Evaluation of Endocan as a Treatment for Acute Inflammatory Respiratory Failure.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition resulting from acute pulmonary inflammation. However, no specific treatment for ARDS has yet been developed. Previous findings suggest that lung injuries related to ARDS could be regulated by endocan (Esm-1). The aim of this study was to evaluate the potential efficiency of endocan in the treatment of ARDS. METHODS: We first compared the features of acute pulmonary inflammation and the severity of hypoxemia in a tracheal LPS-induced acute lung injury (ALI) model performed in knockout (Esm1-/-) and wild type (WT) littermate C57Bl/6 mice. Next, we assessed the effects of a continuous infusion of glycosylated murine endocan in our ALI model in Esm1-/- mice. RESULTS: In our ALI model, we report higher alveolar leukocytes (p < 0.001), neutrophils (p < 0.001), and MPO (p < 0.001), and lower blood oxygenation (p < 0.001) in Esm1-/- mice compared to WT mice. Continuous delivery of glycosylated murine endocan after LPS-induced ALI resulted in decreased alveolar leukocytes (p = 0.012) and neutrophils (p = 0.012), higher blood oxygenation levels (p < 0.001), and reduced histological lung injury (p = 0.04), compared to mice treated with PBS. CONCLUSIONS: Endocan appears to be an effective treatment in an ARDS-like model in C57Bl/6 mice.

Effects of high oxygen tension on healthy volunteer microcirculation.

INTRODUCTION: Previous studies have highlighted hyperoxia-induced microcirculation modifications, but few have focused on hyperbaric oxygen (HBO) effects. Our primary objective was to explore hyperbaric hyperoxia effects on the microcirculation of healthy volunteers and investigate whether these modifications are adaptative or not. METHODS: This single centre, open-label study included 15 healthy volunteers. Measurements were performed under five conditions: T0) baseline value (normobaric normoxia); T1) hyperbaric normoxia; T2) hyperbaric hyperoxia; T3) normobaric hyperoxia; T4) return to normobaric normoxia. Microcirculatory data were gathered via laser Doppler, near-infrared spectroscopy and transcutaneous oximetry (PtcO2). Vascular-occlusion tests were performed at each step. We used transthoracic echocardiography and standard monitoring for haemodynamic investigation. RESULTS: Maximal alterations were observed under hyperbaric hyperoxia which led, in comparison with baseline, to arterial hypertension (mean arterial pressure 105 (SD 12) mmHg vs 95 (11), P < 0.001) and bradycardia (55 (7) beats·min⁻¹ vs 66 (8), P < 0.001) while cardiac output remained unchanged. Hyperbaric hyperoxia also led to microcirculatory vasoconstriction (rest flow 63 (74) vs 143 (73) perfusion units, P < 0.05) in response to increased PtcO2 (104.0 (45.9) kPa vs 6.3 (2.4), P < 0.0001); and a decrease in laser Doppler parameters indicating vascular reserve (peak flow 125 (89) vs 233 (79) perfusion units, P < 0.05). Microvascular reactivity was preserved in every condition. CONCLUSIONS: Hyperoxia significantly modifies healthy volunteer microcirculation especially during HBO exposure. The rise in PtcO2 promotes an adaptative vasoconstrictive response to protect cellular integrity. Microvascular reactivity remains unaltered and vascular reserve is mobilised in proportion to the extent of the ischaemic stimulus.

Band-selective universal 90° and 180° rotation pulses covering the aliphatic carbon chemical shift range for triple resonance experiments on 1.2 GHz spectrometers.

Biomolecular NMR spectroscopy requires large magnetic field strengths for high spectral resolution. Today's highest fields comprise proton Larmor frequencies of 1.2 GHz and even larger field strengths are to be expected in the future. In protein triple resonance experiments, various carbon bandwidths need to be excited by selective pulses including the large aliphatic chemical shift range. When the spectrometer field strength is increased, the length of these pulses has to be decreased by the same factor, resulting in higher rf-amplitudes being necessary in order to cover the required frequency region. Currently available band-selective pulses like Q3/Q5 excite a narrow bandwidth compared to the necessary rf-amplitude. Because the maximum rf-power allowed in probeheads is limited, none of the selective universal rotation pulses reported so far is able to cover the full [Formula: see text]C aliphatic region on 1.2 GHz spectrometers. In this work, we present band-selective 90° and 180° universal rotation pulses (SURBOP90 and SURBOP180) that have a higher ratio of selective bandwidth to maximum rf-amplitude than standard pulses. Simulations show that these pulses perform better than standard pulses, e. g. Q3/Q5, especially when rf-inhomogeneity is taken into account. The theoretical and experimental performance is demonstrated in offset profiles and by implementing the SURBOP pulses in an HNCACB experiment at 1.2 GHz.

Risk factors for difficult ventilatory weaning in intensive care patients with cervical cellulitis.

PURPOSE: Cervical cellulitis is an infrequent but serious infection. The management of the upper airways is difficult, at the actual time of intubation but also regarding the necessity of maintaining mechanical ventilation. The objective of this study is to identify risk factors on admission to the intensive care unit for difficult ventilatory weaning in patients with cervical cellulitis. METHODS: Between January 2013 and December 2018, this retrospective observational study was performed in an intensive care unit with 10 beds in a university hospital recognized as a reference center for the management of cellulitis. All intensive care patients receiving mechanical ventilation after surgery for cervical cellulitis were eligible. Difficult ventilatory weaning was defined as mechanical ventilation lasting more than 7 days or failure of extubation as established by the WIND 2017 study. RESULTS: We included 120 patients with severe cervical cellulitis. The median age was 43 years. Eighteen patients (16%) presented mediastinal extension. The risk factor for difficult ventilatory weaning (n = 49) in multivariate analysis was a high level of procalcitonin on admission (OR at 1.14[1.005-1.29]; p<0.042) and the protective factor was surgery in an expert center (OR at 0.11[0.026-0.47]; p<0.003). Eight patients required a tracheotomy in our study: 3 patients during surgery and at a later time for the other 5 of our 8 patients. CONCLUSION: No intensive care studies have investigated ventilatory weaning risk factors in patients with cervical cellulitis. Yet simple criteria seem to predict this risk. It is now necessary to confirm them by a multicenter prospective study.

Marine Dissolved Organic Matter Shares Thousands of Molecular Formulae Yet Differs Structurally across Major Water Masses.

Most oceanic dissolved organic matter (DOM) is still not fully molecularly characterized. We combined high-field nuclear magnetic resonance (NMR) and ultrahigh-resolution mass spectrometry (Fourier-transform ion cyclotron resonance mass spectrometry, FT-ICR-MS) for the structural and molecular formula-level characterization of solid-phase extracted (SPE) DOM from surface, mesopelagic, and bathypelagic Atlantic and Pacific Ocean samples. Using a MicroCryoProbe, unprecedented low amounts of SPE-DOM (∼1 mg carbon) were sufficient for two-dimensional NMR analysis. Low proportions of olefinic and aromatic relative to aliphatic and carboxylated structures (NMR) at the sea surface were likely related to photochemical transformations. This was consistent with lower molecular masses and higher degrees of saturation and oxygenation (FT-ICR-MS) compared to those of the deep sea. Carbohydrate structures in the mesopelagic North Pacific Ocean suggest export and release from sinking particles. In our sample set, the universal molecular DOM composition, as captured by FT-ICR-MS, appears to be structurally more diverse when analyzed by NMR, suggesting DOM variability across oceanic provinces to be more pronounced than previously assumed. As a proof of concept, our study takes advantage of new complementary approaches resolving thousands of structural and molecular DOM features while applying reasonable instrument times, allowing for the analysis of large oceanic data sets to increase our understanding of marine DOM biogeochemistry.

Vascular skin manifestations in patients with severe COVID-19 in intensive care units: a monocentric prospective study.

Various skin manifestations have been reported during the coronavirus disease 2019 (COVID-19) pandemic. Among these are acral vascular skin lesions in non-severe patients, but few studies have focused specifically on patients with severe COVID-19 admitted to the intensive care unit (ICU) We aimed to assess the frequency of acral vascular skin manifestations (AVSM) in patients admitted to the ICU based on systematic dermatological examination We conducted a clinical, observational and prospective study in the ICU of Lille University Hospital (France). All adult patients with RT-PCR-confirmed severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection were included on May 5th and 6th, 2020 A total of 39 patients with severe COVID-19 were examined (34 males and five females; median age: 61 [55-59]). We observed AVSM in 11/39 patients (28%) including five with acral necrotic lesions, three with haemorrhagic blisters, one with acral livedoid rash, and one with erosive distal lesions. Chilblain or chilblain-like lesions were not seen, unlike ambulatory or non-severe patients described in the literature. There was no difference regarding the median length of stay in the ICU, initial symptoms of COVID-19 or baseline characteristics, except for a lower BMI in patients with AVSM. All patients had biological coagulation abnormalities (e.g. higher levels of fibrinogen or D-dimers), but there was no difference between patients with and without AVSM AVSM are infrequent and heterogenous and seem to be non-specific to patients with severe SARS-CoV-2, and possibly unrelated to COVID-19. The pathophysiology of AVSM described during the COVID-19 pandemic is not fully elucidated.

1H, 13C and 15N assignment of stem-loop SL1 from the 5'-UTR of SARS-CoV-2.

The stem-loop (SL1) is the 5'-terminal structural element within the single-stranded SARS-CoV-2 RNA genome. It is formed by nucleotides 7-33 and consists of two short helical segments interrupted by an asymmetric internal loop. This architecture is conserved among Betacoronaviruses. SL1 is present in genomic SARS-CoV-2 RNA as well as in all subgenomic mRNA species produced by the virus during replication, thus representing a ubiquitous cis-regulatory RNA with potential functions at all stages of the viral life cycle. We present here the 1H, 13C and 15N chemical shift assignment of the 29 nucleotides-RNA construct 5_SL1, which denotes the native 27mer SL1 stabilized by an additional terminal G-C base-pair.

Treating ARDS-associated air embolism: a question of priorities.

Gas embolism is a potential and often life-threatening complication of central venous catheters. We report a case of air embolism after tearing of the central catheter associated with severe acute respiratory distress syndrome. The severity of the clinical situation meant choices had to be made regarding the order of treatments. This clinical case provided useful eye-openers for patient management regarding the prioritization of treatments as well as the possibilities offered by hyperbaric oxygen therapy.

Neurophysiological findings and their prognostic value in critical COVID-19 patients: An observational study.

OBJECTIVE: To describe EEG patterns of critical Coronavirus Disease 2019 (COVID-19) patients with suspicion of encephalopathy and test their association with clinical outcome. METHODS: EEG after discontinuation of sedation in all patients, and somesthesic evoked potentials and brainstem auditive evoked potentials when EEG did not show reactivity, were performed. Clinical outcome was assessed at day 7 and 14 after neurophysiological explorations. RESULTS: 33 patients were included for analysis. We found slowed background activity in 85% of cases, unreactive activity in 42% of cases, low-voltage activity in 21% of cases and rhythmic or periodic delta waves in 61% of cases. EEG epileptic events were never recorded. Clinical outcome at day 14 was associated with unreactive background activity and tended to be associated with rhythmic or periodic delta waves and with low-voltage activity. Results of multimodal evoked potentials were in favor of a preservation of central nervous system somatosensory and auditory functions. CONCLUSIONS: Among critical COVID-19 patients with abnormal arousal at discontinuation of sedation, EEG patterns consistent with encephalopathy are found and are predictive for short term clinical outcome. SIGNIFICANCE: The abnormal EEG with presence of periodic discharges and lack of reactivity could be related to encephalopathy linked to COVID-19.

Almitrine Infusion in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Respiratory Distress Syndrome: A Single-Center Observational Study.

OBJECTIVES: Treating acute respiratory failure in patients with coronavirus disease 2019 is challenging due to the lack of knowledge of the underlying pathophysiology. Hypoxemia may be explained in part by the loss of hypoxic pulmonary vasoconstriction. The present study assessed the effect of almitrine, a selective pulmonary vasoconstrictor, on arterial oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome. DESIGN: Single-center retrospective observational study. SETTING: ICU of Lille Teaching Hospital, France, from February 27, 2020, to April 14, 2020. PATIENTS: Patients with coronavirus disease 2019 pneumonia confirmed by positive reverse transcriptase-polymerase chain reaction for severe acute respiratory syndrome-coronavirus 2 and acute respiratory distress syndrome according to Berlin definition. Data focused on clinicobiological features, ventilator settings, therapeutics, outcomes, and almitrine-related adverse events. INTERVENTIONS: Almitrine was considered in patients with severe hypoxemia (Pao2/Fio2 ratio < 150 mm Hg) in addition to the recommended therapies, at an hourly IV delivery of 10 µg/kg/min. Comparative blood gases were done before starting almitrine trial and immediately after the end of the infusion. A positive response to almitrine was defined by an increase of Pao2/Fio2 ratio greater than or equal to 20% at the end of the infusion. MEASUREMENTS AND MAIN RESULTS: A total of 169 patients were enrolled. Thirty-two patients with acute respiratory distress syndrome received an almitrine infusion trial. In most cases, almitrine was infused in combination with inhaled nitric oxide (75%). Twenty-one patients (66%) were responders. The median Pao2/Fio2 ratio improvement was 39% (9-93%) and differs significantly between the responders and nonresponders (67% [39-131%] vs 6% [9-16%], respectively; p < 0.0001). The 28-day mortality rates were 47.6% and 63.6% (p = 0.39) for the responders and nonresponders, respectively. Hemodynamic parameters remained similar before and after the trial, not suggesting acute cor pulmonale. CONCLUSIONS: Almitrine infusion improved oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome without adverse effects. In a multistep clinical approach to manage severe hypoxemia in this population, almitrine could be an interesting therapeutic option to counteract the loss of hypoxic pulmonary vasoconstriction and redistribute blood flow away from shunting zones.

One Outbreak Could Hide Another.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a major worldwide concern. Guidelines have been issued regarding precautions for healthcare workers caring for SARS-CoV-2-infected patients. Despite accurate observance of infection control measures, including contact precautions, we encountered an OXA-23-producing Acinetobacter baumannii outbreak in 5 intensive care units of 10 beds each in our tertiary care teaching hospital.

Evaluation of pressure in water-filled endotracheal tube cuffs in intubated patients undergoing hyperbaric oxygen treatment.

INTRODUCTION: Inflating endotracheal tube cuffs using water instead of air before hyperbaric oxygen treatment (HBOT) is common. The objective of this study was to assess cuff pressure (Pcuff), when the cuff was inflated using water, in normobaric conditions and during HBOT. METHODS: This was a prospective, observational study taking place in hyperbaric centre and intensive care unit of the University Hospital of Lille. Every patient who required tracheal intubation and HBOT at 253.3 kPa (2.5 atmospheres absolute [atm abs]) was included. Pcuff was measured using a pressure transductor connected to the cuff inflating port. Measurements were performed at 'normobaria' (1 atm abs) and during HBOT at 2.5 atm abs. RESULTS: Thirty patients were included between February and April 2016. Recordings were analysable in 27 patients. Mean Pcuff at normobaria was 60.8 (SD 42) cmH2O. Nineteen (70%) of patients had an excessive Pcuff (higher than 30 cmH2O). Coefficient of variation was 69%. Mean Pcuff at 2.5 atm abs was 51.6 (40.7) cmH2O, significantly lower than at normobaria (P < 0.0001). Coefficient of variation was 79%. In only five (18%) patients was Pcuff < 20 cmH2O at 2.5 atm abs. CONCLUSIONS: In normobaric conditions, when the cuff was inflated using water and not specifically controlled Pcuff was not predictable. The cuff was typically over-inflated exceeding safe pressure. During HBOT Pcuff decreased slightly.

Enabling NMR Studies of High Molecular Weight Systems Without the Need for Deuteration: The XL-ALSOFAST Experiment with Delayed Decoupling.

Current biological research increasingly focusses on large human proteins and their complexes. Such proteins are difficult to study by NMR spectroscopy because they often can only be produced in higher eukaryotic expression systems, where deuteration is hardly feasible. Here, we present the XL-ALSOFAST-[13 C,1 H]-HMQC experiment with much improved sensitivity for fully protonated high molecular weight proteins. For the tested systems ranging from 100 to 240 kDa in size, 3-fold higher sensitivity was obtained on average for fast relaxing signals compared to current state-of-the-art experiments. In the XL-ALSOFAST approach, non-observed magnetisation is optimally exploited and transverse relaxation is minimized by the newly introduced concept of delayed decoupling. The combination of high sensitivity and superior artefact suppression makes it ideal for studying inherently unstable membrane proteins or for analysing therapeutic antibodies at natural 13 C abundance. The XL-ALSOFAST and delayed decoupling will therefore expand the range of biomolecular systems accessible to NMR spectroscopy.

High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation.

OBJECTIVE: The COVID-19 pandemic is rapidly spreading worldwide, notably in Europe and North America where obesity is highly prevalent. The relation between obesity and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has not been fully documented. METHODS: This retrospective cohort study analyzed the relationship between clinical characteristics, including BMI, and the requirement for invasive mechanical ventilation (IMV) in 124 consecutive patients admitted in intensive care for SARS-CoV-2 in a single French center. RESULTS: Obesity (BMI > 30) and severe obesity (BMI > 35) were present in 47.6% and 28.2% of cases, respectively. Overall, 85 patients (68.6%) required IMV. The proportion of patients who required IMV increased with BMI categories (P < 0.01, χ2 test for trend), and it was greatest in patients with BMI > 35 (85.7%). In multivariate logistic regression, the need for IMV was significantly associated with male sex (P < 0.05) and BMI (P < 0.05), independent of age, diabetes, and hypertension. The odds ratio for IMV in patients with BMI > 35 versus patients with BMI < 25 was 7.36 (1.63-33.14; P = 0.02). CONCLUSIONS: The present study showed a high frequency of obesity among patients admitted in intensive care for SARS-CoV-2. Disease severity increased with BMI. Obesity is a risk factor for SARS-CoV-2 severity, requiring increased attention to preventive measures in susceptible individuals.

Cleaved endocan acts as a biologic competitor of endocan in the control of ICAM-1-dependent leukocyte diapedesis.

Dysregulated leukocyte diapedesis is a major contributor to acute severe inflammatory states like sepsis and acute respiratory distress syndrome, which are common conditions in critically ill subjects. Endocan is a circulating proteoglycan that binds to the leukocyte integrin LFA-1 and blocks its interaction with its endothelial ligand ICAM-1, subsequently leading to the inhibition of leukocyte recruitment. Recent data have highlighted the hypothetic role of p14, endocan's major catabolite found in the bloodstream of septic patients, as a potential antagonist of endocan, thus participating in the regulation of acute inflammation. We hereby characterize the role of p14 as a biologic competitor of endocan, through assessment of its molecular interactions with LFA-1, endocan, and ICAM-1, as well as its effects on human leukocyte trafficking. Using immunodetection assay, we report that p14 can bind to LFA-1, thus inhibiting the interaction between LFA-1 and endocan, which in turn leads to the restoration of the ICAM-1/LFA-1 interaction. In primary human T cells trafficking assays, we underline the absence of effect of p14 on ICAM-1-dependent adhesion and migration, as well as on transendothelial migration. However, in those models, p14 reverses the antimigratory effect of endocan. To conclude, our study supports the hypothesis of an antagonistic role of p14 versus endocan in its effect on the LFA-1/ICAM-1-dependent human leukocyte recruitment.

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study.

BACKGROUND: The use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored. METHODS: We conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models. RESULTS: Among 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively. CONCLUSION: Hydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03558646.