The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.
Adoptive Transfer ; Alveolar Epithelial Cells ; pathology ; Animals ; Apoptosis ; Betacoronavirus ; Body Fluids ; metabolism ; CD4-Positive T-Lymphocytes ; immunology ; Clinical Trials as Topic ; Coinfection ; prevention & control ; therapy ; Coronavirus Infections ; complications ; immunology ; Disease Models, Animal ; Endothelial Cells ; pathology ; Extracorporeal Membrane Oxygenation ; Genetic Therapy ; methods ; Genetic Vectors ; administration & dosage ; therapeutic use ; Humans ; Immunity, Innate ; Inflammation Mediators ; metabolism ; Lung ; pathology ; physiopathology ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stem Cells ; physiology ; Multiple Organ Failure ; etiology ; prevention & control ; Pandemics ; Pneumonia, Viral ; complications ; immunology ; Respiratory Distress Syndrome, Adult ; immunology ; pathology ; therapy ; Translational Medical Research

Adolescent ; Adult ; Aged ; China ; Female ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; complications ; Male ; Middle Aged ; Respiratory Distress Syndrome, Adult ; etiology ; therapy ; Young Adult

BACKGROUNDSepsis is one of the main causes of mortality in critically ill patients following progression to septic shock. To investigate the pathophysiologic changes of sepsis, we developed a novel porcine model of septic shock induced by acute respiratory distress syndrome (ARDS) due to methicillin-resistant Staphylococcus aureus(MRSA) pneumonia.

METHODSTwenty-six male Landraces (Lvyuanweiye, Beijing, China) weighing 30 ± 2 kg were divided into four groups: sham group (SH; n = 5); cotton smoke inhalation group (SM; n = 6); MRSA pneumonia group (MR; n = 6); and septic shock group with cotton smoke inhalation + MRSA pneumonia (SS; n = 9). Extensive hemodynamics, oxygen dynamics, and lung function were monitored for 24 h following the injury or until death. Tissues were collected, and histopathology evaluations were carried out.

RESULTSBlood cultures from 6 of 9 animals in the SS group were positive for MRSA. Two hours following the injury, decreased mean arterial blood pressure (60-70 mmHg) and cardiac index (<2 L.min-1.m-2) were observed in the animals in the SS group, while systemic vascular resistance index was increased. The hemodynamic characteristics of septic shock were only observed in the SS group but not significant in the other groups. The PO2/FiO2in the SM and SS groups decreased to 300 and 100, respectively. In the SS group, extravascular lung water index increased to 20 ml/kg, whereas thoracopulmonary compliance decreased to 10 ml/H2O after injury. Deterioration of pulmonary function in the SS group was more serious than the SM and MR groups. Severe lung injury in the SS group was confirmed by the histopathology evaluations. The lung injury confirmed by high-resolution thin-section computed tomography and histopathology in the SS group was more serious than those of other groups.

CONCLUSIONSIn the present study, we developed a novel porcine model of septic shock induced by ARDS due to severe MRSA pneumonia with characteristic hyperdynamic and hypodynamic phases in 24 h, which mimicked the hemodynamic changing of septic shock in human.

Animals ; Disease Models, Animal ; Hemodynamics ; physiology ; Male ; Methicillin-Resistant Staphylococcus aureus ; pathogenicity ; Pneumonia ; microbiology ; pathology ; Respiratory Distress Syndrome, Adult ; complications ; pathology ; Shock, Septic ; etiology ; pathology ; Swine

OBJECTIVETo analyze the reason and treatment of the complications of 61 cases of extracorporeal membrane oxygenation (ECMO) in order to improve survival rate of ECMO treatment.

METHODSECMO records from January 2007 to December 2014 in Shanghai Chest Hospital were investigated retrospectively focusing on complications. There were included 43 male and 18 female patients, age 3 to 66 years. Indications for ECMO included post-operative low cardiac output, viral myocarditis, bridge to heart transplantation, acute respiratory distress syndrome and myocardial infarction. There were 49 cases of veno-arterial ECMO and 12 cases of veno-venous ECMO.

RESULTSECMO duration was 2 to 61 days. Among 43 patients, 37 patients weaned from ECMO successfully and 28 survived to discharge. Various complications occurred to 56 patients, including oxygenator plasma leakage(4 case times), circuit emboli (7), hemolysis (4), bleeding (34), infection (8), acute kidney injury (35), lower limb ischemia (8) and neurologic complications (6). There were 49 cases times of complications in survivors, while 61 cases times in death group. Bleeding (10 time cases) and acute kidney injury (33 time cases) happened in the death group. Progresses in ECMO technique had influences on complications in some parts. For instance, incidence of lower limb ischemia was 6/7 in cutdown cannulating group, but reduced to 2/42(4.8%) when semi-open technique was applied.

CONCLUSIONSComplications in ECMO are relative to patients' outcome intimately. Appropriate prevention and treatment of complication play a major role in the success of ECMO support. The incidences of certain complications reduce significantly due to progresses of equipment and medical experiences.

Acute Disease ; Acute Kidney Injury ; etiology ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Extracorporeal Membrane Oxygenation ; adverse effects ; Female ; Heart Transplantation ; Hemorrhage ; etiology ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; Myocarditis ; virology ; Respiratory Distress Syndrome, Adult ; Retrospective Studies ; Treatment Outcome ; Young Adult

We report a case of bronchiolitis obliterans associated with Stevens-Johnson syndrome. A 59-year-old man presented with respiratory distress that gradually worsened over 3 months. He had been diagnosed with Stevens-Johnson syndrome 3 months before admission. He had no history of previous airway disease. On physical examination, expiratory breathing sounds were not audible, and a chest X-ray revealed a hyperinflated lung. A pulmonary function test indicated a severe obstructive pattern. Computed tomography scans of inspiratory and expiratory phases of respiration showed oligemia and air trapping, and both were more prominent on expiration view than on inspiration view. The pathogenesis of bronchiolitis obliterans associated with Stevens-Johnson syndrome is largely unknown.
Anti-Bacterial Agents/therapeutic use ; Bronchiolitis Obliterans/etiology/*radiography/therapy ; Bronchoscopy ; Dyspnea/*complications ; Fatal Outcome ; Humans ; Male ; Middle Aged ; Radiography, Thoracic ; Respiratory Distress Syndrome, Adult/*etiology/therapy ; Respiratory Function Tests ; Roxithromycin/therapeutic use ; Stevens-Johnson Syndrome/*complications/drug therapy ; Tomography, X-Ray Computed/methods ; Tracheostomy

BACKGROUNDIt was believed that inflammatory response induced by cardiopulmonary bypass (CPB) was blamed for complications after cardiac surgery. To improve the outcome, many pharmacological interventions have been applied to attenuate inflammatory response during CPB. The objective of this study was to investigate the effect of ulinastatin (urinary trypsin inhibitor [UTI]) on outcome after CPB surgery.

METHODSTotally, 208 patients undergoing elective valves replacement between November 2013 and September 2014 were divided into Group U (n = 70) and Group C (n = 138) based on they received UTI or not. Categorical variables were compared between groups using Fisher's exact test, and continuous variables using unpaired Student's t-test or Mann-Whitney U-test. One-way analysis of variance and Dunnett's or Tukey's tests were used to compare values at different time points within the same group. The risk of outcomes was estimated and adjusted by multivariable logistic regression, propensity scoring, and mixed-effect models for all measured variables.

RESULTSBoth the serious complications in total, including death, acute lung injury, acute respiratory distress syndrome and acute kidney injury, and the other complications, including hemodialysis, infection, re-incubation, and tracheotomy were similar between the two groups (P > 0.05). After adjusted by multivariable logistic regression and the propensity score, UTI still cannot be found any benefit to improve any outcomes after cardiac surgery. Also, no statistical differences with regard to duration of postoperative mechanical ventilation, the length of Intensive Care Unit and hospital stays (P > 0.05).

CONCLUSIONUTI did not improve postoperative outcomes in our patients after cardiopulmonary bypass surgery.

Acute Kidney Injury ; etiology ; Adult ; Cardiac Surgical Procedures ; adverse effects ; Cardiopulmonary Bypass ; adverse effects ; Female ; Glycoproteins ; therapeutic use ; Humans ; Length of Stay ; Male ; Middle Aged ; Postoperative Complications ; Respiratory Distress Syndrome, Adult ; etiology ; Retrospective Studies

Abdominal Neoplasms ; complications ; secondary ; therapy ; Acute Lung Injury ; diagnostic imaging ; etiology ; Anemia ; complications ; therapy ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child, Preschool ; Etoposide ; administration & dosage ; Fluoroscopy ; Humans ; Ifosfamide ; administration & dosage ; Kidney Neoplasms ; pathology ; Lung Neoplasms ; complications ; secondary ; therapy ; Male ; Postoperative Complications ; diagnostic imaging ; etiology ; Prosthesis Implantation ; Radiography, Thoracic ; Radiotherapy ; Respiratory Distress Syndrome, Adult ; diagnostic imaging ; etiology ; Transfusion Reaction ; Vascular Access Devices

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that lacks definitive treatment. The cornerstone of management is sound intensive care treatment and early anticipatory ventilation support. A mechanical ventilation strategy aiming at optimal alveolar recruitment, judicious use of positive end-respiratory pressure (PEEP) and low tidal volumes (VT) remains the mainstay for managing this lung disease. Several treatments have been proposed in rescue settings, but confirmation is needed from large controlled clinical trials before they be recommended for routine care. Non-invasive ventilation (NIV) is suggested with a cautious approach and a strict selection of candidates for treatment. Mild and moderate cases can be efficiently treated by NIV, but this is contra-indicated with severe ARDS. The extra-corporeal carbon dioxide removal (ECCO2 R), used as an integrated tool with conventional ventilation, is playing a new role in adjusting respiratory acidosis and CO2. The proposed benefits of ECCO2 R over extra-corporeal membrane oxygenation (ECMO) consist in a reduction of artificial surface contact, avoidance of pump-related side effects and technical complications, as well as lower costs. The advantages and disadvantages of inhaled nitric oxide (iNO) are better recognized today and iNO is not recommended for ARDS and acute lung injury (ALI) in children and adults because iNO results in a transient improvement in oxygenation but does not reduce mortality, and may be harmful. Several trials have found no clinical benefit from various surfactant supplementation methods in adult patients with ARDS. However, studies which are still controversial have shown that surfactant supplementation can improve oxygenation and decrease mortality in pediatric and adolescent patients in specific conditions and, when applied in different modes and doses, also in neonatal respiratory distress syndrome (RDS) of preemies. Management of ARDS remains supportive, aimed at improving gas exchange and preventing complications. Progress in the treatment of ARDS must be addressed toward the new paradigm of the disease pathobiology to be applied to the disease definition and to predict the treatment outcome, also with the perspective to develop predictive and personalized medicine that highlights new and challenging opportunities in terms of benefit for patient's safety and doctor's responsibility, with further medico-legal implication.
Child ; Humans ; Nitric Oxide ; administration & dosage ; Noninvasive Ventilation ; Positive-Pressure Respiration ; Prone Position ; Pulmonary Atelectasis ; etiology ; Pulmonary Surfactants ; therapeutic use ; Respiratory Distress Syndrome, Adult ; therapy

Adult ; Extracorporeal Membrane Oxygenation ; methods ; Humans ; Influenza, Human ; complications ; Male ; Respiratory Distress Syndrome, Adult ; etiology ; therapy

OBJECTIVETo discuss the distribution of the respiratory complications in severely burned patients and the prevention and treatment experience against them.

METHODSMedical records of 922 adult patients with severe or extremely severe burn hospitalized in our burn ICU from January 2005 to December 2012 were screened and retrospectively analyzed, including patients transferred from other hospitals, patients with total burn area above 50% TBSA, the distribution and treatment of respiratory complications, and the mortality. Data were processed with chi-square test.

RESULTSThe constituent ratio of patients transferred to our hospital was 71.1% in 2007 and 40.2% in 2010, while it remained about 50.0% in the other years. The ratios of patients with total burn area larger than 50% TBSA and that of patients with respiratory complications (χ(2) = 2.637, P > 0.05) showed no significant changes each year. Among these 922 burn patients, 523 patients suffered respiratory complications, among which laryngeal edema (50.9%, 266 cases), pulmonary infection (21.6%, 113 cases), and ARDS (11.9%, 62 cases) were the main components, with no significant change each year (with χ(2) values respectively 6.132, 6.319, 0.016, P values above 0.05). Among the patients with respiratory complications, except for 36 were not treated actively, 487 were treated by ventilator among which 228 had undergone tracheostomy, and the constituent ratios in the 8 years were close. Fifteen patients died, with 2 died of laryngeal edema, 3 of ARDS, and 10 of sepsis or MODS as a result of sepsis.

CONCLUSIONSPatients with severe burns were at high risk of respiratory complications, among which laryngeal edema was common, followed by pulmonary infection and ARDS. Prophylactic tracheostomy, mechanical ventilation, wound therapy, and anti-infection were all effective measures of prevention and treatment against these complications.

Adult ; Aged ; Burns ; complications ; therapy ; Humans ; Laryngeal Edema ; etiology ; physiopathology ; therapy ; Lung ; physiopathology ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; etiology ; physiopathology ; therapy ; Retrospective Studies ; Sepsis ; etiology ; physiopathology ; therapy ; Treatment Outcome