Oxygen saturation and heart rate in healthy term and late preterm infants with delayed cord clamping

Blood oxygen in the fetus is substantially lower than in the newborn infant. In the minutes after birth, arterial oxygen saturation rises from around 50–60% to 90–95%. Initial respiratory efforts generate negative trans-thoracic pressures that drive liquid from the airways into the lung interstitium facilitating lung aeration, blood oxygenation, and pulmonary artery vasodilatation. Consequently, intra- (foramen ovale) and extra-cardiac (ductus arteriosus) shunting changes and the sequential circulation switches to a parallel pulmonary and systemic circulation. Delaying cord clamping preserves blood flow through the ascending vena cava, thus increasing right and left ventricular preload. Recently published reference ranges have suggested that delayed cord clamping positively influenced the fetal-to-neonatal transition. Oxygen saturation in babies with delayed cord clamping plateaus significantly earlier to values of 85–90% than in babies with immediate cord clamping. Delayed cord clamping may also contribute to fewer episodes of brady-or-tachycardia in the first minutes after birth, but data from randomized trials are awaited. Impact Delaying cord clamping during fetal to neonatal transition contributes to a significantly earlier plateauing of oxygen saturation and fewer episodes of brady-and/or-tachycardia in the first minutes after birth. We provide updated information regarding the changes in SpO2 and HR during postnatal adaptation of term and late preterm infants receiving delayed compared with immediate cord clamping. Nomograms in newborn infants with delayed cord clamping will provide valuable reference ranges to establish target SpO2 and HR in the first minutes after birth.

Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia

Prior studies have described high venous signal qualitatively using arterial spin labelling (ASL) in patients with sickle cell anemia (SCA), consistent with arteriovenous shunting. We aimed to quantify the effect and explored cross-sectional associations with arterial oxygen content (CaO2), disease-modifying treatments, silent cerebral infarction (SCI), and cognitive performance. 94 patients with SCA and 42 controls underwent cognitive assessment and MRI with single- and multi- inflow time (TI) ASL sequences. Cerebral blood flow (CBF) and bolus arrival time (BAT) were examined across gray and white matter and high-signal regions of the sagittal sinus. Across gray and white matter, increases in CBF and reductions in BAT were observed in association with reduced CaO2 in patients, irrespective of sequence. Across high-signal sagittal sinus regions, CBF was also increased in association with reduced CaO2 using both sequences. However, BAT was increased rather than reduced in patients across these regions, with no association with CaO2. Using the multiTI sequence in patients, increases in CBF across white matter and high-signal sagittal sinus regions were associated with poorer cognitive performance. These novel findings highlight the utility of multiTI ASL in illuminating, and identifying objectively quantifiable and functionally significant markers of, regional hemodynamic stress in patients with SCA.

Efficacy and safety of convalescent plasma therapy for severe COVID-19 patients：case series study and literature review

Background Coronavirus disease 2019 (COVID-19) is a new acute respiratory infectious disease which can lead to multiple organ dysfunction in severe patients. However, it is still a lack of effective antiviral drugs for COVID-19. Herein we investigated the efficacy and safety of convalescent plasma (CP) in the treatment of severe COVID-19, with an attempt to explore new therapeutic method. Methods Clinical data of three imported severe COVID-19 patients with CP treatment, who were under quarantine and treated in a designated COVID-19 hospital from March 2020 to April 2020, were collected and analyzed. Results The three patients were clinically classified as severe type, including one male and two females, aged 57, 59 and 65 years old, respectively. The main underling diseases included hypertension, diabetes, sequela of cerebral infarction and postoperative thyroid adenoma. The common symptoms included cough, fever and short of breath. All the patients received antiviral drugs and other supportive treatments. Additionally, CP treatment was also administrated for them. Forty-eight to seventy-two hours after CP transfusion, all the patients improved with alleviated symptoms, elevated arterial oxygen saturation, decreased C-reactive protein and interleukin-6 markers. And the total lymphocytes, T lymphocytes (CD3+) and their subsets (CD4+, CD8+) also obviously increased. Repeated chest CTs also showed obvious absorption of lesions in bilateral lung. Only one patient had mild allergic reaction during CP infusion, but no severe adverse reactions were found. Conclusions The early application of CP for severe COVID-19 patients can improve the condition rapidly, and the therapy is generally effective and safe.

Risk Factors for Hospital-Acquired Pressure Injury in Adult Critical Care Patients

Background Accurately measuring the risk of pressure injury remains the most important step for effective prevention and intervention. Relative contributions of risk factors for the incidence of pressure injury in adult critical care patients are not well understood. Objective To develop and validate a model to identify risk factors associated with hospital-acquired pressure injuries among adult critical care patients. Methods This retrospective cohort study included 23 806 adult patients (28 480 encounters) with an intensive care unit stay at an academic quaternary care center. Patient encounters were randomly split (7:3) into training and validation sets. The training set was used to develop a multivariable logistic regression model using the least absolute shrinkage and selection operator method. The model’s performance was evaluated with the validation set. Results Independent risk factors identified by logistic regression were length of hospital stay, preexisting diabetes, preexisting renal failure, maximum arterial carbon dioxide pressure, minimum arterial oxygen pressure, hypotension, gastrointestinal bleeding, cellulitis, and minimum Braden Scale score of 14 or less. On validation, the model differentiated between patients with and without pressure injury, with area under the receiver operating characteristic curve of 0.85, and performed better than a model with Braden Scale score alone (P < .001). Conclusions A model that identified risk factors for hospital-acquired pressure injury among adult critical care patients was developed and validated using a large data set of clinical variables. This model may aid in selecting high-risk patients for focused interventions to prevent formation of hospital-acquired pressure injuries.

Association between long-term oxygen therapy provided outside the guidelines and mortality in patients with COPD

IntroductionHypoxaemia is a frequent complication of chronic obstructive pulmonary disease (COPD). To prevent its consequences, supplemental oxygen therapy is recommended by international respiratory societies. However, despite clear recommendations, some patients receive long-term oxygen therapy (LTOT), while they do not meet prescription criteria. While evidence suggests that acute oxygen supply at high oxygenation targets increases COPD mortality, its chronic effects on COPD mortality remain unclear. Thus, the study will aim to evaluate through a systematic review and individual patient data meta-analysis (IPD-MA), the association of LTOT prescription outside the guidelines on survival over time in COPD.MethodsSystematic review and IPD-MA will be conducted according to Preferred Reporting Items for a Systematic Review and Meta-Analyses IPD guidelines. Electronic databases (PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, OpenGrey and BioRxiv/MedRxix) will be scanned to identify relevant studies (cohort of stable COPD with arterial oxygen tension data available, with indication of LTOT filled out at the moment of the study and with a survival follow-up). The anticipated search dates are January–February 2022. The main outcome will be the association between LTOT and time to all-cause mortality according to hypoxaemia severity, after controlling for potential covariates and all available clinical characteristics. Quantitative data at the level of the individual patient will be used in a one-step approach to develop and validate a prognostic model with a Cox regression analysis. The one-step IPD-MA will be conducted to study the association and the moderators of association between supplemental oxygen therapy and mortality. Multilevel survival analyses using Cox-mixed effects models will be performed.Ethics and disseminationAs a protocol for a systematic review, a formal ethics committee review is not required. Only studies with institutional approval from an ethics committee and anonymised IPD will be included. Results will be disseminated through peer-reviewed publications and presentations in conferences.PROSPERO registration numberCRD42020209823.

Late surfactant replacement therapy and its efficacy on severe bronchopulmonary dysplasia in National Children Hospital

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that is most commonly seen in premature infants who require prolonged mechanical ventilation and oxygen therapy. 75% of intubated infants have episodes of dysfunctional surfactants associated with lower levels of surfactant proteins. This study aims to evaluate the effectiveness of late surfactant therapy in treating BPD in premature infants. Nineteen preterm infants diagnosed with severe BPD requiring mechanic ventilation, according to Jobe and Bancalari, were treated with surfactant (Poractant alpha 100mg/kg intra-tracheal). Patients were observed for change in oxygen requirement before and at 1-h, 6-h, 12-h, 24-h, and 48-h after treatment. There were 13 boys and 6 girls; boy to girl ratio was 2.16/1. The mean gestation age was 28.3 ± 2 weeks; the mean birth weight was 1134.7 ± 314 gram. There was an increase in SpO2 (saturation of peripheral oxygen), PaO2 (the partial pressure of oxygen in arterial blood) and reduction in FiO2 (fraction of inspired oxygen), PaCO2 (the partial pressure of carbon dioxide in arterial blood), OI (oxygen index), MAP (mean airway pressure) and AaDO2 (Alveolar-to-arterial oxygen gradient) after surfactant (p < 0.05). Conclusion: In patients with severe BPD, late surfactant therapy has shown initial benefits in lung functions and reducing oxygen requirement.

The physiology of extracorporeal membrane oxygenation: The Fick principle

Extracorporeal membrane oxygenation (ECMO) can be delivered in veno-arterial (VA) and veno-venous (VV) configurations based on the cannulation strategy. VA and VV ECMO are delivered primarily for haemodynamic and respiratory support in patients with severe heart and lung failure, respectively. The Fick principle describes the relationship between blood flow and oxygen consumption – key parameters in the physiological management of extracorporeal support. This review will discuss the application of the Fick principle in: (i) recirculation in VV ECMO; (ii) the quantification of oxygen delivery (DO2) in VV ECMO and (iii) the quantification of transpulmonary blood flow and systemic arterial oxygen saturation in VA ECMO.

Vitamin D Immune-Mediated Responses and SARS-CoV-2 Infection: Clinical Implications in COVID-19

Active vitamin D is a true steroid hormone with pleiotropic biological effects that go beyond the classical concept of bone metabolism regulation. In fact, adequate serum levels of 25-hydroxyvitamin D (>40 ng/mL) are required to support several biological functions, including the control of innate and adaptive immunity in course of infectious, inflammatory and autoimmune diseases. SARS-CoV-2 is responsible for the COVID-19 pandemic and deficient/insufficient serum levels of 25-hydroxyvitamin D are reported in very large cohorts of patients. Of note, vitamin D is involved in different pathophysiological processes, such as expression of SARS-CoV-2 receptor (ACE2), activation of innate (neutrophils with their extracellular traps, monocytes/macrophages, dendritic cells, natural killer cells) and adaptive (T and B lymphocytes) immune cells and clinical manifestations, such as coagulation/thrombotic disorders and acute respiratory distress syndrome. Randomized clinical trials regarding vitamin D supplementation in COVID-19 patients have shown favorable effects on the control of inflammation markers, arterial oxygen saturation/inspired fraction of oxygen ratio, admission to hospital intensive care units and mortality. A target of serum 25-hydroxyvitamin D > 50 ng/mL has been identified as protective for the course of COVID-19, potentially playing an ancillary role in the treatment of the disease.

Impact of Hepatopulmonary Syndrome in Liver Transplantation Candidates and the Role of Angiogenesis

Hepatopulmonary syndrome affects 10–30% of patients with cirrhosis and portal hypertension. We evaluated the serum angiogenic profile of hepatopulmonary syndrome and assessed the clinical impact of hepatopulmonary syndrome in patients evaluated for liver transplantation.The Pulmonary Vascular Complications of Liver Disease 2 study was a multicentre, prospective cohort study of adults undergoing their first liver transplantation evaluation. Hepatopulmonary syndrome was defined as an alveolar-arterial oxygen gradient ≥15 mmHg (≥20 mmHg if age >64 years), positive contrast-enhanced transthoracic echocardiography, and absence of lung disease.We included 85 patients with hepatopulmonary syndrome and 146 patients without hepatopulmonary syndrome. Patients with hepatopulmonary syndrome had more complications of portal hypertension and slightly higher Model for End-stage Liver Disease-Na score compared to those without hepatopulmonary syndrome (median [interquartile range] 15 [12, 19] versus 14 [10, 17], p=0.006). Hepatopulmonary syndrome patients had significantly lower six minute walk distance and worse functional class. Hepatopulmonary syndrome patients had higher circulating angiopoietin-2, Tie2, tenascin-C, c-kit, VCAM-1, and von Willebrand factor levels, and lower E-selectin levels. Patients with hepatopulmonary syndrome had an increased risk of death (hazard ratio 1.80 [1.03–3.16], p=0.04) which persisted despite adjustment for covariates (hazard ratio 1.79 [1.02–3.15], p=0.04). This association did not vary based on levels of oxygenation reflecting the severity of hepatopulmonary syndrome.Hepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death.

Anti-virulence Bispecific Monoclonal Antibody Mediated Protection Against Pseudomonas aeruginosa Ventilator-Associated Pneumonia in a Rabbit Model

Ventilator-associated pneumonia is an important clinical manifestation of the nosocomial pathogen Pseudomonas aeruginosa . We characterized the correlates of protection of MEDI3902, a bispecific human IgG1 mAb that targets the P. aeruginosa type-3-secretion PcrV protein and the Psl exopolysaccharide, in a rabbit model of ventilator-associated pneumonia using lung-protective, low-tidal volume mechanical ventilation. Rabbits infused with MEDI3902 prophylactically were protected, whereas those pretreated with irrelevant isotype-control IgG (c-IgG) succumbed between 12 and 44 hours post infection [100% (8/8) vs. 0% (8/8) survival, P <0.01 by log-rank test]. Lungs from rabbits pretreated with c-IgG, but not those with MEDI3902, had bilateral, multifocal areas of marked necrosis, hemorrhage, neutrophilic inflammatory infiltrate, diffuse fibrinous edema in alveolar spaces. All rabbits pretreated with c-IgG developed worsening bacteremia that peaked at the time of death, whereas only 38% (3/8) rabbits pretreated with MEDI3902 developed such high-grade bacteremia (two-sided Fisher’s exact test, P =0.026). Biomarkers associated with acute respiratory distress syndrome were evaluated longitudinally in blood samples collected every 2-4 hours to assess systemic pathophysiological changes in rabbits pretreated with MEDI3902 or c-IgG. Biomarkers were sharply increased or decreased in rabbits pretreated with c-IgG, but not those pretreated with MEDI3902, including ratio of arterial oxygen partial pressure to fractional inspired oxygen PaO 2 /FiO 2 <300, hypercapnia or hypocapnia, severe lactic acidosis, leukopenia and neutropenia. Cytokines and chemokines associated with ARDS were significantly downregulated in lungs from rabbits pretreated with MEDI3902 compared with c-IgG. These results suggest that MEDI3902 prophylaxis could have potential clinical utility for decreasing severity of P. aeruginosa ventilator-associated pneumonia.