Integrating depth of invasion in T classification improves the prognostic performance of the American Joint Committee on Cancer primary tumor staging system for cutaneous squamous cell carcinoma of the head and neck

BACKGROUND: The last revision of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual included a specific system for cutaneous squamous cell carcinoma (CSCC) of the head and neck. Here, we assessed the prognostic performance of six candidate modified T-classification models in head and neck CSCC patients. METHODS: Analysis of 916 patients with head and neck CSCC given treatment with curative intent at The University of Texas MD Anderson Cancer Center between 1995 and 2019 was performed. The main outcome was disease-specific survival (DSS), and the impact of depth of invasion (DOI) was analyzed using multivariable regression models. Candidate models were developed using the optimal DOI cut points for each AJCC T classification based on goodness of fit of the model and the simplicity of the model. Staging systems were compared using Harrell\u27s concordance index. RESULTS: Median age was 70 years (range, 19-97years) and median follow-up time of 22 months (range, 1-250months). The median DOI was 6.0 mm (range, 0.1-70.0 mm). The five-year DSS rate was 80.7% (95%CI, 77.4-83.7%). We found significant association between DOI (hazard ratio, 1.21 [95%CI: 1.01-1.43]) and DSS on multivariable analysis. Based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves, model 6 surpassed the AJCC staging system. CONCLUSIONS: Incorporation of DOI in the current AJCC staging system improves discrimination of T classifications in head and neck CSCC patients. LAY SUMMARY: The current staging system for head and neck cutaneous squamous cell carcinoma demonstrates wide prognostic variability and provides suboptimal risk stratification. Incorporation of depth of invasion in the T-classification system improves risk prediction and patient counseling. PRECIS: We propose improved head and neck cutaneous squamous cell carcinoma T staging that will include depth of invasion and should be considered in future versions of the American Joint Committee on Cancer after external validation

Livro didático público paranaense "lingua portuguesa e literatura" : o professor-autor e o gênero discursivo

Orientadora: Profa. Dra. Iara Bemquerer CostaAutor não autorizou a divulgação do arquivo digitalTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Humanas, Letras e Artes, Programa de Pós-Graduação em Letras. Defesa: Curitiba, 23/04/2012Bibliografia: fls. 163-178Área de concentração :Resumo: Esta pesquisa descritivo-explicativa tem como objetivo averiguar a relacao dialogica entre o Livro Didatico Publico Paranaense \Lingua Portuguesa e Literatura. (LDP-PR) e os livros representantes do genero discursivo Livro Didatico de Lingua Portuguesa (LD-LP). A partir de uma perspectiva socio-historico-discursiva e empregando fontes bibliografica e documental, desenvolvemos esta pesquisa em duas etapas. Na primeira, procuramos efetuar uma reflexao teorica sobre os Generos Discursivos (BAKHTIN) e sobre como a abordagem sociointeracionista se apropria desta concepcao bakhtiniana e discute a questao da didatizacao dos generos (SCHNEUWLY e DOLZ). Na segunda, aplicamos estes pressupostos ao LDP-PR com o intuito de averiguar o encaminhamento didatico dado aos textos de generos discursivos empregados neste material didatico. A partir desta averiguacao do conteudo tematico do LDP-PR, realizada pelo trabalho com as praticas de leitura, escrita e oralidade, buscamos sustentacao para a analise deste LD como um exemplar do genero LD-LP. Nossos resultados mostram que o LDP-PR inova na escolha do conteudo tematico, mas mantem o estilo (marcado pelo emprego de discursos injuntivos, explicativos e expositivos) e a construcao composicional (de textualidade multimodal) tipicos do genero LD-LP. Creditamos a autoria multipla (constituida por professores da rede escolar), marcada pela experiencia reduzida e a merce da Secretaria de Estado da Educacao do Parana (SEED-PR) este apego ao genero consolidado.Abstract: This descriptive-explanatory research aims to investigate the dialogic relationship between the Parana‘s Public Textbook "Portuguese and Literature" (LDP-PR) and the representative books of the discursive genre of Portuguese Textbook (LP-LD). From a socio-historic-discursive perspective and by the use of bibliographical and documentary sources, we developed this research in two stages. In the first one, we carried out a theoretical reflection about the Discursive Genres (BAKHTIN) and how the social interactionist approach appropriates this Bakhtinian concept and discusses the issue of making genre educational (SCHNEUWLY and DOLZ). In the second one, we applied these assumptions to the LDP-PR with the intent of investigating the educational directions given to the texts of discursive genres employed in such a teaching materials. From this investigation of the LDP-PR‘s thematic contents, performed through the work with reading, writing and speaking skills practices, we sought support for the analysis of this LD as an exemplar of the LD-LP genre. Our results reveal that the LDP-PR innovates the choice of the thematic content but retains the style (marked by the use of injunctive, explanatory and expository discourses) and compositional construction (multimodal textuality) that is typical of the LD-LP genre. We attribute to the multiple authorship (made up of teachers from the public educational system), marked by limited experience and at the mercy of the Parana‘s State Department of Education (SEED-PR), this attachment to the consolidated genre

Effect of tranexamic acid administration on acute traumatic coagulopathy in rats with polytrauma and hemorrhage.

Trauma and hemorrhagic shock can lead to acute traumatic coagulopathy (ATC) that is not fully reversed by prehospital resuscitation as simulated with a limited volume of fresh whole blood (FWB) in a rat model. Tranexamic Acid (TXA) is used as an anti-fibrinolytic agent to reduce surgical bleeding if administered prior to or during surgery, and to improve survival in trauma if given early after trauma. It is not clear from the existing clinical literature whether TXA has the same mechanism of action in both settings. This study sought to explore the molecular mechanisms of TXA activity in trauma and determine whether administration of TXA as a supplement to FWB resuscitation could attenuate the established ATC in a rat model simulating prehospital resuscitation of polytrauma and hemorrhagic shock. In a parallel in-vitro study, the effects on clotting assays of adding plasmin at varying doses along with either simultaneous addition of TXA or pre-incubation with TXA were measured, and the results suggested that maximum anti-fibrinolytic effect of TXA on plasmin-induced fibrinolysis required pre-incubation of TXA and plasmin prior to clot initiation. In the rat model, ATC was induced by polytrauma followed by 40% hemorrhage. One hour after trauma, the rats were resuscitated with FWB collected from donor rats. Vehicle or TXA (10mg/kg) was given as bolus either before trauma (TXA-BT), or 45min after trauma prior to resuscitation (TXA-AT). The TXA-BT group was included to contrast the coagulation effects of TXA when used as it is in elective surgery vs. what is actually feasible in real trauma patients (TXA-AT group). A single dose of TXA prior to trauma significantly delayed the onset of ATC from 30min to 120min after trauma as measured by a rise in prothrombin time (PT). The plasma d-dimer as well as plasminogen/fibrinogen ratio in traumatized liver of TXA-BT were significantly lower as compared to vehicle and TXA-AT. Wet/dry weight ratio and leukocytes infiltration of lungs were significantly decreased only if TXA was administrated later, prior to resuscitation (TXA-AT). In conclusion: Limited prehospital trauma resuscitation that includes FWB and TXA may not correct established systemic ATC, but rather may improve overall outcomes of resuscitation by attenuation of acute lung injury. By contrast, TXA given prior to trauma reduced levels of fibrinolysis at the site of tissue injury and circulatory d-dimer, and delayed development of coagulopathy independent of reduction of fibrinogen levels following trauma. These findings highlight the importance of early administration of TXA in trauma, and suggest that further optimization of dosing protocols in trauma to exploit TXA's various sites and modes of action may further improve patient outcomes

Predictors of Short-Term Trauma Laparotomy Outcomes in an Integrated Military–Civilian Health System: A 23-Year Retrospective Cohort Study

Background: Trauma laparotomy (TL) remains a cornerstone of trauma care. We aimed to investigate prehospital measures associated with in-hospital mortality among casualties subsequently undergoing TLs in civilian hospitals. Methods: This retrospective cohort study cross-referenced the prehospital and hospitalization data of casualties treated by Israel Defense Forces-Medical Corps teams who later underwent TLs in civilian hospitals between 1997 and 2020. Results: Overall, we identified 217 casualties treated by IDF-MC teams that subsequently underwent a TL, with a mortality rate of 15.2% (33/217). The main mechanism of injury was documented as penetrating for 121/217 (55.8%). The median heart rate and blood pressure were within the normal limit for the entire cohort, with a low blood pressure predicting mortality (65 vs. 127, p p p p = 0.002, respectively). Conclusions: Prehospital interventions introduced throughout the study period did not lead to an improvement in survival. Survival was negatively influenced by prehospital ETI, reinforcing previous observations of the potential deleterious effects of definitive airways on hemorrhaging trauma casualties. While a low blood pressure was a predictor of mortality, the median systolic blood pressure for even the sickest patients (ISS > 16) was within normal limits, highlighting the challenges in triage and risk stratification for trauma casualties

Inclusion of extranodal extension in the lymph node classification of cutaneous squamous cell carcinoma of the head and neck

BACKGROUND: The prognostic performance of the recently updated American Joint Committee on Cancer lymph node classification of cutaneous head and neck squamous cell carcinoma (HNSCC) has not been validated. The objective of this study was to assess the prognostic role of extranodal extension (ENE) in cutaneous HNSCC. METHODS: This was a retrospective analysis of 1258 patients with cutaneous HNSCC who underwent surgery with or without adjuvant therapy between 1995 and 2019 at The University of Texas MD Anderson Cancer Center. The primary outcome was disease-specific survival (DSS). Local, regional, and distant metastases-free survival were secondary outcomes. Recursive partitioning analysis (RPA) and a Cox proportional hazards regression model were used to assess the fitness of staging models. RESULTS: No significant differences in 5-year DSS were observed between patients with pathologic lymph node-negative (pN0) disease (67.4%) and those with pN-positive/ENE-negative disease (68.2%; hazard ratio, 1.02; 95% CI, 0.61-1.79) or between patients with pN-positive/ENE-negative disease and those with pN-positive/ENE-positive disease (52.7%; hazard ratio, 0.57; 95% CI, 0.31-1.01). The RPA-derived model achieved better stratification between high-risk patients (category III, ENE-positive with \u3e2 positive lymph nodes) and low-risk patients (category I, pN0; category II, ENE-positive/pN1 and ENE-negative with \u3e2 positive lymph nodes). The performance of the RPA-derived model was better than that of the pathologic TNM classification (Akaike information criterion score, 1167 compared with 1176; Bayesian information criterion score, 1175 compared with 1195). CONCLUSIONS: The number of metastatic lymph nodes and the presence of ENE are independent prognostic factors for DSS in cutaneous HNSCC, and incorporation of these factors in staging systems improves the performance of the American Joint Committee on Cancer lymph node classification