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BACKGROUND & AIMS: A blood-based colorectal cancer (CRC) screening test may increase screening participation. However, blood tests may be less effective than current guideline-endorsed options. The Centers for Medicare & Medicaid Services (CMS) covers blood tests with sensitivity of at least 74% for detection of CRC and specificity of at least 90%. In this study, we investigate whether a blood test that meets these criteria is cost-effective. METHODS: Three microsimulation models for CRC (MISCAN-Colon, CRC-SPIN, and SimCRC) were used to estimate the effectiveness and cost-effectiveness of triennial blood-based screening (from ages 45 to 75 years) compared to no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with an FIT assay, and colonoscopy screening every 10 years. The CMS coverage criteria were used as performance characteristics of the hypothetical blood test. We varied screening ages, test performance characteristics, and screening uptake in a sensitivity analysis. RESULTS: Without screening, the models predicted 77-88 CRC cases and 32-36 CRC deaths per 1000 individuals, costing $5.3-$5.8 million. Compared to no screening, blood-based screening was cost-effective, with an additional cost of $25,600-$43,700 per quality-adjusted life-year gained (QALYG). However, compared to FIT, triennial stool DNA testing combined with FIT, and colonoscopy, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT remained more effective (+5-24 QALYG) and less costly (-$3.2 to -$3.5 million) than blood-based screening even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT. CONCLUSION: Even with higher screening uptake, triennial blood-based screening, with the CMS-specified minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for colorectal cancer screening.
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Colonoscopia , Neoplasias Colorretais , Análise Custo-Benefício , Detecção Precoce de Câncer , Sangue Oculto , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/economia , Pessoa de Meia-Idade , Idoso , Estados Unidos , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/métodos , Feminino , Masculino , Colonoscopia/economia , Colonoscopia/estatística & dados numéricos , Centers for Medicare and Medicaid Services, U.S. , Anos de Vida Ajustados por Qualidade de Vida , Sensibilidade e Especificidade , Valor Preditivo dos Testes , Fezes/química , Simulação por Computador , Modelos EconômicosRESUMO
There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype-phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.
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PURPOSE OF REVIEW: We aim to highlight two recent clinical trials that have altered the approach of the management of stage I nonsmall cell lung cancer. RECENT FINDINGS: The JCOG 0802 and CALGB 140503 trials demonstrated that sublobar resection is noninferior to lobectomy for overall and disease-free survival in patients with stage I nonsmall cell lung cancer. SUMMARY: Since 1962, lobectomy has been deemed the gold standard treatment for operable lung cancer. However, two recent clinical trials have demonstrated that, for select patients, sublobar resection is oncologically noninferior; results, which are leading us into a new era for the surgical management of lung cancer. Notwithstanding the progress made by these studies and the opportunities that have been put forth, questions remain. This review aims at reviewing the results of both trials and to discuss future perspectives for the surgical treatment of lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estadiamento de Neoplasias , Pneumonectomia , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Pneumonectomia/métodos , Intervalo Livre de Doença , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics. CASE REPORT: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures. DISCUSSION: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.
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Epilepsias Mioclônicas Progressivas , Convulsões , Humanos , Epilepsias Mioclônicas Progressivas/complicações , Epilepsias Mioclônicas Progressivas/diagnóstico , Convulsões/diagnóstico , Convulsões/complicações , Convulsões/etiologia , Convulsões/tratamento farmacológico , Mioclonia/diagnóstico , Mioclonia/etiologia , Mioclonia/complicações , Mioclonia/tratamento farmacológico , Masculino , Canais de Potássio Shaw/genética , Feminino , Eletroencefalografia/métodosRESUMO
BACKGROUND: Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized. METHODS: We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases. Selection criteria focused on the four most relevant adult-onset autoinflammatory diseases-deficiency of deaminase 2 (DADA2), tumor necrosis factor receptor associated periodic fever syndrome (TRAPS), cryopyrin associated periodic fever syndrome (CAPS), and familial mediterranean fever (FMF). We extracted clinical, laboratory and radiological features to propose the most common neurological phenotypes. RESULTS: From 276 records, 28 articles were included. The median patient age was 38, with neurological symptoms appearing after a median disease duration of 5 years. Headaches, cranial nerve dysfunction, seizures, and focal neurological deficits were prevalent. Predominant phenotypes included stroke for DADA2 patients, demyelinating lesions and meningitis for FMF, and meningitis for CAPS. TRAPS had insufficient data for adequate phenotype characterization. CONCLUSION: Neurologists should be proactive in diagnosing monogenic autoinflammatory diseases in young adults showcasing clinical and laboratory indications of inflammation, especially when symptoms align with recurrent or chronic meningitis, small vessel disease strokes, and demyelinating lesions.
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Síndromes Periódicas Associadas à Criopirina , Febre Familiar do Mediterrâneo , Doenças Hereditárias Autoinflamatórias , Meningite , Adulto Jovem , Humanos , Adulto , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Neurologistas , Adenosina Desaminase/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Febre Familiar do Mediterrâneo/genética , Síndromes Periódicas Associadas à Criopirina/genética , Febre , FenótipoRESUMO
BACKGROUND: Policy evaluation studies that assess how state-level policies affect health-related outcomes are foundational to health and social policy research. The relative ability of newer analytic methods to address confounding, a key source of bias in observational studies, has not been closely examined. METHODS: We conducted a simulation study to examine how differing magnitudes of confounding affected the performance of 4 methods used for policy evaluations: (1) the two-way fixed effects difference-in-differences model; (2) a 1-period lagged autoregressive model; (3) augmented synthetic control method; and (4) the doubly robust difference-in-differences approach with multiple time periods from Callaway-Sant'Anna. We simulated our data to have staggered policy adoption and multiple confounding scenarios (i.e., varying the magnitude and nature of confounding relationships). RESULTS: Bias increased for each method: (1) as confounding magnitude increases; (2) when confounding is generated with respect to prior outcome trends (rather than levels), and (3) when confounding associations are nonlinear (rather than linear). The autoregressive model and augmented synthetic control method had notably lower root mean squared error than the two-way fixed effects and Callaway-Sant'Anna approaches for all scenarios; the exception is nonlinear confounding by prior trends, where Callaway-Sant'Anna excels. Coverage rates were unreasonably high for the augmented synthetic control method (e.g., 100%), reflecting large model-based standard errors and wide confidence intervals in practice. CONCLUSIONS: In our simulation study, no single method consistently outperformed the others, but a researcher's toolkit should include all methodologic options. Our simulations and associated R package can help researchers choose the most appropriate approach for their data.
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Política Pública , Humanos , Viés , Simulação por ComputadorRESUMO
Anti-NMDA receptor encephalitis (NMDARE), an autoimmune encephalitis associated with autoantibodies against the N-methyl-D-aspartate (NMDA) receptor, affects predominantly young women and is associated with psychiatric symptoms, seizures, movement disorders, and autonomic instability. Traditional treatments of anti-NMDA receptor encephalitis involve corticosteroids, intravenous immunoglobulin, plasmapheresis, cyclophosphamide, and rituximab. However, many controversies remain in the treatment for NMDA receptor encephalitis, such as optimal timing and combination of different immunotherapies, the role of newer strategies (e.g., bortezomib or tocilizumab) for severe and refractory patients, and the need or not for long-term immunosuppression. Our goal was to perform a scoping review to discuss the controversial topics of immunotherapy for NMDA receptor encephalitis and propose operational definitions to guide clinical practice and future research in the field.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Humanos , Feminino , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Receptores de N-Metil-D-Aspartato , Ciclofosfamida/uso terapêutico , Rituximab/uso terapêutico , Autoanticorpos , ImunoterapiaRESUMO
BACKGROUND: A retrospective analysis of neck hematoma, stroke, and mortality after symptomatic and asymptomatic carotid endarterectomy (CEA) was conducted, to determine the most appropriate perioperative medication for these patients. Thirty-day outcomes of moderate and severe neck bleeding were also investigated. METHODS: Patients undergoing CEA in a Vascular Surgery department were analyzed (2015-2019). Preprocedure antithrombotic medication (from the 5 days prior to surgery) was identified. End point predictors were identified by univariate and multivariable analyses and adjusted for confounders. RESULTS: A total of 304 CEA were included. Almost half of the included patients (49.67%) were under low-dose aspirin, 17.55% other single antiplatelet agent, 12.59% dual antiplatelet therapy, 8.61% anticoagulation, and 10.92% no antithrombotic therapy. There was a 8.22% rate of important hematoma, including 4.93% severe (requiring surgical exploration) hematomas and a 30-day all-stroke incidence of 2.94% in symptomatic and 1.79% asymptomatic patients (P = 0.51). When compared to aspirin, severe hematoma was more prevalent with single clopidogrel or triflusal (relative risk [RR] 4.25, P = 0.11), dual antiplatelet group (RR 11.84, P = 0.002), and anticoagulation (RR 8.604, P = 0.02). Dual antiaggregation and anticoagulation did not confer postoperative stroke protection compared to single aspirin in either symptomatic or asymptomatic patients. Nonsignificant higher intrahospital mortality was noted in no medication, dual antiplatelet, and anticoagulation groups in contrast to aspirin. Severe neck bleeding was associated with increased congestive heart failure (9.26-fold, P = 0.03) and longer hospital stay (11.20 ± 24.69 days vs. 3.18 ± 4.79 with no bleeding, P < 0.001), with a tendency for higher hospital readmission at 30 days (4.66-fold, P = 0.13). Mortality and stroke rates were similar. CONCLUSIONS: Double antiaggregation and anticoagulation did not confer better perioperative outcomes after elective CEA in our study. These regimens were associated with an increased risk of neck hematoma, especially severe bleeding, with similar rates of neurologic events in both symptomatic and asymptomatic patients and no mortality benefit. Monotherapy with aspirin appears to be the safest perioperative antithrombotic regimen for elective CEA.
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Endarterectomia das Carótidas , Acidente Vascular Cerebral , Humanos , Endarterectomia das Carótidas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Fatores de Tempo , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Hemorragia/etiologia , Hematoma/etiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
PURPOSE: To investigate the combinations of variables that comprise the biopsychosocial model domains to identify clinical profiles of risk and protection of second anterior cruciate ligament injury. METHODS: One hundred and forty-five patients for return-to-sport testing after anterior cruciate ligament (ACL) reconstruction (ACLR) were contacted, and 97 were deemed eligible. All were evaluated between 6 and 24 months and followed up for 2 years. Participants answered the International Knee Documentation Committee (IKDC) and Anterior Cruciate Ligament-Return to Sport after Injury Scale (ACL-RSI), performed the postural stability assessment using the Biodex Balance System, and assessed muscle strength at 60° and 300°/s on the isokinetic dynamometer. Personal factors (age, gender, body mass index), body structures (graft type and concomitant injuries), and environmental factors (time between surgery and evaluation) were also collected. The participants were asked about the occurrence of a second ACL injury and return to sport after 2 years of follow-up. Classification and regression tree (CART) analysis was used to determine predictors of a second ACL injury. The receiver operating characteristic (ROC) curve was performed to verify the accuracy of the CART analysis, in addition to the sensitivity, specificity, and relative risk (RR) of the model. RESULTS: Of the initial 97 participants, 88 (89.8%) responded to follow-up and 14 (15.9%) had a second ACL injury (11 graft ruptures and three contralateral ACL). CART analysis identified the following variables as predictors of second ACL injury: return to sport, hamstring strength symmetry at 300°/s, ACL-RSI score, hamstrings/quadriceps ratio at 60°/s, and body mass index (BMI). CART correctly identified 9 (64.3%) of the 14 participants who were reinjured and 71 (95.9%) of the 74 participants who were not. The total correct classification was 90.9%. The area under the ROC curve was 0.88 (95% CI 0.72-0.99; p < 0.001), and the model showed a sensitivity of 75% (95% CI 42.8-94.5), specificity of 93.4% (95% CI 85.3-97.8), and RR of 15.9 (95% CI 4.9-51.4; p < 0.0001). CONCLUSION: The combination of hamstring strength symmetry, hamstring/quadriceps ratio (body functions); return to sport (activity and participation); psychological readiness; and BMI (personal factors) could identify three clinical risk profiles for a second ACL injury with good accuracy. LEVEL OF EVIDENCE: IV.
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Interest in Unmanned Aerial Vehicles (UAVs) has increased due to their versatility and variety of applications, however their battery life limits their applications. Heterogeneous multi-robot systems can offer a solution to this limitation, by allowing an Unmanned Ground Vehicle (UGV) to serve as a recharging station for the aerial one. Moreover, cooperation between aerial and terrestrial robots allows them to overcome other individual limitations, such as communication link coverage or accessibility, and to solve highly complex tasks, e.g., environment exploration, infrastructure inspection or search and rescue. This work proposes a vision-based approach that enables an aerial robot to autonomously detect, follow, and land on a mobile ground platform. For this purpose, ArUcO fiducial markers are used to estimate the relative pose between the UAV and UGV by processing RGB images provided by a monocular camera on board the UAV. The pose estimation is fed to a trajectory planner and four decoupled controllers to generate speed set-points relative to the UAV. Using a cascade loop strategy, these set-points are then sent to the UAV autopilot for inner loop control. The proposed solution has been tested both in simulation, with a digital twin of a solar farm using ROS, Gazebo and Ardupilot Software-in-the-Loop (SiL); and in the real world at IST Lisbon's outdoor facilities, with a UAV built on the basis of a DJ550 Hexacopter and a modified Jackal ground robot from DJI and Clearpath Robotics, respectively. Pose estimation, trajectory planning and speed set-point are computed on board the UAV, using a Single Board Computer (SBC) running Ubuntu and ROS, without the need for external infrastructure.
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Comunicação , Dispositivos Aéreos não Tripulados , Espécies Reativas de Oxigênio , Simulação por Computador , Fontes de Energia ElétricaRESUMO
Neural Field Equations (NFE) are intended to model the synaptic interactions between neurons in a continuous neural network, called a neural field. This kind of integro-differential equations proved to be a useful tool to describe the spatiotemporal neuronal activity from a macroscopic point of view, allowing the study of a wide variety of neurobiological phenomena, such as the sensory stimuli processing. The present article aims to study the effects of additive noise in one- and two-dimensional neural fields, while taking into account finite axonal velocity and an external stimulus. A Galerkin-type method is presented, which applies Fast Fourier Transforms to optimise the computational effort required to solve these equations. The explicit Euler-Maruyama scheme is implemented to obtain the stochastic numerical solution. An open-source numerical solver written in Julia was developed to simulate the neural fields in study.
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Modelos Neurológicos , Neurônios , Redes Neurais de Computação , Neurônios/fisiologiaRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which rapidly became a pandemic of global proportions. Sepsis is commonly present with high lethality in the severe forms of the disease. The virus-induced cytokine storm puts the immune system in overdrive at the expense of the pathogen-specific immune response and is likely to underlie the most advanced COVID-19 clinical features, including sepsis-related multiple organ dysfunction as well as the pathophysiological changes found in the lungs. We review the major therapeutic strategies that have been considered for sepsis and might be amenable to repurposing for COVID-19. We also discuss two different immunization strategies that have the potential to confer antiviral heterologous protection: innate-induced trained immunity and adaptive-induced immune response resetting.
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Imunidade Adaptativa , Betacoronavirus/imunologia , Infecções por Coronavirus , Citocinas/imunologia , Imunidade Inata , Insuficiência de Múltiplos Órgãos , Pandemias , Pneumonia Viral , COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Humanos , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/patologia , Insuficiência de Múltiplos Órgãos/terapia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/terapia , SARS-CoV-2RESUMO
BACKGROUND: Chronic post-thrombotic syndrome (PTS) may develop in up to 50% of patients after deep vein thrombosis (DVT), and may reduce patients' quality of life (QoL). We aimed to evaluate the association of PTS severity with QoL in patients with proximal DVT submitted for medical treatment and also to identify modifiable and non-modifiable risk factors related to PTS. METHODS: Patients with iliac or femoropopliteal DVT observed in Vascular Surgery consultation in our institution from 1 year period with unilateral DVT were selected. Patients with total vein recanalization were excluded. Villalta scale was applied to assess PTS degree and VEINES-QoL/Sym questionnaire was used as a disease-specific QoL measure. Correlation between PTS degree and VEINES-QoL/Sym score and predictors of PTS were determined. RESULTS: Fifty-six patients were accepted to enter the study. From those, 66.1% were female, 64.3% (n = 36) had iliac and 35.7% (n = 20) femoropopliteal DVT. PTS was present in 52.8% of iliac and 65.0% of femoropopliteal DVT patients observed for consultation (P = 0.41). There was a significant correlation with PTS degree and both VEINES-QoL and VEINES-Sym scores (P < 0.01). Major depression (odds ratio OR = 5.63, P = 0.04) and regular wear of compressing stockings (OR = 4.69, P = 0.04) were the only independent factors associated with PTS. Patients with depression had lower QoL scores, while patients with PTS who wear compression stockings had similar QoL scores compared to patients without PTS. Ultrasound alterations (OR = 3.28, P = 0.17), age, gender, iliac DVT, multiple DVT and time after DVT (P > 0.20) were not associated with PTS syndrome. CONCLUSIONS: VEINES-QoL/Sym had moderate inverse correlation with PTS degree. Depression was associated with both PTS and lower QoL scores. Patients with PTS criteria compliant to wearing compressing stockings had similar QoL scores to patients without PTS.
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Síndrome Pós-Trombótica , Trombose Venosa , Feminino , Humanos , Masculino , Síndrome Pós-Trombótica/etiologia , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Trombose Venosa/diagnóstico , Trombose Venosa/diagnóstico por imagemRESUMO
Teams of mobile robots can be employed in many outdoor applications, such as precision agriculture, search and rescue, and industrial inspection, allowing an efficient and robust exploration of large areas and enhancing the operators' situational awareness. In this context, this paper describes an active and decentralized framework for the collaborative 3D mapping of large outdoor areas using a team of mobile ground robots under limited communication range and bandwidth. A real-time method is proposed that allows the sharing and registration of individual local maps, obtained from 3D LiDAR measurements, to build a global representation of the environment. A conditional peer-to-peer communication strategy is used to share information over long-range and short-range distances while considering the bandwidth constraints. Results from both real-world and simulated experiments, executed in an actual solar power plant and in its digital twin representation, demonstrate the reliability and efficiency of the proposed decentralized framework for such large outdoor operations.
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Robótica , Reprodutibilidade dos Testes , Agricultura , Conscientização , ComunicaçãoRESUMO
The aim of this study was to translate and culturally adapt the Fear of Falling Avoidance Behavior Questionnaire (FFABQ) into Brazilian-Portuguese (FFABQ-B), and to examine its reliability and validity in Brazilian older adults. The FFABQ-B was translated and tested in 10 Brazilian older adults. We assessed 52 community-dwellers, 68.7 (±6.2) years, using the FFABQ-B, BERG Balance Scale, Activities-specific Balance Confidence Scale, Falls Efficacy Scale, 6-Minute Walk Test, Timed Up and Go test, and activity monitor. Internal consistency, test-retest reliability, construct validity, and floor and ceiling effects were analyzed. The FFABQ-B had adequate internal consistency (Cronbach's α = .90) and test-retest reliability (intraclass correlation coefficient = .81; 95% confidence interval [.68, .90]). The FFABQ-B was associated with 6-Minute Walk Test, Timed Up and Go, BERG Balance Scale, physical activity time (p < .05), Activities-specific Balance Confidence scale, and Falls Efficacy Scale (p < .001). The FFABQ-B is both reliable and valid to assess avoidance behavior in activities and participation due to fear of falling in Brazilian community-dwelling older adults.
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Aprendizagem da Esquiva , Medo , Humanos , Idoso , Brasil , Reprodutibilidade dos Testes , Comparação Transcultural , Equilíbrio Postural , Portugal , Estudos de Tempo e Movimento , Inquéritos e Questionários , PsicometriaRESUMO
OBJECTIVE: To identify the biopsychosocial factors that explain injuries in dancers through use of a Classification and Regression Tree (CART) analysis. METHODS: Cross-sectional study performed with dancers over 18 years of age from dance schools in Brazil. Sociodemographic factors, pain intensity (numerical pain rating scale, NPRS), anxiety (Beck anxiety inventory, BAI), and functioning (WHO Disability Assessment Schedule 2.0, WHODAS) were assessed. We used a classification and regression tree (CART) analysis considering the occurrence of injury as a dependent variable, and the independent variables included age, training load, BAI, pain level, and WHODAS 2.0 score, adjusted for body mass index. RESULTS: The sample included 61 dancers (ballet, jazz, contemporary, tap, and urban dance), and they were mainly women (72.1%) with a mean age of 25.6 (± 5.79) years. Thirty-three percent presented dance-related musculoskeletal injuries in the last 12 months. The CART analysis showed that training load was the main associated factor, explaining 52.4% of injuries in dancers with a workload > 11.5 hrs/wk (p=0.05). When NPRS > 6.5 is added to the high load of training, these two variables explain 100% of the cases of injury (p=0.02). Training load < 11.5 hrs/wk and WHODAS 2.0 score < 68.0 were associated factors for no injury in dancers (80%; p=0.03). CONCLUSIONS: Our results demonstrated that training load, functioning, and pain intensity were factors associated with injury in dancers, and we established cutoff points. The inclusion of functioning in the algorithm suggests the influence of structure, function, activity, and social participation on injury in dancers and strengthens the patient-centered care.
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Dança , Adolescente , Adulto , Brasil/epidemiologia , Estudos Transversais , Dança/lesões , Feminino , Humanos , Dor/epidemiologia , Medição da DorRESUMO
Transforming growth factor-ß (TGF-ß) plays a dual role acting as tumor promoter or suppressor. Along with cyclooxygenase-2 (COX-2) and oncogenic Ras, this multifunctional cytokine is deregulated in colorectal cancer. Despite their individual abilities to promote tumor growth and invasion, the mechanisms of cross regulation between these pathways is still unclear. Here, we investigate the effects of TGF-ß, Ras oncogene and COX-2 in the colorectal cancer context. We used colon adenocarcinoma cell line HT-29 and Ras-transformed IEC-6 cells, both treated with prostaglandin E2 (PGE2 ), TGF-ß or a combined treatment with these agents. We demonstrated that PGE2 alters the subcellular localization of E-cadherin and ß-catenin and enhanced the tumorigenic potential in HT-29 cells. This effect was inhibited by TGF-ß, indicating a tumor suppressor role. Conversely, in Ras-transformed IEC-6 cells, TGF-ß induced COX-2 expression and increased invasiveness, acting as a tumor promoter. In IEC-6 Ras-transformed cells, TGF-ß increased nuclear ß-catenin and Wnt/ß-catenin activation, opposite to what was seen in the PGE2 and TGF-ß joint treatment in HT-29 cells. Together, our findings show that TGF-ß increases COX-2 levels and induces invasiveness cooperating with Ras in a Wnt/ß-catenin activation-dependent manner. This shows TGF-ß dual regulation over COX-2/PGE2 tumor promotion depending on the H-Ras and Wnt/ß-catenin pathways activation status in intestinal cancer cells.
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Carcinogênese/metabolismo , Carcinogênese/patologia , Neoplasias Colorretais/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Via de Sinalização Wnt , Caderinas/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Células HT29 , Humanos , Invasividade Neoplásica , Fatores de Transcrição TCF/metabolismo , Transcrição Gênica , beta Catenina/metabolismoRESUMO
Cure of severe infections, sepsis, and septic shock with antimicrobial drugs is a challenge because morbidity and mortality in these conditions are essentially caused by improper immune response. We have tested the hypothesis that repeated reactivation of established memory to pathogens may reset unfavorable immune responses. We have chosen for this purpose a highly stringent mouse model of polymicrobial sepsis by cecum ligation and puncture. Five weeks after priming with a diverse Ag pool, high-grade sepsis was induced in C57BL/6j mice that was lethal in 24 h if left untreated. Antimicrobial drug (imipenem) alone rescued 9.7% of the animals from death, but >5-fold higher cure rate could be achieved by combining imipenem and two rechallenges with the Ag pool (p < 0.0001). Antigenic stimulation fine-tuned the immune response in sepsis by contracting the total CD3+ T cell compartment in the spleen and disengaging the hyperactivation state in the memory T subsets, most notably CD8+ T cells, while preserving the recovery of naive subsets. Quantitative proteomics/lipidomics analyses revealed that the combined treatment reverted the molecular signature of sepsis for cytokine storm, and deregulated inflammatory reaction and proapoptotic environment, as well as the lysophosphatidylcholine/phosphatidylcholine ratio. Our results showed the feasibility of resetting uncontrolled hyperinflammatory reactions into ordered hypoinflammatory responses by memory reactivation, thereby reducing morbidity and mortality in antibiotic-treated sepsis. This beneficial effect was not dependent on the generation of a pathogen-driven immune response itself but rather on the reactivation of memory to a diverse Ag pool that modulates the ongoing response.
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Sepse/imunologia , Animais , Apoptose/imunologia , Complexo CD3/imunologia , Linfócitos T CD8-Positivos/imunologia , Ceco/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Memória Imunológica/imunologia , Inflamação/imunologia , Lipidômica/métodos , Lisofosfatidilcolinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilcolinas/imunologia , Proteômica/métodos , Choque Séptico/imunologia , Baço/imunologiaRESUMO
BACKGROUND: Recent guidelines raise the concept of the importance of health-related quality of life (QoL). Change in QoL after amputation in ischemic patients is not well described. We aim to evaluate the change in quality of life after major limb amputation in patients with peripheral arterial disease. METHODS: We retrospectively identified all patients submitted to above-knee amputation (AKA) and below-knee amputation in our vascular surgery department in a 2-year period. Trauma excluded. A vascular amputee adapted QoL questionnaire was administered comparing the last 2 weeks to the 2 weeks before amputation. It included subjective and objective questions adapted from WHOQoL-BREEF and SF-36 divided into specific domains of QoL (physical health, role physical, pain, social, and psychological health) that were compared to 2 global items (overall QoL and general health). Independent samples tests and linear correlations were calculated. RESULTS: A total of 106 patients were included, 30-day mortality rate 16.3% and 1-year 39.1%. Patients had an increase in mean total score after amputation of 14.35 out of 100 points, with an improvement of 52.1 points in pain and 11 points in social and psychological health out of 100 (P<0.001). Physical health and role physical scores decreased after amputation. Overall QoL was correlated with total score (P<0.001). Mean QoL total score after amputation was 79.0% ± 12.6. In general, amputees scored higher in the domains social and psychological health. Older people, women, AKA and bilateral amputees had lower physical health scores (P<0.05), prosthesis was correlated with improvement in physical health after amputation (Pâ¯=â¯0.026). Elderly and married people had big improvement in overall QoL after amputation (Pâ¯=â¯0.008 and Pâ¯=â¯0.056, respectively). CONCLUSIONS: QoL does not seem to diminish in advanced ischemic patients after amputation. Older people value more a decrease in pain and family support over physical health. Therefore, patient oriented treatments should be preferred. Future research should be made to validate a disease-specific questionnaire for this population.
Assuntos
Amputação Cirúrgica , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Qualidade de Vida , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica/efeitos adversos , Amputação Cirúrgica/mortalidade , Feminino , Nível de Saúde , Humanos , Isquemia/diagnóstico , Isquemia/mortalidade , Masculino , Saúde Mental , Pessoa de Meia-Idade , Medição da Dor , Preferência do Paciente , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Comportamento Social , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Charlson Comorbidity Index (CCI) is commonly used in outcome studies to adjust for patient comorbid conditions but has not been specifically validated for use in acute embolic lower limb ischaemia (AELLI). OBJECTIVES: The aim of this study was to access whether a high CCI score unadjusted (CCIu) and adjusted (CCIa) by age relates to major amputation and mortality after a first episode of AELLI. METHODS: The last 100 patients presenting with the first event of AELLI submitted to embolectomy at our Vascular Surgery Department were retrospectively evaluated. Patient characteristics, pre- and post-operative period variables were collected and CCIu and CCIa calculated. Survival predictors were analyzed using Cox regression. The area under the curve of the receiver operating characteristic curves was calculated to validate and determine the discriminating ability of CCIu and CCIa in predicting amputation rate and 30-day mortality. Youden index was used to determine the critical value. Survival analysis was performed with Kaplan-Meier method and differences between survival curves were tested with Log-Rank test. A P value of <0.05 was considered statistically significant. RESULTS: The mean age was 80.03±10.776 years and the mean follow-up 19.28±7.929 months. Amputation rate was 16%, 30-day mortality 21% and long-term mortality 42%. Patients with CCIu≥3 compared with patients with CCIu<3 had higher amputation rate (37.5% vs. 1.7%; OR:35.400), 30-day mortality (47.5% vs. 3.3%; OR:35.400) and global mortality (P=0.00). Also, patients with CCIa≥6 compared with patients with CCIa<6 had higher amputation rate (34.1% vs. 1.8%; OR:28.488), 30-day mortality (47.7% vs. 0.0%) and global mortality (P=0.00). Multivariate analysis showed that both CCIu and CCIa were independent predictors of amputation rate and 30-day mortality. CONCLUSION: CCIu and CCIa have proven to be good predictors of amputation rate and survival, thus being a valuable prognostic factor in patients presenting with the first event of AELLI.