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Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Abstract Background Intubation is a lifesaving procedure that is often performed in intensive care unit (ICU) patients, but leads to serious adverse events in 20–40% of cases. Recent trials aimed to provide guidance about which medications, devices, and modalities maximize patient safety. Videolaryngoscopes are being offered in an increasing range of options and used in broadening indications (from difficult to unremarkable intubation). The objective of this study was to describe intubation practices and device availability in French ICUs. Materials and methods We conducted an online nationwide survey by emailing an anonymous 26-item questionnaire to physicians in French ICUs. A single questionnaire was sent to either the head or the intubation expert at each ICU. Results Of 257 ICUs, 180 (70%) returned the completed questionnaire. The results showed that 43% of intubators were not fully proficient in intubation; among them, 18.8% had no intubation training or had received only basic training (lectures and observation at the bedside). Among the participating ICUs, 94.4% had a difficult intubation trolley, 74.5% an intubation protocol, 92.2% a capnography device (used routinely to check tube position in 69.3% of ICUs having the device), 91.6% a laryngeal mask, 97.2% front-of-neck access capabilities, and 76.6% a videolaryngoscope. In case of difficult intubation, 85.6% of ICUs used a bougie (154/180) and 7.8% switched to a videolaryngoscope (14/180). Use of a videolaryngoscope was reserved for difficult intubation in 84% of ICUs (154/180). Having a videolaryngoscope was significantly associated with having an intubation protocol (P = 0.043) and using capnography (P = 0.02). Airtraq® was the most often used videolaryngoscope (39.3%), followed by McGrath®Mac (36.9%) then by Glidescope® (14.5%). Conclusion Nearly half the intubators in French ICUs are not fully proficient with OTI. Access to modern training methods such as simulation is inadequate. Most ICUs own a videolaryngoscope, but reserve it for difficult intubations.

Metabolic studies using the in vitro non-recirculating blood-perfused isolated heart model require large volumes of blood. The present study was designed to determine whether heterologous pig blood collected from a slaughterhouse can be used as perfusate for isolated pig hearts perfused under aerobic and constant reduced flow conditions. Eight isolated working pig hearts perfused for 90 min at a constant flow of 1.5 ml g-1 min-1 with non-recirculated blood diluted with Krebs-Henseleit bicarbonate buffer at a hematocrit of 23% were compared to eight hearts subjected to the same protocol but perfused only with Krebs-Henseleit bicarbonate buffer solution. Hearts were paced at 100 bpm and subjected to aerobic perfusion at 38ºC. Hearts were weighed before perfusion and at the end of the experiment and the results are reported as percent weight gain (mean ± SD). Comparisons between groups were performed by the Student t-test (P

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Abstract  Atherosclerosis is a chronic inflammatory vascular disease. As it is an inflammation process, many cellular and molecular events are involved at each step of the progression of atherosclerosis from an early fatty streak lesion to a highly dangerous rupture-prone plaque. Magnetic resonance imaging (MRI) is a well-established diagnostic tool for many kinds of chronic inflammation in various systems and organs, and recent improvements in spatial resolution and contrast strategies make it a promising technique for the characterization of inflammatory vessel walls. The first part of this review will briefly introduce the main cellular and molecular processes involved in atherosclerotic lesions; the second part will focus on the use of high-resolution MRI and present-generation contrast agents for plaque characterization; and the third part will present some recent and ongoing cellular and molecular MRI studies of atherosclerosis. [ABSTRACT FROM AUTHOR]

Se determina la influencia que tienen los principales parámetros tecnológicos del borado en el crecimiento de las capas y secorrobora el cumplimiento de la ley parabólica para predecir este comportamiento en los aceros Y8A y X12M.El proceso de borado se aplica en una mezcla de carburo de silicio y bórax (70 y 30 %) a la temperatura de 850, 900 y 950 oCdurante un tiempo de 2, 4 y 6 horas. Como variable dependiente se seleccionó la profundidad del recubrimiento, a partir de lacual se obtuvieron los coeficientes del crecimiento parabólico y la energía de activación en función de la temperatura, el tiempodel proceso y el tipo de acero.La caracterización metalográfica reveló la presencia de la fase Fe2BPalabras claves: Borado, recubrimiento superf icial , t ecnología de recubrimiento.__________________________________________________________________________AbstractIt was determined the influence of the main technological parameters of the boriding process, and a mathematical model thatallows to predict this conduct on the steels Y8A and X12M steels was obtained.The boriding process is applied in a mixture of silicon carbide and borax (70 and 30%) at 850, 900 and 950 oC temperatureduring a period of time 2, 4 and 6 hours. As an independent variable the depth of the coat was selected.It was obtained the parabolic growth coefficients, and the activation energy according to temperature, time and the chemicalcomposition of steel.Metallografic analysis reveals the presence of Fe2B phase.Key words: Boriding process, superf icial coat , coat technology.

The effects on the dynamic pattern of egg weight of five traits at sexual maturity were characterized in Campero Casilda hens. When the first egg was laid, body weight, age (an indicator of sexual precocity), weight of the first 10 eggs (an indicator of their initial weight), days needed to lay them (an indicator of regularity) and coefficient of variation of these weights (an indicator of uniformity) were recorded. All the eggs laid between sexual maturity and 72 weeks of age was weighed. Longitudinal data relating weekly average egg weight versus laying age were adjusted by non-linear regression with the Weatherup & Foster model. Birds were categorized by the values of each trait measured at sexual maturity and the category effect on the estimators of the function parameters was evaluated. Less precocious birds were heavier and laid larger eggs at the beginning of the cycle and in the asymptote, without differences on the egg weight maturation rate, in comparison to those more precocious. The latter began the laying period irregularly, requiring a greater number of days to lay the first 10 eggs and the weight of these had a higher coefficient of variation. The birds that began laying more uniform eggs in weight maintained that difference throughout the curve. Early selection of birds that begin laying at an older age, with greater body weight, more regularly and with heavier eggs uniform in size would show a favorable dynamic pattern in egg weight. [ABSTRACT FROM AUTHOR]

ABSTRACT: The Campero-INTA chicken of Argentina was developed to provide a robust bird that can survive under Argentinian pasture conditions with no significant additional nutrition, producing a source of animal protein for small producers or low-income families. In previous work, we described the AH paternal line of Campero and its Major Histocompatibility Complex B region (MHC-B) variation. In this work we analyzed the three remaining synthetic lines used to produce the Campero-INTA production bird: lines AS, A, and E. Because of the association between variation within the MHC of chickens and disease resistance, MHC variation within this breed is of particular interest. MHC variability within the lines used to produce the Campero-INTA chicken was examined using a 90 SNP panel encompassing the chicken MHC-B region plus the VNTR, LEI0258, located within the chicken MHC. Across all 4lines 12 haplotypes were found, with 7 of these being previously reported in North America/European breeds, reflecting the original breed sources for these birds. Three Campero unique haplotypes were found, 2 of which likely originated from MHC recombination events. MHC-B variation for all lines involved with production of the final Campero-INTA bird has now been determined.

Objectives: We aimed to describe longitudinal functional outcome among survivors after an infectious encephalitis (IE) and to analyze risk factors for poor functional outcome., Methods: Patients included in the prospective ENCEIF cohort (France, 2016-2019) were followed-up at 6 months and one year after hospital discharge for assessment of i) functional outcome using modified Rankin scale (mRS); ii) cognitive function and abilities to perform activities of daily living. Risk factors for poor outcome on the full distribution of mRS were estimated using multivariable mixed ordinal regression analysis with time between hospital discharge and follow-up as a covariate., Results: Our follow-up study included 322 patients with 896 mRS evaluations. Median age was 66 [50-74] years, 197/322 were male (61%) and 35/322 were immunocompromised (11%). Causative agents were herpes simplex virus 1 (HSV-1) in 95/322 cases (30%), varicella zoster virus (VZV) in 46/322 cases (14%), others documented IE in 90/322 cases (28%) and unknown in 91/322 cases (28%). Intensive care unit (ICU) admission was necessary for 117/322 patients (36%). Brain imaging was abnormal in 180/311 (58%) of patients. At 6 months, 95/287 (33%) had fully recovered and 181/287 (63%) had persisting symptoms. At 12 months, 124/253 (49%) had fully recovered and 108/253 (43%) had persisting symptoms. The proportion of patients who improved was 41% (117/287) during the first 6 months, and 24% (52/218) between 6 and 12 months. Factors significantly associated with poor functional outcome were age, immunosuppression, ICU admission, abnormal brain imaging and causative agents, notably HSV-1. Follow-up visit during the first 120 days did not detect significant change in functional outcome, but was strongly associated with better outcome at the subsequent evaluation., Conclusions: After IE, improvement may take several months. Functional outcome is associated with baseline health status (age, immunosuppression), abnormal brain imaging, ICU admission, and causative agent., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Rationale: Allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) recipients are still believed to be poor candidates for ICU management. Methods: We investigated outcomes and determinants of mortality in a large multicenter retrospective cohort of Allo-HSCT patients admitted between January 1, 2015, and December 31, 2020, to 14 French ICUs. The primary endpoint was 90-day mortality. Measurements and Main Results: In total, 1,164 patients were admitted throughout the study period. At the time of ICU admission, 765 (66%) patients presented with multiple organ dysfunction, including acute respiratory failure in 40% ( n  = 461). The median sepsis-related organ failure assessment score was 6 (interquartile range, 4-8). Invasive mechanical ventilation, renal replacement therapy, and vasopressors were required in 438 (38%), 221 (19%), and 468 (41%) patients, respectively. ICU mortality was 26% (302 deaths). Ninety-day, 1-year, and 3-year mortality rates were 48%, 63%, and 70%, respectively. By multivariable analysis, age > 56 years (odds ratio [OR], 2.0 [95% confidence interval (CI), 1.53-2.60]; P  < 0.001), time from Allo-HSCT to ICU admission between 30 and 90 days (OR, 1.68 [95% CI, 1.17-2.40]; P  = 0.005), corticosteroid-refractory acute graft-versus-host disease (OR, 1.63 [95% CI, 1.38-1.93]; P  < 0.001), need for vasopressors (OR, 1.9 [95% CI, 1.42-2.55]; P  < 0.001), and mechanical ventilation (OR, 3.1 [95% CI, 2.29-4.18]; P  < 0.001) were independently associated with 90-day mortality. In patients requiring mechanical ventilation, mortality rates ranged from 39% (no other risk factors for mortality) to 100% (four associated risk factors for mortality). Conclusions: Most critically ill Allo-HSCT recipients survive their ICU stays, including those requiring mechanical ventilation, with an overall 90-day survival rate reaching 51.8%. A careful assessment of goals of care is required in patients with two or more risk factors for mortality.

Purpose: To identify the predictors and outcomes of ICU triage decisions in patients with solid malignancies (SM) and to investigate the usefulness of the National Early Warning Score (NEWS) and quick Sequential Organ Failure Assessment (qSOFA) score at triage., Methods: All patients with SM for whom ICU admission was requested between July 2019 and December 2021 in a French university-affiliated hospital were included prospectively., Results: Of the 6262 patients considered for ICU admission, 410 (6.5%) had SM (age, 66 [58-73] years; metastases, 60.1%; and performance status 0-2, 81%). Of these 410 patients, 176 (42.9%) were admitted to the ICU, including 141 (80.1%) subsequently discharged alive. Breast cancer, hemoptysis, and pneumothorax were associated with ICU admission; whereas older age, performance status 3-4, metastatic disease, and request at night were associated with denial of ICU admission. The NEWS, and the qSOFA score in patients with suspected infection, determined at triage performed poorly for predicting hospital mortality (area under the receiver operating characteristics curve, 0.52 and 0.62, respectively). Performance status 3-4 was independently associated with higher 6-month mortality and first-line anticancer treatment with lower 6-month mortality. Hospital mortality was 33.3% in patients admitted to the ICU after refusal of the first request., Conclusion: Patients with SM were frequently denied ICU admission despite excellent in-ICU survival. Poor performance status was associated with ICU admission denial and higher 6-month mortality, but none of the other reasons for denying ICU admission predicted 6-month mortality. Physiological scores had limited usefulness in this setting., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. G. reports receipt of nonfinancial support from Gilead Sciences, MSD, and Pfizer outside the submitted work. F. R. reports receipt of personal fees from AbbVie, AstraZeneca, Gilead Sciences, Janssen, Merck, Roche, and ViiV Healthcare outside the submitted work. E. C. reports personal fees from GILEAD, SANOFI-GENZYME, and BAXTER outside the submitted work. B. T. reports receipt of nonfinancial support from Gilead Sciences and personal fees from AbbVie, Gilead Sciences, Lilly Oncology, and Incyte outside the submitted work. None declared (R. Lécuyer, N. I., F. C., R. Lavergne, F. G., F. M., D. B., A. C., M. G., Y. C., A. N.).

Background: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown., Study Design and Methods: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 10 9 /L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality., Results: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 10 11 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 10 11 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 10 9 /L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied., Conclusions: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

With the increasing use of sustainable energy sources, the electric scooter has become a widely used vehicle. The aim of the study is to analyse the types of facial fracture related to road traffic accidents to outline the need for dedicated road rules. An observational, retrospective, multicentre study was carried out at the Maxillofacial Surgery Units of six Italian hospitals. Fifty patients (mean age was 34.76 years) from January 2020 to January 2024 were enrolled. The severity of trauma was evaluated by the Facial Injury Severity Scale (FISS) by Bagheri et al. Most of the accidents occurred during the day and the weekend in spring or summer; 24 drivers collided with infrastructures or pedestrians, while 26 involved other vehicles. A total of 33 vehicles were rented, and 17 were privately owned. A total of 43 subjects were not wearing helmets, five patients were drunk, and three patients took drugs. In order of frequency, the facial fractures involved: zygomatico-maxillary-orbital complex (ZMOC) (n = 16), mandibular condyle (n = 13), nasal bone (n = 11), orbit floor (n = 8), and mandibular body (n = 7). Fractures such as Le Fort I (n = 4), naso-orbito-ethmoidal NOE (n = 4) and mandibular ramus (n = 4) were less common. Other types of facial fracture were rare. Thirty patients reported multiple facial fractures. The vast majority of the cases showed a low severity grade FISS score. Fifteen patients suffered polytrauma. The mean hospitalisation time was 8.3 days. As accidents with electric scooters are increasing, it is important to characterise the most frequent facial fractures to improve patient management and encourage the introduction of new road rules., (Copyright © 2024 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Post-intensive care syndrome could be responsible for inability to receive proper cancer treatment after ICU stay in patients with solid tumors (ST). Our purpose was to determine the factors associated with cancer treatment resumption and the impact of cancer treatment on the outcome of patients with ST after ICU stay., Methods: We conducted a retrospective study including all patients with ST admitted to the ICU between 2014 and 2019 in a French University-affiliated Hospital., Results: A total of 219 patients were included. Median SAPS II at ICU admission was 44.0 [IQR 32.8, 66.3]. Among the 136 patients who survived the ICU stay, 81 (59.6%) received cancer treatment after ICU discharge. There was an important increase in patients with poor performance status (PS) of 3 or 4 after ICU stay (16.2% at admission vs. 44.5% of patients who survived), with significant PS decline following the ICU stay (median difference - 1.5, 95% confidence interval [-1.5-1.0], p < 0.001). The difference between the PS after and before ICU stay (delta PS) was independently associated with inability to receive cancer treatment (Odds ratio OR 0.34, 95%CI 0.18-0.56, p value < 0.001) and with 1-year mortality in patients who survived at ICU discharge (Hazard ratio HR 1.76, 95%CI 1.34-2.31, p value < 0.001). PS before ICU stay (OR 3.73, 95%IC 2.01-7.82, p value < 0.001) and length of stay (OR 1.23, 95%CI 1.06-1.49, p value 0.018) were independently associated with poor PS after ICU stay. Survival rates at ICU discharge, at 1 and 3 years were 62.3% (n = 136), 27.3% (n = 59) and 17.1% (n = 37), respectively. The median survival for patients who resumed cancer treatment after ICU stay was 771 days (95%CI 376-1058), compared to 29 days (95%CI 15-49) for those who did not resume treatment (p < 0.001)., Conclusion: Delta PS, before and after ICU stay, stands out as a critical determinant of cancer treatment resumption and survival after ICU stay. Multidisciplinary intervention to improve the general condition of these patients, in ICU and after ICU stay, may improve access to cancer treatment and long-term survival., (© 2024. The Author(s).)

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Background: Cytomegalovirus (CMV) infection in patients with cellular immune deficiencies is associated with significant morbidity and mortality. However, data on CMV end-organ disease (CMV-EOD) in critically ill, immunocompromised patients are scarce. Our objective here was to describe the clinical characteristics and outcomes of CMV-EOD in this population., Methods: We conducted a multicenter, international, retrospective, observational study in adults who had CMV-EOD and were admitted to any of 18 intensive care units (ICUs) in France, Israel, and Spain in January 2010-December 2021. Patients with AIDS were excluded. We collected the clinical characteristics and outcomes of each patient. Survivors and non-survivors were compared, and multivariate analysis was performed to identify risk factors for hospital mortality., Results: We studied 185 patients, including 80 (43.2%) with hematologic malignancies, 55 (29.7%) with solid organ transplantation, 31 (16.8%) on immunosuppressants, 16 (8.6%) with solid malignancies, and 3 (1.6%) with primary immunodeficiencies. The most common CMV-EOD was pneumonia (n = 115, [62.2%] including 55 [47.8%] with a respiratory co-pathogen), followed by CMV gastrointestinal disease (n = 64 [34.6%]). More than one organ was involved in 16 (8.8%) patients. Histopathological evidence was obtained for 10/115 (8.7%) patients with pneumonia and 43/64 (67.2%) with GI disease. Other opportunistic infections were diagnosed in 69 (37.3%) patients. Hospital mortality was 61.4% overall and was significantly higher in the group with hematologic malignancies (75% vs. 51%, P = 0.001). Factors independently associated with higher hospital mortality were hematologic malignancy with active graft-versus-host disease (OR 5.02; 95% CI 1.15-27.30), CMV pneumonia (OR 2.57; 95% CI 1.13-6.03), lymphocytes < 0.30 × 10 9 /L at diagnosis of CMV-EOD (OR 2.40; 95% CI 1.05-5.69), worse SOFA score at ICU admission (OR 1.18; 95% CI 1.04-1.35), and older age (OR 1.04; 95% CI 1.01-1.07)., Conclusions: Mortality was high in critically ill, immunocompromised patients with CMV-EOD and varied considerably with the cause of immunodeficiency and organ involved by CMV. Three of the four independent risk factors identified here are also known to be associated with higher mortality in the absence of CMV-EOD. CMV pneumonia was rarely proven by histopathology and was the most severe CMV-EOD., (© 2024. The Author(s).)

Background: Post-intensive care syndrome (PICS), defined as physical, cognitive, and mental-health symptoms persisting long after intensive-care-unit (ICU) discharge, is increasingly recognised as a healthcare priority. Data on screening for PICS are sparse. Our objective here was to describe post-ICU screening in France, with special attention to visit availability and evaluations done during visits., Methods: We conducted an online multicentre survey by emailing an anonymous 43-item questionnaire to French ICUs. For each ICU, a single survey was sent to either the head or the intensivist in charge of follow-up visits., Results: Of 252 ICUs invited to participate, 161 (63.9%) returned the completed survey. Among them, 46 (28.6%) offered follow-up visits. Usually, a single visit led by an intensivist was scheduled 3 to 6 months after ICU discharge. Approximately 50 patients/year/ICU, that is, about 5% of admitted patients, attended post-ICU visits. The main criteria used to select patients for follow-up were ICU stay and/or invasive mechanical ventilation duration longer than 48 h, cardiac arrest, septic shock, and acute respiratory distress syndrome. Among ICUs offering visits, 80% used validated instruments to screen for PICS. Of the 115 ICUs not offering follow-up, 50 (43.5%) indicated an intention to start follow-up within the next year. The main barriers to offering follow-up were lack of available staff and equipment or not viewing PICS screening as a priority. Half the ICUs offering visits worked with an established network of post-ICU care professionals, and another 17% were setting up such a network. Obstacles to network creation were lack of interest among healthcare professionals and lack of specific training in PICS., Conclusion: Only a small minority of ICU survivors received follow-up designed to detect PICS. Less than a third of ICUs offered follow-up visits but nearly another third planned to set up such visits within the next year. Recommendations issued by French health authorities in 2023 can be expected to improve the availability and standardisation of post-ICU follow-up., (© 2024. The Author(s).)

Myocardial infarction (MI) is a serious acute cardiovascular syndrome that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dynamic and exhibits various oxidation-reduction states that have been an early subject of attention in the food industry, specifically for meat consumers. However, rarely if ever have the myoglobin optical properties been used to measure the severity of MI. In the current study, we develop a novel imaging pipeline that integrates tissue clearing, confocal and light sheet fluorescence microscopy, combined with imaging analysis, and processing tools to investigate and characterize the oxidation-reduction states of myoglobin in the ischemic area of the cleared myocardium post-MI. Using spectral imaging, we have characterized the endogenous fluorescence of the myocardium and demonstrated that it is partly composed by fluorescence of myoglobin. Under ischemia-reperfusion experimental settings, we report that the infarcted myocardium spectral signature is similar to that of oxidized myoglobin signal that peaks 3 h post-reperfusion and decreases with cardioprotection. The infarct size assessed by oxidation-reduction imaging at 3 h post-reperfusion was correlated to the one estimated with late gadolinium enhancement MRI at 24 h post-reperfusion. In conclusion, this original work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estimating the size of the MI during early phases of reperfusion., (© 2024. The Author(s).)

Background: Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated., Research Question: Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease?, Study Design and Methods: In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality., Results: Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose ≥ 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010)., Interpretation: Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. G. reports receipt of nonfinancial support from Gilead Sciences, MSD, and Pfizer, outside the submitted work. F. R. reports receipt of personal fees from Abbvie, Astra Zeneca, Gilead Sciences, Janssen, Merck, Roche, and ViiV Healthcare, outside the submitted work. E. C. reports personal fees from Gilead, Sanofi-Genzyme, and Baxter, outside the submitted work. None declared (R. L., N. I., F. C., R.-a. L., F. G., F. M., D. B., A. C., M. G., Y. C., A. N., B. T.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Ventilator-associated pneumonia (VAP) is the leading nosocomial infection in critical care and is associated with adverse outcomes. When VAP is suspected, starting antibiotic therapy (AT) immediately after pulmonary sampling may expose uninfected patients to unnecessary treatment, whereas waiting for bacteriological confirmation may delay AT in infected patients. As no robust data exist to choose between these strategies, the decision must balance the pre-test diagnostic probability, clinical severity, and risk of antimicrobial resistance. The objective of this study in patients with suspected non-severe VAP was to compare immediate AT started after sampling to conservative AT upon receipt of positive microbiological results. The outcomes were antibiotic sparing, AT suitability, and patient outcomes., Methods: This single-center, before-after study included consecutive patients who underwent distal respiratory sampling for a first suspected non-severe VAP episode (no shock requiring vasopressor therapy or severe acute respiratory distress syndrome). AT was started immediately after sampling in 2019 and upon culture positivity in 2022 (conservative strategy). The primary outcome was the number of days alive without AT by day 28. The secondary outcomes were mechanical ventilation duration, day-28 mortality, and AT suitability (active necessary AT or spared AT)., Results: The immediate and conservative strategies were applied in 44 and 43 patients, respectively. Conservative and immediate AT were associated with similar days alive without AT (median [interquartile range], 18.0 [0-21.0] vs. 16.0 [0-20.0], p = 0.50) and without broad-spectrum AT (p = 0.53) by day 28. AT was more often suitable in the conservative group (88.4% vs. 63.6%, p = 0.01), in which 27.9% of patients received no AT at all. No significant differences were found for mechanical ventilation duration (median [95%CI], 9.0 [6-19] vs. 9.0 [6-24] days, p = 0.65) or day-28 mortality (hazard ratio [95%CI], 0.85 [0.4-2.0], p = 0.71)., Conclusion: In patients with suspected non-severe VAP, waiting for microbiological confirmation was not associated with antibiotic sparing, compared to immediate AT. This result may be ascribable to low statistical power. AT suitability was better with the conservative strategy. None of the safety outcomes differed between groups. These findings would seem to allow a large, randomized trial comparing immediate and conservative AT strategies., (© 2024. The Author(s).)

Purpose: Psychological impact of Medical Evacuation (MEDEVAC) in Covid-19 patients is undetermined. The objectives were to evaluate: Post-traumatic Stress Disorder (PTSD) in MEDEVAC patients hospitalized in ICU for Covid-19-related acute respiratory distress syndrome (ARDS) compared to control group; anxiety, depression rates and outcomes in patients and PTSD in relatives., Material and Methods: This is a retrospective multicentric 1/1 paired cohort performed in 10 ICUs in the West of France. Evaluation was performed 18 months after discharge. Patients and closest relatives performed IES-R (Impact and Event Scale-Revised) and/or HADS (Hospital Anxiety and Depression Scale) scales., Results: Twenty-six patients were included in each group. Patients were 64 ± 11 years old, with 83% male. We report 12 vs 20% of PTSD in control vs MEDEVAC groups (p = 0.7). Anxiety disorder affected 43.5 vs 28.0% (p = 0.26) and depression 12.5 vs 14.3% (p > 0.99) in control vs MEDEVAC groups. PTSD affects 33.3 vs 42.1% of closest relatives (p = 0.55). Ways of communication were adapted: video calls were more frequent in MEDEVAC patients (8.7 vs 60.9%, p < 0.01) whereas physical visits concerned more control group (45.8 vs 13.0%, p = 0.01)., Conclusions: PTSD rate were similar between groups. Adaptive ways of communication, restricted visits and global uncertainties could explain the absence of differences., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Invasive fusariosis can be life-threatening, especially in immunocompromised patients who require intensive care unit (ICU) admission. We conducted a multicenter retrospective study to describe clinical and biologic characteristics, patient outcomes, and factors associated with death and response to antifungal therapy. We identified 55 patients with invasive fusariosis from 16 ICUs in France during 2002----2020. The mortality rate was high (56%). Fusariosis-related pneumonia occurred in 76% of patients, often leading to acute respiratory failure. Factors associated with death included elevated sequential organ failure assessment score at ICU admission or history of allogeneic hematopoietic stem cell transplantation or hematologic malignancies. Neither voriconazole treatment nor disseminated fusariosis were strongly associated with response to therapy. Invasive fusariosis can lead to multiorgan failure and is associated with high mortality rates in ICUs. Clinicians should closely monitor ICU patients with a history of hematologic malignancies or stem cell transplantation because of higher risk for death.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy is increasingly used in patients with refractory haematological malignancies but can induce severe adverse events. We aimed to describe the clinical features and outcomes of patients admitted to the intensive care unit (ICU) after CAR-T therapy., Methods: This retrospective observational cohort study included consecutive adults admitted to either of two French ICUs in 2018-2022 within 3 months after CAR-T therapy., Results: Among 238 patients given CAR-T therapy, 84 (35.3%) required ICU admission and were included in the study, a median of 5 [0-7] days after CAR-T infusion. Median SOFA and SAPSII scores were 3 [2-6] and 39 [30-48], respectively. Criteria for cytokine release syndrome were met in 80/84 (95.2%) patients, including 18/80 (22.5%) with grade 3-4 toxicity. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 46/84 (54.8%) patients, including 29/46 (63%) with grade 3-4 toxicity. Haemophagocytic lymphohistiocytosis was diagnosed in 15/84 (17.9%) patients. Tocilizumab was used in 73/84 (86.9%) patients, with a median of 2 [1-4] doses. Steroids were given to 55/84 (65.5%) patients, including 21/55 (38.2%) given high-dose pulse therapy. Overall, 23/84 (27.4%) patients had bacterial infections, 3/84 (3.6%) had fungal infections (1 invasive pulmonary aspergillosis and 2 Mucorales), and 2 (2.4%) had cytomegalovirus infection. Vasopressors were required in 23/84 (27.4%), invasive mechanical ventilation in 12/84 (14.3%), and dialysis in 4/84 (4.8%) patients. Four patients died in the ICU (including 2 after ICU readmission, i.e., overall mortality was 4.8% of patients). One year after CAR-T therapy, 41/84 (48.9%) patients were alive and in complete remission, 14/84 (16.7%) were alive and in relapse, and 29/84 (34.5%) had died. These outcomes were similar to those of patients never admitted to the ICU., Conclusion: ICU admission is common after CAR-T therapy and is usually performed to manage specific toxicities. Our experience is encouraging, with low ICU mortality despite a high rate of grade 3-4 toxicities, and half of patients being alive and in complete remission at one year., (© 2024. The Author(s).)

Background: Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients., Methods: We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes., Results: The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0-27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00-1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32-3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay., Conclusion: Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality., (© 2024. The Author(s).)

Non-human primate studies are unique in translational research, especially in neurosciences where neuroimaging approaches are the preferred methods used for cross-species comparative neurosciences. In this regard, neuroimaging database development and sharing are encouraged to increase the number of subjects available to the community, while limiting the number of animals used in research. Here we present a simultaneous positron emission tomography (PET)/magnetic resonance (MR) dataset of 20 Macaca fascicularis images structured according to the Brain Imaging Data Structure standards. This database contains multiple MR imaging sequences (anatomical, diffusion and perfusion imaging notably), as well as PET perfusion and inflammation imaging using respectively [ 15 O]H 2 O and [ 11 C]PK11195 radiotracers. We describe the pipeline method to assemble baseline data from various cohorts and qualitatively assess all the data using signal-to-noise and contrast-to-noise ratios as well as the median of intensity and the pseudo-noise-equivalent-count rate (dynamic and at maximum) for PET data. Our study provides a detailed example for quality control integration in preclinical and translational PET/MR studies with the aim of increasing reproducibility. The PREMISE database is stored and available through the PRIME-DE consortium repository., (© 2023. The Author(s).)

Background: In immunocompromised patients with acute respiratory failure (ARF), the clinical significance of respiratory virus detection in the nasopharynx remains uncertain., Research Question: Is viral detection in nasopharyngeal swabs associated with causes and outcomes of ARF in immunocompromised patients?, Study Design and Methods: This preplanned post hoc analysis of a randomized controlled trial enrolled immunocompromised patients admitted to 32 ICUs for ARF between May 2016 and December 2017. Nasopharyngeal swabs sampled at inclusion were assessed for 23 respiratory pathogens using multiplex polymerase chain reaction (PCR) assay. Causes of ARF were established by managing physicians and were reviewed by three expert investigators masked to the multiplex PCR assay results. Associations between virus detection in nasopharyngeal swabs, causes of ARF, and composite outcome of day 28 mortality, invasive mechanical ventilation (IMV), or both were assessed., Results: Among the 510 sampled patients, the multiplex PCR assay results were positive in 103 patients (20.2%), and a virus was detected in 102 samples: rhinoviruses or enteroviruses in 35.5%, coronaviruses in 10.9%, and flu-like viruses (influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus) in 52.7%. The cause of ARF varied significantly according to the results of the multiplex PCR assay, especially the proportion of viral pneumonia: 50.0% with flu-like viruses, 14.0% with other viruses, and 3.6% when no virus was detected (P < .001). No difference was found in the composite outcome of day 28 mortality, IMV, or both according to positive assay findings (54.9% vs 54.7%; P = .965). In a pre-established subgroup analysis, flu-like virus detection was associated with a higher rate of day 28 mortality, IMV, or both among recipients of allogeneic hematopoietic stem cell transplantation compared with those without detected virus., Interpretation: In immunocompromised patients with ARF, the results of nasopharyngeal multiplex PCR assays are not associated with IMV or mortality. A final diagnosis of viral pneumonia is retained in one-third of patients with positive assay results and in one-half of the patients with a flu-like virus., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. L. reports receiving personal fees from Qiagen and Abbott Rapid Diagnostics SAS. V. L. received support for article research from Assistance Publique - Hôpitaux de Paris and is treasurer of the GRRR-OH research group, which has received fees from Pfizer, Fisher-Paykel, Gilead, Astellas, Sanofi, and Alexion. F. B. reports personal fees from Merck Sharp and Dohme and BioMérieux outside the submitted work. A. D. reports grants from the French Ministry of Health; grants and personal fees from Philips, Fisher & Paykel, Respinor, and Lungpacer; personal fees from Baxter, Getinge, Gilead, and Lowenstein; and nonfinancial support from Fisher & Paykel outside the submitted work. E. A. has received fees for lectures from MSD, Pfizer, and Alexion; his institution and research group have received support from Baxter, Jazz Pharmaceuticals, Fisher & Paykel, Gilead, Alexion, and Ablynx; and he received support for article research from Assistance Publique - Hôpitaux de Paris. None declared (A. M., M. B., S. M.-D., L. F., S. J., K. K., A. K., L. A., N. B., A.-S. M., E. C., F. P., M. S., D. M.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery., Methods: In this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6 g intravenously followed by a continuous infusion of 6 g/24 h for 3 days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat., Results: Overall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4 days (95% confidence interval [CI], 3-4) in the magnesium sulphate group and 4 days (95% CI 3-5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58-1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80)., Conclusion: Among patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Thrombocytopenia (platelet count < 150 × 10 9 /L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients., Methods: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses., Results: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42)., Conclusion: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic., (© 2023. The Author(s).)

Objective: The accuracy of different non-invasive body temperature measurement methods in intensive care unit (ICU) patients is uncertain. We aimed to study the accuracy of three commonly used methods. Design: Prospective observational study. Setting: ICUs of two tertiary Australian hospitals. Participants: Critically ill patients admitted to the ICU. Interventions: Invasive (intravascular and intra-urinary bladder catheter) and non-invasive (axillary chemical dot, tympanic infrared, and temporal scanner) body temperature measurements were taken at study inclusion and every 4 hours for the following 72 hours. Main outcome measures: Accuracy of non-invasive body temperature measurement methods was assessed by the Bland-Altman approach, accounting for repeated measurements and significant explanatory variables that were identified by regression analysis. Clinical adequacy was set at limits of agreement (LoA) of 1°C compared with core temperature. Results: We studied 50 consecutive critically ill patients who were mainly admitted to the ICU after cardiac surgery. From over 375 observations, invasive core temperature (mostly pulmonary artery catheter) ranged from 33.9°C to 39°C. On average, the LoA between invasive and non-invasive measurements methods were about 3°C. The temporal scanner showed the worst performance in estimating core temperature (bias, 0.66°C; LoA, -1.23°C, +2.55°C), followed by tympanic infrared (bias, 0.44°C; LoA, -1.73°C, +2.61°C) and axillary chemical dot methods (bias, 0.32°C; LoA, -1.64°C, +2.28°C). No methods achieved clinical adequacy even accounting for significant explanatory variables. Conclusions: The axillary chemical dot, tympanic infrared and temporal scanner methods are inaccurate measures of core temperature in ICU patients. These non-invasive methods appeared unreliable for use in ICU patients., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Background: Acute respiratory failure (ARF) is the leading cause of ICU admission. Viruses are increasingly recognized as a cause of pneumonia in immunocompromised patients, but epidemiologic data are scarce. We used the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie's database (2003-2017, 72 intensive care units) to describe the spectrum of critically ill immunocompromised patients with virus-detected ARF and to report their outcomes. Then, patients with virus-detected ARF were matched based on clinical characteristics and severity (1:3 ratio) with patients with ARF from other origins., Results: Of the 4038 immunocompromised patients in the whole cohort, 370 (9.2%) had a diagnosis of virus-detected ARF and were included in the study. Influenza was the most common virus (59%), followed by respiratory syncytial virus (14%), with significant seasonal variation. An associated bacterial infection was identified in 79 patients (21%) and an invasive pulmonary aspergillosis in 23 patients (6%). The crude in-hospital mortality rate was 37.8%. Factors associated with mortality were: neutropenia (OR = 1.74, 95% confidence interval, CI [1.05-2.89]), poor performance status (OR = 1.84, CI [1.12-3.03]), and the need for invasive mechanical ventilation on the day of admission (OR = 1.97, CI [1.14-3.40]). The type of virus was not associated with mortality. After matching, patients with virus-detected ARF had lower mortality (OR = 0.77, CI [0.60-0.98]) than patients with ARF from other causes. This result was mostly driven by influenza-like viruses, namely, respiratory syncytial virus, parainfluenza virus, and human metapneumovirus (OR = 0.54, CI [0.33-0.88])., Conclusions: In immunocompromised patients with virus-detected ARF, mortality is high, whatever the species, mainly influenced by clinical severity and poor general status. However, compared to non-viral ARF, in-hospital mortality was lower, especially for patients with detected viruses other than influenza., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0-3) day after admission., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Both AIDS-defining and non-AIDS-defining cancers (ADC/NADC) predispose people living with HIV (PLHIV) to critical illnesses. The objective of this multicentre study was to investigate the prognostic impact of ADC and NADC in PLHIV admitted to the intensive care unit (ICU)., Methods: All PLHIV admitted over the 2015-2020 period in 12 university-affiliated ICUs in France were included in the study cohort. The effect of ADC and NADC on in-hospital mortality (primary study endpoint) was measured through logistic regression with augmented backward elimination of potential independent variables. The association between ADC/NADC and treatment limitation decision (TLD) during the ICU stay (secondary study endpoint) was analysed. One-year mortality in patients discharged alive from the index hospital admission (exploratory study endpoint) was compared between those with ADC, NADC or no cancer., Results: Amongst the 939 included PLHIV (median age, 52 [43-59] years; combination antiretroviral therapy, 74.4%), 97 (10.3%) and 106 (11.3%) presented with an active NADC (mostly lung and intestinal neoplasms) and an active ADC (predominantly AIDS-defining non-Hodgkin lymphoma), respectively. Inaugural admissions were common. Bacterial sepsis and non-infectious neoplasm-related complications accounted for most of admissions in these subgroups. Hospital mortality was 12.4% in patients without cancer, 30.2% in ADC patients and 45.4% in NADC patients (P < 0.0001). NADC (adjusted odds ratio [aOR], 7.00; 95% confidence interval [CI], 4.07-12.05) and ADC (aOR, 3.11; 95% CI 1.76-5.51) were independently associated with in-hospital death after adjustment on severity and frailty markers. The prevalence of TLD was 8.0% in patients without cancer, 17.9% in ADC patients and 33.0% in NADC patients (P < 0.0001)-organ failures and non-neoplastic comorbidities were less often considered in patients with cancer. One-year mortality in survivors of the index hospital admission was 7.8% in patients without cancer, 17.0% in ADC patients and 33.3% in NADC patients (P < 0.0001)., Conclusions: NADC and ADC are equally prevalent, stand as a leading argument for TLD, and strongly predict in-hospital death in the current population of PLHIV requiring ICU admission., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Thrombotic thrombocytopenic purpura (iTTP) and atypical hemolytic-uremic syndrome (aHUS), once in remission, may cause long-term symptoms, among which mental-health impairments may be difficult to detect. We conducted telephone interviews 72 [48-84] months after ICU discharge to assess symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) and the 36-item Short Form questionnaire (SF-36). Of 103 included patients, 52 had iTTP and 51 aHUS; 74% were female, median age was 39 y (31-54), and 39 (38%) patients were still taking treatment. Symptoms of anxiety, PTSD and depression were present in 50%, 27% and 14% of patients, respectively, with no significant difference between the iTTP and aHUS groups. Patients with PTSD symptoms had significantly greater weight gain and significantly worse perceived physical and/or emotional wellbeing, anxiety symptoms, and depression symptoms. The SF-36 physical and mental components indicated significantly greater quality-of-life impairments in patients with vs. without PTSD symptoms and in those with aHUS and PTSD vs. iTTP with or without PTSD. In the aHUS group, quality of life was significantly better in patients with vs. without eculizumab treatment. Factors independently associated with PTSD symptoms were male sex (odds ratio [OR], 0.11; 95%CI, 0.02-0.53), platelet count ≤20 G/L at acute-episode presentation (OR, 2.68; 1.01-7.38), and current treatment (OR, 2.69; 95%CI, 1.01-7.36). Mental-health screening should be routine in patients with iTTP and aHUS to ensure appropriate care., Competing Interests: Declaration of Competing Interest EA has received fees for lectures from Alexion, Sanofi, Pfizer and Gilead. All other authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To describe the management and outcome of critically-ill patients with Cyclophosphamide (CY)-associated cardiac toxicity., Methods: All patients admitted to the intensive care units (ICUs) of the Nantes and Rennes University Hospitals for a CY-associated cardiac toxicity between January 2015 and December 2020 were included., Results: Of the thirty-four patients included in the study, twenty-four (70%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), four (12%) autologous HSCT, and six (18%) chemotherapy for hematological malignancies. Acute pulmonary edema (65%), cardiac arrest (9%), and cardiac arrhythmia (6%) were the most common reasons for ICU admission. Patients were admitted to the ICU 6.5 (4-12) days after the intravenous administration of a median dose of CY of 100 [60-101] mg/Kg. Echocardiographic findings showed moderate to severe left ventricular systolic dysfunction (69%) and pericardial effusion (52%). Eighteen (53%) patients ultimately developed cardiogenic shock and required vasopressors (47%) and/or inotropes (18%). Invasive mechanical ventilation and renal replacement therapy were required in twenty (59%) and five (14%) patients, respectively. Sixteen (47%) patients died of whom 12 (35.3%) died from refractory cardiogenic shock. The left ventricular ejection fraction improved over time in most survivors with a median time until full recovery of 33 (12-62) days. Two (11%) patients had a persistent left ventricular dysfunction at 6 months., Conclusion: Refractory cardiogenic shock is the primary cause of death of patients with severe CY-related cardiotoxicity. Nonetheless, the cardiac function of most survivors recovered within a month., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Microglial phagocytosis of apoptotic debris prevents buildup damage of neighbor neurons and inflammatory responses. Whereas microglia are very competent phagocytes under physiological conditions, we report their dysfunction in mouse and preclinical monkey models of stroke (macaques and marmosets) by transient occlusion of the medial cerebral artery (tMCAo). By analyzing recently published bulk and single cell RNA sequencing databases, we show that the phagocytosis dysfunction was not explained by transcriptional changes. In contrast, we demonstrate that the impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrient deprivation (OND), which led to reduced process motility, lysosomal exhaustion, and the induction of a protective macroautophagy/autophagy response in microglia. Basal autophagy, in charge of removing and recycling intracellular elements, was critical to maintain microglial physiology, including survival and phagocytosis, as we determined both in vivo and in vitro using pharmacological and transgenic approaches. Notably, the autophagy inducer rapamycin partially prevented the phagocytosis impairment induced by tMCAo in vivo but not by OND in vitro, where it even had a detrimental effect on microglia, suggesting that modulating microglial autophagy to optimal levels may be a hard to achieve goal. Nonetheless, our results show that pharmacological interventions, acting directly on microglia or indirectly on the brain environment, have the potential to recover phagocytosis efficiency in the diseased brain. We propose that phagocytosis is a therapeutic target yet to be explored in stroke and other brain disorders and provide evidence that it can be modulated in vivo using rapamycin. Abbreviations: AIF1/IBA1: allograft inflammatory factor 1; AMBRA1: autophagy/beclin 1 regulator 1; ATG4B: autophagy related 4B, cysteine peptidase; ATP: adenosine triphosphate; BECN1: beclin 1, autophagy related; CASP3: caspase 3; CBF: cerebral blood flow; CCA: common carotid artery; CCR2: chemokine (C-C motif) receptor 2; CIR: cranial irradiation; Csf1r/v-fms : colony stimulating factor 1 receptor; CX3CR1: chemokine (C-X3-C motif) receptor 1; DAPI: 4',6-diamidino-2-phenylindole; DG: dentate gyrus; GO: Gene Ontology; HBSS: Hanks' balanced salt solution; HI: hypoxia-ischemia; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MCA: medial cerebral artery; MTOR: mechanistic target of rapamycin kinase; OND: oxygen and nutrient deprivation; Ph/A coupling: phagocytosis-apoptosis coupling; Ph capacity: phagocytic capacity; Ph index: phagocytic index; SQSTM1: sequestosome 1; RNA-Seq: RNA sequencing; TEM: transmission electron microscopy; tMCAo: transient medial cerebral artery occlusion; ULK1: unc-51 like kinase 1.

Acute myeloid leukemia (AML) can lead to life-threatening complications that may require intensive care unit (ICU) management. It has been advocated that early preemptive (ePE) ICU admission, before the onset of organ failure, could benefit some high-risk patients such as those with hyperleukocytosis. The aim of this study was to retrospectively analyze the outcome of newly diagnosed AML patients who required ICU admission in five academic centers with a special focus on patients with an ePE admission strategy, i.e., those transferred to the ICU without any organ failure (modified SOFA score ≤ 2 [omitting thrombocytopenia] and no life-sustaining intervention in the first 24 h following ICU admission) before the start of induction therapy. Between January 2017 and December 2019, 428 patients were included among which 101 were admitted to the ICU. Among patients requiring life-sustaining interventions (n = 83), 18 (22%) died while in the ICU but ICU survivors had the same survival as those not admitted to the ICU. Patients with an ePE admission (n = 18) had more comorbidities and high-risk disease features such as hyperleukocytosis but required no life-sustaining interventions while in the ICU. In a subgroup analysis of patients with hyperleukocytosis ≥ 50 G/l at diagnosis (n = 85), patients not admitted to the ICU and those admitted with an ePE strategy had similar outcomes. This study provides encouraging results about ICU outcome in AML patients during induction therapy but the potential benefit of an ePE strategy must be confirmed prospectively., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to describe the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching., Results: 76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years, p = 0.002) and had less lower limb (44.7% vs 70.9%, p < 0.001) and more abdomino-perineal NSTIs (43.4% vs 18.8%, p < 0.001). Enterobacterales and non-fermenting gram-negative bacteria were the most frequently isolated microorganisms in neutropenic patients. In-hospital mortality was significantly higher in neutropenic than in non-neutropenic patients (57.9% vs 28.5%, p < 0.001). Granulocyte colony-stimulating factor (G-CSF) administration was associated with a lower risk of in-hospital mortality in univariable Cox (hazard ratio (HR) = 0.43 95% confidence interval (CI) [0.23-0.82], p = 0.010) and multivariable Cox (adjusted HR = 0.46 95% CI [0.22-0.94], p = 0.033) analyses and after overlap propensity score weighting (odds ratio = 0.25 95% CI [0.09; 0.68], p = 0.006)., Conclusions: Critically ill neutropenic patients with NSTIs present different clinical and microbiological characteristics and are associated with a higher hospital mortality than non-neutropenic patients. G-CSF administration was associated with hospital survival., (© 2023. The Author(s).)

Background: Patients with critical illness due to COVID-19 exhibit increased coagulability associated with a high risk of venous thrombo-embolism (VTE). Data on prophylactic anticoagulation for these patients are limited and conflicting. The purpose of this study was to evaluate whether intermediate-dose prophylactic anticoagulation in patients with COVID-19 requiring ICU admission was associated with better outcomes compared to standard-dose prophylactic anticoagulation., Methods: We retrospectively included adults admitted with severe COVID-19 to any of 15 ICUs, in 2020 or 2021. We compared the groups given intermediate-dose vs. standard-dose prophylactic anticoagulation. The primary outcome was all-cause day-90 mortality. Secondary outcomes were VTE (pulmonary embolism or deep vein thrombosis), ICU stay length, and adverse effects of anticoagulation., Results: Of 1174 included patients (mean age, 63 years), 399 received standard-dose and 775 intermediate-dose prophylactic anticoagulation. Of the 211 patients who died within 90 days, 86 (21%) received intermediate and 125 (16%) standard doses. After adjustment on early corticosteroid therapy and critical illness severity, there were no significant between-group differences in day-90 mortality (hazard ratio [HR], 0.73; 95%CI, 0.52-1.04; p = 0.09) or ICU stay length (HR, 0.93; 95%CI, 0.79-1.10; p = 0.38). Intermediate-dose anticoagulation was significantly associated with fewer VTE events (HR, 0.55; 95%CI, 0.38-0.80; p < 0.001). Bleeding events occurred in similar proportions of patients in the two groups (odds ratio, 0.86; 95%CI, 0.50-1.47; p = 0.57)., Conclusions: Mortality on day 90 did not differ between the groups given standard-dose and intermediate-dose prophylactic anticoagulation, despite a higher incidence of VTE in the standard-dose group., (© 2023. The Author(s).)

Reperfusion therapies in acute ischemic stroke have demonstrated their efficacy in promoting clinical recovery. However, ischemia/reperfusion injury and related inflammation remain a major challenge in patient clinical management. We evaluated the spatio-temporal evolution of inflammation using sequential clinical [ 11 C]PK11195 PET-MRI in a non-human primate (NHP) stroke model mimicking endovascular thrombectomy (EVT) with a neuroprotective cyclosporine A (CsA) treatment. The NHP underwent a 110-min transient endovascular middle cerebral artery occlusion. We acquired [ 11 C]PK11195 dynamic PET-MR imaging at baseline, 7 and 30 days after intervention. Individual voxel-wise analysis was performed thanks to a baseline scan database. We quantified [ 11 C]PK11195 in anatomical regions and in lesioned areas defined on per-occlusion MR diffusion-weighted imaging and perfusion [ 15 O 2 ]H 2 OPET imaging. [ 11 C]PK11195 parametric maps showed a clear uptake overlapping the lesion core at D7, which further increased at D30. Voxel-wise analysis identified individuals with significant inflammation at D30, with voxels located within the most severe diffusion reduction area during occlusion, mainly in the putamen. The quantitative analysis revealed that thalamic inflammation lasted until D30 and was significantly reduced in the CsA-treated group compared to the placebo. In conclusion, we showed that chronic inflammation matched ADC decrease at occlusion time, a region exposed to an initial burst of damage-associated molecular patterns, in an NHP stroke model mimicking EVT. We described secondary thalamic inflammation and the protective effect of CsA in this region. We propose that major ADC drop in the putamen during occlusion may identify individuals who could benefit from early personalized treatment targeting inflammation., (© 2023. The Author(s).)

Background: The rise in antimicrobial resistance is a global threat responsible for about 33,000 deaths in 2015 with a particular concern for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and has led to a major increase in the use of carbapenems, last-resort antibiotics., Methods: In this retrospective propensity-weighted multicenter observational study conducted in 11 ICUs, the purpose was to assess the efficacy of non carbapenem regimen (piperacillin-tazobactam (PTZ) + aminoglycosides or 3rd-generation cephalosporin (3GC) + aminoglycosides) as empiric therapy in comparison with carbapenem in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) urinary septic shock. The primary outcome was Day-30 mortality., Results: Among 156 patients included in this study, 69 received a carbapenem and 87 received non carbapenem antibiotics as empiric treatment. Baseline clinical characteristics were similar between the two groups. Patients who received carbapenem had similar Day-30 mortality (10/69 (15%) vs 6/87 (7%), OR = 1.99 [0.55; 5.34] p = 0.16), illness severity, resolution of septic shock, and ESBL-E infection recurrence rates than patients who received an empiric non carbapenem therapy. The rates of secondary infection with C. difficile were comparable., Conclusions: In ESBL-E urinary septic shock, empiric treatment with a non carbapenem regimen, including systematically aminoglycosides, was not associated with higher mortality, compared to a carbapenem regimen., (© 2023. The Author(s).)

The use of chimeric antigen receptor T cells (CAR-T) has increased since their approval in the treatment of several relapsed/refractory B cell malignancies. The management of their specific toxicities, such as cytokine release syndrome (CRS), tends to be better understood and well-defined. During the twelfth edition of practice harmonization workshops of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), a working group focused its work on the management of patients developing CRS following CAR-T cell therapy. A special chapter has been allocated to macrophage activation syndrome (MAS), a rare but life-threatening complication post-CAR-T. In addition to symptomatic measures and preemptive broad-spectrum antibiotics, immunomodulators such as tocilizumab and corticosteroids remain the corner stone for the treatment of CRS. Tocilizumab/corticosteroids-resistant CRS associated with haemophagocytosis markers (spleen and liver enlargement, hyperferritinaemia>10,000ng/mL, hypofibrinogenemia…) should direct the diagnosis towards an overlapping CRS/MAS. An adapted treatment will be based on high-dose IV anakinra and corticosteroids and chemotherapy with etoposide at late refractory stages. These complications and others delignate the need of close collaboration with an intensive care unit., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Calcium accumulation in atherosclerotic plaques predicts cardiovascular mortality, but the mechanisms responsible for plaque calcification and how calcification impacts plaque stability remain debated. Tissue-nonspecific alkaline phosphatase (TNAP) recently emerged as a promising therapeutic target to block cardiovascular calcification. In this study, we sought to investigate the effect of the recently developed TNAP inhibitor SBI-425 on atherosclerosis plaque calcification and progression. TNAP levels were investigated in ApoE-deficient mice fed a high-fat diet from 10 weeks of age and in plaques from the human ECLAGEN biocollection (101 calcified and 14 non-calcified carotid plaques). TNAP was inhibited in mice using SBI-425 administered from 10 to 25 weeks of age, and in human vascular smooth muscle cells (VSMCs) with MLS-0038949. Plaque calcification was imaged in vivo with 18 F-NaF-PET/CT, ex vivo with osteosense, and in vitro with alizarin red. Bone architecture was determined with µCT. TNAP activation preceded and predicted calcification in human and mouse plaques, and TNAP inhibition prevented calcification in human VSMCs and in ApoE-deficient mice. More unexpectedly, TNAP inhibition reduced the blood levels of cholesterol and triglycerides, and protected mice from atherosclerosis, without impacting the skeletal architecture. Metabolomics analysis of liver extracts identified phosphocholine as a substrate of liver TNAP, who's decreased dephosphorylation upon TNAP inhibition likely reduced the release of cholesterol and triglycerides into the blood. Systemic inhibition of TNAP protects from atherosclerosis, by ameliorating dyslipidemia, and preventing plaque calcification., (Copyright © 2022 Elsevier Inc. All rights reserved.)