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Purpose: Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies. Methods: Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100 mmHg) on day-28 mortality. Results: 11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100 mmHg) were associated with day-28 mortality with a dose–effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04–1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20–1.1.44]). Conclusion: In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality. [ABSTRACT FROM AUTHOR]

Background: It remains controversial whether critical illness-related hyperglycemia should be treated or not, since randomized controlled trials (RCTs) have shown context-dependent outcome effects. Whereas pioneer RCTs found improved outcome by normalizing blood glucose in patients receiving early parenteral nutrition (PN), a multicenter RCT revealed increased mortality in patients not receiving early PN. Although withholding early PN has become the feeding standard, the multicenter RCT showing harm by tight glucose control in this context has been criticized for its potentially unreliable glucose control protocol. We hypothesize that tight glucose control is effective and safe using a validated protocol in adult critically ill patients not receiving early PN.Methods: The TGC-fast study is an investigator-initiated, multicenter RCT. Patients unable to eat, with need for arterial and central venous line and without therapy restriction, are randomized upon ICU admission to tight (80-110 mg/dl) or liberal glucose control (only initiating insulin when hyperglycemia >215 mg/dl, and then targeting 180-215 mg/dl). Glucose measurements are performed on arterial blood by a blood gas analyzer, and if needed, insulin is only administered continuously through a central venous line. If the arterial line is no longer needed, glucose is measured on capillary blood. In the intervention group, tight control is guided by the validated LOGIC-Insulin software. In the control arm, a software alert is used to maximize protocol compliance. The intervention is continued until ICU discharge, until the patient is able to eat or no longer in need of a central venous line, whatever comes first. The study is powered to detect, with at least 80% power and a 5% alpha error rate, a 1-day difference in ICU dependency (primary endpoint), and a 1.5% increase in hospital mortality (safety endpoint), for which 9230 patients need to be included. Secondary endpoints include acute and long-term morbidity and mortality, and healthcare costs. Biological samples are collected to study potential mechanisms of organ protection.Discussion: The ideal glucose target for critically ill patients remains debated. The trial will inform physicians on the optimal glucose control strategy in adult critically ill patients not receiving early PN.Trial Registration: ClinicalTrials.gov NCT03665207. Registered on 11 September 2018. [ABSTRACT FROM AUTHOR]

Background: Whether Intensive Care Unit (ICU) clinicians display unconscious bias towards cancer patients is unknown. The aim of this study was to compare the outcomes of critically ill patients with and without perceptions of excessive care (PECs) by ICU clinicians in patients with and without cancer. Methods: This study is a sub-analysis of the large multicentre DISPROPRICUS study. Clinicians of 56 ICUs in Europe and the United States completed a daily questionnaire about the appropriateness of care during a 28-day period. We compared the cumulative incidence of patients with concordant PECs, treatment limitation decisions (TLDs) and death between patients with uncontrolled and controlled cancer, and patients without cancer. Results: Of the 1641 patients, 117 (7.1%) had uncontrolled cancer and 270 (16.4%) had controlled cancer. The cumulative incidence of concordant PECs in patients with uncontrolled and controlled cancer versus patients without cancer was 20.5%, 8.1%, and 9.1% (p < 0.001 and p = 0.62, respectively). In patients with concordant PECs, we found no evidence for a difference in time from admission until death (HR 1.02, 95% CI 0.60–1.72 and HR 0.87, 95% CI 0.49–1.54) and TLDs (HR 0.81, 95% CI 0.33–1.99 and HR 0.70, 95% CI 0.27–1.81) across subgroups. In patients without concordant PECs, we found differences between the time from admission until death (HR 2.23, 95% CI 1.58–3.15 and 1.66, 95% CI 1.28–2.15), without a corresponding increase in time until TLDs (NA, p = 0.3 and 0.7) across subgroups. Conclusions: The absence of a difference in time from admission until TLDs and death in patients with concordant PECs makes bias by ICU clinicians towards cancer patients unlikely. However, the differences between the time from admission until death, without a corresponding increase in time until TLDs, suggest prognostic unawareness, uncertainty or optimism in ICU clinicians who did not provide PECs, more specifically in patients with uncontrolled cancer. This study highlights the need to improve intra- and interdisciplinary ethical reflection and subsequent decision-making at the ICU. [ABSTRACT FROM AUTHOR]

Introduction: Given clinicians' frequent concerns about unfavourable outcomes, Intensive Care Unit (ICU) triage decisions in acutely ill cancer patients can be difficult, as clinicians may have doubts about the appropriateness of an ICU admission. To aid to this decision making, we studied the survival and performance status of cancer patients 2 years following an unplanned ICU admission. Materials and methods: This was a retrospective cohort study in a large tertiary referral university hospital in the Netherlands. We categorized all adult patients with an unplanned ICU admission in 2017 into two groups: patients with or without an active malignancy. Descriptive statistics, Pearson's Chi-square tests and the Mann-Whitney U tests were used to evaluate the primary objective 2-year mortality and performance status. A good performance status was defined as ECOG performance status 0 (fully active) or 1 (restricted in physically strenuous activity but ambulatory and able to carry out light work). A multivariable binary logistic regression analysis was used to identify factors associated with 2-year mortality within cancer patients. Results: Of the 1046 unplanned ICU admissions, 125 (12%) patients had cancer. The 2-year mortality in patients with cancer was significantly higher than in patients without cancer (72% and 42.5%, P <0.001). The median performance status at 2 years in cancer patients was 1 (IQR 0–2). Only an ECOG performance status of 2 (OR 8.94; 95% CI 1.21–65.89) was independently associated with 2-year mortality. Conclusions: In our study, the majority of the survivors have a good performance status 2 years after ICU admission. However, at that point, three-quarter of these cancer patients had died, and mortality in cancer patients was significantly higher than in patients without cancer. ICU admission decisions in acutely ill cancer patients should be based on performance status, severity of illness and long-term prognosis, and this should be communicated in the shared decision making. An ICU admission decision should not solely be based on the presence of a malignancy. [ABSTRACT FROM AUTHOR]

Background: Treatment limitation decisions (TLDs) on the ICU can be challenging, especially in patients with a malignancy. Up-to-date literature regarding TLDs in critically ill patients with a malignancy admitted to the ICU is scarce. The aim was to compare the incidence of written TLDs between patients with an active malignancy, patients with a malignancy in their medical history (complete remission, CR) and patients without a malignancy admitted unplanned to the ICU. Methods: We conducted a retrospective cohort study in a large university hospital in the Netherlands. We identified all unplanned admissions to the ICU in 2017 and categorized the patients in 3 groups: patients with an active malignancy (study population), with CR and without a malignancy. A TLD was defined as a written instruction not to perform life-saving treatments, such as CPR in case of cardiac arrest. A multivariate binary logistic regression analysis was used to identify whether having a malignancy was associated with TLDs. Results: Of the 1046 unplanned admissions, 125 patients (12%) had an active malignancy and 76 (7.3%) patients had CR. The incidence of written TLDs in these subgroups were 37 (29.6%) and 20 (26.3%). Age (OR 1.03; 95% CI 1.01 -1.04), SOFA score at ICU admission (OR 1.11; 95% CI 1.05 -1.18) and having an active malignancy (OR 1.75; 95% CI 1.04-2.96) compared to no malignancy were independently associated with written TLDs. SOFA scores on the day of the TLD were not significantly different in patients with and without a malignancy. Conclusions: This study shows that the presence of an underlying malignancy is independently associated with written TLDs during ICU stay. Patients with CR were not at risk of more written TLDs. Whether this higher incidence of TLDs in patients with a malignancy is justified, is at least questionable and should be evaluated in future research. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is fatal in 90% of patients if left untreated and must be diagnosed early to optimize patient outcomes. However, the very low incidence of TTP is an obstacle to the development of evidence-based clinical practice recommendations, and the very wide variability in survival rates across centers may be partly ascribable to differences in management strategies due to insufficient guidance. We therefore developed an expert statement to provide trustworthy guidance about the management of critically ill patients with TTP. As strong evidence was difficult to find in the literature, consensus building among experts could not be reported for most of the items. This expert statement is timely given the recent advances in the treatment of TTP, such as the use of rituximab and of the recently licensed drug caplacizumab, whose benefits will be maximized if the other components of the management strategy follow a standardized pattern. Finally, unanswered questions are identified as topics of future research on TTP. [ABSTRACT FROM AUTHOR]

In patients with hematologic malignancies, respiratory status may deteriorate during neutropenia recovery. This multicenter, observational study aims to evaluate granulocyte colony-stimulating factor (G-CSF) impact on respiratory status in critically ill neutropenic patients. Among 1011 critically ill patients with hematologic malignancies, 288 were neutropenic and included in this study. 201 (70%) did not receive G-CSF at day 1 or 2. After propensity score matching for the probability of receiving G-CSF at day 1 or 2, there was no association between G-CSF and respiratory deterioration at day 14 (OR =1.19; 95%CI (0.57–2.51); p =.64). Additional sensitivity analysis in patients admitted for acute respiratory failure showed similar results (OR =1.34; 95%CI (0.5–3.59); p =.57). Among patients who recovered from neutropenia, 75% experienced respiratory deterioration during neutropenia recovery. This study confirms that neutropenia recovery is a situation at risk of respiratory deterioration. However, whether G-CSF is an aggravating factor cannot be supported by our results. [ABSTRACT FROM AUTHOR]

The article offers information on understanding of adequate antimicrobial treatment as important to reduce mortality in critically ill patients with infection. Topics discussed include combination antibiotic treatment recommended for non-neutropenic and neutropenic patients with sepsis, issues concerning with β-lactam antibiotics concentrations in critically ill patients and role of rapid diagnostic systems in delaying in microbiological identification of pathogens and susceptibility testing.

Over the coming years, accelerating progress against cancer will be associated with an increased number of patients who require life-sustaining therapies for infectious or toxic chemotherapy-related events. Major changes include increased number of cancer patients admitted to the ICU with full-code status or for time-limited trials, increased survival and quality of life in ICU survivors, changing prognostic factors, early ICU admission for optimal monitoring, and use of noninvasive diagnostic and therapeutic strategies. In this review, experts in the management of critically ill cancer patients highlight recent changes in the use and the results of intensive care in patients with malignancies. They seek to put forward a standard of care for the management of these patients and highlight important updates that are required to care for them. The research agenda they suggest includes important studies to be conducted in the next few years to increase our understanding of organ dysfunction in this population and to improve our ability to appropriately use life-saving therapies or select new therapeutic approaches that are likely to improve outcomes. This review aims to provide more guidance for the daily management of patients with cancer, in whom outcomes are constantly improving, as is our global ability to fight against what is becoming the leading cause of mortality in industrialized and non-industrialized countries. [ABSTRACT FROM AUTHOR]

The article highlights research and developments related to intensive care medicine in 2014. Topics discussed include recent findings about airway management in critically ill patients, evidence showing that there is no indication for using statins either in infection or acute respiratory distress syndrome (ARDS) in intensive care unit (ICU) patients, and research about the pathophysiology of acute liver failure (ALF).

The article presents several medical research papers that were published in the 2014 issues of the journal "Intensive Care (IC) Medicine." Topics covered include cardiac dysfunction, neurocritical care, acute kidney injury, neuromonitoring, neuromuscular disorders that develop after an IC unit admission, and nutrition in the critically ill patient.

The article discusses studies that argue for and against the claim that survival rates in critically ill patients with cancer increased. Topics discussed include a comparison in the survival rates of patients with cancer, severe sepsis and septic shock, argument that survival rates are based on studies performed in heterogeneous populations from different experiences and cultures and survival benefits from earlier and better supportive care provided to patients with less comorbidities.

The article discusses various studies which appeared in "Intensive Care Medicine" journal in 2013. Information is presented on the study in Malaysia which assessed whether early sedation depth was independently associated with delayed extubation and increased mortality. An overview of a review article about efficient weaning and automatic ventilation modes for failing patients.

Background. Central venous catheters are universally used during the treatment of critically ill patients. Their use, however, is associated with a substantial infection risk, potentially leading to increased mortality and costs. We evaluate clinical and economic outcomes associated with nosocomial central venous catheter-related bloodstream infection (CR-BSI) in intensive care unit (ICU) patients. Methods. A retrospective (1992-2002), pairwise-matched (ratio of case patients to control subjects, 1:2 or 1: 1), risk-adjusted cohort study was performed at a 54-bed general ICU at a university hospital. ICU patients with microbiologically documented CR-BSI ( ) were matched with control subjects ( ) on the basis of np176 np315 disease severity, diagnostic category, and length of ICU stay (equivalent or longer) before the onset of CR-BSI in the index case patient. Clinical outcome was principally evaluated by in-hospital mortality. Economic outcome was evaluated on the basis of duration of mechanical ventilation, length of ICU and hospital stays, and total hospital costs, as derived from the patient's hospital invoices. Results. The attributable mortality rate for CR-BSI was estimated to be 1.8% (95% confidence interval, 6.4% to 10.0%); in-hospital mortality rates for patients with CR-BSI and matched control subjects were 27.8% and 26.0%, respectively. CR-BSI was associated with significant excesses in duration of mechanical ventilation, duration of ICU and hospital stays, and a significant increase in total hospital cost. Linear regression analysis with adjustment for duration of hospitalization and clinical covariates, revealed that CR-BSI is independently associated with higher costs. Conclusions. In ICU patients, CR-BSI does not result in increased mortality. It is, however, associated with a significant economic burden, emphasizing the importance of continuous efforts in prevention. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the benefit of direct ICU admission from the emergency department (ED) compared to admission from wards, in patients with hematological malignancies requiring critical care. Methods: Post hoc analysis derived from a prospective, multicenter cohort study of 1011 critically ill adult patients with hematologic malignancies admitted to 17 ICU in Belgium and France from January 2010 to May 2011. The variable of interest was a direct ICU admission from the ED and the outcome was in-hospital mortality. The association between the variable of interest and the outcome was assessed by multivariable logistic regression after multiple imputation of missing data. Several sensitivity analyses were performed: complete case analysis, propensity score matching and multivariable Cox proportional-hazards analysis of 90-day survival. Results: Direct ICU admission from the ED occurred in 266 (26.4%) cases, 84 of whom (31.6%) died in the hospital versus 311/742 (41.9%) in those who did not. After adjustment, direct ICU admission from the ED was associated with a decreased in-hospital mortality (adjusted OR: 0.63; 95% CI 0.45–0.88). This was confirmed in the complete cases analysis (adjusted OR: 0.64; 95% CI 0.45–0.92) as well as in terms of hazard of death within the 90 days after admission (adjusted HR: 0.77; 95% CI 0.60–0.99). By contrast, in the propensity score-matched sample of 402 patients, direct admission was not associated with in-hospital mortality (adjusted OR: 0.92; 95% CI 0.84–1.01). Conclusions: In this study, patients with hematological malignancies admitted to the ICU were more likely to be alive at hospital discharge if they were directly admitted from the ED rather than from the wards. Assessment of early predictors of poor outcome in cancer patients admitted to the ED is crucial so as to allow early referral to the ICU and avoid delays in treatment initiation and mis-orientation. [ABSTRACT FROM AUTHOR]

Background: Although outcomes of critically ill patients with haematological malignancies (HMs) have been fully investigated in terms of organ failure and mortality, data are scarce on health-related quality of life (HRQOL) in this population. We aim to assess post-intensive care unit (ICU) burden and HRQOL of critically ill patients with HMs and to identify risk factors for quality-of-life (QOL) impairment.Results: In total, 1011 patients with HMs who required ICU admission in 17 ICUs in France and Belgium were included in the study; 278 and 117 patients were evaluated for QOL at 3 months and 1 year, respectively, after ICU discharge. HRQOL was determined by applying the interview form of the Short Form 36 (SF-36) questionnaire. Psychological distress symptoms were evaluated using the Hospital Anxiety Depression Score (HADS) and the Impact of Event Scale (IES). In-hospital mortality rates at 3 months and 1 year were, respectively, 39.1, 50.7 and 57.2%, respectively. At 3 months, median [IQR] physical and mental component summary scores (PCS and MCS) (SF-36) were 37 [28-46] and 51 [45-58], respectively. PCS was lower in ICU patients with HMs when compared to general ICU septic patients (52 [5-13], p = 0.00001). The median combined HAD score was 8 [5-13], and the median IES score was 8 [3-16]. However, recovery during the first year after ICU discharge was not consistent in all dimensions of HRQOL. Three months after ICU discharge, the maximum daily Sequential Organ Failure Assessment score and status of the underlying malignancy at ICU admission were significantly associated with MCS impairment (− 0.54 points [95% CI − 0.99; − 0.1], p = 0.018 and − 4.83 points [95% CI − 8.44; − 1.22], p = 0.009, respectively).Conclusion: HRQOL is strongly impaired in critically ill patients with HMs at 3 months and 1 year after ICU discharge. Organ failure and disease status are strongly associated with QOL. The kinetic evaluation of QOL at 3 months and 1 year offers the opportunity to focus on QOL aspects that may be improved by therapeutic interventions during the first year after ICU discharge. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether serum concentration of endothelial cell-specific molecule-1 (Endocan) at ICU admission is associated with the use of ICU resources and outcomes in critically ill hematology patients.Design: Prospective multicenter cohort study.Setting: Seventeen ICUs in France and Belgium.Patients: Seven hundred forty-four consecutive critically ill hematology patients; 72 critically ill septic patients without hematologic malignancy; 276 healthy subjects.Intervention: None.Measurements and Main Results: Median total endocan concentrations were 4.46 (2.7-7.8) ng/mL. Endocan concentrations were higher in patients who had received chemotherapy before ICU admission (4.7 [2.8-8.1] ng/mL vs. 3.7 [2.5-6.3] ng/mL [p = 0.002]). In patients with acute respiratory failure, endocan levels were increased in patients with drug-induced pulmonary toxicity compared with other etiologies (p = 0.038). Total endocan levels higher than 4.46 ng/mL were associated with a higher cumulative probability of renal replacement therapy requirement (p = 0.006), a higher requirement of mechanical ventilation (p = 0.01) and a higher requirement of vasopressors throughout ICU stay (p < 0.0001). By multivariate analysis, total endocan levels at admission were independently associated with ICU mortality (odds ratios, 1.39; 95% CI, 1.06-1.83; p = 0.018). The predictive value of endocan peptide fragments of 14 kDa in terms of mortality and life-sustaining therapies requirement was inferior to that of total endocan. Endocan levels were higher in critically ill hematology patients compared with healthy subjects (p < 0.0001) but lower than endocan values in critically ill septic patients without hematologic malignancy (p = 0.005) CONCLUSIONS:: Serum concentrations of endocan at admission are associated with the use of ICU resources and mortality in critically ill hematology patients. Studies to risk-stratify patients in the emergency department or in the hematology wards based on endocan concentrations to identify those likely to benefit from early ICU management are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Time series often appear in medical databases, but only few machine learning methods exist that process this kind of data properly. Most modeling techniques have been designed with a static data model in mind and are not suitable for coping with the dynamic nature of time series. Recurrent neural networks (RNNs) are often used to process time series, but only a few training algorithms exist for RNNs which are complex and often yield poor results. Therefore, researchers often turn to traditional machine learning approaches, such as support vector machines (SVMs), which can easily be set up and trained and combine them with feature extraction (FE) and selection (FS) to process the high-dimensional temporal data. Recently, a new approach, called echo state networks (ESNs), has been developed to simplify the training process of RNNs. This approach allows modeling the dynamics of a system based on time series data in a straightforwardway. The objective of this study is to explore the advantages of using ESN instead of other traditional classifiers combined with FE and FS in classification problems in the intensive care unit (ICU) when the input data consists of time series. While ESNs have mostly been used to predict the future course of a time series, we use the ESN model for classification instead. Although time series often appear in medical data, little medical applications of ESNs have been studiedyet. Methods and material: ESN is used to predict the need for dialysis between the fifth and tenth day after admission in the ICU. The input time series consist of measured diuresis and creatinine values during the first 3days after admission. Data about 830 patients was used for the study, of which 82 needed dialysis between the fifth and tenth day after admission. ESN is compared to traditional classifiers, a sophisticated and a simple one, namely support vector machines and the naive Bayes (NB) classifier. Prior to the use of the SVM and NB classifier, FE and FS is required to reduce the number of input features and thus alleviate the curse dimensionality. Extensive feature extraction was applied to capture both the overall properties of the time series and the correlation between the different measurements in the time series. The feature selection method consists of a greedy hybrid filter-wrapper method using a NB classifier, which selects in each iteration the feature that improves prediction the best and shows little multicollinearity with the already selected set. Least squares regression with noise was used to train the linear readout function of the ESN to mitigate sensitivity to noise and overfitting. Fisher labeling was used to deal with the unbalanced data set. Parameter sweeps were performed to determine the optimal parameter values for the different classifiers. The area under the curve (AUC) and maximum balanced accuracy are used as performance measures. The required execution time was also measured. Results: The classification performance of the ESN shows significant difference at the 5% level compared to the performance of the SVM or the NB classifier combined with FE and FS. The NB+FE+FS, with an average AUC of 0.874, has the best classification performance. This classifier is followed by the ESN, which has an average AUC of 0.849. The SVM+FE+FS has the worst performance with an average AUC of 0.838. The computation time needed to pre-process the data and to train and test the classifier is significantly less for the ESN compared to the SVM andNB. Conclusion: It can be concluded that the use of ESN has an added value in predicting the need for dialysis through the analysis of time series data. The ESN requires significantly less processing time, needs no domain knowledge, is easy to implement, and can be configured using rules ofthumb. [Copyright &y& Elsevier]