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BACKGROUND: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain. METHODS: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016-December 2018) from 30 sites. PRIMARY OBJECTIVE: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources. RESULTS: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted. CONCLUSION: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events. TRIAL REGISTRATION: Clinical trial registration number: NCT03790397 .
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Acrilamidas/administração & dosagem , Compostos de Anilina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Acrilamidas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
Although the frequency of pregnancy in women on chronic dialysis is extremely low, it is associated with severe maternal and perinatal morbidity and mortality. This situation represents a challenge for the therapeutic team, which requires multidisciplinary management, as well as measures to adequate dialysis treatment. Such efforts include increasing the time and frequency of dialysis session, maintaining low uremia levels and ensuring hemodynamic stability by avoiding intra-treatment arterial hypotension and hydro electrolytic fluctuations. Regarding the dialysis modality, literature makes references to hemodialysis or peritoneal dialysis in pregnancy women, but little is known about the of high volume online hemodiafiltration (HVHDF) as well as the appropriate type of replacement fluid (pre-dilution or post-dilution). We present two cases of patients who were pregnant while being treated with HVHDF modality and had a favorable evolution, where the decision to continue with this dialysis modality was motivated by a best hemodynamic stability and the highest clearance of all types of uremic toxins offered by HVHDF.
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Hemodiafiltração , Insuficiência Renal , Feminino , Hemodinâmica , Humanos , Gravidez , Diálise RenalAssuntos
Carcinoma Pulmonar de Células não Pequenas , Transtornos de Deglutição , Neoplasias Pulmonares , Carbazóis , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/etiologia , Dieta , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Piperidinas , Inibidores de Proteínas QuinasesRESUMO
Introduction: Radium-223 dichloride (Ra-223) is recommended as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral disease, after docetaxel failure, or in patients who are not candidates to receive it. In this study, we aimed to ambispectively analyze overall survival (OS) and prognostic features in mCRPC in patients receiving Ra-223 as per clinical routine practice and identify the most suitable treatment sequence. Patients and methods: This study is observational, multicentric, and ambispective. Eligibility criteria included mCRPC patients treated with Ra-223, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, without visceral metastases, and no more than three cm involved lymph nodes. Results: A total of 145 patients were included; the median age was 73.97 years, and a Gleason score of more than or equal to 7 in 61 (48%) patients; 73 (81%) had previously received docetaxel. The most important benefit was reached by those patients who received Ra-223 in the second-line setting, with a median OS of 17 months (95% CI, 12-21), and by patients who received six cycles of treatment, with a median OS of 19 months (95% CI, 14-21). An alkaline phosphatase (ALP) decrease was also identified as a prognosis marker. When performing the multivariate analysis, the time to develop castration-resistant disease longer than 24 months was the most important prognostic factor to predict the evolution of the patients receiving Ra-223. Ra-223 was well tolerated, with thrombocytopenia, anemia, and diarrhea being the main adverse events. Conclusion: There is a benefit for those patients who received Ra-223 in the second-line setting, regardless of prior use of docetaxel. In addition, a survival benefit for patients presenting with a decline in ALP was observed.
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Down syndrome (DS) is characterized by the trisomy of chromosome 21 and by cognitive deficits that have been related to neuronal morphological alterations in humans, as well as in animal models. The gene encoding for amyloid precursor protein (APP) is present in autosome 21, and its overexpression in DS has been linked to neuronal dysfunction, cognitive deficit, and Alzheimer's disease-like dementia. In particular, the neuronal ability to extend processes and branching is affected. Current evidence suggests that APP could also regulate neurite growth through its role in the actin cytoskeleton, in part by influencing p21-activated kinase (PAK) activity. The latter effect is carried out by an increased abundance of the caspase cleavage-released carboxy-terminal C31 fragment. In this work, using a neuronal cell line named CTb, which derived from the cerebral cortex of a trisomy 16 mouse, an animal model of human DS, we observed an overexpression of APP, elevated caspase activity, augmented cleavage of the C-terminal fragment of APP, and increased PAK1 phosphorylation. Morphometric analyses showed that inhibition of PAK1 activity with FRAX486 increased the average length of the neurites, the number of crossings per Sholl ring, the formation of new processes, and stimulated the loss of processes. Considering our results, we propose that PAK hyperphosphorylation impairs neurite outgrowth and remodeling in the cellular model of DS, and therefore we suggest that PAK1 may be a potential pharmacological target.
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Síndrome de Down , Camundongos , Humanos , Animais , Síndrome de Down/tratamento farmacológico , Síndrome de Down/genética , Trissomia , Neurônios/metabolismo , Neuritos/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Crescimento Neuronal , Caspases/metabolismoRESUMO
INTRODUCTION: The long-term clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) and a complete response (CR) to the tyrosine kinase inhibitor (TKI) sunitinib are poorly known. The characteristics of these patients could reveal previously undetected associations with clinical variables. PATIENTS AND METHODS: This observational, retrospective study (ATILA) used data from a registry of patients with mRCC who had received first-line sunitinib and had achieved CR from 2007 to 2018 in Spain. RESULTS: Sixty-two patients with CR were included; 48 patients (77.4%) received sunitinib in monotherapy and 14 (22.6%) combined with or followed by local treatment. Median age was 58.5 years (range, 32-81). Most patients (79.0%) had clear cell histology and had undergone previous nephrectomy (90.3%). The majority (70.2%) had an intermediate IMDC prognosis, 23% favorable and 7.0% poor. The median time on treatment with sunitinib was 28.2 months (IQR, 16.7-41.0) and the median time to CR was 10.9 months (IQR, 7.2-19.3). After a median follow-up of 8 years (range, 3-13 years), the median PFS was not reached. The overall median duration of complete response was 64.1 months (IQR, 32.2-99.4). The tolerance and safety profile of sunitinib was consistent with previous reports. CONCLUSION: Durable CR to sunitinib was observed in patients regardless the prognosis group, metastasis site or histology type, with 75% of patients remaining in CR after 10 years. CLINICALTRIALS: gov: NCT03916458.
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Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Pessoa de Meia-Idade , Sunitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Antineoplásicos/uso terapêutico , Estudos Retrospectivos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Indóis/uso terapêutico , Pirróis/uso terapêuticoRESUMO
Enterococcus faecalis is a bacterial species present at a subdominant level in the human gut microbiota. This commensal turns into an opportunistic pathogen under specific conditions involving dysbiosis and host immune deficiency. E. faecalis is one of the rare pathobionts identified to date as contributing to liver damage in alcoholic liver disease. We have previously observed that E. faecalis is internalized in hepatocytes. Here, the survival and fate of E. faecalis was examined in hepatocytes, the main epithelial cell type in the liver. Although referred to as an extracellular pathogen, we demonstrate that E. faecalis is able to survive and divide in hepatocytes, and form intracellular clusters in two distinct hepatocyte cell lines, in primary mouse hepatocytes, as well as in vivo. This novel process extends to kidney cells. Unraveling the intracellular lifestyle of E. faecalis, our findings contribute to the understanding of pathobiont-driven diseases.
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Enterococcus faecalis , Microbioma Gastrointestinal , Animais , Disbiose , Hepatócitos , Estilo de Vida , CamundongosRESUMO
Background: The female reproductive tract (FRT) mucosa is the first line of defense against sexually transmitted infection (STI). FRT environmental factors, including immune-cell composition and the vaginal microbiota, interact with each other to modulate susceptibility to STIs. Moreover, the menstrual cycle induces important modifications within the FRT mucosa. Cynomolgus macaques are used as a model for the pathogenesis and prophylaxis of STIs. In addition, their menstrual cycle and FRT morphology are similar to women. The cynomolgus macaque vaginal microbiota is highly diverse and similar to dysbiotic vaginal microbiota observed in women. However, the impact of the menstrual cycle on immune markers and the vaginal microbiota in female cynomolgus macaques is unknown. We conducted a longitudinal study covering three menstrual cycles in cynomolgus macaques. The evolution of the composition of the vaginal microbiota and inflammation (cytokine/chemokine profile and neutrophil phenotype) in the FRT and blood was determined throughout the menstrual cycle. Results: Cervicovaginal cytokine/chemokine concentrations were affected by the menstrual cycle, with a peak of production during menstruation. We observed three main cervicovaginal neutrophil subpopulations: CD11bhigh CD101+ CD10+ CD32a+, CD11bhigh CD101+ CD10- CD32a+, and CD11blow CD101low CD10- CD32a-, of which the proportion varied during the menstrual cycle. During menstruation, there was an increase in the CD11bhigh CD101+ CD10+ CD32a+ subset of neutrophils, which expressed higher levels of CD62L. Various bacterial taxa in the vaginal microbiota showed differential abundance depending on the phase of the menstrual cycle. Compilation of the factors that vary according to hormonal phase showed the clustering of samples collected during menstruation, characterized by a high concentration of cytokines and an elevated abundance of the CD11bhigh CD101+ CD10+ CD32a+ CD62L+ neutrophil subpopulation. Conclusions: We show a significant impact of menstruation on the local environment (cytokine production, neutrophil phenotype, and vaginal microbiota composition) in female cynomolgus macaques. Menstruation triggers increased production of cytokines, shift of the vaginal microbiota composition and the recruitment of mature/activated neutrophils from the blood to the FRT. These results support the need to monitor the menstrual cycle and a longitudinal sampling schedule for further studies in female animals and/or women focusing on the mucosal FRT environment.
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Ciclo Menstrual , Microbiota , Infecções Sexualmente Transmissíveis , Vagina , Animais , Biomarcadores , Citocinas , Feminino , Humanos , Estudos Longitudinais , Macaca fascicularis , Microbiota/genética , Vagina/microbiologiaRESUMO
INTRODUCTION: The COVID-19 pandemic presented universities with the challenge of virtualizing the teaching-learning process. Simulated teleconsultation has been used in undergraduate training, which allows nursing students to interact with simulated patients remotely. Studies have identified that distance imposes communication barriers on all elements-sender, receiver and message-and in both forms of transmission: verbal and nonverbal. OBJECTIVE: To describe the communication of nursing students in teleconsultation with simulated patients in the context of primary health care. METHODS: This was a descriptive, cross-sectional study of 92 fifth-year nursing students. The communication variable was measured with the Connect Identify Understand Agree Help scale. In the data analysis, the mean and standard deviation of the scores on the 29 items of the scale were determined, as were the mean values for the total scale and for the 3 domains of the scale. RESULTS: The items that presented an average of less than 1 were primarily those related to the Agree and Help to Act domain. The total mean was 1.15, and the means for the domains Connect, Identify and Understand Problems and Agree and Help to Act were 1.53, 0.90 and 1.28, respectively. A weakness in the exploration of the psychosocial context of the simulated patients was observed. CONCLUSIONS: The results of this study, which evaluated communication in the context of distance care, corroborate the evidence regarding communication in real or simulated face-to-face situations. Studies that compare communication in various teaching-learning contexts, whether real or virtual, face-to-face or at a distance, are recommended.
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COVID-19 , Consulta Remota , Estudantes de Enfermagem , Comunicação , Estudos Transversais , Humanos , PandemiasRESUMO
Most children are less severely affected by coronavirus-induced disease 2019 (COVID-19) than adults, and thus more difficult to study progressively. Here, we provide a neonatal nonhuman primate (NHP) deep analysis of early immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in blood and mucosal tissues. In addition, we provide a comparison with SARS-CoV-2-infected adult NHP. Infection of the neonate resulted in a mild disease compared with adult NHPs that develop, in most cases, moderate lung lesions. In concomitance with the viral RNA load increase, we observed the development of an early innate response in the blood, as demonstrated by RNA sequencing, flow cytometry, and cytokine longitudinal data analyses. This response included the presence of an antiviral type-I IFN gene signature, a persistent and lasting NKT cell population, a balanced peripheral and mucosal IFN-γ/IL-10 cytokine response, and an increase in B cells that was accompanied with anti-SARS-CoV-2 antibody response. Viral kinetics and immune responses coincided with changes in the microbiota profile composition in the pharyngeal and rectal mucosae. In the mother, viral RNA loads were close to the quantification limit, despite the very close contact with SARS-CoV-2-exposed neonate. This pilot study demonstrates that neonatal NHPs are a relevant model for pediatric SARS-CoV-2 infection, permitting insights into the early steps of anti-SARS-CoV-2 immune responses in infants.
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COVID-19 , SARS-CoV-2 , Animais , Criança , Citocinas , Humanos , Recém-Nascido , Projetos Piloto , Primatas/genética , RNA ViralRESUMO
INTRODUCTION: Topotecan is approved as second-line treatment for small cell lung cancer (SCLC). Irinotecan is also frequently used given its more convenient schedule and superior tolerability. Preclinical studies support disialoganglioside (GD2) as an SCLC target and the combination of dinutuximab, an anti-GD2 antibody, plus irinotecan in this setting. We tested dinutuximab/irinotecan versus irinotecan or topotecan as second-line therapy in relapsed/refractory (RR) SCLC. MATERIALS AND METHODS: Patients with RR SCLC and Eastern Cooperative Oncology Group performance status 0-1 were randomized 2:2:1 to receive dinutuximab 16-17.5 mg/m2 intravenous (IV)/irinotecan 350 mg/m2 IV (day 1), irinotecan 350 mg/m2 IV (day 1), or topotecan 1.5 mg/m2 IV (days 1-5) in 21-day cycles. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR; complete response [CR] + partial response [PR]), and clinical benefit rate (CBR; CR + PR + stable disease). Safety/tolerability were also assessed. RESULTS: A total of 471 patients were randomized to dinutuximab/irinotecan (n = 187), irinotecan (n = 190), or topotecan (n = 94). Age, sex, performance status, prior therapies, and metastatic disease sites were similar between groups. Survival and response rates were not improved for patients receiving dinutuximab/irinotecan versus those receiving irinotecan or topotecan (median OS 6.9 vs 7.0 vs 7.4 months [p = 0.3132]; median PFS 3.5 vs 3.0 vs 3.4 months [p = 0.3482]; ORR confirmed 17.1% vs 18.9% vs 20.2% [p = 0.8043]; and CBR 67.4% vs 58.9% vs 68.1% [p = 0.0989]), respectively. Grade 3/4 adverse events (≥5% receiving dinutuximab/irinotecan) included neutropenia, anemia, diarrhea, and asthenia. CONCLUSIONS: Dinutuximab/irinotecan treatment did not result in improved OS in RR SCLC versus irinotecan alone. Irinotecan administered every 21 days demonstrated comparable activity to topotecan administered daily × 5 every 21 days. CLINICALTRIALS: gov Identifier. NCT03098030.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/patologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Topotecan/uso terapêuticoRESUMO
Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant's microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother-fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant's microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant's health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path.
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BACKGROUND: Nivolumab is an anti PD1 immunotherapy drug approved for advanced Non-Small Cell Lung Cancer (NSCLC) patients who previously received at least one prior line of treatment. Older patients are often not represented in clinical trials and drugs with acceptable safety profiles are necessary. We aim to report the efficacy and safety profile of Nivolumab in the real-world older subgroup of the Galician lung cancer group study. PATIENTS AND METHODS: We retrospectively reviewed 188 advanced NSCLC patients treated with at least one prior therapy. We collected data from patients who were ≥70 years old treated with Nivolumab in second or subsequent lines. Patient characteristics, treatment efficacy (overall survival, progression-free survival, and response rate), and safety profile were reported. RESULTS: Thirty-eight patients aged ≥70 years were included in the subgroup analysis. The median age was 74.5 years, a high percentage of patients were males (95%), most had a Performance Status of 1 (79%) and only 13% were non-smokers. The predominant histology was adenocarcinoma (53%), and 18% of patients received 2 or more lines. The median Progression-Free Survival was 7.53 months (CI 4.3-17.3, p = 0.15) and the median Overall Survival was 14.85 months (CI 10.5-20.7, p = 0.44). The objective response rate was 42%. No new adverse events were reported in comparison to a global population. CONCLUSIONS: The efficacy and safety profile of Nivolumab in advanced NSCLC patients treated with at least one prior therapy and age ≥70 years old can be overlapped to a global population. Further prospective trials are needed to define and confirm these results.
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Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Nivolumabe/efeitos adversos , Estudos RetrospectivosRESUMO
The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57-0.65, p < 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67-0.86; p < 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70-2.63, p < 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC.
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Coastal vegetated ecosystems are major organic carbon (OC) and total nitrogen (TN) sinks, but the mechanisms that regulate their spatial variability need to be better understood. Here we assessed how superficial sedimentary OC and TN within intertidal vegetated assemblages (saltmarsh and seagrass) vary along a flow gradient, which is a major driver of sediment grain size, and thus of organic matter (OM) content. A significant relationship between flow current velocity and OC and TN stocks in the seagrass was found, but not in the saltmarsh. OC and TN stocks of the saltmarsh were larger than the seagrass, even though that habitat experiences shorter hydroperiods. Mixing models revealed that OM sources also varied along the flow gradient within the seagrass, but not in the saltmarsh, showing increasing contributions of microphytobenthos (17-32%) and decreasing contributions of POM (45-35%). As well, OM sources varied vertically as microphytobenthos contribution was highest at the higher intertidal saltmarsh (48%), but not POM (39%). Macroalgae, seagrass and saltmarsh showed low contributions. Local trade-offs between flow current velocities, hydroperiod and structural complexity of vegetation must be considered, at both horizontal and vertical (elevation) spatial dimensions, for better estimates of blue carbon and nitrogen in coastal ecosystems.
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The lung immune prognostic index (LIPI) has been proposed as a new categorical blood-based biomarker to select advanced non-small cell lung cancer (NSCLC) patients for anti-programmed cell death-1 (PD-1) or programmed death ligand 1 (PD-L1) therapy. In this study, we investigate for the first time to the best of our knowledge the prognostic and predictive utility of the LIPI in a multicenter nivolumab monotherapy-based cohort. We retrospectively analyzed the influence of the baseline LIPI on overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and overall response rate (ORR) among 153 patients of a cohort of 188 advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond. Worse LIPI was significantly associated with shorter OS in univariate [hazard ratio (HR) =3.12, 95% confidence interval (CI), 2.12-4.60; P<0.0001] and multivariate (HR =3.67, 95% CI, 1.96-6.86; P<0.0001) analyses. Worse LIPI was associated with shorter PFS (HR =1.45, 95% CI, 1.05-2.03; P=0.03), but this correlation did not reach statistical significance in multivariate analysis (HR =1.49, 95% CI, 0.94-2.38; P=0.09). Worse LIPI was associated with lower DCR in univariate [odds ratio (OR) =0.41, 95% CI, 0.24-0.70; P=0.001] and multivariate (OR =0.44, 95% CI, 0.25-0.78; P=0.005) analyses. This study confirms the utility of the LIPI in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond.
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Resumen Introducción Las Unidades Geriátricas de Agudos (UGAs) son unidades especializadas en atención de Personas Mayores (PM). Específicamente en Chile, existen pocos profesionales dedicados a esta área, pese a establecer más UGAs con un equipo interdisciplinario. Desde terapia ocupacional es posible un abordaje desde una perspectiva ocupacional, no obstante, se encontró escasa evidencia que explicite la contribución de terapia ocupacional en UGAs en el contexto chileno. Objetivo Resumir la contribución de las intervenciones realizadas por terapeutas ocupacionales a personas mayores hospitalizadas en Unidades Geriátricas de Agudos, revisando literatura nacional como internacional. Metodología Revisión bibliográfica narrativa, entre octubre del 2021 y enero del 2022. Resultados Los principales resultados destacan la contribución de terapia ocupacional para el abordaje de la fragilidad en PM, en intervenciones llevadas a cabo por equipos interdisciplinarios, la promoción y respeto por la autonomía e independencia (particularmente en Actividades de la Vida Diaria Básicas e Instrumentales), la recuperación funcional y la preparación del alta, contribuyendo a la reducción de las tasas de re-hospitalización. Conclusión La participación de la terapia ocupacional en UGAs aporta herramientas y fortalece las habilidades de las PM con el fin de permitirles desenvolverse efectivamente en sus ocupaciones, de forma independiente y autónoma en diversos contextos, principalmente en actividades de la vida diaria. Además, se busca concientizar sobre la importancia de aumentar la especialización en esta área y la necesidad de aumentar la cantidad de UGAs a nivel nacional.
Resumo Introdução As Unidades Geriátricas Agudas (UGAs) são unidades especializadas no atendimento ao idoso. Especificamente no Chile, há poucos profissionais dedicados a essa área, apesar de estabelecer unidades geriátricas mais agudas com equipe interdisciplinar. A partir da terapia ocupacional é possível uma abordagem a partir de uma perspectiva ocupacional, no entanto, foram encontradas poucas evidências que expliquem a contribuição da terapia ocupacional em UGAs no contexto chileno. Objetivo Resumir a contribuição das intervenções realizadas por terapeutas ocupacionais a idosos internados em UGAs, revisando a literatura nacional e internacional. Metodologia Revisão bibliográfica narrativa, entre outubro de 2021 e janeiro de 2022. Resultados Os principais resultados destacam a contribuição da terapia ocupacional no enfrentamento da fragilidade em idosos nas intervenções realizadas por equipes interdisciplinares, na promoção e respeito à autonomia e independência (particularmente nas Atividades Básicas e Instrumentais de Vida Diária), na recuperação funcional e na preparação para a alta, contribuindo para a redução das taxas de reinternação. Conclusão A participação da terapia ocupacional na UGAs fornece ferramentas e fortalece as habilidades dos idosos para permitir que eles realizem de forma eficaz em suas ocupações, de forma independente e autônoma em vários contextos, principalmente nas atividades da vida diária. Além disso, procura sensibilizar para a importância de aumentar a especialização nesta área e para a necessidade de aumentar o número de UGAs a nível nacional.
Abstract Introduction The Acute Geriatric Units (AGU) are units specialized in caring for the elderly people. Specifically in Chile, there are few professionals dedicated to this area, despite establishing more acute geriatric units with an interdisciplinary team. From occupational therapy, an approach from an occupational perspective is possible. However, little evidence was found that explains the contribution of occupational therapy in AGU in the Chilean context. Objetive Summarize the contribution of the interventions carried out by occupational therapists to elderly people hospitalized in AGU, reviewing national and international literature. Methodology Narrative bibliographic review, between October 2021 and January 2022. Results The main results highlight the contribution of occupational therapy to address frailty in older people in interventions carried out by interdisciplinary teams, the promotion and respect for autonomy and independence (in Basic and Instrumental Activities of Daily Living), the functional recovery and preparation for discharge, contributing to the reduction of rehospitalization rates. Conclusion The participation of occupational therapy in the AGU provides tools and strengthens the skills of older people in order to allow them to function effectively in their occupations, independently and autonomously in various contexts, mainly in activities of daily living. In addition, it seeks to raise awareness of the importance of increasing specialization in this area and the need to increase the number of AGU nationwide.
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Enterococcus faecalis, an organism generally not pathogenic for healthy humans, has the potential to cause disease in susceptible hosts. While it seems to be equipped to interact with and circumvent host immune defense, most of the molecular and cellular mechanisms underlying the enterococcal infectious process remain elusive. Here, we investigated the role of the Enterococcal Leucine Rich protein A (ElrA), an internalin-like protein of E. faecalis also known as a virulence factor. ElrA was previously shown to prevent adhesion to macrophages. We show that ElrA does not inhibit the basic phagocytic process, but is able to prevent sensing and migration of macrophages toward E. faecalis. Presence or absence of FHL2, a eukaryotic partner of ElrA, does not affect the ElrA-dependent mechanism preventing macrophage migration. However, we highlight a partial contribution of FHL2 in ElrA-mediated virulence in vivo. Our results indicate that ElrA plays at least a dual role of which anti-phagocytic activity may contribute to dissemination of extracellular E. faecalis during infection.
Assuntos
Enterococcus faecalis/metabolismo , Infecções por Bactérias Gram-Positivas/microbiologia , Proteína Estafilocócica A/metabolismo , Fatores de Virulência/metabolismo , Virulência/fisiologia , Animais , Proteínas de Bactérias/metabolismo , Células CACO-2 , Linhagem Celular , Linhagem Celular Tumoral , Células HeLa , Células Hep G2 , Humanos , Leucina/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Células RAW 264.7RESUMO
ABSTRACT Ocular cysticercosis is a parasitic infection caused by Taenia solium. Its early diagnosis and treatment decreases the possibility of visual morbidity. It can either compromise the anterior chamber or the posterior segment, which translates into an very variable and interspecific presentation that changes depending on the site of the infection. It is important to report this case due to its low presentation rate and the fact that a high suspicion index is required to make an assertive and timely diagnosis. This is especially important in geographical areas that are endemic to this parasite due to the direct relationship between an early diagnosis and treatment and better visual outcomes. In this case report, we will discuss the multidisciplinary interventions of a pediatric patient in a high complexity hospital.
RESUMO A cisticercose ocular é uma infecção parasitária causada pela Taenia solium. O diagnóstico e tratamento precoces diminuem a possibilidade de morbidade visual. Ela pode comprometer a câmara anterior ou o segmento posterior, o que se traduz em uma apresentação muito variável e interespecífica, que muda dependendo do local da infecção. É importante relatar esse caso devido à sua baixa taxa de apresentação e ao fato de que é necessário um alto índice de suspeita para fazer um diagnóstico assertivo e oportuno. Isso é especialmente importante em áreas geográficas endêmicas para esse parasita, devido à relação direta entre diagnóstico e tratamento precoces e melhores resultados visuais. Neste relato de caso, discutiremos as intervenções multidisciplinares de um paciente pediátrico em um hospital de alta complexidade.