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BACKGROUND: High flow oxygen therapy (HFO) is a widely used intervention for pulmonary complications. Amid the coronavirus infectious disease 2019 (COVID-19) pandemic, HFO became a popular alternative to conventional oxygen supplementation therapies. Risk stratification tools have been repurposed -and new ones developed- to estimate outcome risks among COVID-19 patients. This study aims to provide a simple risk stratification system to predict invasive mechanical ventilation (IMV) or death among COVID-19 inpatients on HFO. METHODS: Among 529 adult inpatients with COVID-19 pneumonia, we selected unadjusted clinical risk factors for developing the composite endpoint of IMV or death. The risk for the primary outcome by each category was estimated using a Cox proportional hazards model. Bootstrapping was used to validate the results. RESULTS: Age above 62, eGFR under 60 ml/min, room air SpO2 ≤89 % upon admission, history of hypertension, history of diabetes, and any comorbidity (cancer, cardiovascular disease, COPD/ asthma, hypothyroidism, or autoimmune disease) were considered for the score. Each of the six criteria scored 1 point. The score was further simplified into 4 categories: 1) 0 criteria, 2) 1 criterion, 3) 2-3 criteria, and 4) ≥4 criteria. Taking the first category as the reference, risk estimates for the primary endpoint were HR; 2.94 [1.67 - 5.26], 4.08 [2.63 - 7.05], and 6.63 [3.74 - 11.77], respectively. In ROC analysis, the AUC for the model was 0.72. CONCLUSIONS: Our score uses simple criteria to estimate the risk for IMV or death among COVID-19 inpatients with HFO. Higher category reflects consistent increases in risk for the endpoint.
Assuntos
COVID-19 , Doenças Transmissíveis , Humanos , Adulto , COVID-19/epidemiologia , COVID-19/terapia , SARS-CoV-2 , Oxigênio/uso terapêutico , Pacientes InternadosRESUMO
This study evaluated the potential antimicrobial properties of a polyguanidine (CatDex) on two oral bacteria. Chlorhexidine gluconate 1340 µmoL L-1 (CHX 0.12%) was used as control. Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis) were grown in BHI media. Bacterial sensitivity and antimicrobial activity were determined by the minimum inhibitory concentration (MIC) and Kirby-Bauer methods. To study side effects, that is, toxicity, dental pulp stem cells (DPSCs) were used. Fluorometric cytotoxicity and confocal microscopy assays were used in order to test cell viability. CatDex inhibited growth of S. mutans at all concentrations and growth of P. gingivalis at all concentrations except 25 µmoL L-1. The MIC of CatDex was 50 µmoL L-1 for both S. mutans and P. gingivalis. The inhibition of bacteria exposed for 8 h at 50 µmoL L-1 of CatDex exhibited increased antimicrobial activity over time, with 91% inhibition in both bacteria. The antimicrobial activities of CatDex and CHX were similar when tested on two common bacteria. CatDex was significantly less toxic to DPSCs. CatDex toxicity depended on time and not on concentration. With regard to clinical relevance, CatDex may have potential as a novel antimicrobial agent. Further studies are in progress.
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Variation in foraging behavior may indicate differences in food availability and allow assessment of restoration actions. Ants are prominent bioindicators used in assessing ecological responses to disturbance. However, behavioral data have been poorly incorporated as an index. The foraging performance of red harvester ants was quantified in order to evaluate the success of a restoration ecology experiment in the tropical dry forest of Sierra de Huautla, Morelos, in central Mexico. Foraging performance by granivorous, Pogonomyrmex barbatus, ants was diminished after 6 and 8 years of cattle grazing and wood harvest were excluded as part of a restoration experiment in a highly degraded biome. Despite investing more time in foraging, ant colonies in exclusion plots showed lower foraging success and acquired less seed biomass than colonies in control plots. In line with the predictions of optimal foraging theory, in restored plots where ant foraging performance was poor, ants harvested a higher diversity of seeds. Reduced foraging success and increased harvest of non-preferred foods in exclusion plots were likely due to the growth of herbaceous vegetation, which impedes travel by foragers. Moreover, by 8 years of exclusion, 37% of nests in exclusion plots had disappeared compared to 0% of nests in control plots. Ants' foraging success and behavior were sensitive to changes in habitat quality due to the plant successional process triggered by a restoration intervention. This study spotlights on the utility of animal foraging behavior in the evaluation of habitat restoration programs.
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Formigas/fisiologia , Conservação dos Recursos Naturais , Comportamento Alimentar/fisiologia , Florestas , Herbivoria , Animais , MéxicoRESUMO
Various guidelines recommend that women with triple-negative breast cancer should be tested for BRCA1 mutations, but the prevalence of mutations may vary with ethnic group and with geographic region, and the optimal cutoff age for testing has not been established. We estimated the frequencies of BRCA1 and BRCA2 (BRCA) mutations among 190 women with triple-negative breast cancer, unselected for family history, diagnosed at age 50 or less at a single hospital in Mexico City. Patients were screened for 115 recurrent BRCA mutations, which have been reported previously in women of Hispanic origin, including a common large rearrangement Mexican founder mutation (BRCA1 ex9-12del). A BRCA mutation was detected in 44 of 190 patients with triple-negative breast cancer (23 %). Forty-three mutations were found in BRCA1 and one mutation was found in BRCA2. Seven different mutations accounted for 39 patients (89 % of the total mutations). The Mexican founder mutation (BRCA1 ex9-12del) was found 18 times and accounted for 41 % of all mutations detected. There is a high prevalence of BRCA1 mutations among young triple-negative breast cancer patients in Mexico. Women with triple-negative breast cancer in Mexico should be screened for mutations in BRCA1.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de Mama Triplo Negativas/genética , Adulto , Análise Mutacional de DNA , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Mutação , Prevalência , Neoplasias de Mama Triplo Negativas/epidemiologia , Adulto JovemRESUMO
We tested whether diethylcarbamazine (DEC) or ivermectin (IVM), both antiparasitic drugs with reported immunomodulatory properties, were able to affect the immune system to potentiate host defense mechanisms and protect against actinomycetoma in a mouse model. Male BALB/c mice of 10-12 weeks of age were injected with either Nocardia brasiliensis or saline solution. Recorded were the effects of a treatment by DEC (6 mg/kg per os daily for one week) or IVM (200 µg/kg subcutaneously on days 1 and 3) on (i) the development of mycetoma lesion, (ii) the expression of reactive oxygen intermediates (ROI) by phagocytes, (iii) the proliferation index of lymphocytes and (iv) antibody production of IgG and IgM. After an initial lesion in all mice, DEC inhibited a full development and progression of actinomycetoma resulting in a reduced lesion size (p < 0.001). IVM had no inhibitory effect on the development of mycetoma. Furthermore, DEC treatment was associated with a significant enhancement of ROI expression (p < 0.05) by polymorphonuclear neutrophils at day 3 after infection. Lymphocyte proliferation in response to N. brasiliensis antigens and concanavalin A in DEC-treated group was higher than in non-treated group at day 21 and 28 postinfection (p < 0.01). Significant changes in antibody response were not observed. By all parameters tested, DEC was superior to IVM regarding immunostimulatory potency. In conclusion, DEC expressed an in vivo influence on the immune status during the infection by N. brasiliensis leading to retrogression of the mycetoma and increasing cellular immune responses. Our findings may indicate a potential use of DEC as a putative adjuvant in infectious disease or vaccination.
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Antiparasitários/administração & dosagem , Dietilcarbamazina/administração & dosagem , Ivermectina/administração & dosagem , Micetoma/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Nocardia/imunologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Humanos , Imunomodulação , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Micetoma/imunologia , Neutrófilos/fisiologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Obesity and overweight are established risk factors for the development of breast cancer. They are also associated with poor prognosis for higher risk of disease recurrence and lower overall survival (OS). The aim of this study was to evaluate the influence of overweight and obesity in OS in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy. This is a retrospective analysis that included 819 patients diagnosed with LABC between January 2004 and December 2008. The patients were treated with neoadjuvant chemotherapy (NAT) based on anthracyclines, taxanes, or both, followed by surgery. For comparison, patients were divided into the normal weight (NW) group or the overweight/obesity (OW/OB) group. The prevalence of overweight/obesity was 74 %. General characteristics of the patients, including age, tumor size, clinical stage, nuclear grade, hormone receptors, and HER2 expression, were similar between both groups. At a median follow-up of 28 months, we found a statistically significant difference in OS between the two groups, achieving a 91.5 % in NW patients versus 85.9 % in the OW/OB group (P = 0.050). Cox multivariate analysis demonstrated that obesity was an independent factor for poor prognosis, with a hazard ratio of 1.79 (95 % CI (Confidence Interval) 1.09-2.96; P = 0.022). This is the first Mexican study that confirms the role of OW/OB as a risk factor for poor outcome among patients with LABC. Obesity in our country is a public health problem and requires strong preventive intervention strategies for its control, especially among patients diagnosed with breast cancer.
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Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Sobrepeso/epidemiologia , Adulto , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Comorbidade , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Obesidade/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND: There is an unmet therapeutic need in endocrine-resistant, hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (BC). Preclinical studies support the hypothesis that the mammalian target of rapamycin (mTOR) inhibition could potentially overcome resistance to endocrine therapy. MATERIALS AND METHODS: A literature review regarding BC and mTOR inhibitors was undertaken. The reference lists from retrieved manuscripts were reviewed to identify further studies. RESULTS: Phase II studies have reported that the combination of mTOR inhibitors with endocrine therapy shows efficacy in patients with advanced disease that progressed after treatment with aromatase inhibitors. The recent findings of the phase III BOLERO-2 confirmed that everolimus in combination with exemestane significantly improved progression-free survival and response rate, with a manageable safety profile. CONCLUSIONS: The addition of everolimus to exemestane for women with HR-positive metastatic BC is now considered a new therapeutic strategy. However, a word of caution should be added regarding toxic effects, which might limit practical use and compliance. It is essential that clinicians are educated about key recommendations for toxicity management and specific guideline dose modifications. Additional research efforts with the addition of these compounds in the early-stage setting is greatly needed to improve the survival of patients with HR-positive BC.