Neurocysticercotic Calcifications And Hippocampal Sclerosis: A Case-control Study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Objective The exact role of calcified neurocysticercotic lesions (CNLs) in epilepsy is yet unknown and controversial. Although the relationship between CNLs, epilepsy and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) has already been addressed, to our knowledge, no study has actually provided strong statistical evidence, nor reported the ODDS ratio for these associations. Therefore, we designed this case-control study to assess the likelihood of having MTLE-HS versus other forms of epilepsy in the presence of CNLs. Methods In this case-control study we included 119 consecutive patients with epilepsy and 106 disease controls (headache) with previous CT scans. We subdivided cases into MTLE-HS and other epilepsies. We used brain CT scans to define presence or absence of CNLs. After exploratory analyses, we used logistic regression to analyze the association between CNLs, epilepsy subgroups and disease controls. Results CNLs were found in 31.09% of cases and in 11.32% of controls (p<0.001). The initial analysis comparing epilepsy versus controls revealed a significant association between CNLs and epilepsy (OR = 5.32; 95%CI = 2.43-11.54; p<0.001). However, when we compared MTLE-HS versus other epilepsies versus controls we confirmed that CNLs were associated with MTLE-HS (OR = 11.27, 95%CI = 4.73-26.85; p<0.001) but other epilepsies were not. We found no difference in the CNLs load and no difference in the location of the CNLs when we compared patients with MTLE-HS, other epilepsies and disease controls. Significance The inclusion of controls allowed us to estimate the likelihood of having epilepsy in the presence of CNLs. We found that patients with CNLs were 11 times more likely to have MTLE-HS; however, the presence of CNLs did not change the odds of having other types of epilepsy. These findings raise the possibility of neurocysticercosis playing a role in the pathophysiology of MTLE-HS and need further confirmation in other series.107Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2013/21265-2, 2013/07559-3

A abordagem inicial do Trauma Cranioencefálico em crianças e idosos para o cirurgião geral no cenário do trauma: uma revisão de literatura: The initial approach to Head Trauma in children and the elderly for the general surgeon in the trauma setting: a literature review

O Traumatismo Cranioencefálico (TCE) é uma lesão cerebral estrutural resultante de uma força física externa transmitida à cabeça, o objetivo principal do tratamento dos doentes com suspeita de TCE grave é prevenir a lesão cerebral secundária. Como foco do estudo da revisão proposta, objetiva-se compreender o TCE como uma das principais causas de incapacidade a longo prazo entre crianças e pacientes geriátricos. A idade do paciente e o estado geral de saúde influenciam no prognóstico, com maior risco de morbidade e mortalidade associado ao trauma cranioencefálico em pacientes idosos. A presença de TCE em pacientes pediátricos merece grande atenção e importância, principalmente por suas peculiaridades, desafios e dificuldades no manejo

A reposição volêmica e a transfusão maciça para o cirurgião geral no cenário do trauma: uma revisão de literatura: Volume replacement and massive transfusion for the general surgeon in the trauma setting: a literature review

O choque, uma anormalidade do sistema circulatório, evidenciado pelo colapso hemodinâmico, é uma causa importante de admissão no cenário do trauma. A partir da definição da perda sanguínea estimada, propõem-se a reposição de fluídos, que deve ser orientada conforme a reposição de fluídos inicial. Como foco do estudo da revisão proposta, para determinar as soluções cristalóide/colóide, objetiva-se conhecer seus benefícios e malefícios, que serão discutidos em tópico posterior. Além disso, de acordo com a resposta do paciente, pelo grau do choque e seus sinais clínicos, pode suceder a necessidade de uma reposição de sangue (concentrado de hemácias, plasma e plaquetas), e a demanda de um protocolo de transfusão maciça

A reposição volêmica e a transfusão maciça para o Cirurgião geral no cenário do trauma: uma revisão de literatura

O choque, uma anormalidade do sistema circulatório, evidenciado pelo colapso hemodinâmico, é uma causa importante de admissão no cenário do trauma. A partir da definição da perda sanguínea estimada, propõem-se a reposição de fluídos, que deve ser orientada conforme a reposição de fluídos inicial. Como foco do estudo da revisão proposta, para determinar as soluções cristalóide/colóide, objetiva-se conhecer seus benefícios e malefícios, que serão discutidos em tópico posterior. Além disso, de acordo com a resposta do paciente, pelo grau do choque e seus sinais clínicos, pode suceder a necessidade de uma reposição de sangue (concentrado de hemácias, plasma e plaquetas), e a demanda de um protocolo de transfusão maciça

Independent validation of CT radiomics models in colorectal liver metastases:predicting local tumour progression after ablation

Objectives:Independent internal and external validation of three previously published CT-based radiomics models to predict local tumor progression (LTP) after thermal ablation of colorectal liver metastases (CRLM). Materials and methods: Patients with CRLM treated with thermal ablation were collected from two institutions to collect a new independent internal and external validation cohort. Ablation zones (AZ) were delineated on portal venous phase CT 2–8 weeks post-ablation. Radiomics features were extracted from the AZ and a 10 mm peri-ablational rim (PAR) of liver parenchyma around the AZ. Three previously published prediction models (clinical, radiomics, combined) were tested without retraining. LTP was defined as new tumor foci appearing next to the AZ up to 24 months post-ablation. Results: The internal cohort included 39 patients with 68 CRLM and the external cohort 52 patients with 78 CRLM. 34/146 CRLM developed LTP after a median follow-up of 24 months (range 5–139). The median time to LTP was 8 months (range 2–22). The combined clinical-radiomics model yielded a c-statistic of 0.47 (95%CI 0.30–0.64) in the internal cohort and 0.50 (95%CI 0.38–0.62) in the external cohort, compared to 0.78 (95%CI 0.65–0.87) in the previously published original cohort. The radiomics model yielded c-statistics of 0.46 (95%CI 0.29–0.63) and 0.39 (95%CI 0.28–0.52), and the clinical model 0.51 (95%CI 0.34–0.68) and 0.51 (95%CI 0.39–0.63) in the internal and external cohort, respectively. Conclusion: The previously published results for prediction of LTP after thermal ablation of CRLM using clinical and radiomics models were not reproducible in independent internal and external validation. Clinical relevance statement: Local tumour progression after thermal ablation of CRLM cannot yet be predicted with the use of CT radiomics of the ablation zone and peri-ablational rim. These results underline the importance of validation of radiomics results to test for reproducibility in independent cohorts. </p

PARP inhibitor efficacy depends on CD8+ T cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer.

Combinatorial clinical trials of PARP inhibitors with immunotherapies are ongoing, yet the immunomodulatory effects of PARP inhibition have been incompletely studied. Here, we sought to dissect the mechanisms underlying PARP inhibitor-induced changes in the tumor microenvironment of BRCA1-deficient triple-negative breast cancer (TNBC). We demonstrate that the PARP inhibitor olaparib induces CD8+ T cell infiltration and activation in vivo, and that CD8+ T cell depletion severely compromises anti-tumor efficacy. Olaparib-induced T cell recruitment is mediated through activation of the cGAS/STING pathway in tumor cells with paracrine activation of dendritic cells and is more pronounced in HR-deficient compared to HR-proficient TNBC cells and in vivo models. CRISPR-knockout of STING in cancer cells prevents proinflammatory signaling and is sufficient to abolish olaparib-induced T cell infiltration in vivo. These findings elucidate an additional mechanism of action of PARP inhibitors and provide rationale for combining PARP inhibition with immunotherapies for the treatment of TNBC

Serial-omics of P53−/−, Brca1−/− Mouse Breast Tumor and Normal Mammary Gland

This study demonstrates a liquid-liquid extraction for the sequential tandem mass spectrometry (LC-MS/MS) analysis of non-polar lipids, polar metabolites, proteins and phosphorylation sites from a single piece of tissue. Extraction of 10 mg BRCA−/−, p53−/− breast tumor tissue or normal mammary gland tissue with methyl-tert-butyl ether (MTBE) results in three phases: an upper non-polar phase containing 1,382 lipids, a lower polar phase with 805 metabolites and a precipitated protein pellet with 4,792 proteins with 1,072 phosphorylation sites. Comparative analysis revealed an activated AKT-mTOR pathway in tumors. Tumors also showed a reduction of phosphorylation sites involved in transcription and RNA splicing and decreased abundance of enzymes in lipid synthesis. Analysis of polar metabolites revealed a reduction in glycolysis, pentose phosphate pathway, polyamines and nucleotides, but an increase in TCA and urea cycle intermediates. Analysis of lipids revealed a shift from high triglycerides in mammary gland to high phospholipid levels in tumors. The data were integrated into a model showing breast tumors exhibit features on the proteomic, lipidomic and metabolomic level that are distinct from normal breast tissue. Our integrative technique lends itself to samples such as tumor biopsies, dried blood spots and fluids including urine and CSF to develop biomarkers of disease

Neurocysticercotic Calcifications and Hippocampal Sclerosis: A Case-Control Study

<div><p>Objective</p><p>The exact role of calcified neurocysticercotic lesions (CNLs) in epilepsy is yet unknown and controversial. Although the relationship between CNLs, epilepsy and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) has already been addressed, to our knowledge, no study has actually provided strong statistical evidence, nor reported the ODDS ratio for these associations. Therefore, we designed this case-control study to assess the likelihood of having MTLE-HS versus other forms of epilepsy in the presence of CNLs.</p><p>Methods</p><p>In this case-control study we included 119 consecutive patients with epilepsy and 106 disease controls (headache) with previous CT scans. We subdivided cases into MTLE-HS and other epilepsies. We used brain CT scans to define presence or absence of CNLs. After exploratory analyses, we used logistic regression to analyze the association between CNLs, epilepsy subgroups and disease controls.</p><p>Results</p><p>CNLs were found in 31.09% of cases and in 11.32% of controls (p<0.001). The initial analysis comparing epilepsy versus controls revealed a significant association between CNLs and epilepsy (OR = 5.32; 95%CI = 2.43-11.54; p<0.001). However, when we compared MTLE-HS versus other epilepsies versus controls we confirmed that CNLs were associated with MTLE-HS (OR = 11.27, 95%CI = 4.73-26.85; p<0.001) but other epilepsies were not. We found no difference in the CNLs load and no difference in the location of the CNLs when we compared patients with MTLE-HS, other epilepsies and disease controls.</p><p>Significance</p><p>The inclusion of controls allowed us to estimate the likelihood of having epilepsy in the presence of CNLs. We found that patients with CNLs were 11 times more likely to have MTLE-HS; however, the presence of CNLs did not change the odds of having other types of epilepsy. These findings raise the possibility of neurocysticercosis playing a role in the pathophysiology of MTLE-HS and need further confirmation in other series.</p></div

Multinomial logistic regression model for association with CNLs.

<p>Multinomial logistic regression model for association with CNLs.</p