Intensive care of the cancer patient: recent achievements and remaining challenges

A few decades have passed since intensive care unit (ICU) beds have been available for critically ill patients with cancer. Although the initial reports showed dismal prognosis, recent data suggest that an increased number of patients with solid and hematological malignancies benefit from intensive care support, with dramatically decreased mortality rates. Advances in the management of the underlying malignancies and support of organ dysfunctions have led to survival gains in patients with life-threatening complications from the malignancy itself, as well as infectious and toxic adverse effects related to the oncological treatments. In this review, we will appraise the prognostic factors and discuss the overall perspective related to the management of critically ill patients with cancer. The prognostic significance of certain factors has changed over time. For example, neutropenia or autologous bone marrow transplantation (BMT) have less adverse prognostic implications than two decades ago. Similarly, because hematologists and oncologists select patients for ICU admission based on the characteristics of the malignancy, the underlying malignancy rarely influences short-term survival after ICU admission. Since the recent data do not clearly support the benefit of ICU support to unselected critically ill allogeneic BMT recipients, more outcome research is needed in this subgroup. Because of the overall increased survival that has been reported in critically ill patients with cancer, we outline an easy-to-use and evidence-based ICU admission triage criteria that may help avoid depriving life support to patients with cancer who can benefit. Lastly, we propose a research agenda to address unanswered questions

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Plant vascular development: from early specification to differentiation.

Vascular tissues in plants are crucial to provide physical support and to transport water, sugars and hormones and other small signalling molecules throughout the plant. Recent genetic and molecular studies have identified interconnections among some of the major signalling networks that regulate plant vascular development. Using Arabidopsis thaliana as a model system, these studies enable the description of vascular development from the earliest tissue specification events during embryogenesis to the differentiation of phloem and xylem tissues. Moreover, we propose a model for how oriented cell divisions give rise to a three-dimensional vascular bundle within the root meristem

Evidence Provided By Sims and Exafs, of Ge Microclusters in Gaas Epitaxial Layers Obtained On Ge By Csvt

GaAs epitaxial layers from 200 to 10,000 angstrom thick were grown by close spaced vapor transport (CSVT) on (100) Ge substrates, using H2O as transport agent. The heavily Ge-doped films (N(D)-N(A) approximately 10(19) cm-3) were characterized by secondary ion mass spectrometry (SIMS) and by extended x-ray absorption fine structure (EXAFS) at the Ga, Ge, and As K edges. EXAFS at the Ga and As K edge for all layers ranging from 250 to 10,000 angstrom thick gives spectra equivalent to bulk GaAs with a 2.45 angstrom distance between the excited atom and its four nearest neighbors. The oxide concentration in GaAs films is found to be at the SIMS background level, even if Ga and Ge are transported as oxides in CSVT. Besides substitution on lattice sites, Ge is also present as microclusters in the layers. The total Ge concentration decreases with the film thickness from 200 to 2000 angstrom. For thicker films, the Ge concentration remains constant at 1.5% of the value measured in the thinnest film. Due to matrix effects, the absolute Ge concentration cannot be obtained by SIMS. A coordination number, N approximately 2, and a distance R = 2.45 angstrom are obtained with EXAFS for the first neighbor Ge shell. It indicates that the Ge clusters are structurally disconnected from the host GaAs lattice. If the diamond structure of bulk Ge also applies to Ge clusters, an aggregate structure having between two and three Ge shells around a central Ge atom could be postulated. However, a distribution of microcluster sizes cannot be excluded

Doping and Residual Impurities in Gaas-layers Grown By Close-spaced Vapor Transport

The close-spaced vapor transport (CSVT) technique is used to grow GaAs epitaxial layers from various n- or p-type doped GaAs sources. The transport agent is H2O with P(H2O) = 4.58 Torr. n-type layers can be grown with Te- or Ge-doped GaAs sources. The transport coefficients of both dopants (ratio of the electrically active dopant concentration in the layer to the electrically active dopant concentration in the source) is 100% for Te or Ge, in the substrate temperature range comprised between 750 and 850-degrees-C. p-type layers are obtained with Zn-doped GaAs sources. The transport coefficient of Zn is about 1% and is also independent of the substrate temperature. The transport coefficients and their independence on temperature are in agreement with a mass-transport controlled model based on the hypothesis that the transport-t reactions of GaAs and the doping impurities are in equilibrium at the source and substrate temperatures. Si-doped GaAs cannot be used as a source to obtain conductive n-type layers. When undoped semi-insulating (SI)-GaAs wafers are used as sources in CSVT, n-type layers are obtained. They are characterized by N(D) - N(A) = 9 X 10(15) - 3 X 10(16) cm-3 and mu300 K = 3000-4000 cm2 V-1 s-1, independent of the temperature, in the temperature range investigated. Glow discharge mass spectroscopy analyses performed on a source and on a layer indicate that C, O, Si, and S are the major residual impurities in the GaAs layer. All these impurities have their origin in the technique (reactor, transport agent). Ge is also present in the layers, as indicated by photoluminescence. It is a minor impurity. Its origin is probably the SI-GaAs source

Noninvasive Ventilation in Patients with Solid Tumors

During the last two decades, new chemotherapeutic agents, including targeted therapies, and improvement in radiotherapy techniques led to a better prognosis for cancer patients. These new treatments, however, expose patients to various life-threatening complications such as infection, hemorrhage, and drug- or radiation-related toxicity that can require intensive care unit (ICU) admission. The overall survival of oncological patients admitted to the ICU remains disappointing, with recent studies showing mortality rates close to 50 % [1, 2].SCOPUS: ch.binfo:eu-repo/semantics/publishe