Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients.

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).

Symbiosis between Cretaceous dinosaurs and feather-feeding beetles.

Extant terrestrial vertebrates, including birds, have a panoply of symbiotic relationships with many insects and arachnids, such as parasitism or mutualism. Yet, identifying arthropod-vertebrate symbioses in the fossil record has been based largely on indirect evidence; findings of direct association between arthropod guests and dinosaur host remains are exceedingly scarce. Here, we present direct and indirect evidence demonstrating that beetle larvae fed on feathers from an undetermined theropod host (avian or nonavian) 105 million y ago. An exceptional amber assemblage is reported of larval molts (exuviae) intimately associated with plumulaceous feather and other remains, as well as three additional amber pieces preserving isolated conspecific exuviae. Samples were found in the roughly coeval Spanish amber deposits of El Soplao, San Just, and Peñacerrada I. Integration of the morphological, systematic, and taphonomic data shows that the beetle larval exuviae, belonging to three developmental stages, are most consistent with skin/hide beetles (family Dermestidae), an ecologically important group with extant keratophagous species that commonly inhabit bird and mammal nests. These findings show that a symbiotic relationship involving keratophagy comparable to that of beetles and birds in current ecosystems existed between their Early Cretaceous relatives.

Diagnostic value of regional homogeneity and fractional amplitude of low-frequency fluctuations in the classification of schizophrenia and bipolar disorders.

Schizophrenia (SCZ) and bipolar disorders (BD) show significant neurobiological and clinical overlap. In this study, we wanted to identify indexes of intrinsic brain activity that could differentiate these disorders. We compared the diagnostic value of the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) estimated from resting-state functional magnetic resonance imaging in a support vector machine classification of 59 healthy controls (HC), 40 individuals with SCZ, and 43 individuals with BD type I. The best performance, measured by balanced accuracy (BAC) for binary classification relative to HC was achieved by a stacking model (87.4% and 90.6% for SCZ and BD, respectively), with ReHo performing better than fALFF, both in SCZ (86.2% vs. 79.4%) and BD (89.9% vs. 76.9%). BD were better differentiated from HC by fronto-temporal ReHo and striato-temporo-thalamic fALFF. SCZ were better classified from HC using fronto-temporal-cerebellar ReHo and insulo-tempo-parietal-cerebellar fALFF. In conclusion, we provided evidence of widespread aberrancies of spontaneous activity and local connectivity in SCZ and BD, demonstrating that ReHo features exhibited superior discriminatory power compared to fALFF and achieved higher classification accuracies. Our results support the complementarity of these measures in the classification of SCZ and BD and suggest the potential for multivariate integration to improve diagnostic precision.

Post-cardiac surgery fungal mediastinitis: clinical features, pathogens and outcome.

OBJECTIVES: The occurrence of mediastinitis after cardiac surgery remains a rare and severe complication associated with poor outcomes. Whereas bacterial mediastinitis have been largely described, little is known about their fungal etiologies. We report incidence, characteristics and outcome of post-cardiac surgery fungal mediastinitis. METHODS: Multicenter retrospective study among 10 intensive care units (ICU) in France and Belgium of proven cases of fungal mediastinitis after cardiac surgery (2009-2019). RESULTS: Among 73,688 cardiac surgery procedures, 40 patients developed fungal mediastinitis. Five were supported with left ventricular assist device and five with veno-arterial extracorporeal membrane oxygenation before initial surgery. Twelve patients received prior heart transplantation. Interval between initial surgery and mediastinitis was 38 [17-61] days. Only half of the patients showed local signs of infection. Septic shock was uncommon at diagnosis (12.5%). Forty-three fungal strains were identified: Candida spp. (34 patients), Trichosporon spp. (5 patients) and Aspergillus spp. (4 patients). Hospital mortality was 58%. Survivors were younger (59 [43-65] vs. 65 [61-73] yo; p = 0.013), had lower body mass index (24 [20-26] vs. 30 [24-32] kg/m2; p = 0.028) and lower Simplified Acute Physiology Score II score at ICU admission (37 [28-40] vs. 54 [34-61]; p = 0.012). CONCLUSION: Fungal mediastinitis is a very rare complication after cardiac surgery, associated with a high mortality rate. This entity should be suspected in patients with a smoldering infectious postoperative course, especially those supported with short- or long-term invasive cardiac support devices, or following heart transplantation.

Barotrauma in COVID-19 acute respiratory distress syndrome: retrospective analysis of the COVADIS prospective multicenter observational database.

BACKGROUND: Despite evidence suggesting a higher risk of barotrauma during COVID-19-related acute respiratory distress syndrome (ARDS) compared to ARDS due to other causes, data are limited about possible associations with patient characteristics, ventilation strategy, and survival. METHODS: This prospective observational multicenter study included consecutive patients with moderate-to-severe COVID-19 ARDS requiring invasive mechanical ventilation and managed at any of 12 centers in France and Belgium between March and December 2020. The primary objective was to determine whether barotrauma was associated with ICU mortality (censored on day 90), and the secondary objective was to identify factors associated with barotrauma. RESULTS: Of 586 patients, 48 (8.2%) experienced barotrauma, including 35 with pneumothorax, 23 with pneumomediastinum, 1 with pneumoperitoneum, and 6 with subcutaneous emphysema. Median time from mechanical ventilation initiation to barotrauma detection was 3 [0-17] days. All patients received protective ventilation and nearly half (23/48) were in volume-controlled mode. Barotrauma was associated with higher hospital mortality (P < 0.001) even after adjustment on age, sex, comorbidities, PaO2/FiO2 at intubation, plateau pressure at intubation, and center (P < 0.05). The group with barotrauma had a lower mean body mass index (28.6 ± 5.8 vs. 30.3 ± 5.9, P = 0.03) and a higher proportion of patients given corticosteroids (87.5% vs. 63.4%, P = 0.001). CONCLUSION: Barotrauma during mechanical ventilation for COVID-19 ARDS was associated with higher hospital mortality.

Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial.

BACKGROUND: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. METHODS: We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. RESULTS: Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. CONCLUSIONS: Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.

Learning from terrorist mass casualty incidents: a global survey.

BACKGROUND: Reports published directly after terrorist mass casualty incidents frequently fail to capture difficulties that may have been encountered. An anonymised consensus-based platform may enable discussion and collaboration on the challenges faced. Our aim was to identify where to focus improvement for future responses. METHODS: We conducted a mixed methods study by email of clinicians' experiences of leading during terrorist mass casualty incidents. An initial survey identified features that worked well, or failed to, during terrorist mass casualty incidents plus ongoing challenges and changes that were implemented as a result. A follow-up, quantitative survey measured agreement between responses within each of the themes using a Likert scale. RESULTS: Thirty-three participants responded from 22 hospitals that had received casualties from a terrorist incident, representing 17 cities in low-middle, middle and high income countries. The first survey identified themes of sufficient (sometimes abundant) human resource, although coordination of staff was a challenge. Difficulties highlighted were communication, security, and management of blast injuries. The most frequently implemented changes were education on specific injuries, revising future plans and preparatory exercises. Persisting challenges were lack of time allocated to training and psychological well-being. The follow-up survey recorded highest agreement amongst correspondents on the need for re-triage at hospital (90% agreement), coordination roles (85% agreement), flexibility (100% agreement), and large-scale exercises (95% agreement). CONCLUSION: This survey collates international experience gained from clinicians managing terrorist mass casualty incidents. The organisation of human response, rather than consumption of physical supplies, emerged as the main finding. NHSH Clinical Effectiveness Unit project registration number: 2020/21-036.

Adverse Events in Intensive Care and Continuing Care Units During Bed-Bath Procedures: The Prospective Observational NURSIng during critical carE (NURSIE) Study.

OBJECTIVES: Standard nursing interventions, especially bed-baths, in ICUs can lead to complications or adverse events defined as a physiologic change that can be life-threatening or that prolongs hospitalization. However, the frequency and type of these adverse events are rarely reported in the literature. The primary objective of our study was to describe the proportion of patients experiencing at least one serious adverse event during bed-bath. The secondary objectives were to determine the incidence of each type of serious adverse event and identify risk factors for these serious adverse events. DESIGN: Prospective multicenter observational study. SETTING: Twenty-four ICUs in France, Belgium, and Luxembourg. PATIENTS: The patients included in this study had been admitted to an ICU for less than 72 hours and required at least one of the following treatments: invasive ventilation, vasopressors, noninvasive ventilation, high-flow oxygen therapy. Serious adverse events were defined as cardiac arrest, accidental extubation, desaturation and/or mucus plugging/inhalation, hypotension and/or arrhythmia and/or agitation requiring therapeutic intervention, acute pain, accidental disconnection or dysfunction of equipment, and patient fall requiring additional assistance. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 253 patients from May 1, 2018, to July 31, 2018 in 24 ICUs, representing 1,529 nursing procedures. The mean Simplified Acute Physiology Score II was 54 ± 19. Nursing care was administered by an average of 2 ± 1 caregivers and lasted between 11 and 20 minutes. Of the 253 patients included, 142 (56%) experienced at least one serious adverse event. Of the 1,529 nursing procedures, 295 (19%) were complicated by at least one serious adverse event. In multivariate analysis, the factors associated with serious adverse event were as follows: presence of a specific protocol (p = 0.011); tracheostomy (p = 0.032); administration of opioids (p = 0.007); presence of a physician (p = 0.0004); duration of nursing care between 6 and 10 minutes (p = 0.003), duration of nursing care between 11 and 20 minutes (p = 0.005), duration of nursing care greater than 40 minutes (p = 0.04) with a reference duration of nursing care between 20 and 40 minutes. CONCLUSIONS: Serious adverse events were observed in one-half of patients and concerned one-fifth of nurses, confirming the need for caution. Further studies are needed to test systematic serious adverse event prevention strategies.

Flowers of Apocynaceae in amber from the early Eocene of India.

PREMISE: Early Eocene ambers of the Cambay lignite in Gujarat, India, are well known for their diverse insect fauna and dispersed pollen, but the included flowers have received limited attention. The fossil record of Apocynaceae is relatively poor, and the distinctive floral characters of this family have not been recognized in the fossil record before. METHODS: Remains of tiny flowers in amber were studied by micro-CT scanning, reflected light, and epifluorescence microscopy. RESULTS: Flowers of Maryendressantha succinifera gen. et. sp. n. have actinomorphic, pentamerous, tubular corollas 2.2-2.3 mm wide, and 1.7-2.1 mm deep with sinistrorse aestivation and androecia consisting of a whorl of five stamens attached by short filaments to the lower half of the corolla tube. Anthers are ovate, rounded basally and apically tapered with their connectives convergent with one another in a conical configuration. The pollen is globose, psilate, tricolporate, and very small (10-11 µm). The combined characters indicate a position within the grade known as subfamily Rauvolfioideae. CONCLUSIONS: These fossils, as the oldest remains of Rauvolfioids, complement the fossil records of Apocynoid and Asclepioid fossil seeds from other regions, demonstrating that the Apocynaceae were well established by the early Eocene, mostly consistent with prior divergence estimates for the phylogeny of this family. Potential pollinators, also preserved in the Cambay amber, include mosquitos, gnats, small moths, and stingless bees.

Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study.

BACKGROUND: Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. METHODS: In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. RESULTS: The mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98-1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13-3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88-0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O, p < 0.001). The decrease in Crs was not associated with day-28 outcome. CONCLUSION: In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH2O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.

Prevalence of pressure injuries among critically ill patients and factors associated with their occurrence in the intensive care unit: The PRESSURE study.

BACKGROUND: The prevalence of pressure injuries (PIs) in critically ill patients has been extensively studied, but there is uncertainty regarding the risk factors. The main objective of this study was to describe the prevalence of PIs in critically ill patients. Secondary objectives were to describe PI, use of preventive measures for PI, and factors associated with occurrence of PI in the intensive care unit (ICU). MATERIAL AND METHODS: This was a 1-day point-prevalence study performed on a weekday in June 2017 in ICUs in France. On the same day, we noted the presence or absence of PI in all hospitalised patients of the participating ICUs, data on the ICUs, and the characteristics of patients and of PI. RESULTS: Eighty-six participating ICUs allowed the inclusion of 1228 patients. The prevalence of PI on the study day was 18.7% (95% confidence interval: 16.6-21.0). PIs acquired in the ICU were observed in 12.5% (95% confidence interval: 10.6-14.3) of critically ill patients on the study day. The most frequent locations of PI were the sacrum (57.4%), heel (35.2%), and face (8.7%). Severe forms of PI accounted for 40.8% of all PIs. Antiulcer mattresses were used in 91.5% of the patients, and active and/or passive mobilisation was performed for all the patients. Multiple logistic regression analysis identified longer length of stay in the ICU, a higher Simplified Acute Physiology Score, higher body weight, motor neurological disorder, high-dose steroids, and absence of oral nutrition on the study day as factors independently associated with occurrence of PI in the ICU. CONCLUSION: This large point-prevalence study shows that PIs are found in about one of five critically ill patients despite extensive use of devices for preventing PI. Acquisition of PI in the ICU is strongly related to the patient's severity of illness on admission to the ICU and length of stay in the ICU.

Higher Intensity Thromboprophylaxis Regimens and Pulmonary Embolism in Critically Ill Coronavirus Disease 2019 Patients.

OBJECTIVES: To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients. DESIGN: Retrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020. SETTING: ICU of an University Hospital in Belgium. PATIENTS AND INTERVENTIONS: Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin). MEASUREMENTS AND MAIN RESULTS: Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4-8 d) since ICU admission and 12 days (9-16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78-1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%-odds ratio 0.13 [0.02-0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24-3.26]; p = 0.99). CONCLUSIONS: In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.

Meningococcaemia causing necrotizing cellulitis associated with acquired complement deficiency after gastric bypass surgery: a case report.

BACKGROUND: Neisseria meningitidis has rarely been described as an agent of necrotic soft tissue infection. CASE PRESENTATION: We report a case of a septic shock with necrotizing cellulitis due to Neisseria meningitidis serogroup W, treated by urgent extensive surgical debridement followed by skin grafts. The invasive meningococcal disease occurred together with a complement deficiency, possibly acquired after bypass surgery that took place 1 year before. CONCLUSIONS: Necrotic tissue infections should be considered part of the invasive meningococcal diseases spectrum and should prompt clinicians to look for complement deficiencies. Gastric bypass surgery associated malnutrition may be implicated but further verification is needed.

Non-occlusive Mesenteric Ischemia as a Fatal Complication in Acute Pancreatitis: A Case Series.

BACKGROUND: Vascular complications of severe acute pancreatitis are well known and largely described unlike non-occlusive mesenteric ischemia, which is a rare and potentially fatal complication. Non-occlusive mesenteric ischemia is an acute mesenteric ischemia without thrombotic occlusion of blood vessels, poorly described as a complication of acute pancreatitis. METHODS: We retrospectively reviewed a prospectively maintained registry of all pancreatic diseases referred to our center from 2013 to 2018, in order to determine the causes of early death. We identified three patients who died within 48 h after hospital admission from severe acute pancreatitis complicated by irreversible non-occlusive mesenteric ischemia. Their clinical presentation, management, and outcomes were herein reported. RESULTS: Three consecutive patients with severe acute pancreatitis developed non-occlusive mesenteric ischemia within the first 5 days after onset of symptoms and died 48 h after non-occlusive mesenteric ischemia diagnosis despite optimal intensive care management and surgery, giving a prevalence of 3/609 (0.5%). Symptoms were unspecific with consequently potential delayed diagnosis and management. High doses of norepinephrine required for hemodynamic support (n = 3) potentially leading to splanchnic vessels vasoconstriction, transient hypotension (n = 3), and previous severe ischemic cardiomyopathy (n = 1) could be involved as precipitating factors of non-occlusive mesenteric ischemia. CONCLUSION: Non-occlusive mesenteric ischemia can be a fatal complication of acute pancreatitis but is also challenging to diagnose. Priority is to reestablish a splanchno-mesenteric perfusion flow. Surgery should be offered in case of treatment failure or deterioration but is still under debate in early stage, to interrupt the vicious circle of intestinal hypoperfusion and ischemia.

A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol.

BACKGROUND: The COVID-19 pandemic reached Europe in early 2020. Convalescent plasma is used without a consistent evidence of efficacy. Our hypothesis is that passive immunization with plasma collected from patients having contracted COVID-19 and developed specific neutralizing antibodies may alleviate symptoms and reduce mortality in patients treated with mechanical ventilation for severe respiratory failure during the evolution of SARS-CoV-2 pneumonia. METHODS: We plan to include 500 adult patients, hospitalized in 16 Belgian intensive care units between September 2020 and 2022, diagnosed with SARS-CoV-2 pneumonia, under mechanical ventilation for less than 5 days and a clinical frailty scale less than 6. The study treatment will be compared to standard of care and allocated by randomization in a 1 to 1 ratio without blinding. The main endpoint will be mortality at day 28. We will perform an intention to treat analysis. The number of patients to include is based on an expected mortality rate at day 28 of 40 percent and an expected relative reduction with study intervention of 30 percent with α risk of 5 percent and ß risk of 20 percent. DISCUSSION: This study will assess the efficacy of plasma in the population of mechanically ventilated patients. A stratification on the delay from mechanical ventilation and inclusion will allow to approach the optimal time use. Selecting convalescent plasmas with a high titer of neutralizing antibodies against SARS-CoV-2 will allow a homogeneous study treatment. The inclusion in the study is based on the consent of the patient or his/her legal representative, and the approval of the Investigational Review Board of the University hospital of Liège, Belgium. A data safety monitoring board (DSMB) has been implemented. Interim analyses have been planned at 100, 2002, 300 and 400 inclusions in order to decide whether the trail should be discontinued prematurely for ethical issues. We plan to publish our results in a peer-reviewed journal and to present them at national and international conferences. FUNDING AND REGISTRATION: The trial is funded by the Belgian Health Care Knowledge Center KCE # COV201004 TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT04558476. Registered 14 September 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04558476.

Cardiac Arrest in Patients Managed for Convulsive Status Epilepticus: Characteristics, Predictors, and Outcome.

OBJECTIVES: Cardiac arrest is a catastrophic event that may arise during the management of convulsive status epilepticus. We aimed to report the clinical characteristics, outcomes, and early predictors of convulsive status epilepticus-related cardiac arrest. DESIGN: Retrospective multicenter study. SETTING: Seventeen university or university affiliated participating ICUs in France and Belgium. PATIENTS: Consecutive patients admitted to the participating ICUs for management of successfully resuscitated out-of-hospital cardiac arrest complicating the initial management of convulsive status epilepticus between 2000 and 2015. Patients were compared with controls without cardiac arrest identified in a single-center registry of convulsive status epilepticus patients, regarding characteristics, management, and outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 49 cases with convulsive status epilepticus-cardiac arrest and 235 controls. In the cases, median time from medical team arrival to cardiac arrest was 25 minutes (interquartile range, 5-85 min). First recorded rhythm was asystole in 25 patients (51%) and pulseless electrical activity in 13 patients (27%). A significantly larger proportion of patients had a favorable 1-year outcome (Glasgow Outcome Scale score of 5) among controls (90/235; 38%) than among cases (10/49; 21%; p = 0.02). By multivariate analysis, independent predictors of cardiac arrest were pulse oximetry less than 97% on scene (odds ratio, 2.66; 95% CI, 1.03-7.26; p = 0.04), drug poisoning as the cause of convulsive status epilepticus (odds ratio, 4.13; 95% CI, 1.27-13.53; p = 0.02), and complications during early management (odds ratio, 11.98; 95% CI, 4.67-34.69; p < 0.0001). Having at least one comorbidity among cardiac, respiratory, and neurologic (other than epilepsy) conditions predicted absence of cardiac arrest (odds ratio, 0.28; 95% CI, 0.10-0.80; p = 0.02). CONCLUSIONS: In patients managed for convulsive status epilepticus, relative hypoxemia, on-scene management complications, and drug poisoning as the cause of convulsive status epilepticus were strong early predictors of cardiac arrest, suggesting areas for improvement.

A late Cretaceous fagalean inflorescence preserved in amber from New Jersey.

PREMISE OF THE STUDY: An inflorescence with three pistillate flowers in amber from the early Upper Cretaceous (Turonian, ~90-94 million years ago) of central New Jersey represents the oldest known flowers with features present in an early stem complex of the Fagales. The inflorescence has characteristics of Nothofagaceae, but also has strikingly distinct characters that suggest it is intermediate between Nothofagus and other Fagales. This intermediacy is consistent with its northern hemisphere distribution. METHODS: We investigated this new fossil by comparing it with extant and fossil members of the Fagales using light microscopy and nano-computed tomography. In addition, for exploring its relationships, we mapped the morphological characters onto a widely accepted molecular-based tree of modern basal Fagales using standard methods of character optimization. KEY RESULTS: The phylogenetic position of the fossil inflorescence can be unequivocally determined by the presence of unique features, singly and in combination, that are found only in "basal" members of Fagales. The fossil adds critical information on the features of the early stem Fagales, evolution of the cupule in Nothofagaceae and Fagaceae, and a reasonable biogeographic hypothesis for the differentiation of southern (e.g., Nothofagaceae) and northern hemisphere Fagales. CONCLUSIONS: This new fossil provides insight into the early evolution of Fagales and suggests that early stem Fagales that had not yet differentiated into modern families were present in the Late Cretaceous of North America. Based on available evidence, the fossil is best interpreted as an early stem member of the Fagales, with features that suggest a transition from a more generalized Nothofagus-like fagalean ancestor with some unique presumably plesiomorphic features. The presence of an enlarged perianth and flexuous styles also suggests the possibility of insect pollination, which has been lost in all Fagales with the exception of some members of subfamily Castaneoideae in Fagaceae sensu stricto (which otherwise are very different from this fossil). The poorly developed, bract-like cupule valves of the fossil can be interpreted as primitive (i.e., incipient) or as reduced from more developed cupules that are found in most modern Fagaceae and Nothofagaceae.

Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With Emphasis on Rescue Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe the characteristics, management, and outcome of patients admitted to ICUs for pheochromocytoma crisis. DESIGN: A 16-year multicenter retrospective study. SETTING: Fifteen university and nonuniversity ICUs in France. PATIENTS: Patients admitted in ICU for pheochromocytoma crisis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 34 patients with a median age of 46 years (40-54 yr); 65% were males. At admission, the median Sequential Organ Failure Assessment score was 8 (4-12) and median Simplified Acute Physiology Score II 49.5 (27-70). The left ventricular ejection fraction was consistently decreased with a median value of 30% (15-40%). Mechanical ventilation was required in 23 patients, mainly because of congestive heart failure. Vasoactive drugs were used in 23 patients (68%) and renal replacement therapy in eight patients (24%). Extracorporeal membrane oxygenation was used as a rescue therapy in 14 patients (41%). Pheochromocytoma was diagnosed by CT in 33 of 34 patients. When assayed, urinary metanephrine and catecholamine levels were consistently elevated. Five patients underwent urgent surgery, including two during extracorporeal membrane oxygenation. Overall ICU mortality was 24% (8/34), and overall 90-day mortality was 27% (9/34). Crude 90-day mortality was not significantly different between patients managed with versus without extracorporeal membrane oxygenation (22% vs 30%) (p = 0.7) despite higher severity scores at admission in the extracorporeal membrane oxygenation group. CONCLUSIONS: Mortality is high in pheochromocytoma crisis. Routinely considering this diagnosis and performing abdominal CT in patients with unexplained cardiogenic shock may allow an earlier diagnosis. Extracorporeal membrane oxygenation and adrenalectomy should be considered as a therapeutic in most severe cases.