Factors Associated with Pediatric In-Hospital Recurrent Cardiac Arrest

The objective of this article was to identify demographic and clinical factors associated with early recurrent arrest (RA) (<48 hours) and late RA (≥48 hours) among pediatric inpatients following an initial in-hospital cardiac arrest. A retrospective cohort study of inpatients was performed in a free-standing academic quaternary care children's hospital. All inpatients were <18 years old with a cardiac arrest event requiring ≥1 minute of cardiopulmonary resuscitation with the return of spontaneous circulation sustained for ≥20 minutes at Seattle Children's Hospital from February 1, 2012 to September 18, 2019. Of the 237 included patients, 20 (8%) patients had an early RA and 30 (13%) had a late RA. Older age and severe pre-arrest acidosis were associated with a higher risk of early RA, odds ratios (OR) 1.2 (95% confidence interval [CI] 1.1–1.3) per additional year and 4.6 (95% CI 1.2–18.1), respectively. Pre-arrest organ dysfunction was also associated with a higher risk of early RA with an OR of 3.3 (95% CI 1.1–9.4) for respiratory dysfunction, OR 1.4 (95% CI 1.1–1.9) for each additional dysfunctional organ system, and OR 1.1 (95% CI 1–1.2) for every one-point increase in PELOD2 score. The neonatal illness category was associated with a lower risk of late RA, OR 0.3 (95% CI 0.1–0.97), and severe post-arrest acidosis was associated with a higher risk of late RA, OR 4.2 (95% CI 1.1–15). Several demographic and clinical factors offer some ability to identify children who sustain a recurrent cardiac arrest, offering a potential opportunity for intervention to prevent early recurrent arrest.

Pathophysiological Basis of COVID-19

The World Health Organization (WHO) recognized the coronavirus disease (COVID-19) as a worldwide pandemic caused by a newly discovered coronavirus responsible for Severe Acute Respiratory Syndrome (SARS-Cov2). The virus appeared in Wuhan, China in December 2019 and spread throughout the world, causing several mortality cases particularly in older people and those with chronic diseases. A body of evidence suggests a multi-target of SARS-Cov2, which may act beyond the respiratory system being responsible for other pathological complications, including the gastrointestinal tract, nervous, and the renal functions. The chapter will provide a literature review of the recent data on COVID-19 physiopathology involving in addition to the respiratory dysfunction all the potential physiological functions which could be independently and directly impaired by the SARS-Cov2.

Respiratory Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Respiratory dysfunction is a component of every organ failure scoring system developed, reflecting the significance of the lung in multiple organ dysfunction syndrome. However, existing systems do not reflect current practice and are not consistently evidence based. OBJECTIVE We aimed to review the literature to identify the components of respiratory failure associated with outcomes in children, with the purpose of developing an operational and evidence-based definition of respiratory dysfunction. DATA SOURCES Electronic searches of PubMed and Embase were conducted from 1992 to January 2020 by using a combination of medical subject heading terms and text words to define respiratory dysfunction, critical illness, and outcomes. STUDY SELECTION We included studies of critically ill children with respiratory dysfunction that evaluated the performance of metrics of respiratory dysfunction and their association with patient-centered outcomes. Studies in adults, studies in premature infants (≤36 weeks’ gestational age), animal studies, reviews and commentaries, case series with sample sizes ≤10, and studies not published in English in which we were unable to determine eligibility criteria were excluded. DATA EXTRACTION Data were abstracted into a standard data extraction form. RESULTS We provided binary (no or yes) and graded (no, nonsevere, or severe) definitions of respiratory dysfunction, prioritizing oxygenation and respiratory support. The proposed criteria were approved by 82% of members in the first round, with a score of 8 of 9 (interquartile range 7–8). LIMITATIONS Exclusion of non-English publications, heterogeneity across the pediatric age range, small sample sizes, and incomplete handling of confounders are limitations. CONCLUSIONS We propose definitions for respiratory dysfunction in critically ill children after an exhaustive literature review.

A rare case of Interstitial lung disease complicated by overlapping syndrome with obstructive ventilatory dysfunction as the first symptom

Interstitial lung disease is often a serious complication of connective tissue disease（CTD）, representing the first cause of death in CTD. However, there are few reports of SSc-RA overlap-associated interstitial pneumonia. Respiratory dysfunction as the first clinical manifestation is even rarely reported. We herein described a case of a male patient who developed significant respiratory dysfunction as the principal clinical sign for the past 6 months, plus newly developed skin thickening in bilateral upper limbs and pain and swelling of multiple joints for the past 6 weeks. Extensive immunological screening showed high titer of antinuclear antibodies(ANA), rheumatoid factor(RF), anti-cyclic peptide containing citrulline (anti-CCP)，and positive anti-Scl-70 antibody. Chest high resolution computed tomography(HRCT) was performed and hence ILD was confirmed. Pulmonary function test (PFT) revealed obstructive ventilatory dysfunction rather than restrictive ventilatory dysfunction. So bronchodilation test was performed and asthma was considered. Finally, after a multidisciplinary team (MDT) discussion, the diagnosis of asthma and ILD associated with SSc-RA overlap was established. It is important to note that CTD associated pulmonary interstitial fibrosis must be considered as the differential diagnosis of any newly diagnosed interstitial pulmonary disease. In addition, if patient with dyspnea is highly suspicious of pulmonary interstitial fibrosis, bronchodilation test is still needed to exclude asthma in order to avoid misdiagnosis.

Investigations on the Respiratory Function in COVID-19 Patients: A Prospective Cohort Study

Introduction. Coronavirus disease 2019 (COVID-19) is a global public health crisis. However, whether it can cause respiratory dysfunction or physical and psychological disorders in patients remains unknown. Thus, this study was conducted to investigate the respiratory function, activities of daily living, quality of life, and mental status of patients with COVID-19. Participants and outcomes. Data was collected from the follow-up of eligible patients who attended the fever clinic of three hospitals in Jiangxi Province, from March to May 2020. The outcomes included respiratory muscle function, degree of dyspnea, aerobic capacity, activities of daily living, quality of life, and mental status. Results. A total of 139 patients (72 men and 67 women) were included in this study. The proportions of mild, moderate, severe, and critical cases of COVID-19 were 7.1% (10 cases), 68.3% (95 cases), 20.1% (28 cases), and 4.2% (6 cases), respectively. The rates of abnormal maximal inspiratory pressure were 10.0%, 25.2%, 25.0%, and 16.7%, respectively. There were 50%, 65.3%, 50%, and 66.7% of the patients with abnormal dyspnea in the four clinical classifications, respectively. Patients generally show a decline in quality of life, anxiety, and depression symptoms. Conclusions. Respiratory dysfunction, decreased quality of life, and psychological disorders were present in each clinical classification of COVID-19. Therefore, it is necessary to carry out respiratory rehabilitation and psychological intervention for COVID-19 patients.

Spirometric lung age for predicting the risk of pulmonary complications after thoracic surgeries

Annotation. Surgical interventions for diseases of the thoracic cavity are one of the most invasive surgical procedures, which are often accompanied by postoperative complications, which increase mortality, prolong hospital stays, require additional costs and correlate with poor long-term survival. However, respiratory complications remain the most common of non-surgical complications and their frequency varies from 13 to 38%. So far, several studies have shown that respiratory dysfunction is an independent risk factor for postoperative pneumonia. The aim – investigate whether it is possible to use spirometric lung age to predict the occurrence of postoperative pneumonia after thoracic surgeries. The study was performed on 192 patients with diseases of the thoracic cavity (esophagus, lungs, mediastinum), underwent surgery in the thoracoabdominal department of the Shalimov’s National Institute of Surgery and Transplantation. Statistical software EZR v.1.54 was used for statistical calculations (graphical user interface for statistical software R version 4.0.3, R Foundation for Statistical Computing, Vienna, Austria). We found a very strong association between the risk of developing pulmonary complications and the age of the lungs, AUC=0.97 (95% confidence interval from 0.94 to 0.99). When choosing the optimal point for predicting the risk of pulmonary complications obtained: Lung age critical = 99.6 years. Thus, at Lung age >99.6 years, the development of postoperative pulmonary complications is predicted. At Lung age <99.6 years, the absence of postoperative pulmonary complications is predicted. When choosing this decision point, the sensitivity is 93.5% (82.1-98.6%), specificity – 95.9% (91.3-98.5%). Therefore, spirometric age of the lungs was associated with the incidence of postoperative pulmonary complications in patients undergoing surgery for thoracic disease. This parameter deserves attention as a predictor of the probability of developing postoperative pneumonia after thoracic surgeries and can help in assessing the state of respiratory function of patients.

Inhibition of Prostaglandin F2α Receptors Exaggerates HCl-Induced Lung Inflammation in Mice

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory disorders that are caused by aspiration, sepsis, trauma, and pneumonia. A clinical feature of ALI/ARDS is the acute onset of severe hypoxemia, and the mortality rate, which is estimated at 38–50%, remains high. Although prostaglandins (PGs) are detected in the bronchoalveolar lavage fluid of patients with ALI/ARDS, the role of PGF2α in ALI remains unclear. We aimed to clarify the role of PGF2α/PGF2α receptor (FP) signaling in acid-induced ALI using an FP receptor antagonist, AL8810. Intratracheal injection of hydrochloric acid (HCl) increased neutrophil migration into the lungs, leading to respiratory dysfunction. Pre-administration of AL8810 further increased these features. Moreover, pre-treatment with AL8810 enhanced the HCl-induced expression of pro-inflammatory cytokines and neutrophil migratory factors in the lungs. Administration of HCl decreased the gene expression of lung surfactant proteins, which was further reduced by co-administration of AL8810. Administration of AL8810 also increased lung edema and reduced mRNA expression of epithelial sodium channel in the lungs, indicating that AL8810 reduced fluid clearance. Furthermore, AL8810 also increased lipopolysaccharide-induced expression of adhesion molecules such as intracellular adhesion molecule-1 and E-selectin in human umbilical vein endothelial cells. These results indicate that inhibition of FP receptors by AL8810 exacerbated HCl-induced ALI.

Kidney Dysfunction and Its Progression in Patients Hospitalized Duo to COVID-19: Contribution to the Clinical Course and Outcomes

The disease caused by coronavirus SARS-CoV-2 (COVID-19) can affect almost all organs of the human body, including kidneys. We conducted a one-center study to comprehensively analyze the effects of kidney involvement on the course and outcomes in patients hospitalized with COVID-19, depending on the estimated glomerular filtration rate (eGFR) at admission. Out of the 1958 patients, 1342 (68.54%) had eGFR ≥ 60 mL/min/1.73 m2 (group A) and 616 (31.46%) had eGFR < 60 mL/min/1.73 m2 (group B). Group B was additionally divided into subgroups B1, B2, and B3 based on eGFR. We found that mortality rates during hospitalization, as well as after 90 and 180 days, were much higher in group B than group A. The highest mortality was observed in the B2 subgroup with eGFR of 15–29. The mortality of B patients was associated with comorbidities, respiratory dysfunction, immunological impairment, and more frequent development of AKI. AKI had a negative impact on patients’ survival, regardless of the initial renal function. At discharge, 7.4% of patients had serum creatinine levels 30% higher, or more, as compared to admission. The disease course and outcomes in COVID-19 patients are associated with baseline eGFR; however, AKI during hospitalization is a more significant predictor of poor prognosis regardless of the initial renal function.

Relating spinal injury-induced neuropathic pain and spontaneous afferent activity to sleep and respiratory dysfunction

Spinal cord injury (SCI) can induce dysfunction in a multitude of neural circuits including those that lead to impaired sleep, respiratory dysfunction and neuropathic pain. We used a lower thoracic rodent contusion SCI model - known to develop mechanosensory stimulus hypersensitivity, and spontaneous activity in primary afferents that associates neuropathic pain - and paired this with new approaches that enabled chronic capture of three state sleep and respiration to characterize dysfunction and assess possible interrelations. Noncontact electric field sensors were embedded into home cages for noninvasive capture in naturally behaving mice of the temporal evolution of sleep and respiration changes for 6 weeks after SCI. Hindlimb mechanosensitivity was assessed weekly, and terminal experiments measured primary afferent spontaneous activity in situ from intact lumbar dorsal root ganglia (DRG). We observed that SCI led to increased spontaneous primary afferent activity (both firing rate and the number of spontaneously active DRGs) that correlated with reduced hindpaw mechanical sensitivity, increased respiratory rate variability, and increased sleep fragmentation. This is the first study to measure and link sleep dysfunction and variability in respiratory rate in a SCI model of neuropathic pain, and thereby provide broader insight into the magnitude of overall stress burden initiated by neural circuit dysfunction after SCI.

Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19

Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress.