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PURPOSE: Langerhans cell histiocytosis (LCH) is a rare condition arising from the monoclonal expansion of myeloid precursor cells, which results in granulomatous lesions that characteristically express CD1a/CD207. We report a case of LCH in a 3-year-old male involving the sphenoid bone with extension into the sellar/suprasellar region. CASE REPORT: A 3-year-old male presented with progressively worsening headaches and associated night sweats, neck stiffness, and fatigue over the previous 4 weeks. Magnetic resonance imaging (MRI) revealed a 2.4-cm lytic lesion within the basisphenoid, exerting mass effect upon the pituitary gland. A biopsy was performed to determine the etiology of the lesion. Postoperatively, the patient developed an intralesional hematoma with visual complications requiring emergent surgical resection via endoscopic endonasal approach. Final pathology confirmed LCH. The patient had improvement in his vision long term. CONCLUSIONS: LCH extending into the sella is a rare but important diagnosis to consider in pediatric patients presenting with lesions in this region. We presented a case of a pediatric patient presenting with LCH of the sphenoid bone extending into the sella, with subsequent apoplexy and vision loss. Review of the literature showed varying treatment options for these patients, including purely surgical and non-surgical treatments. Early intervention may be necessary to avoid potentially devastating neurologic sequelae.
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Histiocitose de Células de Langerhans , Imageamento por Ressonância Magnética , Humanos , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/cirurgia , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/patologia , Masculino , Pré-Escolar , Sela Túrcica/diagnóstico por imagem , Sela Túrcica/patologia , Sela Túrcica/cirurgia , Osso Esfenoide/cirurgia , Osso Esfenoide/diagnóstico por imagem , Osso Esfenoide/patologiaRESUMO
OBJECTIVE: Baseball and softball pose unique risks for sport-related concussion (SRC). Although these are not collision sports, concussions in baseball and softball can nonetheless involve high-speed impacts. In a regional, single-institution cohort of baseball and softball athletes who sustained an SRC, the current study sought to 1) describe the mechanisms of injury that led to SRC, and 2) compare initial symptom burden and recovery metrics across mechanisms, including time to return to learn (RTL), time to symptom resolution, and time to return to play (RTP) by mechanism of injury. METHODS: A retrospective cohort study was performed of baseball and softball athletes 12 to 23 years old who sustained an SRC between November 2017 and April 2022. Mechanisms of injury were divided into two categories: 1) contact mechanism (i.e., what initiated contact with the injured player, such as head-to-ball), and 2) player mechanism (i.e., the action the injured player was performing at the time of injury, such as fielding). The recovery outcomes of time to RTL, symptom resolution, and RTP were compared between mechanisms using bivariate analysis and multivariable regression analysis, controlling for sex, age, time to present to concussion clinic, and initial total symptom score. RESULTS: The sample included 58 baseball and softball players (60.3% female, mean age 16.0 ± 1.9 years). Most SRCs (62.1%) occurred during competition. Head-to-ball (50.0%) was the most common contact mechanism, followed by head-to-head/body (31.0%) and head-to-wall/ground/equipment (17.2%). Fielding (63.8%) was the most common player mechanism, followed by drills (20.7%) and running (13.8%). SRCs sustained in practice had significantly longer RTL (median 10.0 [interquartile range (IQR) 3.3-16.3] vs 4.0 [IQR 2.0-8.0] days; U = 421.5, p = 0.031) and symptom resolution (37.0 [IQR 18.0-90.0] vs 14.0 [IQR 7.0-41.0] days; U = 406.5, p = 0.025) compared with SRCs sustained in competition. Multivariable regression analysis revealed that head-to-wall/ground/equipment contact mechanism was associated with longer RTL (ß = 0.30, 95% CI 0.07-0.54, p = 0.013). CONCLUSIONS: The current study found that SRCs in baseball and softball occurred more often in competition than in practice. Head-to-ball and fielding were the most common contact and player mechanisms, respectively. SRCs sustained in practice were associated with longer time to RTL and symptom resolution, and head-to-wall/ground/equipment was associated with longer RTL in multivariable regression analysis. These results provide empirical data to improve concussion safety in baseball/softball.
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Traumatismos em Atletas , Beisebol , Concussão Encefálica , Recuperação de Função Fisiológica , Humanos , Concussão Encefálica/epidemiologia , Beisebol/lesões , Masculino , Feminino , Adolescente , Adulto Jovem , Estudos Retrospectivos , Recuperação de Função Fisiológica/fisiologia , Criança , Estudos de Coortes , Atletas , Volta ao Esporte/estatística & dados numéricosRESUMO
OBJECTIVE: Prior studies have investigated associations between gender, symptom resolution, and time to return to play following sport-related concussion (SRC). However, there is a notable gap in research regarding the association between gender and return to learn (RTL) in adolescents. Therefore, this study 1) compared the patterns of RTL between boys and girls who are high school student athletes, and 2) evaluated the possible association between gender and time to RTL after adjusting for covariates. METHODS: A retrospective cohort study of a prospective surveillance program that monitored concussion recovery of athletes in high schools throughout the state of Maine between February 2015 and January 2023 was performed. The primary independent variable was gender, dichotomized as boys and girls. The primary outcome was time to RTL, defined by the number of days for an athlete to return to school without accommodations. Mann-Whitney U-tests were used to compare RTL between the boys and girls. Each athlete's RTL status was dichotomized (i.e., returned vs had not returned) at several time points following injury (i.e., 1, 2, 3, and 4 weeks), and chi-square tests were performed to compare the proportions who achieved RTL between groups. Multivariable linear regression analyses were performed to evaluate the predictive value of gender on RTL. Covariates included age, number of previous concussions, history of learning disability or attention-deficit disorder or attention-deficit/hyperactivity disorder, history of a psychological condition, history of headaches or migraines, initial Sport Concussion Assessment Tool (SCAT3/SCAT5) score, and days to evaluation. RESULTS: Of 895 high school athletes, 488 (54.5%) were boys and 407 (45.5%) were girls. There was no statistically significant difference in median [IQR] days to RTL between genders (6.0 [3.0-11.0] vs 6.0 [3.0-12.0] days; U = 84,365.00, p < 0.375). A greater proportion of boys successfully returned to learn without accommodations by 3 weeks following concussion (93.5% vs 89.4%; χ2 = 4.68, p = 0.030), but no differences were found at 1, 2, or 4 weeks. A multivariable model predicting days to RTL showed that gender was not a significant predictor of RTL (p > 0.05). Longer days to evaluation (ß = 0.10, p = 0.021) and higher initial SCAT3/SCAT5 scores (ß = 0.15, p < 0.001) predicted longer RTL. CONCLUSIONS: In a cohort of high school athletes, RTL did not differ between boys and girls following SRC. Gender was not a significant predictor of RTL. Longer days to evaluation and higher initial symptom scores were associated with longer RTL.
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Atletas , Traumatismos em Atletas , Concussão Encefálica , Estudantes , Humanos , Masculino , Feminino , Concussão Encefálica/epidemiologia , Adolescente , Traumatismos em Atletas/epidemiologia , Estudos Retrospectivos , Caracteres Sexuais , Recuperação de Função Fisiológica/fisiologia , Fatores Sexuais , Aprendizagem/fisiologia , Estudos de Coortes , Estudos Prospectivos , Instituições Acadêmicas , Retorno à Escola , Volta ao EsporteRESUMO
OBJECTIVE: To identify microRNA (miRNA) characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer-specific survival (CSS) in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue. MATERIALS AND METHODS: RNA was isolated from nephrectomy and kidney biopsy specimens (n = 156 and n = 46, respectively). Samples were grouped: benign, non-progressive, and progressive ccRCC. MiRNAs were profiled by microarray and validated by quantitative reverse transcription-polymerase chain reaction. Biomarker signatures were developed to predict cancer status in nephrectomy and biopsy specimens. CSS was examined using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Microarray analysis revealed 20 differentially expressed miRNAs comparing non-progressive with progressive tumours. A biomarker signature validated in nephrectomy specimens had a sensitivity of 86.7% and a specificity of 92.9% for differentiating benign and ccRCC specimens. A second signature differentiated non-progressive vs progressive ccRCC with a sensitivity of 93.8% and a specificity of 83.3%. These biomarkers also discriminated cancer status in biopsy specimens. Levels of miR-10a-5p, -10b-5p, and -223-3p were associated with CSS. CONCLUSION: This study identified miRNAs differentially expressed in ccRCC samples; as well as those correlating with CSS. Biomarkers identified in this study have the potential to identify patients who are likely to have progressive ccRCC, and although preliminary, these results may aid in differentiating aggressive and indolent ccRCC based on biopsy specimens.
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Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/patologia , Perfilação da Expressão Gênica/métodos , Neoplasias Renais/epidemiologia , Neoplasias Renais/patologia , MicroRNAs/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma de Células Renais/metabolismo , Análise por Conglomerados , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Rim/química , Rim/patologia , Neoplasias Renais/metabolismo , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Análise em Microsséries , Pessoa de Meia-Idade , Nefrectomia , Sensibilidade e Especificidade , Adulto JovemRESUMO
A 67-year-old male patient presented with right scrotal swelling and underwent a right hydrocelectomy. A 1 cm paratesticular lesion was found within the hydrocele sac after entering the tunica vaginalis. Local excision grossly removed this in its entirety. Pathology returned as well differentiated papillary mesothelioma of the tunica vaginalis. Pathologic features and management options are discussed.
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Neoplasias dos Genitais Masculinos/patologia , Mesotelioma/patologia , Escroto , Idoso , Neoplasias dos Genitais Masculinos/cirurgia , Humanos , Masculino , Mesotelioma/cirurgia , Hidrocele Testicular/cirurgiaRESUMO
BACKGROUND: Sport-related concussions (SRC) represent a significant concern for athletes. While popular contact sports such as football and soccer have been the focus of much SRC research, wrestling has received comparatively little attention. The current study aimed to: 1) describe the mechanisms of injury leading to SRC in wrestling; and 2) compare recovery outcomes based on mechanism of injury. METHODS: A retrospective, cohort study of wrestlers aged 12-18 who sustained a concussion between 11/2017-04/2022 was performed. Contact mechanism was defined as what initiated contact with the athlete's head/body. Player mechanism was defined as the activity the injured athlete was performing when the concussion occurred. Recovery outcomes were compared using Mann-Whitney-U Tests and multivariable regression analysis. RESULTS: Seventy-three (age=15.8±1.4 years; boys=73 [100.0%]) wrestlers were included. SRCs occurred more often in competition than in practice (66.2% vs. 33.8%, respectively). Head-to-ground/wall (56.2%) and takedown (58.9%) were the most common contact and player mechanisms, respectively. Bivariate analysis showed that head-to-head/body SRCs had longer time to symptom resolution compared to head-to-ground/wall SRCs (23.0 [14.8-46.5] vs. 14.0 [6.0-30.0] days; U=149.00, P=0.029), though the difference did not persist in multivariable analysis. For player mechanism, non-takedowns SRCs had longer time to symptom resolution than takedown SRCs (15.0 [6.0-24.0] vs. 28.5 [13.0-49.3]; U=166.5, P=0.019), but the difference also did not persist in multivariable analysis. Bivariate analysis revealed no significant difference in RTL between takedown and non-takedown SRCs (3.0 [2.0-6.0] vs. 4.0 [1.5-7.0]; U=484.50, P=0.708); however, in multivariable analysis, takedown SRCs were associated with longer RTL (ß=0.23, 95% CI: 0.02, 9.27; P=0.049). CONCLUSIONS: The current study found that SRCs occurred more commonly during competitions, and head-to-ground/wall and takedown were the most common contact and player mechanism, respectively. SRCs that occurred during takedowns were associated with longer RTL.
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Background: This study examines the lasting impact of historical redlining on contemporary neurosurgical care access, highlighting the need for equitable healthcare in historically marginalized communities. Objective: To investigate how redlining affects neurosurgeon distribution and reimbursement in U.S. neighborhoods, analyzing implications for healthcare access. Methods: An observational study was conducted using data from the Center for Medicare and Medicaid Services (CMS) National File, Home Owner's Loan Corporation (HOLC) neighborhood grades, and demographic data to evaluate neurosurgical representation across 91 U.S. cities, categorized by HOLC Grades (A, B, C, D) and gentrification status. Results: Of the 257 neighborhoods, Grade A, B, C, and D neighborhoods comprised 5.40%, 18.80%, 45.8%, and 30.0% of the sample, respectively. Grade A, B, and C neighborhoods had more White and Asian residents and less Black residents compared to Grade D neighborhoods (p < 0.001). HOLC Grade A (OR = 4.37, 95%CI: 2.08, 9.16, p < 0.001), B (OR = 1.99, 95%CI: 1.18, 3.38, p = 0.011), and C (OR = 2.37, 95%CI: 1.57, 3.59, p < 0.001) neighborhoods were associated with a higher representation of neurosurgeons compared to Grade D neighborhoods. Reimbursement disparities were also apparent: neurosurgeons practicing in HOLC Grade D neighborhoods received significantly lower reimbursements than those in Grade A neighborhoods ($109,163.77 vs. $142,999.88, p < 0.001), Grade B neighborhoods ($109,163.77 vs. $131,459.02, p < 0.001), and Grade C neighborhoods ($109,163.77 vs. $129,070.733, p < 0.001). Conclusion: Historical redlining continues to shape access to highly specialized healthcare such as neurosurgery. Efforts to address these disparities must consider historical context and strive to achieve more equitable access to specialized care.
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Neurocirurgiões , Humanos , Estados Unidos , Neurocirurgiões/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Características da Vizinhança , Características de Residência/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricosRESUMO
Traumatic brain injury (TBI) is a critical public health concern with profound consequences for affected individuals. This comprehensive literature review delves into TBI intricacies, encompassing primary injury biomechanics and the molecular pathophysiology of the secondary injury cascade. Primary TBI involves a complex interplay of forces, including impact loading, blast overpressure, and impulsive loading, leading to diverse injury patterns. These forces can be categorized into inertial (e.g., rotational acceleration causing focal and diffuse injuries) and contact forces (primarily causing focal injuries like skull fractures). Understanding their interactions is crucial for effective injury management. The secondary injury cascade in TBI comprises multifaceted molecular and cellular responses, including altered ion concentrations, dysfunctional neurotransmitter networks, oxidative stress, and cellular energy disturbances. These disruptions impair synaptic function, neurotransmission, and neuroplasticity, resulting in cognitive and behavioral deficits. Moreover, neuroinflammatory responses play a pivotal role in exacerbating damage. As we endeavor to bridge the knowledge gap between biomechanics and molecular pathophysiology, further research is imperative to unravel the nuanced interplay between mechanical forces and their consequences at the molecular and cellular levels, ultimately guiding the development of targeted therapeutic strategies to mitigate the debilitating effects of TBI. In this study, we aim to provide a concise review of the bridge between biomechanical processes causing primary injury and the ensuing molecular pathophysiology of secondary injury, while detailing the subsequent clinical course for this patient population. This knowledge is crucial for advancing our understanding of TBI and developing effective interventions to improve outcomes for those affected.
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Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/fisiopatologia , Fenômenos Biomecânicos/fisiologia , AnimaisRESUMO
Stroke is a major health concern in the USA, disproportionately affecting socioeconomically disadvantaged groups. This study investigates the link between persistent poverty and stroke mortality rates in residents aged 65 and above, positing that sustained economic challenges at the county level correlate with an increase in stroke-related deaths. Persistent poverty refers to a long-term state where a significant portion of a population lives below the poverty threshold for an extended period, typically measured over several decades. It captures the chronic nature of economic hardship faced by a community across multiple generations. Utilizing data from the CDC Wonder database and the American Community Survey, we conducted a comprehensive analysis across US counties, differentiating them by persistent poverty status. Our results indicate a statistically significant link between persistent poverty and increased mortality from ischemic and hemorrhagic strokes; counties afflicted by long-standing poverty were associated with an additional 33.49 ischemic and 8.16 hemorrhagic stroke deaths per 100,000 residents annually compared to their wealthier counterparts. These disparities persisted when controlling for known stroke risk factors and other socioeconomic variables. These results highlight the need for targeted public health strategies and interventions to address the disparities in stroke mortality rates and the broader implications for healthcare equity. The study underscores the vital role of socioeconomic context in health outcomes and the urgency of addressing long-term poverty as a key determinant of public health.
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OBJECTIVE: Signal regulatory protein α (SIRPα) is found primarily on myeloid cells, including macrophages and neutrophils; binds to CD47; and regulates phagocytosis, antigen presentation, cellular fusion, cell proliferation, and migration. Therefore, SIRPα may be involved in the pathogenesis of autoimmune diseases, including systemic vasculitis. This study aimed to assess SIRPα expression in tissue samples from patients with vasculitis. METHODS: Immunohistochemical staining for SIRPα was performed on temporal artery (TA), kidney, and lung biopsy samples from patients with giant cell arteritis (GCA), patients with microscopic polyangiitis (MPA), patients with granulomatosis with polyangiitis (GPA), and patients without vasculitis. A score of SIRPα+ expression was calculated, derived from the percentages of monocytes, macrophages, and dendritic cells and neutrophils with different staining intensities in affected tissues. RESULTS: A total of 46 samples from patients with different vasculitides (GCA, MPA, and GPA) were included in the study. Tissue samples included TA samples from 15 patients with GCA; kidney samples from 11 and 9 patients with GPA and MPA, respectively; and lung samples from 11 patients with GPA. Most tissue samples from patients with active vasculitis (15 of 15 TA samples, 17 of 20 kidney samples, and 9 of 11 lung samples) showed SIRPα staining. SIRPα staining intensity was less in kidney samples compared to TA and lung samples. CONCLUSION: This study demonstrates high-level expression of SIRPα in macrophages and monocytes in affected tissue in systemic vasculitis. These findings provide a foundation for further studies exploring the role of the SIRPα-CD47 pathway in the pathogenesis of systemic vasculitis and the potential for the blockade of SIRPα and/or the depletion of SIRPα+ cells as treatment of systemic vasculitis.
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STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: In patients undergoing elective posterior cervical laminectomy and fusion (PCLF) with a minimum of 5-year follow-up, we sought to compare reoperation rates between patients with an upper instrumented vertebra (UIV) of C2 versus C3/4. SUMMARY OF BACKGROUND DATA: The long-term outcomes of choosing between C2 versus C3/4 as the UIV in PCLF remain unclear. METHODS: A single-institution, retrospective cohort study from a prospective registry was conducted of patients undergoing elective, degenerative PCLF from December 2010 to June 2018. The primary exposure was UIV of C2 versus C3/4. The primary outcome was reoperation. Multivariable logistic regression controlled for age, smoking, diabetes, and fusion to the thoracic spine. RESULTS: Of the 68 patients who underwent PCLF with 5-year follow-up, 27(39.7%) had a UIV of C2, and 41(60.3%) had a UIV of either C3/4. Groups had similar duration of symptoms (P=0.743), comorbidities (P>0.999), and rates of instrumentation to the thoracic spine (70.4% vs. 53.7%, P=0.210). The C2 group had significantly longer operative time (231.8±65.9 vs. 181.6±44.1 mins, P<0.001) and more fused segments (5.9±1.8 vs. 4.2±0.9, P<0.001). Reoperation rate was lower in the C2 group compared with C3/4 (7.4% vs. 19.5%), though this did not reach statistical significance (P=0.294). Multivariable logistic regression showed increased odds of reoperation for the C3/4 group compared with the C2 group (OR=3.29, 95%CI=0.59-18.11, P=0.170), though statistical significance was not reached. Similarly, the C2 group had a lower rate of instrumentation failure (7.4% vs. 12.2%, P=0.694) and adjacent segment disease/disk herniation (0% vs. 7.3%, P=0.271), though neither trend attained statistical significance. CONCLUSIONS: Patients with a UIV of C2 had less than half the number of reoperations and less adjacent segment disease, though neither trend was statistically significant. Despite a lack of statistical significance, whether a clinically meaningful difference exists between UIV of C2 versus C3/4 should be validated in larger samples with long-term follow-up. LEVEL OF EVIDENCE: Level-3.
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OBJECTIVE: Obtaining timely postoperative radiotherapy (RT) following separation surgery is critical to avoid local recurrence of disease yet can be a challenge due to scheduling conflicts, insurance denials, and travel arrangements. In patients undergoing metastatic spine surgery for spinal cord compression, the authors sought to: 1) report the rate of postoperative RT, 2) describe reasons for patients not receiving postoperative RT, and 3) investigate factors that may predict whether a patient receives postoperative RT. METHODS: A single-center retrospective case series was undertaken of all patients who underwent metastatic spine surgery for extradural disease between January 2010 and January 2021. Inclusion criteria were patients with intermediate or radioresistant tumors with evidence of spinal cord compression who underwent surgery. The primary outcome was the occurrence of RT within 3 months following surgery. Multivariable logistic regression analysis was performed controlling for age, BMI, race, total number of decompressed levels, tumor size, other organ metastasis, and preoperative RT or chemotherapy to predict patients receiving postoperative RT. RESULTS: Of 239 patients undergoing spine surgery for metastatic disease, 113 (47.3%) received postoperative RT while 126 (52.7%) did not. In the postoperative RT group, 24 (21.2%) received stereotactic body radiation therapy while 89 (78.8%) received conventional external-beam radiation therapy. The most common reasons for patients not receiving postoperative RT included death or transfer to hospice (31.0%), RT not being recommended by radiation oncology (30.2%), and loss to follow-up (23.8%). On critical review with the radiation oncology department, the authors estimated that 101 of 126 (80.2%) patients who did not receive postoperative RT were potential candidates for postoperative RT. Patients who received postoperative RT had more documented inpatient (48.7% vs 32.5%, p < 0.001) and outpatient (100.0% vs 65.1%, p < 0.001) radiation oncology consultations than those who did not. Additionally, patients who received postoperative RT had a higher rate of postoperative chemotherapy (53.1% vs 25.4%, p < 0.001), while patients who did not receive postoperative RT had a higher rate of preoperative RT (7.1% vs 31.0%, p < 0.001). Multivariable analysis confirmed that patients who received preoperative RT had lower odds of undergoing postoperative RT (OR 0.14, 95% CI 0.06-0.34; p < 0.001), and patients who underwent postoperative chemotherapy had higher odds of undergoing postoperative RT (OR 3.83, 95% CI 2.05-7.17; p < 0.001). CONCLUSIONS: In the current study reflecting real-world care of patients with metastatic spine disease after undergoing separation surgery, 47% of patients did not receive postoperative RT, and 80% of those patients were potential candidates for postoperative RT. Radiation oncology consultation and postoperative chemotherapy were significantly associated with receiving postoperative RT, whereas preoperative RT was significantly associated with not receiving postoperative RT. The lack of timely postoperative RT highlights a potential gap in metastatic spine tumor care and underscores the necessity for prompt radiation oncology consultation and effective planning.
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Many targets have been identified in solid tumors for antibody therapy but it is less clear what surface antigens may be most commonly expressed on disseminated tumor cells. Using malignant pleural effusions as a source of disseminated tumor cells, we compared a panel of 35 antigens for their cancer specificity, antigen abundance and functional significance. These antigens have been previously implicated in cancer metastasis and fall into four categories: (i) cancer stem cell, (ii) epithelial-mesenchymal transition, (iii) metastatic signature of in vivo selection and (iv) tyrosine kinase receptors. We determined the antigen density of all 35 antigens on the cell surface by flow cytometry, which ranges from 3 × 10(3) -7 × 10(6) copies per cell. Comparison between the malignant and benign pleural effusions enabled us to determine the antigens specific for cancer. We further chose six antigens and examined the correlation between their expression levels and tumor formation in immunocompromised mice. We concluded that CD24 is one of the few antigens that could simultaneously meet all three criteria of an ideal target. It was specifically and abundantly expressed in malignant pleural effusions; CD24(high) tumor cells formed tumors in mice at a faster rate than CD24(low) tumor cells, and shRNA-mediated knockdown of CD24 in HT29 cells confirmed a functional requirement for CD24 in the colonization of the lung. Concomitant consideration of antigen abundance, specificity and functional importance can help identify potentially useful markers for disseminated tumor cells.
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Antígenos de Superfície/análise , Biomarcadores Tumorais/análise , Antígeno CD24/análise , Derrame Pleural Maligno/imunologia , Animais , Antígenos de Neoplasias/análise , Antígeno CD24/fisiologia , Moléculas de Adesão Celular/análise , Molécula de Adesão da Célula Epitelial , Células HT29 , Xenoenxertos , Humanos , Neoplasias Pulmonares/secundário , Camundongos , Transplante de Neoplasias , Derrame Pleural Maligno/patologiaRESUMO
Healthcare finance teams should perform an enterprisewide assessment to determine what ICD-10 means to their organization, strategically, operationally, and financially. CFOs should strategically evaluate the impact of ICD-10 on the organization's entire financial operation. Organizations should have a contingency plan in place across all processes.
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Economia Hospitalar/organização & administração , Fidelidade a Diretrizes , Classificação Internacional de Doenças , Eficiência Organizacional , Programas Obrigatórios , Sistemas Multi-Institucionais , Estudos de Casos Organizacionais , PennsylvaniaRESUMO
The microtubule-associated protein tau is an abundant component of neurons of the central nervous system. In Alzheimer's disease and other neurodegenerative tauopathies, tau is found hyperphosphorylated and aggregated in neurofibrillary tangles. To obtain a better understanding of the cellular perturbations that initiate tau pathogenesis, we performed a CRISPR-Cas9 screen for genetic modifiers that enhance tau aggregation. This initial screen yielded three genes, BANF1, ANKLE2, and PPP2CA, whose inactivation promotes the accumulation of tau in a phosphorylated and insoluble form. In a complementary screen, we identified three additional genes, LEMD2, LEMD3, and CHMP7, that, when overexpressed, provide protection against tau aggregation. The proteins encoded by the identified genes are mechanistically linked and recognized for their roles in the maintenance and repair of the nuclear envelope. These results implicate the disruption of nuclear envelope integrity as a possible initiating event in tauopathies and reveal targets for therapeutic intervention.
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Doença de Alzheimer , Tauopatias , Doença de Alzheimer/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Membrana Nuclear/metabolismo , Proteínas Nucleares/metabolismo , Fosforilação , Tauopatias/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismoAssuntos
Ressecção Endoscópica de Mucosa/métodos , Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Neoplasias Gástricas/cirurgia , Instrumentos Cirúrgicos , Dispepsia , Ressecção Endoscópica de Mucosa/instrumentação , Endossonografia , Feminino , Gastroscopia/instrumentação , Humanos , Pessoa de Meia-Idade , Gastropatias/patologia , Gastropatias/cirurgia , Neoplasias Gástricas/patologiaRESUMO
Using the Aspen Young Leaders Fellowship as a case study, the authors assert that leadership educators have a responsibility to apply critical perspectives to their work with evidence-based practice, which involves interrogating assumptions as well as reconstructing pedagogical and design practices to increase equity in leadership education.
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Aptidão , Currículo , Bolsas de Estudo , Liderança , Desenvolvimento de Programas , Estudantes , Adolescente , Adulto , Humanos , Organizações sem Fins Lucrativos , Adulto JovemRESUMO
Invasive breast cancer has a high risk of recurrence to incurable disease and needs improved prognostic and therapeutic tools. Our work combines clinical and molecular analyses to show that the transcriptional repressor HBP1 may be a new target for invasive breast cancer. Previous work indicated that HBP1 regulated proliferation and senescence and inhibited Wnt signaling. Two of these functions have been associated with invasive breast cancer. In 76 breast tumors, we identified 10 HBP1 mutations/variants that were associated with fully invasive breast cancer. In a separate analysis, we found that a subset of invasive breast cancer specimens also had reduced HBP1 mRNA levels. These clinical correlations suggested that mutation or reduction of HBP1 occurs in invasive breast cancer and that HBP1 might regulate the proliferation and invasiveness of this breast cancer type. Analysis of the HBP1 mutants showed they were functionally defective for suppressing Wnt signaling. To test the consequences of reduced HBP1 levels, we used RNA interference to knock down HBP1 and observed increased Wnt signaling, tumorigenic proliferation, and invasiveness in cell and animal breast cancer models. Lastly, statistical analysis of a breast cancer patient database linked reduced HBP1 expression to breast cancer recurrence. In considering two-gene criteria for relapse potential, reduced expression of HBP1 and SFRP1, which is another Wnt inhibitor that was recently linked to invasive breast cancer, strikingly correlated with recurrence. Together, these data indicate that HBP1 may be a molecularly and clinically relevant regulator of breast cancer transitions that eventually lead to poor prognosis.
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Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/biossíntese , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas Repressoras/biossíntese , Proteínas Repressoras/genética , Transcrição Gênica , Animais , Feminino , Humanos , Camundongos , Camundongos SCID , Mutação , Células NIH 3T3 , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias , Resultado do TratamentoRESUMO
Recognizing that young people are resilient in many ways, they need adequate and adaptive models to utilize as they address the complexities that are part of today's world. This chapter introduces critical perspectives as an essential framework for learning about youth capacity-building for international leadership.