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Journal of Clinical Medicine Mar 2023Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals... (Review)
Review
Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals who died. Active autopsy results may be crucial for understanding how COVID-19 infection operates and preventing severe effects. In contrast to younger persons, however, the patient's age, lifestyle, and concomitant comorbidities might alter the morpho-pathological aspects of the damaged lungs. Through a systematic analysis of the available literature until December 2022, we aimed to provide a thorough picture of the histopathological characteristics of the lungs in patients older than 70 years who died of COVID-19. A thorough search was conducted on three electronic databases (PubMed, Scopus, and Web of Science), including 18 studies and a total of 478 autopsies performed. It was observed that the average age of patients was 75.6 years, of which 65.4% were men. COPD was identified in an average of 16.7% of all patients. Autopsy findings indicated significantly heavier lungs, with an average weight of the right lung of 1103 g, while the left lung mass had an average weight of 848 g. Diffuse alveolar damage was a main finding in 67.2% of all autopsies, while pulmonary edema had a prevalence of between 50% and 70%. Thrombosis was also a significant finding, while some studies described focal and extensive pulmonary infarctions in 72.7% of elderly patients. Pneumonia and bronchopneumonia were observed, with a prevalence ranging from 47.6% to 89.5%. Other important findings described in less detail comprise hyaline membranes, the proliferation of pneumocytes and fibroblasts, extensive suppurative bronchopneumonic infiltrates, intra-alveolar edema, thickened alveolar septa, desquamation of pneumocytes, alveolar infiltrates, multinucleated giant cells, and intranuclear inclusion bodies. These findings should be corroborated with children's and adults' autopsies. Postmortem examination as a technique for studying the microscopic and macroscopic features of the lungs might lead to a better knowledge of COVID-19 pathogenesis, diagnosis, and treatment, hence enhancing elderly patient care.
PubMed: 36902856
DOI: 10.3390/jcm12052070 -
Pediatric Critical Care Medicine : a... May 2023The indication, complications, and outcomes of extracorporeal membrane oxygenation (ECMO) in children with COVID-19-related illnesses remain unelucidated. Our study... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The indication, complications, and outcomes of extracorporeal membrane oxygenation (ECMO) in children with COVID-19-related illnesses remain unelucidated. Our study aimed to investigate the characteristics and outcomes of ECMO in children with COVID-19-related illnesses.
DATA SOURCES
We searched PubMed and EMBASE databases in March 2022.
STUDY SELECTION
We retrieved all studies involving children (age ≤ 18 yr) with COVID-19-related illnesses who received ECMO.
DATA EXTRACTION
Two authors independently extracted data and assessed the risk of bias. Mortality, successful weaning rate, and complications while on ECMO were synthesized by a one-group meta-analysis using a random-effect model. Meta-regression was performed to explore the risk factors for mortality.
DATA SYNTHESIS
We included 18 observational studies, four case series, and 22 case reports involving 110 children with COVID-19-related illnesses receiving ECMO. The median age was 8 years (range, 10 d to 18 yr), and the median body mass index was 21.4 kg/m 2 (range, 12.3-56.0 kg/m 2 ). The most common comorbidities were obesity (11% [7/63]) and congenital heart disease (11% [7/63]), whereas 48% (30/63) were previously healthy. The most common indications for ECMO were multisystem inflammatory syndrome in children (52% [47/90]) and severe acute respiratory distress syndrome (40% [36/90]). Seventy-one percent (56/79) received venoarterial-ECMO. The median ECMO runtime was 6 days (range, 3-51 d) for venoarterial ECMO and 11 days (range, 3-71 d) for venovenous ECMO. The mortality was 26.6% (95% CI, 15.9-40.9), and the successful weaning rate was 77.0% (95% CI, 55.4-90.1). Complications were seen in 37.0% (95% CI, 23.1-53.5) while on ECMO, including stroke, acute kidney injury, pulmonary edema, and thromboembolism. Corticosteroids and IV immunoglobulin therapies were associated with lower mortality.
CONCLUSIONS
The mortality of children on ECMO for COVID-19 was relatively low. This invasive treatment can be considered as a treatment option for critically ill children with COVID-19.
Topics: Humans; Child; COVID-19; Extracorporeal Membrane Oxygenation; Respiratory Distress Syndrome; Acute Kidney Injury; Retrospective Studies
PubMed: 36516348
DOI: 10.1097/PCC.0000000000003113 -
Frontiers in Oncology 2022Dysregulation of the mesenchymal epithelial transition (MET) pathway contributes to poor clinical outcomes in patients with non-small cell lung cancer (NSCLC). Numerous... (Review)
Review
BACKGROUND
Dysregulation of the mesenchymal epithelial transition (MET) pathway contributes to poor clinical outcomes in patients with non-small cell lung cancer (NSCLC). Numerous clinical trials are currently investigating several therapies based on modulation of the MET pathway.
OBJECTIVES
This study aimed to systematically evaluate the activity and safety of MET inhibitors in patients with NSCLC.
METHODS
We searched PubMed, Embase, and the Cochrane Library from inception to June 02, 2022. The objective response rate (ORR) and disease control rate (DCR) were extracted as the main outcomes and pooled using the weighted mean proportion with fixed- or random-effects models in cases of significant heterogeneity ( >50%). Safety analysis was performed based on adverse events reported in all studies.
RESULTS
Eleven studies (882 patients) were included in the meta-analysis. The pooled ORR was 28.1% (95% confidence interval [CI], 0.223-0.354), while the pooled DCR was 69.1% (95% CI, 0.631-0.756). ORRs were higher for tepotinib (44.7% [95% CI, 0.365-0.530]) and savolitinib (42.9% [95% CI, 0.311-0.553]) than for other types of MET inhibitors. Patients with NSCLC with exon 14 skipping exhibited higher ORRs (39.3% (95% CI, 0.296-0.522)) and DCRs (77.8% (95% CI, 0.714-0.847)) than those with MET protein overexpression or amplification. Intracranial response rate and intracranial disease control rates were 40.1% (95% CI, 0.289-0.556) and 95.4% (95% CI, 0.892-0.100), respectively. Adverse events were mild (grade 1 to 2) in 87.2% of patients. Common adverse events above grade 3 included lower extremity edema (3.5% [95% CI, 0.027-0.044]), alanine aminotransferase (ALT) elevation (2.4% [95% CI, 0.014-0.033]), and lipase elevation (2.2% [95% CI, 0.016-0.031]).
CONCLUSION
MET inhibitors, which exhibited a satisfactory safety profile in the current study, may become a new standard of care for addressing MET dysregulation in patients with advanced or metastatic NSCLC, and even in those with brain metastases, particularly tepotinib, savolitinib and capmatinib. Further randomized trials are required to establish standard predictive biomarkers for MET therapies and to compare the effects of different MET inhibitors in NSCLC with MET dysregulation.
PubMed: 36387098
DOI: 10.3389/fonc.2022.1013299 -
Medical Ultrasonography Jun 2023Lung ultrasound (LUS) has been rapidly developed to evaluate pulmonary extravascular fluid. A systematic review was conducted to study the dynamic changes of LUS... (Meta-Analysis)
Meta-Analysis Review
AIMS
Lung ultrasound (LUS) has been rapidly developed to evaluate pulmonary extravascular fluid. A systematic review was conducted to study the dynamic changes of LUS findings of pulmonary congestion before and after hemodialysis and examine the application of LUS for the prognosis of hemodialysis patients.
MATERIAL AND METHODS
This study searched online databases for articles on hemodialysis patients that used LUS to evaluate dynamic changes during hemodialysis or prognosis. Articles published in English or Chinese until September 2021 with ≥30 patients were included in this study.
RESULTS
Of the 1329 articles, 14 met the inclusion criteria: 9 reported dynamic changes during dialysis in LUS (438 patients), and 5 reported the prognosis of hemodialysis patients in LUS (1274 patients). As indicated by a further meta-analysis, eight studies found that the combined standardized effect size was -0.74. The all-cause mortality rate of the dialysis patient group with high B-line scores was three times that of the dialysis patient group with low B-line scores. In dialysis patients, no difference was found between the LUS guided treatment and the conventional care in reducing the all-cause mortality (HR=0.92 95%CI: 0.67-1.27) and cardiovascular events (HR=0.98 95%CI: 0.72 -1.34).
CONCLUSIONS
LUS can be used to effectively evaluate the volume status of hemodialysis patients in real time. The level of B-line before dialysis is significantly correlated with the poor prognosis. However, compared with the routine nursing group, the treatment of hemodialysis patients with LUS-guided volume management cannot effectively reduce mortality and cardiovascular events.
Topics: Humans; Lung; Prognosis; Pulmonary Edema; Renal Dialysis; Ultrasonography
PubMed: 36191243
DOI: 10.11152/mu-3654 -
Archives of Computational Methods in... 2023Airway disease is a major healthcare issue that causes at least 3 million fatalities every year. It is also considered one of the foremost causes of death all around the... (Review)
Review
Airway disease is a major healthcare issue that causes at least 3 million fatalities every year. It is also considered one of the foremost causes of death all around the globe by 2030. Numerous studies have been undertaken to demonstrate the latest advances in artificial intelligence algorithms to assist in identifying and classifying these diseases. This comprehensive review aims to summarise the state-of-the-art machine and deep learning-based systems for detecting airway disorders, envisage the trends of the recent work in this domain, and analyze the difficulties and potential future paths. This systematic literature review includes the study of one hundred fifty-five articles on airway diseases such as cystic fibrosis, emphysema, lung cancer, Mesothelioma, covid-19, pneumoconiosis, asthma, pulmonary edema, tuberculosis, pulmonary embolism as well as highlights the automated learning techniques to predict them. The study concludes with a discussion and challenges about expanding the efficiency and machine and deep learning-assisted airway disease detection applications.
PubMed: 36189431
DOI: 10.1007/s11831-022-09818-4 -
Frontiers in Pharmacology 2022The clinical efficiency of terpenoids in treating human acute lung injury (ALI) is yet to be determined. The lipopolysaccharide-induced rat model of ALI is a...
The clinical efficiency of terpenoids in treating human acute lung injury (ALI) is yet to be determined. The lipopolysaccharide-induced rat model of ALI is a well-established and widely used experimental model for studying terpenoids' effects on ALI. Using a systematic review and meta-analysis, the therapeutic efficiency of terpenoid administration on the lung wet-to-dry weight ratio in rats was investigated. Using the Cochrane Library, Embase, and PubMed databases, a comprehensive literature search for studies evaluating the therapeutic efficacy of terpenoids on ALI in rats was conducted. The lung wet-to-dry weight ratio was extracted as the main outcome. The quality of the included studies was assessed using the Systematic Review Center for Laboratory Animal Experimentation's risk of bias tool. In total, 16 studies were included in this meta-analysis. In general, terpenoids significantly lowered the lung wet-to-dry weight ratio when compared with the control vehicle ( = 0.0002; standardized mean difference (SMD): -0.16; 95% confidence interval (CI): -0.24, -0.08). Subgroup analysis revealed that low dose (≤10 μmol/kg) ( 0.0001; SMD: -0.68; 95% CI: -1.02, -0.34), intraperitoneal injection ( = 0.0002; SMD: -0.43; 95% CI: -0.66, -0.20), diterpenoid ( = 0.004; SMD: -0.13; 95% CI: -0.23, -0.04), and triterpenoid ( = 0.04; SMD: -0.28; 95% CI: -0.54, -0.01) significantly lowered the lung wet-to-dry weight ratio when compared with the control vehicle. A low dose of diterpenoid and triterpenoid administered intraperitoneally is effective in alleviating ALI. This systematic review and meta-analysis provides a valuable mirror for clinical research aiming at the advancement of terpenoids for preventive and therapeutic use. CRD42022326779.
PubMed: 36034851
DOI: 10.3389/fphar.2022.946554 -
Frontiers in Immunology 2022Phosgene (COCl) gas is a chemical intermediate of high-volume production with numerous industrial applications worldwide. Due to its high toxicity, accidental exposure...
Phosgene (COCl) gas is a chemical intermediate of high-volume production with numerous industrial applications worldwide. Due to its high toxicity, accidental exposure to phosgene leads to various chemical injuries, primarily resulting in chemical-induced lung injury due to inhalation. Initially, the illness is mild and presents as coughing, chest tightness, and wheezing; however, within a few hours, symptoms progress to chronic respiratory depression, refractory pulmonary edema, dyspnea, and hypoxemia, which may contribute to acute respiratory distress syndrome or even death in severe cases. Despite rapid advances in medicine, effective treatments for phosgene-inhaled poisoning are lacking. Elucidating the pathophysiology and pathogenesis of acute inhalation toxicity caused by phosgene is necessary for the development of appropriate therapeutics. In this review, we discuss extant literature on relevant mechanisms and therapeutic strategies to highlight novel ideas for the treatment of phosgene-induced acute lung injury.
Topics: Acute Lung Injury; Humans; Lung; Phosgene; Pulmonary Edema; Respiratory Distress Syndrome
PubMed: 35983054
DOI: 10.3389/fimmu.2022.917395 -
The Cochrane Database of Systematic... Jun 2022Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID-19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA). This approach is potentially associated with both advantages (e.g. a preserved diaphragmatic motility and an optimised ventilation-perfusion ratio of the ventilated lung), as well as risks (e.g. a higher rate of ventilator-induced lung injury or a worsening of pulmonary oedema due to increases in transpulmonary pressure). As a consequence, spontaneous breathing in people with COVID-19-ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists.
OBJECTIVES
To assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID-19 with ARDS compared to ventilation strategies that avoid spontaneous breathing.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, Clinical Trials.gov WHO ICTRP, and medRxiv) and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies from their inception to 2 March 2022.
SELECTION CRITERIA
Eligible study designs comprised randomised controlled trials (RCTs) that evaluated spontaneous breathing in participants with COVID-19-related ARDS compared to ventilation strategies that avoided spontaneous breathing (e.g. using NMBA or deep sedation levels). Additionally, we considered controlled before-after studies, interrupted time series with comparison group, prospective cohort studies and retrospective cohort studies. For these non-RCT studies, we considered a minimum total number of 50 participants to be compared as necessary for inclusion. Prioritised outcomes were all-cause mortality, clinical improvement or worsening, quality of life, rate of (serious) adverse events and rate of pneumothorax. Additional outcomes were need for tracheostomy, duration of ICU length of stay and duration of hospitalisation.
DATA COLLECTION AND ANALYSIS
We followed the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently screened all studies at the title/abstract and full-text screening stage. We also planned to conduct data extraction and risk of bias assessment in duplicate. We planned to conduct meta-analysis for each prioritised outcome, as well as subgroup analyses of mortality regarding severity of oxygenation impairment and duration of ARDS. In addition, we planned to perform sensitivity analyses for studies at high risk of bias, studies using NMBA in addition to deep sedation level to avoid spontaneous breathing and a comparison of preprints versus peer-reviewed articles. We planned to assess the certainty of evidence using the GRADE approach.
MAIN RESULTS
We identified no eligible studies for this review.
AUTHORS' CONCLUSIONS
We found no direct evidence on whether early spontaneous breathing in SARS-CoV-2-induced ARDS is beneficial or detrimental to this particular group of patients. RCTs comparing early spontaneous breathing with ventilatory strategies not allowing for spontaneous breathing in SARS-CoV-2-induced ARDS are necessary to determine its value within the treatment of severely ill people with COVID-19. Additionally, studies should aim to clarify whether treatment effects differ between people with SARS-CoV-2-induced ARDS and people with non-SARS-CoV-2-induced ARDS.
Topics: COVID-19; Humans; Neuromuscular Blocking Agents; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2; Systematic Reviews as Topic
PubMed: 35767435
DOI: 10.1002/14651858.CD015077 -
Translational Pediatrics Apr 2022Neonatal respiratory distress syndrome (NRDS), if caused by a lack of pulmonary surfactant (PS), leads to progressive alveolar collapse. Glucocorticoids have...
BACKGROUND
Neonatal respiratory distress syndrome (NRDS), if caused by a lack of pulmonary surfactant (PS), leads to progressive alveolar collapse. Glucocorticoids have anti-inflammatory and anti-allergic effects and can reduce bronchial and pulmonary edema. This research hopes to systematically evaluate the efficacy and safety of animal-derived PS combined with the glucocorticoid drug budesonide in the treatment of NRDS.
METHODS
Electronic databases (i.e., Wanfang, Weipu, CNKI, PubMed, Embase, Cochrane Library) were searched from inception until May 30th, 2021. Studies relevant to the treatment of pulmonary surfactant combined with budesonide in the treatment of neonatal respiratory distress syndrome were identified. Consequently, all the studies that met the inclusion criteria were considered qualified for screening. For the meta-analysis, all data were analyzed using RevMan 5.3 software. Furthermore, subgroup analysis was performed to evaluate the administration method of budesonide (nebulized inhalation, intratracheal instillation) combined with intratracheal instillation of pulmonary surfactant.
RESULTS
A total of 10 articles were included in this study, involving 527 children. This meta-analysis suggests that the treatment of intratracheal infusion of pulmonary surfactant combined with budesonide therapy can effectively (I) reduce the time of mechanical ventilation (OR =-1.72,95% CI: -2.44 to -1.01, P<0.00001); (II) reduce the length of stay (OR =-5.17, 95% CI: -9.35 to -0.99, P=0.02); (III) reduce the incidence of bronchopulmonary dysplasia (BPD) (OR =0.52, 95% CI: 0.39-0.68, P<0.00001); and (IV) reduce the incidence of BPD (RR =0.73, 95% CI: 0.40-1.35, P=0.32). There was no significant difference in the incidence of retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), or sepsis between the experimental group and the control group.
DISCUSSION
The treatment of animal-derived pulmonary surfactant combined with budesonide can effectively shorten the hospital stay and reduce the time of invasive mechanical ventilation and the incidence of BPD. Meanwhile, it does not increase the risk of related complications or death. This approach can be applied clinically.
PubMed: 35558978
DOI: 10.21037/tp-22-8 -
Frontiers in Cardiovascular Medicine 2022Patients with a Fontan circulation are at risk for sequelae of Fontan physiology during follow-up. Fontan physiology affects all organ systems and an overview of...
INTRODUCTION
Patients with a Fontan circulation are at risk for sequelae of Fontan physiology during follow-up. Fontan physiology affects all organ systems and an overview of end-organ damage is needed.
METHODS
We performed a systematic review of abnormalities in multiple organ systems for patients with a longstanding Fontan circulation. We searched online databases for articles describing abnormalities in multiple organ systems. Cardio-pulmonary abnormalities, protein losing enteropathy, and Fontan associated liver disease have already extensively been described and were excluded from this systematic review.
RESULTS
Our search returned 5,704 unique articles. After screening, we found 111 articles relating to multiple organ systems. We found abnormalities in, among others, the nervous system, pituitary, kidneys, and musculoskeletal system. Pituitary edema-relating to the unique pituitary vasculature- may affect the thyroid axis. Renal dysfunction is common. Creatinine based renal function estimates may be inappropriate due to myopenia. Both lean muscle mass and bone mineral density are decreased. These abnormalities in multiple organ systems may be related to Fontan physiology, cyanosis, iatrogenic factors, or lifestyle.
CONCLUSIONS
Health care providers should be vigilant for hypothyroidism, visual or hearing deficits, and sleep disordered breathing in Fontan patients. We recommend including cystatin C for assessment of renal function. This review may aid health care providers and guide future research. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232461, PROSPERO, identifier: CRD42021232461.
PubMed: 35391839
DOI: 10.3389/fcvm.2022.826096