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1.
Annu Rev Immunol ; 30: 295-312, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22224773

RESUMO

The mammalian inflammatory response is a rapid and complex physiological reaction to noxious stimuli including microbial pathogens. Although inflammation plays a valuable role in combating infection, its dysregulation often occurs in people and can cause a variety of pathologies, ranging from chronic inflammation, to autoimmunity, to cancer. In recent years, our understanding of both the cellular and molecular networks that regulate inflammation has improved dramatically. Although much of the focus has been on the study of protein regulators of inflammation, recent evidence also points to a critical role for a specific class of noncoding RNAs, called microRNAs (miRNAs), in managing certain features of the inflammatory process. In this review, we discuss recent advances in our understanding of miRNAs and their connection to inflammatory responses. Additionally, we consider the link between perturbations in miRNA levels and the onset of human inflammatory diseases.


Assuntos
Inflamação/genética , MicroRNAs/genética , Imunidade Adaptativa/genética , Animais , Autoimunidade/genética , Doenças Transmissíveis/genética , Doenças Transmissíveis/imunologia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Humanos , Imunidade Inata/genética , Inflamação/imunologia
2.
Mol Ther ; 32(5): 1311-1327, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38449314

RESUMO

While studying transgene expression after systemic administration of lentiviral vectors, we found that splenic B cells are robustly transduced, regardless of the types of pseudotyped envelope proteins. However, the administration of two different pseudotypes resulted in transduction of two distinct B cell populations, suggesting that each pseudotype uses unique and specific receptors for its attachment and entry into splenic B cells. Single-cell RNA sequencing analysis of the transduced cells demonstrated that different pseudotypes transduce distinct B cell subpopulations characterized by specific B cell receptor (BCR) genotypes. Functional analysis of the BCRs of the transduced cells demonstrated that BCRs specific to the pseudotyping envelope proteins mediate viral entry, enabling the vectors to selectively transduce the B cell populations that are capable of producing antibodies specific to their envelope proteins. Lentiviral vector entry via the BCR activated the transduced B cells and induced proliferation and differentiation into mature effectors, such as memory B and plasma cells. BCR-mediated viral entry into clonally specific B cell subpopulations raises new concepts for understanding the biodistribution of transgene expression after systemic administration of lentiviral vectors and offers new opportunities for BCR-targeted gene delivery by pseudotyped lentiviral vectors.


Assuntos
Linfócitos B , Vetores Genéticos , Lentivirus , Receptores de Antígenos de Linfócitos B , Transdução Genética , Transgenes , Proteínas do Envelope Viral , Lentivirus/genética , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores de Antígenos de Linfócitos B/genética , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , Animais , Camundongos , Linfócitos B/metabolismo , Linfócitos B/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Tropismo Viral , Humanos , Internalização do Vírus
3.
RNA Biol ; 21(1): 1-14, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38329136

RESUMO

In recent years, advances in biomedicine have revealed an important role for post-transcriptional mechanisms of gene expression regulation in pathologic conditions. In cancer in general and leukaemia specifically, RNA binding proteins have emerged as important regulator of RNA homoeostasis that are often dysregulated in the disease state. Having established the importance of these pathogenetic mechanisms, there have been a number of efforts to target RNA binding proteins using oligonucleotide-based strategies, as well as with small organic molecules. The field is at an exciting inflection point with the convergence of biomedical knowledge, small molecule screening strategies and improved chemical methods for synthesis and construction of sophisticated small molecules. Here, we review the mechanisms of post-transcriptional gene regulation, specifically in leukaemia, current small-molecule based efforts to target RNA binding proteins, and future prospects.


Assuntos
Neoplasias Hematológicas , Leucemia , Humanos , Regulação da Expressão Gênica , RNA/genética , Neoplasias Hematológicas/genética , Leucemia/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
4.
Radiographics ; 44(10): e240037, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39356632

RESUMO

The past decade has seen exponential advancements in molecular markers and the genetics of tumors, recognizing the limitations of conventional histopathology for grading, classification, and prognostication. Such advances have resulted in changes to classification systems, for example, with the incorporation of objective molecular and genetic information into the 2021 World Health Organization (WHO) classification of central nervous system tumors. The fifth edition of the WHO classification of head and neck tumors (HN5) (beta online version, 2022) also introduced major changes based on molecular markers, including additions, deletions, and reclassifications of entities, with the idea of being more objective and standardized. These changes are highly relevant to therapy decisions, prognosis, and clinical research and for patients with resistant diseases to explore options in clinical trials. The HN5, for the first time, included a radiologist as a member of the writing team to incorporate pertinent imaging findings into the classification. It is important for the radiologist, as an integral part of the multidisciplinary team, to be up to date about these changes for a better understanding of tumor biology, to integrate this into their clinical practice, and to provide more value in their interpretations. The authors provide a basic understanding of pathology and genetics for the radiologist, highlighting the molecular changes in epithelial (including squamous cell) and nonepithelial tumors of the head and neck. The authors also highlight newly recognized and reclassified tumor entities and provide a brief discussion on the genetic tumor syndromes. ©RSNA, 2024 Supplemental material is available for this article. See the invited commentary by Junn and Baugnon in this issue.


Assuntos
Biomarcadores Tumorais , Neoplasias de Cabeça e Pescoço , Organização Mundial da Saúde , Humanos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/classificação
5.
Emerg Radiol ; 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39304569

RESUMO

PURPOSE: For acute stroke patients requiring MR examination and unable to provide a reliable history, screening for potentially MRI-incompatible objects (PMIOs) typically necessitates the use of plain-film radiographs (PFRs). However, using a whole body CT scout at the time of non-contrast head CT scans can preclude critical delays. Here, we aim to compare the effectiveness of PFRs and CT scouts in detecting PMIOs. METHODS: A case-control study was conducted at a tertiary care institution, involving 408 imaging studies from 200 patients, half of which contained PMIOs. The diagnostic performances of CT scouts and PFRs were evaluated by six blinded readers, including two board-certified neuroradiologists, one neuroradiology fellow, and three radiology residents. RESULTS: 2448 interpretations from the 6 readers were analyzed. The diagnostic performance of combined CT scout images (full-body and regional) was not significantly different from that of PFRs for all six readers (p = 0.06). However, PFRs outperformed full-body CT scouts in PMIO detection (p = 0.01), with no significant differences observed between PFRs and regional CT scouts (p = 0.4). Notably, the diagnostic accuracy of the radiology residents was found to be equivalent to radiologists across all imaging techniques. CONCLUSION: Integrating CT scouts in acute stroke protocols may help expedite MRI screening. The scouts should include the head, neck, chest, upper arms, abdomen, pelvis, and thighs. Including radiology residents in the screening process for PMIOs may be an avenue for resource optimization in acute care settings.

6.
Immunity ; 41(4): 605-19, 2014 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-25367574

RESUMO

Chronic inflammation is a contributing factor to most life-shortening human diseases. However, the molecular and cellular mechanisms that sustain chronic inflammatory responses remain poorly understood, making it difficult to treat this deleterious condition. Using a mouse model of age-dependent inflammation that results from a deficiency in miR-146a, we demonstrate that miR-155 contributed to the progressive inflammatory disease that emerged as Mir146a(-/-) mice grew older. Upon analyzing lymphocytes from inflamed versus healthy middle-aged mice, we found elevated numbers of T follicular helper (Tfh) cells, germinal center (GC) B cells, and autoantibodies, all occurring in a miR-155-dependent manner. Further, Cd4-cre Mir155(fl/fl) mice were generated and demonstrated that miR-155 functions in T cells, in addition to its established role in B cells, to promote humoral immunity in a variety of contexts. Taken together, our study discovers that miR-146a and miR-155 counterregulate Tfh cell development that drives aberrant GC reactions during chronic inflammation.


Assuntos
Centro Germinativo/imunologia , Inflamação/imunologia , MicroRNAs/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Transferência Adotiva , Animais , Autoanticorpos/biossíntese , Autoanticorpos/imunologia , Linfócitos B/imunologia , Antígenos CD4/biossíntese , Diferenciação Celular/imunologia , Modelos Animais de Doenças , Antígeno 2 Relacionado a Fos/genética , Centro Germinativo/citologia , Imunidade Humoral , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , Interferência de RNA , RNA Interferente Pequeno
7.
J Natl Compr Canc Netw ; 21(5): 503-513, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37156478

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. It is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths from leukemias in the United States. Like AML, blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a myeloid malignancy. It is a rare malignancy characterized by the aggressive proliferation of precursors of plasmacytoid dendritic cells that frequently involves the bone marrow, skin, central nervous system, and other organs and tissues. This discussion section focuses on the diagnosis and management of BPDCN as outlined in the NCCN Guidelines for AML.


Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Neoplasias Cutâneas , Adulto , Humanos , Células Dendríticas/patologia , Neoplasias Hematológicas/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/patologia , Oncologia , Neoplasias Cutâneas/diagnóstico
8.
J Neurooncol ; 161(3): 481-489, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36692832

RESUMO

PURPOSE: Benign intracranial meningioma is one of the most common primary brain neoplasms. Proton therapy has been increasingly utilized for nonoperative management of this neoplasm, yet few long-term outcomes studies exist. METHODS: The medical records of a total of 59 patients with 64 lesions were reviewed under a prospective outcomes tracking protocol for histologically proven or radiographically benign meningioma. The patients were treated with proton therapy at the University of Florida Proton Therapy Institute between 2007 and 2019 and given a median dose of 50.4 GyRBE at 1.8 GyRBE (relative biological effectiveness) (range 48.6-61.2 GyRBE) in once-daily treatments. RESULTS: With a median clinical and imaging follow-up of 6.3 and 4.7 years, the rates of 5-year actuarial local progression and cumulative incidence of grade 3 or greater toxicity were 6% (95% confidence interval [CI] 1%-14%), and 2% (95% CI < 1%-15%), respectively. Two patients experienced local progression after 5 years. The 5-year actuarial overall survival rate was 87% (95% CI 74-94%). CONCLUSION: Fractionated PBT up to 50.4 GyRBE is a safe and highly effective therapy for treating benign intracranial meningioma.


Assuntos
Neoplasias Meníngeas , Meningioma , Terapia com Prótons , Humanos , Meningioma/diagnóstico por imagem , Meningioma/radioterapia , Estudos Prospectivos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/radioterapia
9.
Naturwissenschaften ; 110(3): 23, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37219696

RESUMO

Some visual antipredator strategies involve the rapid movement of highly contrasting body patterns to frighten or confuse the predator. Bright body colouration, however, can also be detected by potential predators and used as a cue. Among spiders, Argiope spp. are usually brightly coloured but they are not a common item in the diet of araneophagic wasps. When disturbed, Argiope executes a web-flexing behaviour in which they move rapidly and may be perceived as if they move backwards and towards an observer in front of the web. We studied the mechanisms underlying web-flexing behaviour as a defensive strategy. Using multispectral images and high-speed videos with deep-learning-based tracking techniques, we evaluated body colouration, body pattern, and spider kinematics from the perspective of a potential wasp predator. We show that the spider's abdomen is conspicuous, with a disruptive colouration pattern. We found that the body outline of spiders with web decorations was harder to detect when compared to spiders without decorations. The abdomen was also the body part that moved fastest, and its motion was composed mainly of translational (vertical) vectors in the potential predator's optical flow. In addition, with high contrast colouration, the spider's movement might be perceived as a sudden change in body size (looming effect) as perceived by the predator. These effects alongside the other visual cues may confuse potential wasp predators by breaking the spider body outline and affecting the wasp's flight manoeuvre, thereby deterring the wasp from executing the final attack.


Assuntos
Aranhas , Vespas , Animais , Tamanho Corporal , Sinais (Psicologia) , Gravação de Videoteipe
10.
J Comput Assist Tomogr ; 47(1): 102-107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36668982

RESUMO

OBJECTIVE: There are currently no guidelines for when to use intravenous contrast with head computed tomography (CT) when there is suspected acute intracranial infection. The purpose of our study was to determine the proportion of cases with enhancing findings on CT that also have conspicuous correlating associated findings on noncontrast CT, which would have on their own merited further evaluation with magnetic resonance imaging, the criterion standard for evaluating central nervous system pathology. METHODS: A retrospective keyword search of the history and clinical information fields in radiology reports for CT examinations of the head without and with contrast from the period January 1, 2004, to October 31, 2021 was performed. Patients with prior head surgery or a history of cancer were excluded. For remaining patients, the noncontrast CT was reviewed for vasogenic edema or mass effect as markers of a possible acute infection, and the presence of background hypodense white matter changes was noted and graded as either absent, mild/scattered, or confluent. Subsequently, the companion contrast-enhanced CT was reviewed for an enhancing abnormality. Chart review was performed to confirm that an infectious process was the ultimate clinical diagnosis in patients with enhancing abnormalities. RESULTS: Of 343 patients meeting study inclusion/exclusion criteria, 39 had acute infections with an enhancing abnormality on CT (prevalence 11.3%). Thirty-two of these 39 patients also had correlative findings on the noncontrast CT. Noncontrast CT had a positive predictive value of 100%, negative predictive value of 97.7%, sensitivity of 82.1%, specificity of 100%, and accuracy of 98.0% for detecting markers (vasogenic edema and/or mass effect) associated with an enhancing abnormality. Vasogenic edema was the most common noncontrast CT finding in patients who had an infectious enhancing lesion (32 of 39), followed by mass effect (22 of 39). The 7 cases where the acute infection was occult on noncontrast CT were due to leptomeningitis (n = 3), confluent background white matter changes masking the vasogenic edema surrounding intra-axial lesions (n = 3), and a small 0.5 cm extra-axial abscess. CONCLUSIONS: Most acute intracranial infections with an enhancing CT finding also have a correlative conspicuous noncontrast finding that on its own would merit further evaluation with magnetic resonance imaging, the criterion standard for investigating central nervous system disease, and therefore, in the setting of suspected intracranial infection, contrast-enhanced CT is redundant in most cases. Contrast-enhanced CT primarily provides diagnostic benefit in patients with confluent background white matter changes that may mask vasogenic edema on noncontrast CT.


Assuntos
Cabeça , Tomografia Computadorizada por Raios X , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Valor Preditivo dos Testes , Imageamento por Ressonância Magnética
11.
J Comput Assist Tomogr ; 47(3): 460-466, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37185011

RESUMO

OBJECTIVE: This study aimed to retrospectively distinguish true- from false-positive fractures of anterior subaxial cervical osteophytes, which were reported on noncontrast computed tomography reports, and to correlate the imaging findings with patient symptoms and analyze the downstream impact on management of both true and false positive fractures. METHODS: A total of 127 patients had computed tomography reports of anterior osteophyte fractures. Radiology reports and imaging studies were evaluated to distinguish true fractures from fracture mimics. We analyzed imaging features including rigid spine (RS), prevertebral soft tissue swelling (PVSTS), and instability. We categorized symptoms and examination findings into 3 groups (0, asymptomatic; 1, neck pain; 2, neurological symptoms). Management was categorized into 3 groups (0, no treatment; 1, external bracing; 2, surgery). Associations between imaging features, fracture classification, clinical symptoms, magnetic resonance imaging utilization, and management were calculated using χ2 with Cramer V test to determine effect size. RESULTS: Eighty patients had false-positive fractures, and 47 were true positive. There were significant associations between magnetic resonance imaging utilization and fracture classification (P ≤ 0.001), PVSTS (P ≤ 0.005), patient symptoms (P ≤ 0.001), and patient management (P ≤ 0.001). There were significant associations between patient management and fracture classification (P ≤ 0.001), patient symptoms (P ≤ 0.001), PVSTS (P ≤ 0.001), imaging findings of instability (P ≤ 0.001), and RS (P ≤ 0.021). There were significant associations between fracture classification and patient symptoms (P ≤ 0.045), and RS (P ≤ 0.006). CONCLUSIONS: Subaxial isolated anterior osteophyte fractures fell into 3 major categories. By our methodology, if a suspected fracture was determined to be a fracture mimic in an asymptomatic patient, it was unlikely to be clinically significant. Isolated anterior osteophyte fractures without neurological symptoms or more concerning imaging findings can be treated conservatively. Finally, fractures that demonstrate indirect signs of instability or are associated with RS are more associated with surgical management.


Assuntos
Fraturas Ósseas , Osteófito , Fraturas da Coluna Vertebral , Humanos , Osteófito/diagnóstico por imagem , Osteófito/complicações , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/terapia , Vértebras Cervicais/diagnóstico por imagem
12.
Emerg Radiol ; 30(2): 235-238, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36877323

RESUMO

High-pressure paint injection injury to the orbit is a rare type of orbital trauma. We present an unfortunate case of high-pressure paint injury to the right orbit of a young patient. High-pressure injection injury presents with a unique injury mechanism and resultant deep tissue damage. The superficial appearance of the entry site injury is deceiving; therefore, a thorough evaluation is necessary. Debridement is usually required if foreign body material is present. Antibiotics and steroids are commonly used in such cases.


Assuntos
Traumatismos Oculares , Doenças Orbitárias , Humanos , Órbita/diagnóstico por imagem , Órbita/lesões , Pintura
13.
Emerg Radiol ; 30(3): 333-342, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37085742

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study was to identify and classify the different types of anterior atlanto-occipital membrane complex injuries on MRI and evaluate for the presence, size, and location of a prevertebral effusion on the preceding CT exams. MATERIALS AND METHODS: Patients who suffered an anterior atlanto-occipital membrane complex injury were identified retrospectively utilizing Nuance mPower software. An anatomic-based description of the location of the anterior atlanto-occipital membrane complex injury was recorded along with any additional osteoligamentous trauma of the craniocervical junction. The preceding cervical CT exams for these patients were reviewed for the presence and location of a prevertebral effusion. RESULTS: Fifty patients were identified with an acute, post-traumatic anterior atlanto-occipital membrane complex injury. Three distinct patterns of anterior atlanto-occipital membrane complex injury were observed. Nineteen patients demonstrated increased STIR signal with disruption of the anterior atlanto-occipital membrane, ten patients demonstrated increased STIR signal with disruption of the anterior atlanto-axial membrane, and twenty-one patients demonstrated increased STIR signal with disruption of both the anterior atlanto-occipital membrane and anterior atlanto-axial membrane. An effusion at the C1-C2 level was present in greater than 90% of patients with anterior atlanto-occipital membrane complex injury. CONCLUSIONS: The presence of a craniocervical prevertebral effusion on CT in trauma patients may raise suspicion for an injury to the anterior atlanto-occipital membrane complex and potentially trigger additional investigation with cervical MRI.


Assuntos
Articulação Atlantoaxial , Articulação Atlantoccipital , Luxações Articulares , Humanos , Estudos Retrospectivos , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/lesões , Luxações Articulares/diagnóstico por imagem , Pescoço , Imageamento por Ressonância Magnética , Articulação Atlantoccipital/diagnóstico por imagem , Articulação Atlantoccipital/lesões
14.
Gen Dent ; 71(6): 68-72, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37889247

RESUMO

Silver diamine fluoride (SDF), an effective topical fluoride agent for arresting caries, has a reputation for staining the teeth. Potassium iodide (KI) has been reported to minimize such staining, but doubts remain over its long-term efficacy and potential adverse influence on the effectiveness of SDF. This in vitro study used quantitative evaluation of color changes and the silver and fluoride release of treated tooth specimens to determine the effect of KI on the staining and caries-arresting properties of SDF. Twenty-one noncarious premolars were sectioned buccolingually to create 42 tooth specimens that were divided into 3 groups for color comparison and ion release measurements. The specimens in the experimental group were treated with a combined SDF + KI product (n = 16), the specimens in the positive control group were treated with SDF (n = 16), and the specimens in the negative control group were untreated (n = 10). Digital color analysis was performed weekly for a month according to the CIE L*a*b* color system of the International Commission on Illumination. Atomic spectrophotometry and ion-selective electrodes were used to measure the quantity of fluoride and silver ions released after 24 and 48 hours. The data from the color measurements were analyzed with the Friedman and Fisher tests, while the data from the ion release measurements were analyzed with the Mann-Whitney U and Wilcoxon signed rank tests. The analysis revealed that KI reduced the dentinal staining caused by SDF, but its effectiveness decreased over time as evidenced by the significantly deteriorating perceptual lightness (L*) values of SDF + KI-treated tooth specimens. The SDF + KI-treated specimens released significantly less silver and fluoride ions than the SDF-treated specimens. Because KI lost its stain-reducing property over time and reduced the effectiveness of SDF, a better "antidote" to SDF staining is needed.


Assuntos
Cárie Dentária , Fluoretos Tópicos , Humanos , Fluoretos Tópicos/farmacologia , Fluoretos Tópicos/uso terapêutico , Fluoretos , Iodeto de Potássio/farmacologia , Iodeto de Potássio/uso terapêutico , Compostos de Amônio Quaternário/farmacologia , Compostos de Amônio Quaternário/uso terapêutico
15.
J Exp Biol ; 225(24)2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36478243

RESUMO

Visual animal communication, whether to the same or to other species, is largely conducted through dynamic and colourful signals. For a signal to be effective, the signaller must capture and retain the attention of the receiver. Signal efficacy is also dependent on the sensory limitations of the receiver. However, most signalling studies consider movement and colour separately, resulting in a partial understanding of the signal in question. We explored the structure and function of predator-prey signalling in the jumping spider-tephritid fly system, where the prey performs a wing waving display that deters an attack from the predator. Using a custom-built spider retinal tracker combined with visual modelling, as well as behavioural assays, we studied the effect of fly wing movement and colour on the jumping spider's visual system. We show that jumping spiders track their prey less effectively during wing display and this can be attributed to a series of fluctuations in chromatic and achromatic contrasts arising from the wing movements. These results suggest that displaying flies deter spider attacks by manipulating the movement biases of the spider's visual system. Our results emphasise the importance of receiver attention on the evolution of interspecific communication.


Assuntos
Dípteros , Aranhas , Animais , Comportamento Predatório , Comportamento Animal , Comunicação Animal
16.
J Neurooncol ; 157(3): 425-433, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35278157

RESUMO

PURPOSE: To report disease control and treatment-related side effects among adult patients with craniopharyngioma treated with radiotherapy. METHODS: We performed a single-institution review of adult patients (> 21 years old) with craniopharyngioma treated with radiotherapy either definitively or postoperatively for gross residual disease. We report disease control, survival, and radiotherapy-related side effects. RESULTS: A total of 49 adult patients with craniopharyngioma were included, 27 of whom were treated at initial presentation and 22 for recurrent disease following initial surgery and observation. Overall, 77% received radiotherapy postoperatively (either after primary surgery or surgery for recurrence). With a median clinical and radiographic follow-up of 4.2 (range, 0.4-21.6) years and 3.0 (range, 0-21.5) years, the 5- and 10-year local control rates were 100 and 94%, respectively. The 5- and 10-year overall survival rates were 80 and 66%, respectively. Eleven percent of patients experienced grade 2 vision deterioration and 18% suffered grade 2 endocrinopathies following radiotherapy. CONCLUSIONS: Radiotherapy provides excellent disease control with acceptable toxicity among adult patients with craniopharyngioma. These data support the use of fractionated radiotherapy in adult patients with recurrent or gross residual disease after surgery. For inoperable patients or those with moderate or high surgical risk to neurologic and/or vascular structures, we advocate for limited surgical resection and postoperative radiotherapy to balance optimal tumor control with tumor- and treatment-related morbidity.


Assuntos
Craniofaringioma , Neoplasias Hipofisárias , Adulto , Craniofaringioma/radioterapia , Craniofaringioma/cirurgia , Humanos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual/cirurgia , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
17.
Acta Oncol ; 61(8): 1026-1031, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35897132

RESUMO

BACKGROUND: Dose escalation for skull-based malignancies often presents risks to critical adjacent neural structures, including the brainstem. We report the incidence of brainstem toxicity following fractionated high-dose conformal proton therapy and associated dosimetric parameters. MATERIAL AND METHODS: We performed a single-institution review of patients with skull-base chordoma or chondrosarcoma who were treated with proton therapy between February 2007 and January 2020 on a prospective outcomes-tracking protocol. The primary endpoint was grade ≥2 brainstem toxicity. No patients received concurrent chemotherapy, and brainstem toxicity was censored for analysis if it coincided with local disease progression. RESULTS: We analyzed 163 patients who received a minimum of 45 GyRBE to 0.03 cm3 of the brainstem. Patients were treated to a median total dose of 73.8 (range 64.5-74.4) GyRBE at 1.8 GyRBE per fraction with 17 patients undergoing twice-daily treatment at 1.2 GyRBE per fraction. With a median follow-up of 4 years, the 5-year cumulative incidence of grade ≥2 brainstem injury was 1.3% (95% CI 0.25-4.3%). There was one grade 2, one grade 3, and no grade 4 or 5 events, with all patients recovering function with medical management. CONCLUSION: In delivering curative-intent radiotherapy for skull-base chordoma and chondrosarcoma in adults, small volumes of the brainstem can safely receive at least 64 GyRBE with minimal risk of serious brainstem injury.


Assuntos
Condrossarcoma , Cordoma , Terapia com Prótons , Neoplasias da Base do Crânio , Adulto , Tronco Encefálico/patologia , Condrossarcoma/patologia , Condrossarcoma/radioterapia , Cordoma/radioterapia , Humanos , Incidência , Estudos Prospectivos , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Prótons , Dosagem Radioterapêutica , Crânio , Neoplasias da Base do Crânio/radioterapia
18.
J Immunol ; 204(8): 2064-2075, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32161096

RESUMO

Aging-related chronic inflammation is a risk factor for many human disorders through incompletely understood mechanisms. Aged mice deficient in microRNA (miRNA/miR)-146a succumb to life-shortening chronic inflammation. In this study, we report that miR-155 in T cells contributes to shortened lifespan of miR-146a-/- mice. Using single-cell RNA sequencing and flow cytometry, we found that miR-155 promotes the activation of effector T cell populations, including T follicular helper cells, and increases germinal center B cells and autoantibodies in mice aged over 15 months. Mechanistically, aerobic glycolysis genes are elevated in T cells during aging, and upon deletion of miR-146a, in a T cell miR-155-dependent manner. Finally, skewing T cell metabolism toward aerobic glycolysis by deleting mitochondrial pyruvate carrier recapitulates age-dependent T cell phenotypes observed in miR-146a-/- mice, revealing the sufficiency of metabolic reprogramming to influence immune cell functions during aging. Altogether, these data indicate that T cell-specific miRNAs play pivotal roles in regulating lifespan through their influences on inflammaging.


Assuntos
Modelos Animais de Doenças , Inflamação/genética , Longevidade/genética , MicroRNAs/genética , Linfócitos T/metabolismo , Fatores Etários , Animais , Feminino , Inflamação/imunologia , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Linfócitos T/imunologia , Linfócitos T/patologia
19.
Emerg Radiol ; 29(2): 383-393, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35029773

RESUMO

BACKGROUND AND PURPOSE: Craniocervical dissociation is a rare and life-threatening injury that results from a significant hyperflexion-hyperextension force. Occult craniocervical dissociation is defined as an unstable craniocervical injury in the absence of atlanto-occipital joint space widening or other skull base line abnormality. The early and accurate diagnosis of craniocervical dissociation is crucial since the early diagnosis and subsequent stabilization with occipital-cervical fusion has been shown to reduce neurologic morbidity and mortality. Several normative skull base lines have been developed to predict craniocervical dissociation. The purpose of our study was to measure the atlanto-occipital joint space and four other common skull base lines in patients who underwent occipital-cervical fusion for post-traumatic craniocervical instability. MATERIALS AND METHODS: Patients who underwent occipital-cervical fusion for craniocervical injury were identified retrospectively using a keyword search of radiology reports using Nuance mPower software. The cervical CT and MRI exams for these patients were reviewed and the atlanto-occipital joint space, Powers ratio, Wackenheim line, posterior axial line, and basion dens interval were measured. Detailed descriptions of craniocervical ligament injuries on MRI were recorded along with patient demographic information, clinical history, management, and outcome. RESULTS: Nine adult patients who underwent occipital-cervical fusion for an acute craniocervical injury were identified. Six patients demonstrated an atlanto-occipital joint space measuring 2 mm or less on cervical spine CT with no additional abnormality in the Powers ratio, Wackenheim line, posterior axial line, or basion-dens interval. Three patients demonstrated widening of the atlanto-occipital joint space with two patients demonstrating an abnormality in at least two additional skull base lines. Clinical outcomes were variable with nearly half of the patients demonstrating persistent neurologic deficits, including one quadriplegic patient. CONCLUSIONS: A normal atlanto-occipital joint space and skull base line measurements on cervical CT demonstrated a low predictive value for detecting unstable craniocervical injuries. Occult craniocervical dissociation was present in two-thirds of patients who underwent occipital cervical fusion for acute, craniocervical trauma. A high clinical and radiologic index of suspicion for craniocervical trauma with subsequent follow-up cervical MRI to directly evaluate ligamentous integrity is necessary to accurately diagnose and triage patients with high velocity trauma.


Assuntos
Articulação Atlantoccipital , Luxações Articulares , Traumatismos do Sistema Nervoso , Adulto , Articulação Atlantoccipital/diagnóstico por imagem , Articulação Atlantoccipital/lesões , Articulação Atlantoccipital/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/lesões , Vértebras Cervicais/cirurgia , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Emerg Radiol ; 29(1): 197-205, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34491452

RESUMO

Dental infections are a common presentation in the emergency department (ED). To help guide clinical management for these infections, the radiologist must be familiar with the anatomy of the oral cavity and neighboring structures, the range of appearance of dental infections, and the routes along which they may spread. Computed tomography (CT) is often performed when severe dental infections are suspected. This pictorial essay reviews the anatomy pertinent to the imaging evaluation of dental infections and depicts a spectrum of pathology that may be encountered, ranging from simple dentoalveolar infections to complex multispatial infections.


Assuntos
Serviço Hospitalar de Emergência , Tomografia Computadorizada por Raios X , Humanos
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