Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

BACKGROUND: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets. METHODS: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed. FINDINGS: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032). INTERPRETATION: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications. FUNDING: French Ministry of Health.

Relationship of Extravascular Lung Water and Pulmonary Vascular Permeability to Respiratory Mechanics in Patients with COVID-19-Induced ARDS.

During acute respiratory distress syndrome (ARDS), the increase in pulmonary vascular permeability and lung water induced by pulmonary inflammation may be related to altered lung compliance. A better understanding of the interactions between respiratory mechanics variables and lung water or capillary permeability would allow a more personalized monitoring and adaptation of therapies for patients with ARDS. Therefore, our main objective was to investigate the relationship between extravascular lung water (EVLW) and/or pulmonary vascular permeability index (PVPI) and respiratory mechanic variables in patients with COVID-19-induced ARDS. This is a retrospective observational study from prospectively collected data in a cohort of 107 critically ill patients with COVID-19-induced ARDS from March 2020 to May 2021. We analyzed relationships between variables using repeated measurements correlations. We found no clinically relevant correlations between EVLW and the respiratory mechanics variables (driving pressure (correlation coefficient [CI 95%]: 0.017 [-0.064; 0.098]), plateau pressure (0.123 [0.043; 0.202]), respiratory system compliance (-0.003 [-0.084; 0.079]) or positive end-expiratory pressure (0.203 [0.126; 0.278])). Similarly, there were no relevant correlations between PVPI and these same respiratory mechanics variables (0.051 [-0.131; 0.035], 0.059 [-0.022; 0.140], 0.072 [-0.090; 0.153] and 0.22 [0.141; 0.293], respectively). In a cohort of patients with COVID-19-induced ARDS, EVLW and PVPI values are independent from respiratory system compliance and driving pressure. Optimal monitoring of these patients should combine both respiratory and TPTD variables.

Hydrogen Bonding Propagated Phase Separation in Quasi-Epitaxial Single Crystals: A Pd-Br Molecular Insulator.

In condensed matter, phase separation is strongly related to ferroelasticity, ferroelectricity, ferromagnetism, electron correlation, and crystallography. These ferroics are important for nano-electronic devices such as non-volatile memory. However, the quantitative information regarding the lattice (atomic) structure at the border of phase separation is unclear in many cases. Thus, to design electronic devices at the molecular level, a quantitative electron-lattice relationship must be established. Herein, we elucidated a PdII-PdIV/PdIII-PdIII phase transition and phase separation mechanism for [Pd(cptn)2Br]Br2 (cptn = 1R,2R-diaminocyclopentane), propagated through a hydrogen-bonding network. Although the Pd···Pd distance was used to determine the electronic state, the differences in the Pd···Pd distance and the optical gap between Mott-Hubbard (MH) and charge-density-wave (CDW) states were only 0.012 Å and 0.17 eV, respectively. The N-H···Br···H-N hydrogen-bonding network functioned as a jack, adjusting the structural difference dynamically, and allowing visible ferroelastic phase transition/separation in a fluctuating N2 gas flow. Additionally, the effect of the phase separation on the spin susceptibility and electrical conductivity were clarified to represent the quasi-epitaxial crystals among CDW-MH states. These results indicate that the phase transitions and separations could be controlled via atomic and molecular level modifications, such as the addition of hydrogen bonding.

Venous return and mean systemic filling pressure: physiology and clinical applications.

Venous return is the flow of blood from the systemic venous network towards the right heart. At steady state, venous return equals cardiac output, as the venous and arterial systems operate in series. However, unlike the arterial one, the venous network is a capacitive system with a high compliance. It includes a part of unstressed blood, which is a reservoir that can be recruited via sympathetic endogenous or exogenous stimulation. Guyton's model describes the three determinants of venous return: the mean systemic filling pressure, the right atrial pressure and the resistance to venous return. Recently, new methods have been developed to explore such determinants at the bedside. In this narrative review, after a reminder about Guyton's model and current methods used to investigate it, we emphasize how Guyton's physiology helps understand the effects on cardiac output of common treatments used in critically ill patients.

Elucidating 2D Charge-Density-Wave Atomic Structure in an MX-Chain by the 3D-ΔPair Distribution Function Method.

The front cover artwork is provided by Prof. Masahiro Yamashita's group at Tohoku University and designed by Dr. Laurent Guérin at University of Rennes 1. The image illustrates that the atomic structure of a 2D charge density wave can be revealed although the planes associated to this local 2D order are randomly stacked preventing the use of conventional structure determination techniques. Read the full text of the Research Article at 10.1002/cphc.202100857.

Elucidating 2D Charge-Density-Wave Atomic Structure in an MX-Chain by the 3D-ΔPair Distribution Function Method.

Many solids, particularly low-dimensional systems, exhibit charge density waves (CDWs). In one dimension, charge density waves are well understood, but in two dimensions, their structure and their origin are difficult to reveal. Herein, the 2D charge-density-wave atomic structure and stabilization mechanism in the bromide-bridged Pd compound [Pd(cptn)2 Br]Br2 (cptn=1R,2R-diaminocyclopentane) is investigated by means of single-crystal X-ray diffraction employing the 3D-Δpair distribution function (3D-ΔPDF) method. Analysis of the diffuse scattering using 3D-ΔPDF shows that a 2D-CDW is stabilized by a hydrogen-bonding network between Br- counteranion and the amine (NH2 ) group of the cptn in-plane ligand, and that 3D ordering is prevented due to a weak plane to plane correlation. We extract the effective displacements of the atoms describing the atomic structure quantitatively and discuss the stabilization mechanism of the 2D-CDW. Our study provides a method to identify and measure the key interaction responsible for the dimensionality and stability of the CDW that can help further progress of rational design.

Handgrip strength to predict extubation outcome: a prospective multicenter trial.

BACKGROUND: ICU-acquired weakness (ICUAW) has been shown to be associated with prolonged duration of mechanical ventilation and extubation failure. It is usually assessed through Medical Research Council (MRC) score, a time-consuming score performed by physiotherapists. Handgrip strength (HG) can be monitored very easily at the bedside. It has been shown to be a reproducible and reliable marker of global muscular strength in critical care patients. We sought to test if muscular weakness, as assessed by handgrip strength, was associated with extubation outcome. METHODS: Prospective multicenter trial over an 18 months period in six mixed ICUs. Adults receiving mechanical ventilation for at least 48 h were eligible. Just before weaning trial, HG, Maximal Inspiratory Pressure (MIP), Peak Cough Expiratory Flow (PCEF) and Medical Research Council (MRC) score were registered. The attending physicians were unaware of the tests results and weaning procedures were conducted according to guidelines. Occurrence of unscheduled reintubation, non-invasive ventilation (NIV) or high-flow nasal continuous oxygen (HFNC) because of respiratory failure within 7 days after extubation defined extubation failure. The main outcome was the link between HG and extubation outcome. RESULTS: 233 patients were included. Extubation failure occurred in 51 (22.5%) patients, 39 (17.2%) required reintubation. Handgrip strength was 12 [6-20] kg and 12 [8-20] kg, respectively, in extubation success and failure (p = 0.85). There was no association between extubation outcome and MRC score, MIP or PCEF. Handgrip strength was well correlated with MRC score (r = 0.718, p < 0.0001). ICU and hospital length of stay were significantly higher in the subset of patients harboring muscular weakness as defined by handgrip performed at the first weaning trial (respectively, 15 [10-25] days vs. 11 [7-17] days, p = 0.001 and 34 [19-66] days vs. 22 [15-43] days, p = 0.002). CONCLUSION: No association was found between handgrip strength and extubation outcome. Whether this was explained by the appropriateness of the tool in this specific setting, or by the precise impact of ICUAW on extubation outcome deserves to be further evaluated. Trial registration Clinical Trials; NCT02946502, 10/27/2016, URL: https://clinicaltrials.gov/ct2/results?cond=&term=gripwean&cntry=&state=&city=&dist=.

Norepinephrine potentiates the efficacy of volume expansion on mean systemic pressure in septic shock.

BACKGROUND: Through venous contraction, norepinephrine (NE) increases stressed blood volume and mean systemic pressure (Pms) and exerts a "fluid-like" effect. When both fluid and NE are administered, Pms may not only result from the sum of the effects of both drugs. Indeed, norepinephrine may enhance the effects of volume expansion: because fluid dilutes into a more constricted, smaller, venous network, fluid may increase Pms to a larger extent at a higher than at a lower dose of NE. We tested this hypothesis, by mimicking the effects of fluid by passive leg raising (PLR). METHODS: In 30 septic shock patients, norepinephrine was decreased to reach a predefined target of mean arterial pressure (65-70 mmHg by default, 80-85 mmHg in previously hypertensive patients). We measured the PLR-induced increase in Pms (heart-lung interactions method) under high and low doses of norepinephrine. Preload responsiveness was defined by a PLR-induced increase in cardiac index ≥ 10%. RESULTS: Norepinephrine was decreased from 0.32 [0.18-0.62] to 0.26 [0.13-0.50] µg/kg/min (p < 0.0001). This significantly decreased the mean arterial pressure by 10 [7-20]% and Pms by 9 [4-19]%. The increase in Pms (∆Pms) induced by PLR was 13 [9-19]% at the higher dose of norepinephrine and 11 [6-16]% at the lower dose (p < 0.0001). Pms reached during PLR at the high dose of NE was higher than expected by the sum of Pms at baseline at low dose, ∆Pms induced by changing the norepinephrine dose and ∆Pms induced by PLR at low dose of NE (35.6 [11.2] mmHg vs. 33.6 [10.9] mmHg, respectively, p < 0.01). The number of preload responders was 8 (27%) at the high dose of NE and 15 (50%) at the low dose. CONCLUSIONS: Norepinephrine enhances the Pms increase induced by PLR. These results suggest that a bolus of fluid of the same volume has a greater haemodynamic effect at a high dose than at a low dose of norepinephrine during septic shock.

Comparison of a preventive or curative strategy of fluid removal on the weaning of mechanical ventilation: a study protocol for a multicentre randomised open-label parallel-group trial.

INTRODUCTION: Fluid overload is associated with a poor prognosis in the critically ill patients, especially at the time of weaning from mechanical ventilation as it may promote weaning failure from cardiac origin. Some data suggest that early administration of diuretics would shorten the duration of mechanical ventilation. However, this strategy may expose patients to a higher risk of haemodynamic and metabolic complications. Currently, there is no recommendation for the use of diuretics during weaning and there is an equipoise on the timing of their initiation in this context. METHODS AND ANALYSIS: This study is a multicentre randomised controlled trial comparing two strategies of fluid removal during weaning in 13 French intensive care units (ICU). The preventive strategy is initiated systematically when the fluid balance or weight change is positive and the patients have criteria for clinical stability; the curative strategy is initiated only in case of weaning failure documented as of cardiac origin. Four hundred and ten patients will be randomised with a 1:1 ratio. The primary outcome is the duration of weaning from mechanical ventilation, defined as the number of days between randomisation and successful extubation (alive without reintubation nor tracheostomy within the 7 days after extubation) at day 28. Secondary outcomes include daily and cumulated fluid balance, metabolic and haemodynamic complications, ventilator-associated pneumonia, weaning complications, number of ventilator-free days, total duration of mechanical ventilation, the length of stay in ICU and mortality in ICU, in hospital and, at day 28. A subgroup analysis for the primary outcome is planned in patients with kidney injury (Kidney Disease: Improving Global Outcomes class 2 or more) at the time of randomisation. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee (Comité de Protection des Personnes Paris 1) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04050007. PROTOCOL VERSION: V.1; 12 March 2019.

Seasonal burden of severe influenza virus infection in the critically ill patients, using the Assistance Publique-Hôpitaux de Paris clinical data warehouse: a pilot study.

PURPOSE: At the critical care level, the flu surveillance system is limited in France, with heterogeneous regional modalities of implementation. MATERIALS, PATIENTS AND METHODS: We aimed at assessing the relevance of the Assistance Publique-Hôpitaux de Paris (AP-HP) clinical data warehouse for estimating the burden of the influenza epidemic on medical adult critical care units of the AP-HP, and outcome of patients during the flu season 2017-2018. This exploratory multi-site epidemiological study comprised all consecutive adult stays (n = 320) in 18 medical intensive care units (ICU) or intermediate care wards (ICW) for probable or confirmed Influenza virus infection during the 2017-2018 flu season. RESULTS: Patients admitted to ICU/ICW had low vaccination coverage (21%), required life support in 60% of cases, stayed in the ICU for a median of 8 days, and had high 28-day mortality rate (19.7%; 95% confidence interval 15.5-24.5). Early prognostic factors included age, core temperature, the acute organ failures score, and the early administration of antiviral therapy. CONCLUSIONS: Data directly extracted from the electronic medical records stored in the data warehouse provide detailed clinical, care pathway and prognosis information. The real-time availability should enable to detect and assess the burden of the most severe cases. By a firmer and more acute monitoring and adjustment of care and patient management, hospitals could generate more ICU/ICW capacities, sensitize their emergency department and contribute to the recommendations from health authorities. This pilot study is of particular relevance in the context of emerging epidemics of severe acute respiratory diseases.

Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

INTRODUCTION: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. METHODS AND ANALYSIS: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. ETHICS AND DISSEMINATION: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03573739.

Effects of Prone Positioning on Venous Return in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: To examine the effects of prone positioning on venous return and its determinants such as mean systemic pressure and venous return resistance in patients with acute respiratory distress syndrome. DESIGN: Prospective monocentric study. SETTINGS: A 25-bed medical ICU. PATIENTS: About 22 patients with mild-to-severe acute respiratory distress syndrome in whom prone positioning was decided. INTERVENTIONS: We obtained cardiac index, mean systemic pressure, and venous return resistance (the latter two estimated through the heart-lung interactions method) before and during prone positioning. Preload responsiveness was assessed at baseline using an end-expiratory occlusion test. MEASUREMENTS AND MAIN RESULTS: Prone positioning significantly increased mean systemic pressure (from 24 mm Hg [19-34 mm Hg] to 35 mm Hg [32-46 mm Hg]). This was partly due to the trunk lowering performed before prone positioning. In seven patients, prone positioning increased cardiac index greater than or equal to 15%. All were preload responsive. In these patients, prone positioning increased mean systemic pressure by 82% (76-95%), central venous pressure by 33% (21-59%), (mean systemic pressure - central venous pressure) gradient by 144% (83-215)%, while it increased venous return resistance by 71% (60-154%). In 15 patients, prone positioning did not increase cardiac index greater than or equal to 15%. In these patients, prone positioning increased mean systemic pressure by 28% (18-56%) (p < 0.05 vs. patients with significant increase in cardiac index), central venous pressure by 21% (7-54%), (mean systemic pressure - central venous pressure) gradient by 28% (23-86%), and venous return resistance by 37% (17-77%). Eleven of these 15 patients were preload unresponsive. CONCLUSIONS: Prone positioning increased mean systemic pressure in all patients. The resulting change in cardiac index depended on the extent of increase in (mean systemic pressure - central venous pressure) gradient, of preload responsiveness, and of the increase in venous return resistance. Cardiac index increased only in preload-responsive patients if the increase in venous return resistance was lower than the increase in the (mean systemic pressure -central venous pressure) gradient.

OHCA (Out-of-Hospital Cardiac Arrest) and CAHP (Cardiac Arrest Hospital Prognosis) scores to predict outcome after in-hospital cardiac arrest: Insight from a multicentric registry.

AIM: We assessed the ability of the Out-of-Hospital Cardiac Arrest (OHCA) and the Cardiac Arrest Hospital Prognosis (CAHP) scores to predict neurological outcome following in-hospital cardiac arrest (IHCA). METHODS: Retrospective review of a seven-year French multicentric database including ten intensive care units. Primary endpoint was the outcome at hospital discharge using the Cerebral Performance Category score (CPC) in all IHCA patients. OHCA and CAHP scores, sequential organ failure assessment (SOFA) score and the simplified acute physiological score 2 (SAPS-2) were compared using area under ROC curves (AUROC) and Delong tests. RESULTS: Among 381 included patients, 125 (33%) were discharged alive with favourable outcome (CPC 1-2). Among 256 patients (77%) with unfavourable outcome (CPC 3-5), 10 were discharged alive with CPC 3 (4%), 130 died from withdrawal of life sustaining therapies because of severe neurological impairment (51%), 107 died from multiorgan failure (42%) and 9 died after discharge from complications and comorbidities (3%). OHCA and CAHP scores were independently associated with unfavourable outcome. The AUROCs to predict unfavourable outcome for OHCA, CAHP, SAPS-2 and SOFA scores were 0.76 [0.70-0.80], 0.74 [0.69-0.79], 0.72 [0.67-0.77], and 0.69 [0.64-0.74] respectively, with a significant difference observed only between OHCA and SOFA scores AUROCs (p = 0.04). CONCLUSION: In parallel with CAHP score, OHCA score could be used to early predict outcome at hospital discharge after IHCA. However, prediction accuracy for all scores remains modest, suggesting the use of other dedicated means to early predict IHCA patients' outcome.

Oseltamivir Resistance in Severe Influenza A(H1N1)pdm09 Pneumonia and Acute Respiratory Distress Syndrome: A French Multicenter Observational Cohort Study.

In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).

Methodological elements for optimising the spatial monitoring design to support regional benthic ecosystem assessments.

Benthic habitat condition assessments are a requirement under various environmental directives. The Marine Strategy Framework Directive (MSFD), for example, challenges member states in a European sea region to perform comparable assessments of good environmental status and improve coherence of their monitoring programmes by 2020. Currently, North Sea countries operate independent monitoring programmes using nationally defined assessment areas. Lack of an agreed OSPAR or EU scale monitoring method and programme has been identified as a priority science need. This paper proposes a method for the development of a coherent and efficient spatial sampling design for benthic habitats on regional level and gives advice on optimal monitoring effort to get more accurate assessments. We use ecologically relevant assessment areas (strata) across national borders and test spatial sample allocation methods. Furthermore, we investigate the number of samples needed in each stratum to reduce the variance for estimating mean number of taxa and abundance. The stratification needs to take into account the spatial heterogeneity of the entire ecosystem. The total sample effort is optimal when sample allocation takes into account the size and benthic variability within those strata. Change point analysis helps to find a balance between sampling effort and precision of the benthic parameter estimate. A joint sampling design for the North Sea could be generated by combining current efforts, and where needed adapting existing national programmes. This serves a coordinated, region-wide, benthic condition status assessment and strengthens regional cooperation to fulfil multiple monitoring tasks, with a scientifically underpinned common approach.

Long-term Quality of Life in Adult Patients Surviving Purpura Fulminans: An Exposed-Unexposed Multicenter Cohort Study.

BACKGROUND: Long-term health-related quality of life (HR-QOL) of patients surviving the acute phase of purpura fulminans (PF) has not been evaluated. METHODS: This was a French multicenter exposed-unexposed cohort study enrolling patients admitted in 55 intensive care units (ICUs) for PF from 2010 to 2016. Adult patients surviving the acute phase of PF (exposed group) were matched 1:1 for age, sex, and Simplified Acute Physiology Score II with septic shock survivors (unexposed group). HR-QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36) questionnaire, the Hospital Anxiety and Depression (HAD) scale, the Impact of Event Scale-Revised (IES-R), and the activity of daily living (ADL) and instrumental ADL (IADL) scales. The primary outcome measure was the physical component summary (PCS) of the SF-36 questionnaire. RESULTS: Thirty-seven survivors of PF and 37 of septic shock were phone-interviewed at 55 (interquartile range [IQR], 35-83) months and 44 (IQR, 35-72) months, respectively, of ICU discharge (P = .23). The PCS of the SF-36 was not significantly different between exposed and unexposed patients (median, 47 [IQR, 36-53] vs 54 [IQR, 36-57]; P = .18). There was also no significant difference between groups regarding the mental component summary of the SF-36, and the HAD, IES-R, ADL and IADL scales. Among the 37 exposed patients, those who required limb amputation (n = 12/37 [32%]) exhibited lower PCS (34 [IQR, 24-38] vs 52 [IQR, 42-56]; P = .001) and IADL scores (7 [IQR, 4-8] vs 8 [IQR, 7-8]; P = .021) compared with nonamputated patients. CONCLUSIONS: Long-term HR-QOL does not differ between patients surviving PF and those surviving septic shock unrelated to PF. Amputated patients have an impaired physical HR-QOL but a preserved mental health. CLINICAL TRIALS REGISTRATION: NCT03216577.

Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study.

PURPOSE: Data on purpura fulminans (PF) in adult patients are scarce and mainly limited to meningococcal infections. Our aim has been to report the clinical features and outcomes of adult patients admitted in the intensive care unit (ICU) for an infectious PF, as well as the predictive factors for limb amputation and mortality. METHODS: A 17-year national multicenter retrospective cohort study in 55 ICUs in France from 2000 to 2016, including adult patients admitted for an infectious PF defined by a sudden and extensive purpura, together with the need for vasopressor support. Primary outcome variables included hospital mortality and amputation during the follow-up period (time between ICU admission and amputation, death or end of follow-up). RESULTS: Among the 306 included patients, 126 (41.2%; 95% CI 35.6-46.9) died and 180 (58.8%; 95% CI 53.3-64.3) survived during the follow-up period [13 (3-24) days], including 51/180 patients (28.3%, 95% CI 21.9-35.5) who eventually required limb amputations, with a median number of 3 (1-4) limbs amputated. The two predominantly identified microorganisms were Neisseria meningitidis (63.7%) and Streptococcus pneumoniae (21.9%). By multivariable Cox model, SAPS II [hazard-ratio (HR) = 1.03 (1.02-1.04); p < 0.001], lower leucocytes [HR 0.83 (0.69-0.99); p = 0.034] and platelet counts [HR 0.77 (0.60-0.91); p = 0.007], and arterial blood lactate levels [HR 2.71 (1.68-4.38); p < 0.001] were independently associated with hospital death, while a neck stiffness [HR 0.51 (0.28-0.92); p = 0.026] was a protective factor. Infection with Streptococcus pneumoniae [sub-hazard ratio 1.89 (1.06-3.38); p = 0.032], together with arterial lactate levels and ICU admission temperature, was independently associated with amputation by a competing risks analysis. CONCLUSION: Purpura fulminans carries a high mortality and morbidity. Pneumococcal PF leads to a higher risk of amputation. TRIALS REGISTRATION: NCT03216577.

First Step Towards a Devil's Staircase in Spin-Crossover Materials.

The unprecedented bimetallic 2D coordination polymer {Fe[(Hg(SCN)3 )2 ](4,4'-bipy)2 }n exhibits a thermal high-spin (HS)↔low-spin (LS) staircase-like conversion characterized by a multi-step dependence of the HS molar fraction γHS . Between the fully HS (γHS =1) and LS (γHS =0) phases, two steps associated with different ordering appear in terms of spin-state concentration waves (SSCW). On the γHS ≈0.5 step, a periodic SSCW forms with a HS-LS-HS-LS sequence. On the γHS ≈0.34 step, the 4D superspace crystallography structural refinement reveals an aperiodic SSCW, with a HS-LS sequence incommensurate with the molecular lattice. The formation of these different long-range spatially ordered structures of LS and HS states during the multi-step spin-crossover is discussed within the framework of "Devil's staircase"-type transitions. Spatially modulated phases are known in various types of materials but are uniquely related to molecular HS/LS bistability in this case.

The Use of Ultrasound in Caring for Patients with Sepsis.

Echocardiography is a noninvasive and accurate tool used in the intensive care unit to assess cardiac function and monitor hemodynamics in shocked patients. During severe sepsis or septic shock, several mechanisms can lead to hemodynamic failure and have to be quickly and precisely diagnosed to propose adequate, personalized, and timely hemodynamic therapy. Echocardiography truly provides intensivists with this diagnostic possibility, whether or not there is fluid responsiveness, cardiac dysfunction, or persistent vasoplegia. Acquiring skills in critical care echocardiography is mandatory in improving management and monitoring of patients with sepsis at the bedside. How critical care echocardiography in managing patients with septic shock improves prognosis remains to be elucidated.