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Lately, attention has focussed on the impact of pre-admission characteristics, factors often unrelated to the acute event but with a large impact on ICU admission and outcomes. Variations in ICU mortality between ICUs could, to a substantial extent, be explained by their policy differences as to forgoing LST. Dear Editor, Mortality in intensive care units (ICUs) depends on many factors with variable contributions. [Extracted from the article]

Migration of cells is important for tissue maintenance, immune response, and often altered in disease. While biochemical aspects, including cell adhesion, have been studied in detail, much less is known about the role of the mechanical properties of cells. Previous measurement methods rely on contact with artificial surfaces, which can convolute the results. Here, we used a non-contact, microfluidic optical stretcher to study cell mechanics, isolated from other parameters, in the context of tissue infiltration by acute promyelocytic leukemia (APL) cells, which occurs during differentiation therapy with retinoic acid. Compliance measurements of APL cells reveal a significant softening during differentiation, with the mechanical properties of differentiated cells resembling those of normal neutrophils. To interfere with the migratory ability acquired with the softening, differentiated APL cells were exposed to paclitaxel, which stabilizes microtubules. This treatment does not alter compliance but reduces cell relaxation after cessation of mechanical stress six-fold, congruent with a significant reduction of motility. Our observations imply that the dynamical remodeling of cell shape required for tissue infiltration can be frustrated by stiffening the microtubular system. This link between the cytokeleton, cell mechanics, and motility suggests treatment options for pathologies relying on migration of cells, notably cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: The number of adults requiring prolonged mechanical ventilation (PMV) including those with cognitive impairment or disorders of consciousness is escalating. We aimed to compare in a long-term acute care hospital (LTACH) mortality and length of stay (LOS) among three age groups (40-59y, 60-79y, ≥80y) of hospitalized PMV patients, and according to consciousness and cognitive state at admission. Methods: We obtained data from the health records of 308 adults aged ≥40 years requiring PMV hospitalized at a Chronic Ventilator Dependent Unit in a LTACH between 01/01/2015 to 06/30/2019 and followed-up until discharge or death or until 12/31/2019. Results: At admission to LTACH, 42.2% of PMV patients were in a vegetative state/minimally conscious state (VS/MCS); 32.5% were severely cognitively impaired, 11.0% were mildly to moderately cognitively impaired, 12.3% had no cognitive impairment, and 1.9% had intellectual disability/psychiatric disorder. In-LTACH LOS (months) decreased from 34.6 ±42.6 at age 40-59y, 19.1 ± 22.3 at 60-79y to 14.4 ± 19.3 at age ≥80y (p = .006). In-LTACH mortality was 30.6% for 40-59y, 41.1% for 60-79y and 54.8% for age ≥80y. In-LTACH LOS (months) was 23.8 ± 30.7 for VS/MCS, 15.1 ± 19.5 for the severely cognitively impaired, 10.0 ± 12.8 for mild to moderate cognitive impairment and 18.9 ± 21.9 for those without cognitive impairment (p = .02). In-LTACH mortality was 50.8% for VS/MCS, 58.0% for the severely cognitively impaired, 26.5% for mild to moderate cognitive impairment and 13.2% for those without cognitive impairment (p < .001). Conclusion: In this population requiring PMV, mortality and in-LTACH LOS worsened with age. In-LTACH LOS was longest for VS/MCS patients, who had a mean survival of about two years, followed by those without cognitive impairment and then those with severe cognitive impairment. Mortality was associated with worse consciousness and cognitive state. These findings highlight the importance of discussing end-of-life decisions with patients and family members regarding resuscitation/intubation and the long-term management of these patients. [ABSTRACT FROM AUTHOR]

Shock is a life-threatening condition. This study evaluated if sublingual microcirculatory perfusion on admission is associated with 30-day mortality in older intensive care unit (ICU) shock patients. This trial prospectively recruited ICU patients (≥ 80 years old) with arterial lactate above 2 mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of shock cause. All patients received sequential sublingual measurements on ICU admission (± 4 h) and 24 (± 4) hours later. The primary endpoint was 30-day mortality. From September 4th, 2022, to May 30th, 2023, 271 patients were screened, and 44 included. Patients were categorized based on the median percentage of perfused small vessels (sPPV) into those with impaired and sustained microcirculation. 71% of videos were of good or acceptable quality without safety issues. Patients with impaired microcirculation had significantly shorter ICU and hospital stays (p = 0.015 and p = 0.019) and higher 30-day mortality (90.0% vs. 62.5%, p = 0.036). Cox regression confirmed the independent association of impaired microcirculation with 30-day mortality (adjusted hazard ratio 3.245 (95% CI 1.178 to 8.943, p = 0.023). Measuring sublingual microcirculation in critically ill older patients with shock on ICU admission is safe, feasible, and provides independent prognostic information about outcomes. Trial registration NCT04169204. [ABSTRACT FROM AUTHOR]

In Europe, tax-based healthcare systems (THS) and social health insurance systems (SHI) coexist. We examined differences in 30-day mortality among critically ill patients aged ≥ 70 years treated in intensive care units in a THS or SHI. Retrospective cohort study. 2406 (THS n = 886; SHI n = 1520) critically ill ≥ 70 years patients in 129 ICUs. Generalized estimation equations with robust standard errors were chosen to create population average adjusted odds ratios (aOR). Data were adjusted for patient-specific variables, organ support and health economic data. The primary outcome was 30-day-mortality. Numerical differences between SHI and THS in SOFA scores (6 ± 3 vs. 5 ± 3; p = 0.002) were observed, but clinical frailty scores were similar (> 4; 17% vs. 14%; p = 0.09). Higher rates of renal replacement therapy (18% vs. 11%; p < 0.001) were found in SHI (aOR 0.61 95%CI 0.40–0.92; p = 0.02). No differences regarding intubation rates (68% vs. 70%; p = 0.33), vasopressor use (67% vs. 67%; p = 0.90) and 30-day-mortality rates (47% vs. 50%; p = 0.16) were found. Mortality remained similar between both systems after multivariable adjustment and sensitivity analyses. The retrospective character of this study. Baseline risk and mortality rates were similar between SHI and THS. The type of health care system does not appear to have played a role in the intensive care treatment of critically ill patients ≥ 70 years with COVID-19 in Europe. [ABSTRACT FROM AUTHOR]

Background: Sepsis-associated immune dysregulation, involving hyper-inflammation and immunosuppression, is common in intensive care patients, often leading to multiple organ dysfunction and death. The aim of this study was to identify the main driving force underlying immunosuppression in sepsis, and to suggest new therapeutic avenues for controlling this immune impairment and alleviating excessive pathogen load. Methods: We developed two minimalistic (skeletal) mathematical models of pathogen-associated inflammation, which focus on the dynamics of myeloid, lymphocyte, and pathogen numbers in blood. Both models rely on the assumption that the presence of the pathogen causes a bias in hematopoietic stem cell differentiation toward the myeloid developmental line. Also in one of the models, we assumed that continuous exposure to pathogens induces lymphocyte exhaustion. In addition, we also created therapy models, both by antibiotics and by immunotherapy with PD-1/PD-L1 checkpoint inhibitors. Assuming realistic parameter ranges, we simulated the pathogen-associated inflammation models in silico with or without various antibiotic and immunotherapy schedules. Results: Computer simulations of the two models show that the assumption of lymphocyte exhaustion is a prerequisite for attaining sepsis-associated immunosuppression, and that the ability of the innate and adaptive immune systems to control infections depends on the pathogen's replication rate. Simulation results further show that combining antibiotics with immune checkpoint blockers can suffice for defeating even an aggressive pathogen within a relatively short period. This is so as long as the drugs are administered soon after diagnosis. In contrast, when applied as monotherapies, antibiotics or immune checkpoint blockers fall short of eliminating aggressive pathogens in reasonable time. Conclusions: Our results suggest that lymphocyte exhaustion crucially drives immunosuppression in sepsis, and that one can efficiently resolve both immunosuppression and pathogenesis by timely coupling of antibiotics with an immune checkpoint blocker, but not by either one of these two treatment modalities alone. Following experimental validation, our model can be adapted to explore the potential of other therapeutic options in this field. [ABSTRACT FROM AUTHOR]

The demographic shift, together with financial constraint, justify a re-evaluation of the trajectory of care of very old critically ill patients (VIP), defined as older than 80 years. We must avoid over- as well as under-utilisation of critical care interventions in this patient group and ensure the inclusion of health care professionals, the patient and their caregivers in the decision process. This new integrative approach mobilises expertise at each step of the process beginning prior to intensive care unit (ICU) admission and extending to long-term follow-up. In this review, several international experts have contributed to provide recommendations that can be universally applied. Our aim is to define a minimum core dataset of information to be shared and discussed prior to ICU admission and to facilitate the shared-decision-making process with the patient and their caregivers, throughout the patient journey. Documentation of uncertainty may contribute to a tailored level of care and ultimately to discussions around possible limitations of life sustaining treatments. The goal of ICU care is not only to avoid death, but more importantly to maintain an acceptable quality of life and functional autonomy after hospital discharge. Societal consideration is important to highlight, together with alternatives to ICU admission. We discuss challenges for the future and potential areas of research. In summary, this review provides a state-of-the-art current overview and aims to outline future directions to address the challenges in the treatment of VIP. [ABSTRACT FROM AUTHOR]

Background: Non-invasive ventilation (NIV) has been commonly used to treat acute respiratory failure due to COVID-19. In this study we aimed to compare outcomes of older critically ill patients treated with NIV before and during the COVID-19 pandemic. Methods: We analysed a merged cohort of older adults admitted to intensive care units (ICUs) due to respiratory failure. Patients were enrolled into one of two prospective observational studies: before COVID-19 (VIP2—2018 to 2019) and admitted due to COVID-19 (COVIP—March 2020 to January 2023). The outcomes included: 30-day mortality, intubation rate and NIV failure (death or intubation within 30 days). Results: The final cohort included 1986 patients (1292 from VIP2, 694 from COVIP) with a median age of 83 years. NIV was used as a primary mode of respiratory support in 697 participants (35.1%). ICU admission due to COVID-19 was associated with an increased 30-day mortality (65.5% vs. 36.5%, HR 2.18, 95% CI 1.71 to 2.77), more frequent intubation (36.9% vs. 17.5%, OR 2.63, 95% CI 1.74 to 3.99) and NIV failure (76.2% vs. 45.3%, OR 4.21, 95% CI 2.84 to 6.34) compared to non-COVID causes of respiratory failure. Sensitivity analysis after exclusion of patients in whom life supporting treatment limitation was introduced during primary NIV confirmed higher 30-day mortality in patients with COVID-19 (52.5% vs. 23.4%, HR 2.64, 95% CI 1.83 to 3.80). Conclusion: The outcomes of patients aged ≥80 years treated with NIV during COVID-19 pandemic were worse compared then those treated with NIV in the pre-pandemic era. [ABSTRACT FROM AUTHOR]

In this narrative review, we describe the most important age-related "syndromes" found in the old ICU patients. The syndromes are frailty, comorbidity, cognitive decline, malnutrition, sarcopenia, loss of functional autonomy, immunosenescence and inflam-ageing. The underlying geriatric condition, together with the admission diagnosis and the acute severity contribute to the short-term, but also to the long-term prognosis. Besides mortality, functional status and quality of life are major outcome variables. The geriatric assessment is a key tool for long-term qualitative outcome, while immediate severity accounts for acute mortality. A poor functional baseline reduces the chances of a successful outcome following ICU. This review emphasises the importance of using a geriatric assessment and considering the older patient as a whole, rather than the acute illness in isolation, when making decisions regarding intensive care treatment. [ABSTRACT FROM AUTHOR]

Background: Limiting life-sustaining treatment (LST) in the intensive care unit (ICU) by withholding or withdrawing interventional therapies is considered appropriate if there is no expectation of beneficial outcome. Prognostication for very old patients is challenging due to the substantial biological and functional heterogeneity in that group. We have previously identified seven phenotypes in that cohort with distinct patterns of acute and geriatric characteristics. This study investigates the relationship between these phenotypes and decisions to limit LST in the ICU. Methods: This study is a post hoc analysis of the prospective observational VIP2 study in patients aged 80 years or older admitted to ICUs in 22 countries. The VIP2 study documented demographic, acute and geriatric characteristics as well as organ support and decisions to limit LST in the ICU. Phenotypes were identified by clustering analysis of admission characteristics. Patients who were assigned to one of seven phenotypes (n = 1268) were analysed with regard to limitations of LST. Results: The incidence of decisions to withhold or withdraw LST was 26.5% and 8.1%, respectively. The two phenotypes describing patients with prominent geriatric features and a phenotype representing the oldest old patients with low severity of the critical condition had the largest odds for withholding decisions. The discriminatory performance of logistic regression models in predicting limitations of LST after admission to the ICU was the best after combining phenotype, ventilatory support and country as independent variables. Conclusions: Clinical phenotypes on ICU admission predict limitations of LST in the context of cultural norms (country). These findings can guide further research into biases and preferences involved in the decision-making about LST. Trial registration Clinical Trials NCT03370692 registered on 12 December 2017. [ABSTRACT FROM AUTHOR]

BACKGROUND: COVID-19 is associated with cytokine release in critical disease states. Thus, cytokine absorption has been proposed as a therapeutic option. This study investigated the influence of cytokine absorption on mortality in old critical patients with COVID-19 and renal failure admitted to intensive care units (ICU). METHODS: This retrospective analysis of a prospective international observation study (the COVIP study) analysed ICU patients≥70 years with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, clinical frailty scale (CFS), ICU therapy details including renal replacement therapy (RRT) with/without cytokine absorption were collected. The cytokine absorption group was compared to patients receiving RRT without cytokine absorption RESULTS: Among 3927 patients, 503 received RRT; among them 47 patients were treated with cytokine absorption. Mortality rates were high in both groups with increased rates in the cytokine group for ICU mortality and 30-day mortality, but not for 3-month mortality. Logistic regression analysis indicated that SOFA-score, but not cytokine absorption was associated with mortality. CONCLUSIONS: Critical COVID-19 patients with renal failure treated with cytokine absorption showed higher short term mortality rates when compared to patients with renal replacement therapy alone. Mortality is associated with disease severity, but not cytokine absorption in a multivariate analysis. [ABSTRACT FROM AUTHOR]

Aims: Anemia is common in the old and often observed in critically ill patients. Increased age is associated with higher mortality following a COVID-19 infection, making old patients prone to poor outcomes. We investigated whether anemia at admission to the ICU or the need for blood transfusion was associated with 90-day mortality in older, critically ill COVID-19 patients. Methods: In this prospective multicenter study, the 90-day mortality of COVID-19 patients≥70 years treated in 138 intensive care units (ICU) was analyzed. Associations between anemia (WHO definition) at admission and discharge from ICU and the use of red blood cell (RBC) transfusions with mortality were assessed. Hemoglobin thresholds of RBC transfusions in old, critically ill COVID-19 patients were recorded. Results: In 493 patients (350 anemic, 143 non-anemic), anemia (WHO definition) at the time of ICU admission was not associated with impaired overall survival. Transfusion and severe anemia (hemoglobin≤10 g/dL) at ICU discharge were independently associated with a higher risk of 90-day mortality. Conclusion: The need for red blood cell transfusions and severe anemia at ICU discharge, but not at the timepoint of admission, were independently associated with 90-day mortality in critically-ill old COVID-19 patients. [ABSTRACT FROM AUTHOR]

An early paper about frailty in the intensive care unit (ICU) context was published in 2014 [[2]] and frailty has since attained considerable attraction and has been found to be closely related to an adverse outcome after ICU admissions [[3]]. 2021; 11: 22. 10.1186/s13613-021-00815-7 12 Bruno RR, Wernly B, Flaatten H, Scholzel F, Kelm M, Jung C. The hospital frailty risk score is of limited value in intensive care unit patients. 1 Frailty assessment in the ICU In summary, frailty should be evaluated in clinical practice in old ICU patients. In that study 42% of acutely admitted patients developed increased frailty measured with the Clinical Frailty Scale (CFS) after one year, but many patients (35%) also had also reduced frailty. [Extracted from the article]

Purpose: The biological and functional heterogeneity in very old patients constitutes a major challenge to prognostication and patient management in intensive care units (ICUs). In addition to the characteristics of acute diseases, geriatric conditions such as frailty, multimorbidity, cognitive impairment and functional disabilities were shown to influence outcome in that population. The goal of this study was to identify new and robust phenotypes based on the combination of these features to facilitate early outcome prediction. Methods: Patients aged 80 years old or older with and without limitations of life-sustaining treatment and with complete data were recruited from the VIP2 study for phenotyping and from the COVIP study for external validation. The sequential organ failure assessment (SOFA) score and its sub-scores taken on admission to ICU as well as demographic and geriatric patient characteristics were subjected to clustering analysis. Phenotypes were identified after repeated bootstrapping and clustering runs. Results: In patients from the VIP2 study without limitations of life-sustaining treatment (n = 1977), ICU mortality was 12% and 30-day mortality 19%. Seven phenotypes with distinct profiles of acute and geriatric characteristics were identified in that cohort. Phenotype-specific mortality within 30 days ranged from 3 to 57%. Among the patients assigned to a phenotype with pronounced geriatric features and high SOFA scores, 50% died in ICU and 57% within 30 days. Mortality differences between phenotypes were confirmed in the COVIP study cohort (n = 280). Conclusions: Phenotyping of very old patients on admission to ICU revealed new phenotypes with different mortality and potential need for anticipatory intervention. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported regional differences in end‐of‐life care (EoLC) for critically ill patients in Europe. Objectives: The purpose of this post‐hoc analysis of the prospective multicentre COVIP study was to investigate variations in EoLC practices among older patients in intensive care units during the coronavirus disease 2019 pandemic. Methods: A total of 3105 critically ill patients aged 70 years and older were enrolled in this study (Central Europe: n = 1573; Northern Europe: n = 821; Southern Europe: n = 711). Generalised estimation equations were used to calculate adjusted odds ratios (aORs) to population averages. Data were adjusted for patient‐specific variables (demographic, disease‐specific) and health economic data (gross domestic product, health expenditure per capita). The primary outcome was any treatment limitation, and 90‐day mortality was a secondary outcome. Results: The frequency of the primary endpoint (treatment limitation) was highest in Northern Europe (48%), intermediate in Central Europe (39%) and lowest in Southern Europe (24%). The likelihood for treatment limitations was lower in Southern than in Central Europe (aOR 0.39; 95% confidence interval [CI] 0.21–0.73; p = 0.004), even after multivariable adjustment, whereas no statistically significant differences were observed between Northern and Central Europe (aOR 0.57; 95%CI 0.27–1.22; p = 0.15). After multivariable adjustment, no statistically relevant mortality differences were found between Northern and Central Europe (aOR 1.29; 95%CI 0.80–2.09; p = 0.30) or between Southern and Central Europe (aOR 1.07; 95%CI 0.66–1.73; p = 0.78). Conclusion: This study shows a north‐to‐south gradient in rates of treatment limitation in Europe, highlighting the heterogeneity of EoLC practices across countries. However, mortality rates were not affected by these results. [ABSTRACT FROM AUTHOR]