Advanced waveform analysis of diaphragm surface EMG allows for continuous non-invasive assessment of respiratory effort in critically ill patients at different PEEP levels.

BACKGROUND: Respiratory effort should be closely monitored in mechanically ventilated ICU patients to avoid both overassistance and underassistance. Surface electromyography of the diaphragm (sEMGdi) offers a continuous and non-invasive modality to assess respiratory effort based on neuromuscular coupling (NMCdi). The sEMGdi derived electrical activity of the diaphragm (sEAdi) is prone to distortion by crosstalk from other muscles including the heart, hindering its widespread use in clinical practice. We developed an advanced analysis as well as quality criteria for sEAdi waveforms and investigated the effects of clinically relevant levels of PEEP on non-invasive NMCdi. METHODS: NMCdi was derived by dividing end-expiratory occlusion pressure (Pocc) by sEAdi, based on three consecutive Pocc manoeuvres at four incremental (+ 2 cmH2O/step) PEEP levels in stable ICU patients on pressure support ventilation. Pocc and sEAdi quality was assessed by applying a novel, automated advanced signal analysis, based on tolerant and strict cut-off criteria, and excluding inadequate waveforms. The coefficient of variations (CoV) of NMCdi after basic manual and automated advanced quality assessment were evaluated, as well as the effect of an incremental PEEP trial on NMCdi. RESULTS: 593 manoeuvres were obtained from 42 PEEP trials in 17 ICU patients. Waveform exclusion was primarily based on low sEAdi signal-to-noise ratio (Ntolerant = 155, 37%, Nstrict = 241, 51% waveforms excluded), irregular or abrupt cessation of Pocc (Ntolerant = 145, 35%, Nstrict = 145, 31%), and high sEAdi area under the baseline (Ntolerant = 94, 23%, Nstrict = 79, 17%). Strict automated assessment allowed to reduce CoV of NMCdi to 15% from 37% for basic quality assessment. As PEEP was increased, NMCdi decreased significantly by 4.9 percentage point per cmH2O. CONCLUSION: Advanced signal analysis of both Pocc and sEAdi greatly facilitates automated and well-defined identification of high-quality waveforms. In the critically ill, this approach allowed to demonstrate a dynamic NMCdi (Pocc/sEAdi) decrease upon PEEP increments, emphasising that sEAdi-based assessment of respiratory effort should be related to PEEP dependent diaphragm function. This novel, non-invasive methodology forms an important methodological foundation for more robust, continuous, and comprehensive assessment of respiratory effort at the bedside.

Computational physiological models for individualised mechanical ventilation: a systematic literature review focussing on quality, availability, and clinical readiness.

BACKGROUND: Individualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness. METHODS: A systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards. RESULTS: Out of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively. CONCLUSION: CPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential. Trial registration number PROSPERO- CRD42022301715 . Registered 05 February, 2022.

Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Attitudes of Dutch intensive care unit clinicians towards oxygen therapy.

BACKGROUND: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands. METHODS: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios. RESULTS: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO2) of 85-90% as acceptable for 15 minutes, and a PaO2 7-10 kPa (53-75 mmHg) and SaO2 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO2) if SaO2 was 90-95% or PaO2 was 12 kPa (90 mmHg). CONCLUSION: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO2 targets in the lower physiological range and would adjust ventilation settings accordingly.

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals.

BACKGROUND: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. AIM: To determine the prevalence of Do Not Resuscitate (DNR)-orders, to describe recollection of CPR-directive conversations and factors associated with patient recollection and understanding. METHODS: This was a two-week nationwide multicentre cross-sectional observational study using a study-specific survey. The study population consisted of patients admitted to non-monitored wards in 13 hospitals. Data were collected from the electronic medical record (EMR) concerning CPR-directive, comorbidity and at-home medication. Patients reported their perception and expectations about CPR-counselling through a questionnaire. RESULTS: A total of 1136 patients completed the questionnaire. Patients' CPR-directives were documented in the EMR as follows: 63.7% full code, 27.5% DNR and in 8.8% no directive was documented. DNR was most often documented for patients >80 years (66.4%) and in patients using >10 medications (45.3%). Overall, 55.8% of patients recalled having had a conversation about their CPR-directive and 48.1% patients reported the same CPR-directive as the EMR. Most patients had a good experience with the CPR-directive conversation in general (66.1%), as well as its timing (84%) and location (94%) specifically. CONCLUSIONS: The average DNR-prevalence is 27.5%. Correct understanding of their CPR-directive is lowest in patients aged ≥80 years and multimorbid patients. CPR-directive counselling should focus more on patient involvement and their correct understanding.

Permanently densified SiO2 glasses: a structural approach.

Densified silica can be obtained by different pressure and temperature paths and for different stress conditions, hydrostatic or including shear. The density is usually the macroscopic parameter used to characterize the different compressed silica samples. The aim of our present study is to compare structural modifications for silica glass, densified from several routes. For this, densified silica glasses are prepared from cold and high temperature (up to 1020 °C) compressions. The different densified glasses obtained in our study are characterized by micro-Raman spectroscopy. Intertetrahedral angles from the main band relative to the bending mode decrease and their values are larger for densified samples from high temperature compression than those samples from cold compression. The relative amount of 3-membered rings deduced from the D2 line area increases as a function of density for cold compression. The temperature increase during the compression process induces a decrease of the 3 fold ring population. Moreover, 3 fold rings are more deformed and stressed for densified samples at room temperature at the expense of those densified at high temperature. Temperature plays a main role in the reorganization structure during the densification and leads to obtaining a more relaxed structure with lower stresses than glasses densified from cold compression. The role of hydrostatic or non-hydrostatic applied stresses on the glass structure is discussed. From the Sen and Thorpe central force model, intertetrahedral angle average value and their distribution are estimated.

Background elimination and interferometric capability in optical coherence tomography by a nonlinear optical gating based on type-II second-harmonic generation.

A novel method that uses nonlinear optical gating to control background illumination in optical coherence tomography is presented. With this method, the user can adjust the amount of undesired backscattering or eliminate it completely, which enables dark-field measurements. The interferometric capability of the method in a nonlinear optical regime is demonstrated with the coupling of three overlapping input waves to yield Fizeau fringes. The measurement of a 265 nm step is performed to validate this method, which was originally conceived for 3D MEMS characterization.

A transfer hamiltonian model for devices based on quantum dot arrays.

We present a model of electron transport through a random distribution of interacting quantum dots embedded in a dielectric matrix to simulate realistic devices. The method underlying the model depends only on fundamental parameters of the system and it is based on the Transfer Hamiltonian approach. A set of noncoherent rate equations can be written and the interaction between the quantum dots and between the quantum dots and the electrodes is introduced by transition rates and capacitive couplings. A realistic modelization of the capacitive couplings, the transmission coefficients, the electron/hole tunneling currents, and the density of states of each quantum dot have been taken into account. The effects of the local potential are computed within the self-consistent field regime. While the description of the theoretical framework is kept as general as possible, two specific prototypical devices, an arbitrary array of quantum dots embedded in a matrix insulator and a transistor device based on quantum dots, are used to illustrate the kind of unique insight that numerical simulations based on the theory are able to provide.

Synthesis of bio-inspired multilayer polarizers and their application to anti-counterfeiting.

Some insects, such as Papilio blumei and Suneve coronata, are known for exhibiting polarization effects on light such as color contrast or geometrical polarization rotation by reflection on their wing scales. The photonic structures found on these species that show these properties are multilayered spherical cavities or triangular grooves which polarize the light due to multiple inner reflections. These polarization effects, in addition to the intrinsic color-mixing properties of these photonic structures, are of interest in the anti-counterfeiting field due to their invisibility to the naked eye. In this paper, we report micro-fabrication techniques to produce bio-inspired cylindrical grooves (C-grooves) and triangular grooves (V-grooves) that demonstrate the same properties. Theoretical analyses were carried out by using multi-scale simulation (MS) as well as by finite-difference time-domain (FDTD) in order to compare the polarization capability of both structures. The V-grooves show greater polarization contrast than the C-grooves, but the spectrum is specular. The C-grooves exhibit lower polarization effects but have a dispersive spectrum. In both cases, the structures show additional optical properties, such as diffraction, macroscopic color contrast under a polarizer, and contrast inversion due to geometries which contribute to their uniqueness.

Flexible sensor based on carbon nanofibers with multifunctional sensing features.

Herein, we present the fabrication and characterization of a flexible gas sensor based on carbon nanofibers. The sensing device is composed of interdigitated silver electrodes deposited by inkjet printing on Kapton substrates, subsequently coated with carbon nanofibers as sensing element. Gas sensing response to CO, NH3 and humidity has been characterized in detail. Thermal, mechanical and electromagnetic radiation effects have also been studied and discussed from the point of view of the cross-sensitivity. The obtained results open the door for a new generation of flexible sensors with multifunctional sensing features, which are producible with scalable techniques based on low cost nanomaterials.

Activated protein C attenuates pulmonary coagulopathy in patients with acute respiratory distress syndrome.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) frequently complicates critical illness. We hypothesized that an infusion of recombinant human activated protein C (rh-APC), a natural anticoagulant, would attenuate pulmonary coagulopathy and injury. METHODS: In this sub study of a multicenter open-label randomized controlled trial of patients with ARDS, we compared an intravenous (i.v.) infusion of rh-APC (24 mcg kg(-1)  h(-1) for 96 h) with placebo. Patients with sepsis or septic shock were excluded. RESULTS: In 27 patients serial non-directed bronchoalveolar lavage fluid (NBLF) samples were obtained: 16 patients were treated with rh-APC and 11 patients with placebo. The rh-APC infusion was associated with higher APC levels in plasma during the infusion period of 4 days (P = 0.001), as well as higher APC levels in NBLF up to day 5 after the start of the infusion (P = 0.028). An infusion of rh-APC was associated with lower levels of thrombin-antithrombin complexes (P = 0.009) and soluble tissue factor (P = 0.011) in NBLF, compared with treatment with placebo. An infusion of rh-APC affected fibrinolysis, as plasminogen activator activity levels in NBLF were higher in the patients treated with rh-APC (P = 0.01), presumably as a result of lower NBLF levels of plasminogen activator inhibitor 1, (P = 0.01). The rh-APC infusion decreased the lung injury score (P = 0.005) and simplified the acute physiology score (P = 0.013) on day 5, when compared with baseline. The rh-APC infusion was not associated with bleeding complications. CONCLUSION: An infusion of rh-APC in patients with ARDS attenuates pulmonary coagulopathy and injury.

Functional characterization of new allelic polymorphisms identified in the promoter region of the human MxA gene.

The Mx proteins are high-molecular-weight dynamin-like proteins whose expression depends strictly on type-I and type-III interferons (IFN). Some isoforms are able to inhibit the life cycle of one or several viruses and are thus components of innate immune response. The human MxA protein displays the broadest antiviral spectrum which makes it appear as a key antiviral effector of innate immunity. Allelic polymorphisms located in the MxA gene promoter can be expected to affect the magnitude of MxA mRNA transcription in response to IFNs and therefore to alter the severity of viral diseases in humans. Here, three single nucleotide polymorphism sites (-309, -101 and +20) were examined for their ability to alter MxA gene promoter-driven reporter expression. We show that, besides the previously reported role of -123A and -88T, the presence of -101G is equally important. Moreover, when a promoter construct carries these three critical nucleotides, a first additional positive effect is conferred by a C at position -309 and, in this latter case, a second additional effect is produced by a A at position +20. This finding is clinically useful to improve prediction of IFN-responsiveness in patients not only with viral diseases for which type-I IFN therapy is used.

[Pregnancy and antiphospholipid syndrome]. / Grossesse et syndrome des antiphospholipides.

Antiphospholipid syndrome (APS) is associated with a risk of obstetrical complications, affecting both the mother and the fetus. Obstetrical APS is defined by a history of three consecutive spontaneous miscarriages before 10 weeks of gestation (WG), an intra-uterine fetal death after 10 WG, or a premature birth before 34 WG because of severe pre-eclampsia, eclampsia or placental adverse outcomes (intrauterine growth retardation, oligohydramnios). Pregnancy in women with a diagnosis of obstetric APS is at increased risk for placental abruption, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome and thrombosis that may be part of a catastrophic antiphospholipid syndrome (CAPS). A previous thrombosis and the presence of a lupus anticoagulant are risk factors for pregnancy failure. A multidisciplinary approach, associating the internist, the anesthesiologist and the obstetrician, is recommended for these high-risk pregnancies. Preconception counseling is proposed to identify pregnancy contraindications, and to define and adapt the treatment prior and during the upcoming pregnancy. Heparin and low-dose aspirin are the main treatments. The choice between therapeutic or prophylactic doses of heparin will depend on the patient's medical history. The anticoagulant therapeutic window for delivery should be as narrow as possible and adapted to maternal thrombotic risk. There is a persistent maternal risk in the postpartum period (thrombosis, HELLP syndrome, CAPS) justifying an antithrombotic coverage during this period. We suggest a monthly clinical and biological monitoring which can be more frequent towards the end of pregnancy. The persistence of notches at the Doppler-ultrasound evaluation seems to be the best predictor for a higher risk of placental vascular complications. Treatment optimization and multidisciplinary antenatal care improve the prognosis of pregnancies in women with obstetric APS, leading to a favorable outcome most of the time.

Management of obstetric perineal tears: do obstetrics and gynaecology residents receive adequate training? Results of an anonymous survey.

Background/Aim. To evaluate the obstetrics and gynaecology residents' perspective of their training and experience in the management of perineal tears that occur during assisted vaginal delivery. We hypothesised that residents would perceive room for improvement in their knowledge of pelvic floor anatomy and the training received in tears repair. Design. Descriptive cross-sectional study. Population/Setting. Seventy-two major residents from all teaching hospitals in Catalonia. Methods. A questionnaire was designed to evaluate experience, perception of the training and supervision provided. Results. The questionnaire was sent to all residents (n = 72), receiving 46 responses (64%). The participants represented 15 out of the 16 teaching hospitals included in the study (94% of the hospitals represented). Approximately, 52% of residents were in their third year while 48% were in their fourth. The majority of them thought that their knowledge of pelvic floor anatomy was poor (62%), although 98% felt confident that they would know when an episiotomy was correctly indicated. The survey found that they lacked experience in the repair of major degree tears (70% had repaired fewer than ten), and most did not carry out followup procedures. Conclusion. The majority of them indicated that more training in this specific area is necessary (98%).

Pulmonary effects of red blood cell transfusion in critically ill, non-bleeding patients.

The aim of the study is to evaluate the effects of red blood cell (RBC) transfusions on pulmonary parameters in critically ill, non-bleeding patients. Retrospective chart analysis was performed on critically ill patients without overt bleeding in the intensive care unit (ICU) of a university hospital. In 83 patients in a 5-month period, who had received at least 1 RBC unit and stayed at least 24 h in the ICU, 199 transfusions of median 2 RBCs per transfusion (n = 504) were studied. Pulmonary parameters were retrieved during the period between 24 h before the start of transfusion and 24-48 h after transfusion. Outcome was assessed. The P(a)O(2)/F(I)O(2) dose-dependently decreased from 250 +/- 105 at baseline to 240 +/- 102 mmHg at 24 h after RBC transfusion (P = 0.003), irrespective of acute lung injury at baseline and RBC storage time. The lung injury score (LIS) also increased dose-dependently, whereas, at 48 h, oxygenation and LIS largely returned to baseline. For every seven RBCs transfused, the LIS transiently increased by 1 unit. There were no changes in haemodynamics, lung mechanics or chest radiography. The total number of RBCs given in the ICU did not directly contribute to ICU and 1-year mortality prediction. Transfusion of RBCs decreases oxygenation thereby increasing the LIS, dose-dependently and transiently, in a heterogeneous population of critically ill, non-bleeding patients, independent of prior cardiorespiratory status and RBC storage time. The effects are subtle, may go unseen and unreported and may represent subclinical transfusion-related acute lung injury. They do not adversely affect outcome, even at 1-year follow-up.

Direct imaging of the visible emission bands from individual ZnO nanowires by near-field optical spectroscopy.

Room-temperature photoluminescence (PL) measurements have been performed on single-crystal ZnO nanowires grown on SiO2/Si and quartz substrates by the vapor transport method using Au as a catalyst. Two emission bands are apparent, one in the UV spectral region around 380 nm (3.26 eV) associated with exciton recombination processes and a much broader structure in the visible range from 420 to 700 nm, which exhibits two distinct peak-like features around 520 and 590 nm (2.38 and 2.10 eV). Spectrally resolved scanning near-field optical microscopy (SNOM) of single ZnO nanowires have been performed for a direct imaging of the PL emission with spatial resolution below 100 nm. SNOM results provide evidence that the yellow emission band observed at 590 nm is a unique property of the ZnO nanowires, being most likely related to radiative recombination processes associated with Au impurities introduced during the catalytic growth.

[Maternal adrenal necrosis in the third trimester of pregnancy: a rare complication of antiphospholipid syndrome]. / Nécrose des surrénales maternelles au troisième trimestre de la grossesse dans le cadre d'un syndrome des antiphospholipides: à propos d'un cas.

Adrenal necrosis, a rare life threatening complication of antiphospholipid syndrome, is difficult to diagnose during pregnancy. We report the case of a 33-year-old woman with bilateral adrenal necrosis which started during the third trimester of her second pregnancy. Antiphospholipid syndrome had been diagnosed few years ago, after a thrombotic event. The pregnancy was uneventful until 36 weeks plus five days, when the patient was admitted for bilateral back ache, initially considered as uterine contractions. Labour was induced because pain persisted and was associated with major thrombocytopenia. A healthy infant was delivered vaginally on the second day, adrenal failure was diagnosed based on intense asthenia, persistent severe lumbar pain, low blood sodium and cortisol. Bilateral adrenal oedema was documented by CT scan and MRI. Symptoms resolved following administration of hydrocortisone and fludrocortisone. This case illustrates the difficulty to diagnose adrenal necrosis in the third trimester of pregnancy.

Changes in enoxaparin pharmacokinetics during pregnancy and implications for antithrombotic therapeutic strategy.

Enoxaparin is frequently prescribed for pregnant women who are at high risk for thromboembolic complications. We conducted a population pharmacokinetics study with 75 pregnant women and 38 nonpregnant women as controls to evaluate enoxaparin pharmacokinetics during pregnancy and the postpartum period. Clearance of the drug was higher in the pregnant women throughout pregnancy when compared with nonpregnant women (0.78 +/- 0.03 l/h vs. 0.52 +/- 0.03 l/h, respectively P < 0.001) with the stage of the pregnancy having no influence. The volume of distribution was influenced by stage of the pregnancy, characterized by a two-step increase, with an initial rise paralleling the woman's increase in body weight during the first two trimesters, followed by an additional increase of 41% during the last 2 months of pregnancy, independent of changes in weight. Using enoxaparin pharmacokinetic parameters to simulate anti-Xa time profiles, we observed that the maintenance of the same doses throughout pregnancy resulted in a progressive reduction in mean and peak anti-Xa activities. We recommend the administration of doses normalized for body weight changes so as to counteract enoxaparin pharmacokinetic changes that accompany various stages of pregnancy.

Determination of paper filler Z-distribution by low-vacuum SEM and EDX.

Paper, mainly constituted of cellulose fibres, often contains mineral fillers. These fillers increase some of the properties of the paper (whiteness, printability, etc.) and are cheaper than the cellulose fibres. Nevertheless, the fillers reduce the mechanical properties of the sheet. Paper presents an anisotropy corresponding to three main directions. This anisotropy characterises the sheet mechanical properties, structure and filler distribution. Analyses of the cross section of the paper sheet with a low-vacuum scanning electron microscope with an energy dispersive spectrometer analysis module can show this distribution. The procedure developed consists in analysing discrete profiles to build the mean profile known as filler Z-distribution for each of the fillers. To develop this method, problems such as determination of the surface points, the number of points to analyse to define a cross section profile and the time required for the test, have been solved. Paper is sensitive to electron irradiation. In order to avoid deterioration of the material and to obtain satisfactory results, the time span for analyses is restricted to 40 s with a 12 kV electron beam accelerating voltage. Monte Carlo simulations are used to determine the diffusion cloud size and thus to determine the number of points that constitute a profile. The samples are gold sputtered and, with the aid of backscattered imaging, the coated surface allows determination of the sample surface points.