Abstract Comprehensive genomic profiling is highly recommended for treatment decision in nonsquamous, non-small cell lung cancer (NSCLC). However, rare genomic alterations are still being unveiled, ...with scarce data to guide therapy. Herein, we describe the treatment journey of a 56-year-old, never-smoker Caucasian woman with a metastatic NSCLC harboring a CD47-MET fusion, initially classified as a variant of unknown significance. She had undergone 3 lines of therapy over the course of 3 years, including chemotherapy, immunotherapy, and anti-angiogenic therapy. After reanalysis of her next-generation sequencing data in our service, the fusion was reclassified as likely oncogenic. The patient was started with fourth-line capmatinib, with a good tolerance so far and a complete metabolic response in the active sites of disease, currently ongoing for 18 months. In conclusion, we highlight the sensitivity of a novel MET fusion to capmatinib and emphasize the need for comprehensive panels in NSCLC and molecular tumor board discussions with specialized centers when rare findings arise.
Purpose
Knowledge on whether low expressions of HER2 have prognostic impact in early-stage breast cancer (BC) and on its response to current chemotherapy protocols can contribute to medical practice ...and development of new drugs for this subset of patients, changing treatment paradigms. This study aims to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy (NACT) and survival outcomes in early-stage HER2-negative BC.
Methods
Records from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. HER2-negative (immunohistochemistry IHC 0, + 1, or + 2 non-amplified by in situ hybridization ISH) patients were included. HER2-low was defined by IHC + 1 or + 2 ISH non-amplified and HER2-0 by IHC 0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) between luminal/HER2-low versus luminal/HER2-0 populations and between triple negative (TNBC)/HER2-low versus TNBC/HER2-0.
Results
In total, 855 HER2-negative patients were identified. The median follow-up was 59 months. 542 patients had luminal subtype (63.4%) and 313 had TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal patients, 145 had HER2 IHC + 1 (26.8%) and 91 had IHC + 2/ISH non-amplified (16.8%). In TNBC, 36 had HER2 IHC + 1 (11.5%) and 13 had IHC + 2/ISH non-amplified (4.2%). Most patients had locally advanced tumors, regardless of subtype or HER2-low status. For luminal disease, pCR was achieved in 13% of HER2-low tumors versus 9.5% of HER2-0 (
p
= 0.27). Similarly, there was no difference in pCR rates among TNBC: 51% versus 47% in HER2-low versus HER2-0, respectively (
p
= 0.64). HER2-low was also not prognostic for RFS, with 5-year RFS rates of 72.1% versus 71.7% (
p
= 0.47) for luminal HER2-low/HER2-0, respectively, and 75.6% versus 70.8% (
p
= 0.23) for TNBC HER2-low/HER2-0.
Conclusion
Our data does not support HER2-low as a biologically distinct BC subtype, with no prognostic value on survival outcomes and no predictive effect for pCR after conventional NACT.
Wheat blast, caused by
lineage, is a major constraint to wheat production, mainly in the tropics of Brazil, where severe epidemics have been more frequent. We analyzed disease and wheat yield data ...from 42 uniform field trials conducted over 9 years (2012 to 2020) to assess whether the percent control and yield response were influenced by fungicide type, region (tropical or subtropical), and year. Six treatments were selected, all evaluated in at least 19 trials. Two fungicides were applied as solo active ingredients (MANCozeb, and TEBUconazole), and four were premixes (AZOXystrobin plus TEBU, TriFLoXystrobin plus PROThioconazole, TFLX plus TEBU, and PYRAclostrobin plus EPOXiconazole). Percent control, calculated from back-transforming estimates by a meta-analysis network model fitted to the log of the means, ranged from 43 to 58%, with all but PYRA plus EPOX showing efficacy >52% on average, not differing among them. The variation in both efficacy and yield response was explained by region, and all but TEBU performed better in the subtropics than in the tropics. Yield response from using three sequential sprays was approximately two times greater in the subtropics (319 to 532 kg/ha) than in the tropics (149 to 241.3 kg/ha). No significant decline in fungicide efficacy or yield response was observed in 9 years of study for any of the fungicides. These results reinforce the need to improve control by adopting an integrated management approach in the tropics given poorer performance and lower profitability, especially for the premixes, than in the subtropics.
This study aimed to evaluate the performance of fungicides against wheat head blast (WHB) under various environments and to determine scenarios best suited for fungicide applications. Field ...experiments were conducted at 23 environments in Brazil and Bolivia from 2012 to 2015. Data from all trials within the same country were combined for estimating mean WHB control efficacy and yield benefits from using a set of fungicides. Experiments were classified, based on disease index in the check treatment, as having low (CDI = 10), moderate (CDI = 40), and high (CDI = 70) disease pressure and this variable was tested as a covariate in the model. In Brazil, greater disease reduction and yield increase, in trials with moderate to high disease pressure, were obtained when using mancozeb-based fungicides, but with yield gains below 1276 kg/ha. In Bolivia, all fungicides reduced the disease at moderate to high disease pressure, but specific QoI + DMI premixes led to higher yield gains averaging 1834 kg/ha. Based on the evidence provided, we concluded that current WHB chemical strategies could have radically different results depending on country and disease pressure. Although WHB chemical control can be effective even under environmental conditions that favor the disease, integrated management strategies should be explored. Our results are useful for aiding decisions on fungicide application and identifying priorities for future research.
Abstract Introduction This study evaluated the risk of men developing coronary heart disease and its determinant variables, comparing these results through two validated coronary risk scales. Methods ...A cross sectional epidemiological analytical study in which data were collected by spontaneous demand, through a semi-structured questionnaire, clinical examination, and blood collection. The Chi-square test, logistic regression and Kappa for statistical analysis were performed. Results The study included 637 men. Age was a determining factor ( p < 0.05) in blood pressure (BP) changes, central obesity, BMI, glycemia, total cholesterol, LDL and triglycerides. From this group of 637, 252 presented BP above the recommended values. It was found that 34.54% of men had high total cholesterol, 19.94% had high LDL, 46.78% presented HDL below normal values and 36.42% had elevated triglycerides. Metabolic syndrome was found in 24.96% of the men. With the Framingham scale, 637 men were evaluated, 12.56% were at intermediate-risk and 5.49% elevated risk, while on the ASCVD Risk scale 553 men were evaluated, and 7.05% had moderate risk and none had high coronary risk. In this study, 50.43% of men still had no previous diagnosis for any disease that increases the risk factors. Conclusions The determinant clinical variables were age, blood pressure, smoking, central obesity, race and education. The Framingham scale allowed the assessment of cardiac risk of all men in the study, with no age restriction or cholesterol value, so in population studies it shows advantages over the ASCVD Risk due to its comprehensive feature of including all individuals.
Abstract
Disclosure: A.W. Maciel: None. T. Freitas: None. D.L. Danilovic: None. G.F. Fagundes: None. F. Freitas-Castro: None. L. Santana: None. A. Guimaraes: None. A. Pio-Abreu: None. J. V. Silveira: ...None. F. Consolim-Colombo: None. L. Bortolotto: None. M.C. Fragoso: None. A. Latronico: None. L. Drager: None. B.B. Mendonca: None. A.O. Hoff: None. M.Q. Almeida: None.
Introduction: Aldosterone excess can cause oxidative stress leading to DNA damage in vitro and in vivo. Single case reports demonstrated a coincidence of primary aldosteronism (PA) with different malignancies. A higher prevalence of thyroid nodules and non-toxic multinodular goiter was described in patients with PA compared to those with essential hypertension (HT). A single study showed an association between PA and papillary thyroid cancer (PTC), but without a paired control group. Objective: To assess PA prevalence in a transversal cohort of patients with PTC and HT compared to a paired control group with HT. Methods: In this cross-sectional case-control study, PA was investigated in all patients with PTC and HT (n= 114), regardless of HT severity, under active surveillance at a cancer institute from 2019 to 2022. The control group included 228 (2:1) age-, sex- and body mass index (BMI)-matched individuals from a retrospective cohort of HT previously investigated for PA from 2011 to 2022. Serum aldosterone and plasma direct renin concentrations were measured by a chemiluminescent immunoassay. A positive PA screening was defined by aldosterone ≥10 ng/dL and aldosterone to renin ratio ≥2 ng/dL/μUI/mL. Results: Age, sex and BMI were not statistically different between PTC and control groups, respectively (age 59.8 ± 12 vs. 58.9 ± 12.3 yrs, p= 0.67; 79% vs. 81% women, p= 0.67; BMI 30.7 ± 5.8 vs. 30.8 ± 6.5 Kg/m2, p= 0.98). PA was diagnosed in 35 out of 114 PTC patients with HT. The prevalence of PA in the PTC group (30.5%, confidence interval (IC) 22.6%-40.1%) was significantly higher when compared to the paired control group with HT (11.84%, CI 8.08%-16.93%; p< 0.0001). Although PA prevalence was higher in the PTC group, only 20.2% had stage 3/resistant HT (vs. 38% in the control group, p= 0.003). The number of anti-hypertensive medications was lower in the PTC group compared to controls (2 drugs, 1 to 3 vs. 4 drugs, 3 to 5, respectively; p< 0.001). When analyzing only PA patients in both groups, frequency of stage 3/resistant HT and number of medications were lower in the PTC group (p< 0.001 and p< 0.001, respectively). Although HT was more severe in PA patients without PTC, aldosterone and renin levels were not different in PA patients from PTC and control groups, respectively (p= 0.15 and p= 0.34). Conclusion: PA prevalence was strikingly high among patients with PTC and HT, supporting the recommendation of PA screening in this patient group, regardless of HT severity.
Presentation: Thursday, June 15, 2023
The objective of this study was to evaluate the effect of inclusion of lipid residue of biodiesel originated in the processing of palm oil (Elaeis guineensis) in the diet on the digestibility of ...feedlot lambs. Twenty-five crossbred male castrated lambs, weighing 20±1.61 kg, were distributed in randomized blocks with five treatments and five replications. The experimental period lasted 22 days; 15 for diet adaptation, 2 for the adaptation to the indicator LIPE (lignin from Eucalyptus grandis isolated, purified and enriched, UFMG, Minas Gerais) and 5 for fecal sampling. Diets were formulated with 64% concentrate based on corn and soybean meal, 31% Massai grass (Panicum maximum cv. Massai) hay and 5% lipid supplementation from increasing levels of substitution of 0, 25, 50, 75 and 100% of palm oil for biodiesel oil from palm residue. The lambs were offered two meals a day, at 7h00 and 16h00. There was linear effect of inclusion of the residue from palm oil biodiesel on dry matter intake. There was no change in digestibility of nutrients except for ether extract. The use of biodiesel from palm oil residue up to 100% replacement for the lipid supplementation of sheep positively influences the consumption without altering the digestibility of nutrients.
Introdução: A amiloidose cardíaca (AC) é uma condição rara causada pelo acúmulo de proteínas amiloides no coração, resultando em comprometimento da função cardíaca. A AC é frequentemente ...subdiagnosticada devido à sua clínica inespecífica e à falta de conscientização sobre a doença. Este artigo visa compreender a fisiopatologia, diagnóstico e manejo da AC. Metodologia: Realizou-se uma revisão sistemática utilizando bases de dados como Scielo e Pubmed, utilizando os descritores “Amyloidosis” AND “Cardiovascular System”, obtendo-se 3306 estudos, dos quais 23 foram selecionados por abordarem melhor o tema escolhido e serem publicados em inglês ou português. Os critérios de inclusão e exclusão foram aplicados para garantir a qualidade dos estudos selecionados. Resultados: A AC pode ser causada por diferentes tipos de amiloidose, sendo a amiloidose de cadeia leve (AL) e a amiloidose associada à transtirretina (ATTR) as mais comuns. Os sintomas são inespecíficos e incluem dispneia, fadiga e edema, levando frequentemente a erros diagnósticos. O diagnóstico envolve uma combinação de métodos, incluindo exames de imagem e biópsia tecidual. O tratamento visa retardar a progressão da doença e aliviar os sintomas, sendo personalizado de acordo com o tipo e estágio da AC. Conclusão: A AC representa um desafio diagnóstico e terapêutico devido à sua apresentação clínica variada e complexidade. A conscientização sobre os sinais e sintomas da doença é crucial para um diagnóstico precoce e um melhor manejo dos pacientes. O desenvolvimento contínuo de abordagens clínicas e terapêuticas é necessário para otimizar os resultados para os pacientes afetados por essa condição debilitante.
PDF
