Cumulative Prognostic Score Predicting Mortality in Patients Older Than 80 Years Admitted to the ICU.

OBJECTIVES: To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs). DESIGN: Prospective cohort study. SETTING: A total of 306 ICUs from 24 European countries. PARTICIPANTS: Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81-87 y]; 51.8% male). MEASUREMENTS: Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30-day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves. RESULTS: The 30-day-mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30-day mortality in 91.1% of all patients who die. CONCLUSION: A predictive model of cumulative events predicts 30-day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision-making capacity

Insetos em presépios e as "formigas vestidas" de Jules Martin (1832-1906): uma curiosa manufatura paulistana do final do século XIX

Encontrados no Brasil desde os primórdios da colonização portuguesa, os presépios logo tiveram de adaptar-se à realidade local, circunstância muito propícia ao aparecimento de concepções heterodoxas e ao emprego de elementos exóticos da fauna e flora de cada região. Como registros envolvendo insetos são muito pouco comuns, chama a atenção que fêmeas de saúva, Atta sp. (Hymenoptera, Formicidae), tenham sido aproveitadas na composição de presépios no estado de São Paulo. Tendo subsistido pelo menos até a década 1960, os "presépios de formigas" existentes em cidades como Embu das Artes poderiam estar relacionados às "formigas vestidas" criadas por Jules Martin, curiosa manufatura paulistana do último quartel do século XIX.Present in Brazil since the beginning of Portuguese colonization, crèche nativity scenes were soon adapted to local reality, a propitious circumstance for the appearance of heterodox conceptions and the use of exotic elements of the fauna and flora peculiar to each region. As records about insects are very uncommon, it is noteworthy that females of leaf-cutting ants, Atta sp. (Hymenoptera, Formicidae), were used to compose crèche nativity scenes in São Paulo State. Having subsisted at least up to the decade of 1960, the "ant crèches" of cities such as Embu das Artes could be related to the then famous "dressed ants" created by Jules Martin, a curious manufacture of the city of São Paulo in the last quarter of the 19th century

Clinically relevant radioresistant rhabdomyosarcoma cell lines: Functional, molecular and immune-related characterization

Background: The probability of local tumor control after radiotherapy (RT) remains still miserably poor in pediatric rhabdomyosarcoma (RMS). Thus, understanding the molecular mechanisms responsible of tumor relapse is essential to identify personalized RT-based strategies. Contrary to what has been done so far, a correct characterization of cellular radioresistance should be performed comparing radioresistant and radiosensitive cells with the same isogenic background. Methods: Clinically relevant radioresistant (RR) embryonal (RD) and alveolar (RH30) RMS cell lines have been developed by irradiating them with clinical-like hypo-fractionated schedule. RMS-RR cells were compared to parental isogenic counterpart (RMS-PR) and studied following the radiobiological concept of the "6Rs", which stand for repair, redistribution, repopulation, reoxygenation, intrinsic radioresistance and radio-immuno-biology. Results: RMS-RR cell lines, characterized by a more aggressive and in vitro pro-metastatic phenotype, showed a higher ability to i) detoxify from reactive oxygen species; ii) repair DNA damage by differently activating non-homologous end joining and homologous recombination pathways; iii) counteract RT-induced G2/M cell cycle arrest by re-starting growth and repopulating after irradiation; iv) express cancer stem-like profile. Bioinformatic analyses, performed to assess the role of 41 cytokines after RT exposure and their network interactions, suggested TGF-β, MIF, CCL2, CXCL5, CXCL8 and CXCL12 as master regulators of cancer immune escape in RMS tumors. Conclusions: These results suggest that RMS could sustain intrinsic and acquire radioresistance by different mechanisms and indicate potential targets for future combined radiosensitizing strategies

Hot Vents Beneath an Icy Ocean: The Aurora Vent Field, Gakkel Ridge, Revealed

Evidence of hydrothermal venting on the ultra-slow spreading Gakkel Ridge in the Central Arctic Ocean has been available since 2001, with first visual evidence of black smokers on the Aurora Vent Field obtained in 2014. But it was not until 2021 that the first ever remotely operated vehicle (ROV) dives to hydrothermal vents under permanent ice cover in the Arctic were conducted, enabling the collection of vent fluids, rocks, microbes, and fauna. In this paper, we present the methods employed for deep-sea ROV operations under drifting ice. We also provide the first description of the Aurora Vent Field, which includes three actively venting black smokers and diffuse flow on the Aurora mound at ~3,888 m depth on the southern part of the Gakkel Ridge (82.5°N). The biological communities are dominated by a new species of cocculinid limpet, two small gastropods, and a melitid amphipod. The ongoing analyses of Aurora Vent Field samples will contribute to positioning the Gakkel Ridge hydrothermal vents in the global biogeographic puzzle of hydrothermal vents

The role of B-mode ultrasonography in the musculoskeletal anatomical evaluation of the cervical region of the dog spine

This study characterized the normal musculoskeletal anatomy of the cervical segment of the spine of dogs by means of B-mode ultrasonography. The objective was to establish the role of B-mode ultrasonography for the anatomical evaluation of the cervical spine segment in dogs, by comparing the ultrasonographic findings with images by computed tomography and magnetic resonance imaging. The ultrasound examination, in transverse and median sagittal sections, allowed to identify a part of the epaxial cervical musculature, the bone surface of the cervical vertebrae and parts of the spinal cord through restricted areas with natural acoustic windows, such as between the atlanto-occipital joint, axis and atlas, and axis and the third cervical vertebra. The images, on transverse and sagittal planes, by low-field magnetic resonance imaging, were superior for the anatomical identification of the structures, due to higher contrast between the different tissues in this modality. Computed tomography showed superiority for bone detailing when compared with ultrasonography. As for magnetic resonance imaging, in addition to the muscles and cervical vertebrae, it is possible to identify the cerebrospinal fluid and differentiate between the nucleus pulposus and annulus fibrosus of the intervertebral discs. Although not the scope of this study, with knowledge of the ultrasonographic anatomy of this region, it is believed that some lesions can be identified, yet in a limited manner, when compared with the information obtained mainly with magnetic resonance imaging. The ultrasound examination presented lower morphology diagnostic value compared with the other modalities.Este estudo caracterizou a anatomia musculoesquelética normal do segmento cervical da coluna vertebral de cães por meio da ultrassonografia modo B. O objetivo do trabalho foi estabelecer o papel da ultrassonografia modo B na avaliação anatômica do segmento cervical de cães, comparando os achados ultrassonográficos com imagens por tomografia computadorizada e ressonância magnética. O exame ultrassonográfico, em cortes transversais e sagitais mediano, permitiu a identificação de parte da musculatura epaxial do pescoço, superfície óssea das vértebras cervicais e medula espinhal em áreas restritas com janelas acústicas naturais, como entre a articulação atlantoccipital, áxis e atlas, e áxis e terceira vértebra cervical. As imagens, em planos transversais e sagitais, por ressonância magnética de baixo campo foram superiores na identificação anatômica das estruturas, devido ao maior contraste entre os diferentes tecidos nessa modalidade. A tomografia computadorizada se mostrou superior no detalhamento ósseo da região quando comparada ao exame ultrassonográfico. Já a ressonância magnética, além dos músculos e vértebras cervicais, permitiu a identificação do líquido cefalorraquidiano, e diferenciar núcleo pulposo e anel fibroso dos discos intervertebrais. Embora não seja objetivo direto deste estudo, com o conhecimento da anatomia ultrassonográfica dessa região, acredita-se que algumas lesões possam ser identificadas, contudo de maneira restrita, quando comparadas as informações obtidas, principalmente na imagem por ressonância magnética. O exame ultrassonográfico apresentou valor morfológico inferior.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Estadual Paulista Faculdade de Medicina Veterinária e Zootecnia Departamento de Reprodução Animal e Radiologia VeterináriaUniversidade de São Paulo Faculdade de Zootecnia e Engenharia de Alimentos Departamento de Medicina VeterináriaUniversidade Federal de Viçosa Centro de Ciências Biológicas e da Saúde Departamento de VeterináriaUniversity of Florida College of Veterinary MedicineUniversidade Estadual Paulista Faculdade de Medicina Veterinária e Zootecnia Departamento de Reprodução Animal e Radiologia Veterinári

Murine Dendritic Cells Transcriptional Modulation upon Paracoccidioides brasiliensis Infection

Limited information is available regarding the modulation of genes involved in the innate host response to Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis. Therefore, we sought to characterize, for the first time, the transcriptional profile of murine bone marrow-derived dendritic cells (DCs) at an early stage following their initial interaction with P. brasiliensis. DCs connect innate and adaptive immunity by recognizing invading pathogens and determining the type of effector T-cell that mediates an immune response. Gene expression profiles were analyzed using microarray and validated using real-time RT-PCR and protein secretion studies. A total of 299 genes were differentially expressed, many of which are involved in immunity, signal transduction, transcription and apoptosis. Genes encoding the cytokines IL-12 and TNF-α, along with the chemokines CCL22, CCL27 and CXCL10, were up-regulated, suggesting that P. brasiliensis induces a potent proinflammatory response in DCs. In contrast, pattern recognition receptor (PRR)-encoding genes, particularly those related to Toll-like receptors, were down-regulated or unchanged. This result prompted us to evaluate the expression profiles of dectin-1 and mannose receptor, two other important fungal PRRs that were not included in the microarray target cDNA sequences. Unlike the mannose receptor, the dectin-1 receptor gene was significantly induced, suggesting that this β-glucan receptor participates in the recognition of P. brasiliensis. We also used a receptor inhibition assay to evaluate the roles of these receptors in coordinating the expression of several immune-related genes in DCs upon fungal exposure. Altogether, our results provide an initial characterization of early host responses to P. brasiliensis and a basis for better understanding the infectious process of this important neglected pathogen

Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.

BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85]. CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)