUSION: Our results demonstrate CSF-derived EVs contain RNA signatures reflective of the underlying molecular genetic status of GBMs in terms of wtEGFR expression and EGFRvIII status. The high specificity of the CSF-derived EV diagnostic test gives us an accurate determination of positive EGFRvIII tumor status and is essentially a less invasive "liquid biopsy" that might direct mutation-specific therapies for GBMs.