Search

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was

Abstract Background Mental health symptoms among healthcare professionals (HCP) in intensive care units (ICUs) are a significant concern affecting both HCP well-being and patient care outcomes. Cross-sectional studies among members of the European Society of Intensive Care Medicine (ESICM) report up to 50% burnout rates. Determinants of burnout include communication, team cohesion, psychological support, and well-being promotion. We designed the 'Hello Bundle' intervention to mitigate burnout among ICU-HCPs by fostering positive social interactions and a supportive work environment. This justification synthesizes evidence from social psychology, positive psychology, and healthcare communication research to support the intervention. The 'Hello Bundle' aims to enhance interpersonal relationships, improve team cohesion, and reduce burnout rates. The six components include: Hello campaign posters, email reminders, integrating greetings in morning huddles, hello jars, lead-by-example initiatives, and a daily updated hello board in each ICU. This protocol describes a cluster randomized controlled trial to evaluate the effectiveness of the intervention. Methods This protocol describes a cluster randomized controlled trial (RCT) conducted among ESICM-affiliated ICUs, consisting of at least 73 clusters with in average of 50 respondents per cluster, totaling approximately 7300 participants. Intervention clusters will implement the 6-component Hello Bundle between October 14 and November 10, 2024, while control clusters will be wait-listed to receive the intervention in January 2025 after the RCT concludes. Clusters will be matched based on ICU size (fewer or more than 20 beds), region, and average 2023 mortality. The primary outcome is the proportion of HCPs with burnout between intervention and control clusters at the end of the intervention. Secondary outcomes include comparing the following between clusters: (1) number of HCPs with high emotional exhaustion; (2) number with high depersonalization; (3) number with loss of accomplishment; (4) perception of ethical climate (5) satisfaction at work (VAS); (6) professional conflicts; (7) intention to leave the ICU (VAS); (8) patient-centered care rating; (9) family-centered care rating. The last secondary outcome is the comparison of burnout rates before and after the intervention in the intervention cluster. Outcomes will be based on HCP reports collected within four weeks before and after the intervention. Discussion This is the first large trial of healthcare communication, social, and positive psychology intervention among ICU-HCPs. It holds the potential to provide valuable insights into effective strategies for addressing burnout in ICU settings, ultimately benefiting both HCPs and patients. Trial registration: This trial was registered on ClinicalTrials.Gov on June 18, 2024. Registration: NCT06453616.

The Fourth Cell Stress Society International workshop on small heat shock proteins (sHSPs), a follow-up to successful workshops held in 2014, 2016 and 2018, took place as a virtual meeting on the 17-18 November 2022. The meeting was designed to provide an opportunity for those working on sHSPs to reconnect and discuss their latest work. The diversity of research in the sHSP field is reflected in the breadth of topics covered in the talks presented at this meeting. Here we summarise the presentations at this meeting and provide some perspectives on exciting future topics to be addressed in the field.

Abstract Background Fluid administration is the first line treatment in intensive care unit (ICU) patients with sepsis and septic shock. While fluid boluses administration can be titrated by predicting preload dependency, the amount of other forms of fluids may be more complex to be evaluated. We conducted a retrospective analysis in a tertiary hospital, to assess the ratio between fluids given as boluses and total administered fluid intake during early phases of ICU stay, and to evaluate the impact of fluid strategy on ICU mortality. Data related to fluid administration during the first four days of ICU stay were exported from an electronic health records system (ICCA®, Philips Healthcare). Demographic data, severity score, norepinephrine dose at ICU admission, overall fluid balance and the percentage of different fluid components of the overall volume administered were included in a multivariable logistic regression model, evaluating the association with ICU survival. Results We analyzed 220 patients admitted with septic shock and sepsis-induced hypotension from 1st July 2021 to 31st December 2023. Fluid boluses and maintenance represented 49.3% ± 22.8 of the overall fluid intake, being balanced solution the most represented (40.4% ± 22.0). The fluid volume for drug infusion represented 34.0% ± 2.9 of the total fluid intake, while oral or via nasogastric tube fluid intake represented 18.0% ± 15.7 of the total fluid intake. Fluid volume given as boluses represented 8.6% of the total fluid intake over the four days, with a reduction from 25.1% ± 24.0 on Day 1 to 4.8% ± 8.7 on Day 4. A positive fluid balance [OR 1.167 (1.029–1.341); p = 0.021] was the most important factor associated with ICU mortality. Non-survivors (n = 66; 30%) received a higher amount of overall inputs than survivors only on Day 1 [2493 mL vs. 1855 mL; p = 0.022]. Conclusions This retrospective analysis of fluids given over the early phases of septic shock and sepsis-induced hypotension showed that the overall volume given by boluses ranges from about 25% on Day 1 to about 5% on Day 4 from ICU admission. Our data confirms that a positive fluid balance over the first 4 days of ICU is associated with mortality.

Abstract Background Value-based healthcare (VBHC) is an approach that focuses on delivering the highest possible value for patients while driving cost efficiency in health services. It emphasizes improving patient outcomes and experiences while optimizing the use of resources, shifting the healthcare system’s focus from the volume of services to the value delivered. Our study assessed the effectiveness of implementing a VBHC-principled, tailored preoperative evaluation in enhancing patient care and outcomes, as well as reducing healthcare costs. Methods We employed a quality improvement, before-and-after approach to assessing the effects of implementing VBHC strategies on the restructuring of the preoperative evaluation clinics at Humanitas Research Hospital. The intervention introduced a VBHC-tailored risk matrix during the postintervention phase (year 2021), and the results were compared with those of the preintervention phase (2019). The primary study outcome was the difference in the number of preoperative tests and visits at baseline and after the VBHC approach. Secondary outcomes were patient outcomes and costs. Results A total of 9722 patients were included: 5242 during 2019 (baseline) and 4,480 during 2021 (VBHC approach). The median age of the population was 63 (IQR 51–72), 23% of patients were classified as ASA 3 and 4, and 26.8% (2,955 cases) were day surgery cases. We found a considerable decrease in the number of preoperative tests ordered for each patient [6.2 (2.5) vs 5.3 (2.6) tests, p

Variability in disease onset and progression is a hallmark of amyotrophic lateral sclerosis (ALS), both in sporadic and genetic forms. Recently, we found that SOD1-G93A transgenic mice expressing the same amount of mutant SOD1 but with different genetic backgrounds, C57BL/6JOlaHsd and 129S2/SvHsd, show slow and rapid muscle wasting and disease progression, respectively. Here, we investigated the different molecular mechanisms underlying muscle atrophy. Although both strains showed similar denervation-induced degradation of muscle proteins, only the rapidly progressing mice exhibited early and sustained STAT3 activation that preceded atrophy in gastrocnemius muscle. We therefore investigated the therapeutic potential of sunitinib, a tyrosine kinase inhibitor known to inhibit STAT3 and prevent cancer-induced muscle wasting. Although sunitinib treatment reduced STAT3 activation in the gastrocnemius muscle and lumbar spinal cord, it did not preserve spinal motor neurons, improve neuromuscular impairment, muscle atrophy and disease progression in the rapidly progressing SOD1-G93A mice. Thus, the effect of sunitinib is not equally positive in different diseases associated with muscle wasting. Moreover, given the complex role of STAT3 in the peripheral and central compartments of the neuromuscular system, the present study suggests that its broad inhibition may lead to opposing effects, ultimately preventing a potential positive therapeutic action in ALS.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

Abstract Purpose To identify key components and variations in family-centered care practices. Methods A cross-sectional study, conducted across ESICM members. Participating ICUs completed a questionnaire covering general ICU characteristics, visitation policies, team-family interactions, and end-of-life decision-making. The primary outcome, self-rated family-centeredness, was assessed using a visual analog scale. Additionally, respondents completed the Maslach Burnout Inventory and the Ethical Decision Making Climate Questionnaire to capture burnout dimensions and assess the ethical decision-making climate. Results The response rate was 53% (respondents from 359/683 invited ICUs who actually open the email); participating healthcare professionals (HCPs) were from Europe (62%), Asia (9%), South America (6%), North America (5%), Middle East (4%), and Australia/New Zealand (4%). The importance of family-centeredness was ranked high, median 7 (IQR 6–8) of 10 on VAS. Significant differences were observed across quartiles of family centeredness, including in visitation policies availability of a waiting rooms, family rooms, family information leaflet, visiting hours, night visits, sleep in the ICU, and in team-family interactions, including daily information, routine day-3 conference, and willingness to empower nurses and relatives. Higher family centeredness correlated with family involvement in rounds, participation in patient care and end-of-life practices. Burnout symptoms (41% of respondents) were negatively associated with family-centeredness. Ethical climate and willingness to empower nurses were independent predictors of family centeredness. Conclusions This study emphasizes the need to prioritize healthcare providers’ mental health for enhanced family-centered care. Further research is warranted to assess the impact of improving the ethical climate on family-centeredness.

Auroral kilometric radiation (AKR) is a terrestrial radio emission excited by the same accelerated electrons which excite auroral emissions. Although it is well correlated with auroral and geomagnetic activity, the coupling timescales between AKR and different magnetospheric or ionospheric regions have yet to be determined. Estimation of these coupling timescales is non-trivial as a result of complex, non-linear processes which rarely occur in isolation. In this study, the mutual information between AKR intensity and different geomagnetic indices is used to assess the correlation between variables. Indices are shifted to different temporal lags relative to AKR intensity, and the lag at which the variables have the most shared information is found. This lag is interpreted as the coupling timescale. The AKR source region receives the effects of a shared driver before the auroral ionosphere. Conversely, the polar ionosphere reacts to a shared driver before the AKR source region. Bow shock interplanetary magnetic field BZ is excited about 1 h before AKR enhancements. This work provides quantitatively determined temporal context to the coupling timelines at Earth. The results suggest that there is a sequence of excitation following the onset of a shared driver: first, the polar ionosphere feels the effects, followed by the AKR source region and then the auroral ionosphere.

Abstract Background Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. Methods Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted over a 6 months period to an ICU between May 2018 and May 2019. Only emergency (acute) ICU admissions in adult patients ≥ 80 years of age were eligible. Patients who were admitted after planned/elective surgery were excluded. We measured the Clinical Frailty Scale (CFS), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), disability with the Katz activities of daily living (ADL) score, comorbidities and a Polypharmacy Score (CPS). Results Overall, the VIP2 study included 3920 patients. During ICU stay 1191 patients died (30.9%), and another 436 patients (11.1%) died after ICU discharge but within the first 30 days of admission, and an additional 895 patients died hereafter but within the first 6 months after admission (22.8%). The 6 months mortality was 64%. The median CFS was 4 (IQR 3–6). Frailty (CFS ≥ 5) was present in 26.6%. Cognitive decline (IQCODE above 3.5) was found in 30.2%. The median IQCODE was 3.19. A Katz ADL of 4 or less was present in 27.7%. Patients who surviving > 6 months were slightly younger (median age survivors 84 with IQR 81–86) than patients dying within the first 6 months (median age 84, IQR 82–87, p = 0.013), were less frequently frail (CFS > 5 in 19% versus 34%, p

Abstract Saturn Kilometric Radiation (SKR), being the dominant radio emission at Saturn, has been extensively investigated. The low‐frequency extension of SKR is of particular interest due to its strong association with Saturn's magnetospheric dynamics. However, the highly anisotropic beaming of SKR poses challenges for observations. In most cases, the propagation of SKR is assumed to follow straight‐line paths. We explore the propagation characteristics of SKR across different frequencies in this study. An extended equatorial shadow region for low‐frequency SKR is identified, resulting from the merging of the Enceladus plasma torus and the previously known equatorial shadow zone. Ray‐tracing simulations reveal that low‐frequency (≲100 kHz) SKR is unable to enter the shadow region and is instead reflected toward high latitudes. In contrast, high‐frequency SKR (≳100 kHz) generally propagates without hindrance. Observations suggest that some low‐frequency SKR can enter the shadow region through reflection by the magnetosheath or leakage from the plasma torus.

Introduction Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting.Methods and analysis The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status—distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality.Ethics and dissemination This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences.Trial registration number NCT05379413.

Solar radio spikes are short lived, narrow bandwidth features in low frequency solar radio observations. The timing of their occurrence and the number of spikes in a given observation is often unpredictable. The high temporal and frequency of resolution of modern radio telescopes such as NenuFAR mean that manually identifying radio spikes is an arduous task. Machine learning approaches to data exploration in solar radio data is on the rise. Here we describe a convolutional neural network to identify the per pixel location of radio spikes as well as determine some simple characteristics of duration, spectral width and drift rate. The model, which we call SpikeNet, was trained using an Nvidia Tesla T4 16GB GPU with ~100000 sample spikes in a total time of 2.2 hours. The segmentation performs well with an intersection over union in the test set of ~0.85. The root mean squared error for predicted spike properties is of the order of 23%. Applying the algorithm to unlabelled data successfully generates segmentation masks although the accuracy of the predicted properties is less reliable, particularly when more than one spike is present in the same 64 X 64 pixel time-frequency range. We have successfully demonstrated that our convolutional neural network can locate and characterise solar radio spikes in a number of seconds compared to the weeks it would take for manual identification.

Abstract Background Blood pressure has become one of the most important vital signs to monitor in the perioperative setting. Recently, the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) recommended, with low level of evidence, continuous monitoring of blood pressure during the intraoperative period. Continuous monitoring allows for early detection of hypotension, which may potentially lead to a timely treatment. Whether the ability to detect more hypotension events by continuous noninvasive blood pressure (C-NiBP) monitoring can improve patient outcomes is still unclear. Here, we report the rationale, study design, and statistical analysis plan of the niMON trial, which aims to evaluate the effect of intraoperative C-NiBP compared with intermittent (I-NiBP) monitoring on postoperative myocardial and renal injury. Methods The niMon trial is an investigator-initiated, multicenter, international, open-label, parallel-group, randomized clinical trial. Eligible patients will be randomized in a 1:1 ratio to receive C-NiBP or I-NiBP as an intraoperative monitoring strategy. The proportion of patients who develop myocardial injury in the first postoperative week is the primary outcome; the secondary outcomes are the proportions of patients who develop postoperative AKI, in-hospital mortality rate, and 30 and 90 postoperative days events. A sample size of 1265 patients will provide a power of 80% to detect a 4% absolute reduction in the rate of the primary outcome. Conclusions The niMON data will provide evidence to guide the choice of the most appropriate intraoperative blood pressure monitoring strategy. Clinical trial registration Clinical Trial Registration: NCT05496322, registered on the 5th of August 2023.

Abstract Background The intraoperative period is often characterized by hemodynamic instability, and intraoperative hypotension is a common complication. The optimal mean arterial pressure (MAP) target in hypertensive patients is still not clear. We hereby describe the protocol and detailed statistical analysis plan for the high versus standard blood pressure target in hypertensive high-risk patients undergoing elective major abdominal surgery: the HISTAP randomized clinical trial. The HISTAP trial aims at addressing whether the use of a higher intraoperative MAP target in high-risk hypertensive surgical patients scheduled for elective abdominal surgery would improve postoperative outcomes, as compared to the standard and recommended perioperative MAP, by using a composite outcome including a 30-day mortality from surgical intervention and at least one major organ dysfunction or new onset of sepsis and septic shock occurring 7 days after surgery. Methods The HISTAP trial is an investigator-initiated, pragmatic, parallel-grouped, randomized, stratified, analyst-blinded trial with adequate allocation sequence generation, and allocation concealment. We will allocate 636 patients to a MAP target ≥ 80 mmHg (treatment group) or to a MAP target ≥65 mmHg (control group). The primary outcome is a composite outcome including a 30-day mortality from the operation and major organ complications. Secondary outcomes are mortality at 30 days, intensive care unit (ICU) length of stay, ICU readmission, Sequential Organ Failure Assessment (SOFA) scores recorded up to postoperative day 7, overall intraoperative fluid balance, vasopressors use, and the need for reoperation. An unadjusted χ 2 test will be used for the primary outcome analysis. A Cox proportional hazards model will be used to adjust the association between the primary outcome and baseline covariates. Conclusions The HISTAP trial results will provide important evidence to guide clinicians’ choice regarding the intraoperative MAP target in high-risk hypertensive patients scheduled for elective abdominal surgery.