Monitoring, management, and outcome of hypotension in Intensive Care Unit patients, an international survey of the European Society of Intensive Care Medicine

INTRODUCTION: Hypotension in the ICU is common, yet management is challenging and variable. Insight in management by ICU physicians and nurses may improve patient care and guide future hypotension treatment trials and guidelines. METHODS: We conducted an international survey among ICU personnel to provide insight in monitoring, management, and perceived consequences of hypotension. RESULTS: Out of 1464 respondents, 1197 (81.7%) were included (928 physicians (77.5%) and 269 nurses (22.5%)). The majority indicated that hypotension is underdiagnosed (55.4%) and largely preventable (58.8%). Nurses are primarily in charge of monitoring changes in blood pressure, physicians are in charge of hypotension treatment. Balanced crystalloids, dobutamine, norepinephrine, and Trendelenburg position were the most frequently reported fluid, inotrope, vasopressor, and positional maneuver used to treat hypotension. Reported complications believed to be related to hypotension were AKI and myocardial injury. Most ICUs do not have a specific hypotension treatment guideline or protocol (70.6%), but the majority would like to have one in the future (58.1%). CONCLUSIONS: Both physicians and nurses report that hypotension in ICU patients is underdiagnosed, preventable, and believe that hypotension influences morbidity. Hypotension management is generally not protocolized, but the majority of respondents would like to have a specific hypotension management protocol

Definition and incidence of hypotension in intensive care unit patients, an international survey of the European Society of Intensive Care Medicine

Introduction: Although hypotension in ICU patients is associated with adverse outcome, currently used definitions are unknown and no universally accepted definition exists. Methods: We conducted an international, peer-reviewed survey among ICU physicians and nurses to provide insight in currently used definitions, estimations of incidence, and duration of hypotension. Results: Out of 1394 respondents (1055 physicians (76%) and 339 nurses (24%)), 1207 (82%) completed the questionnaire. In all patient categories, hypotension definitions were predominantly based on an absolute MAP of 65 mmHg, except for the neuro(trauma) category (75 mmHg, p &lt; 0.001), without differences between answers from physicians and nurses. Hypotension incidence was estimated at 55%, and time per day spent in hypotension at 15%, both with nurses reporting higher percentages than physicians (estimated mean difference 5%, p = 0.01; and 4%, p &lt; 0.001). Conclusions: An absolute MAP threshold of 65 mmHg is most frequently used to define hypotension in ICU patients. In neuro(trauma) patients a higher threshold was reported. The majority of ICU patients are estimated to endure hypotension during their ICU admission for a considerable amount of time, with nurses reporting a higher estimated incidence and time spent in hypotension than physicians.</p

Analytical model of interwoven spiral arrays

We present C2–C6 nonmethane hydrocarbon (NMHC) measurements from canister samples obtained in the extratropical lower stratosphere during the fall (November/December 1995), winter (March 1997), and summer seasons (July 1998) as part of the stratosphere‐troposphere experiments by aircraft measurements campaign. The flights were carried out from Amsterdam (Netherlands, 52°N, 4.5°E) during fall, from Kiruna (Sweden, 68°N, 20°E) during winter, and from Timmins (Canada, 48.2°N, 70.3°W) during summer. The NMHC measurements have been evaluated along with concurrent in situ measurements of acetone (CH3COCH3), CO, O3, N2O, and CFC‐12 (CCl2F2). The vertical distributions of NMHC and acetone as a function of O3 and potential temperature in the lowermost stratosphere show a strong seasonality. Enhanced concentrations of NMHC + CH3COCH3 were found during July up to potential temperatures of Θ = 370 K, whereas during March this was limited to Θ = 340 K, in agreement with stronger isentropic cross‐tropopause transport during summer. Increasing methyl chloride (CH3Cl) concentrations with altitude were measured during July, pointing to mixing at the subtropical tropopause. During summer and fall, mean NMHC + acetone concentrations were more than a factor of 2 higher than that during winter. Box model calculations indicate that the observed acetone levels of 0.5–1 ppbv can explain 30–50% of the enhanced OH radical concentrations in the summertime lowermost stratosphere. Using mass balance calculations, we show that a significant tropospheric fraction (≤30%) was present up to Θ = 370 K in the summertime lowermost stratosphere. During winter, the tropospheric fraction approached zero at about Θ = 350 K. The time between selected troposphere‐to‐stratosphere mixing events and the aircraft measurements has been estimated at 3–14 days. Our results emphasize that isentropic cross‐tropopause transport can be a fast process occurring on timescales of days to weeks

The "sex gap" in COVID-19 trials: a scoping review

Contains fulltext : 229328.pdf (publisher's version ) (Open Access)BACKGROUND: Many studies investigate the role of pharmacological treatments on disease course in Corona Virus Disease 2019 (COVID-19). Sex disparities in genetics, immunological responses, and hormonal mechanisms may underlie the substantially higher fatality rates reported in male COVID-19 patients. To optimise care for COVID-19 patients, prophylactic and therapeutic studies should include sex-specific design and analyses. Therefore, in this scoping review, we investigated whether studies on pharmacological treatment in COVID-19 were performed based on a priori sex-specific design or post-hoc sex-specific analyses. METHODS: We systematically searched PubMed, EMBASE, UpToDate, clinical trial.org, and MedRxiv for studies on pharmacological treatment for COVID-19 until June 6th, 2020. We included case series, randomized controlled trials, and observational studies in humans (≥18 years) investigating antiviral, antimalarial, and immune system modulating drugs. Data were collected on 1) the proportion of included females, 2) whether sex stratification was performed (a priori by design or post-hoc), and 3) whether effect modification by sex was investigated. FINDINGS: 30 studies were eligible for inclusion, investigating remdesivir (n = 2), lopinavir/ritonavir (n = 5), favipiravir (n = 1), umifenovir (n = 1), hydroxychloroquine/chloroquine (n = 8), convalescent plasma (n = 6), interleukin-6 (IL-6) pathway inhibitors (n = 5), interleukin-1 (IL-1) pathway inhibitors (n = 1) and corticosteroids (n = 3). Only one study stratified its data based on sex in a post-hoc analysis, whereas none did a priori by design. None of the studies investigated effect modification by sex. A quarter of the studies included twice as many males as females. INTERPRETATION: Analyses assessing potential interference of sex with (side-)effects of pharmacological therapy for COVID-19 are rarely reported. Considering sex differences in case-fatality rates and genetic, immunological, and hormonal mechanisms, studies should include sex-specific analyses in their design to optimise COVID-19 care. FUNDING: None

Better COVID-19 Intensive Care Unit survival in females, independent of age, disease severity, comorbidities, and treatment

Although male Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients have higher Intensive Care Unit (ICU) admission rates and a worse disease course, a comprehensive analysis of female and male ICU survival and underlying factors such as comorbidities, risk factors, and/or anti-infection/inflammatory therapy administration is currently lacking. Therefore, we investigated the association between sex and ICU survival, adjusting for these and other variables. In this multicenter observational cohort study, all patients with SARS-CoV-2 pneumonia admitted to seven ICUs in one region across Belgium, The Netherlands, and Germany, and requiring vital organ support during the first pandemic wave were included. With a random intercept for a center, mixed-effects logistic regression was used to investigate the association between sex and ICU survival. Models were adjusted for age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, comorbidities, and anti-infection/inflammatory therapy. Interaction terms were added to investigate effect modifications by sex with country and sex with obesity. A total of 551 patients (29% were females) were included. Mean age was 65.4 +/- 11.2 years. Females were more often obese and smoked less frequently than males (p-value 0.001 and 0.042, respectively). APACHE II scores of females and males were comparable. Overall, ICU mortality was 12% lower in females than males (27% vs 39% respectively, p-value 0.23 and 0.84, respectively). ICU survival in female SARS-CoV-2 patients was higher than in male patients, independent of age, disease severity, smoking, obesity, comorbidities, anti-infection/inflammatory therapy, and country. Sex-specific biological mechanisms may play a role, emphasizing the need to address diversity, such as more sex-specific prediction, prognostic, and therapeutic approach strategies

Monitoring, management, and outcome of hypotension in Intensive Care Unit patients, an international survey of the European Society of Intensive Care Medicine

Introduction: Hypotension in the ICU is common, yet management is challenging and variable. Insight in management by ICU physicians and nurses may improve patient care and guide future hypotension treatment trials and guidelines. Methods: We conducted an international survey among ICU personnel to provide insight in monitoring, management, and perceived consequences of hypotension. Results: Out of 1464 respondents, 1197 (81.7%) were included (928 physicians (77.5%) and 269 nurses (22.5%)). The majority indicated that hypotension is underdiagnosed (55.4%) and largely preventable (58.8%). Nurses are primarily in charge of monitoring changes in blood pressure, physicians are in charge of hypotension treatment. Balanced crystalloids, dobutamine, norepinephrine, and Trendelenburg position were the most frequently reported fluid, inotrope, vasopressor, and positional maneuver used to treat hypotension. Reported complications believed to be related to hypotension were AKI and myocardial injury. Most ICUs do not have a specific hypotension treatment guideline or protocol (70.6%), but the majority would like to have one in the future (58.1%). Conclusions: Both physicians and nurses report that hypotension in ICU patients is underdiagnosed, preventable, and believe that hypotension influences morbidity. Hypotension management is generally not protocolized, but the majority of respondents would like to have a specific hypotension management protocol

Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRPα axis and a target for cancer immunotherapy

Cancer cells can evade immune surveillance through the expression of inhibitory ligands that bind their cognate receptors on immune effector cells. Expression of programmed death ligand 1 in tumor microenvironments is a major immune checkpoint for tumor-specific T cell responses as it binds to programmed cell death protein-1 on activated and dysfunctional T cells 1 . The activity of myeloid cells such as macrophages and neutrophils is likewise regulated by a balance between stimulatory and inhibitory signals. In particular, cell surface expression of the CD47 protein creates a ‘don’t eat me’ signal on tumor cells by binding to SIRPα expressed on myeloid cells 2–5 . Using a haploid genetic screen, we here identify glutaminyl-peptide cyclotransferase-like protein (QPCTL) as a major component of the CD47-SIRPα checkpoint. Biochemical analysis demonstrates that QPCTL is critical for pyroglutamate formation on CD47 at the SIRPα binding site shortly after biosynthesis. Genetic and pharmacological interference with QPCTL activity enhances antibody-dependent cellular phagocytosis and cellular cytotoxicity of tumor cells. Furthermore, interference with QPCTL expression leads to a major increase in neutrophil-mediated killing of tumor cells in vivo. These data identify QPCTL as a novel target to interfere with the CD47 pathway and thereby augment antibody therapy of cancer