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1.
Int J Mol Sci ; 21(14)2020 Jul 08.
Article in English | MEDLINE | ID: covidwho-1934087

ABSTRACT

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are characterized by an inflammatory response, alveolar edema, and hypoxemia. ARDS occurs most often in the settings of pneumonia, sepsis, aspiration of gastric contents, or severe trauma. The prevalence of ARDS is approximately 10% in patients of intensive care. There is no effective remedy with mortality high at 30-40%. Most functional proteins are dynamic and stringently governed by ubiquitin proteasomal degradation. Protein ubiquitination is reversible, the covalently attached monoubiquitin or polyubiquitin moieties within the targeted protein can be removed by a group of enzymes called deubiquitinating enzymes (DUBs). Deubiquitination plays an important role in the pathobiology of ALI/ARDS as it regulates proteins critical in engagement of the alveolo-capillary barrier and in the inflammatory response. In this review, we provide an overview of how DUBs emerge in pathogen-induced pulmonary inflammation and related aspects in ALI/ARDS. Better understanding of deubiquitination-relatedsignaling may lead to novel therapeutic approaches by targeting specific elements of the deubiquitination pathways.


Subject(s)
Acute Lung Injury/metabolism , Deubiquitinating Enzymes/metabolism , Respiratory Distress Syndrome/metabolism , Animals , Humans , Pneumonia/metabolism , Signal Transduction/physiology , Ubiquitin/metabolism , Ubiquitination/physiology
2.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Article in English | MEDLINE | ID: covidwho-1931217

ABSTRACT

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Cough/etiology , Inflammation/etiology , Nervous System Diseases/etiology , Neuroimmunomodulation , Cough/physiopathology , Humans , Inflammation/physiopathology , Nervous System Diseases/physiopathology , SARS-CoV-2 , Syndrome
3.
J Am Coll Emerg Physicians Open ; 1(6): 1354-1356, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1898685

ABSTRACT

SARS-CoV-2 is a novel strain of coronavirus that was first identified in Wuhan, China; it has since spread rapidly throughout the world. Most of the patients with COVID-19 present with respiratory symptoms, including cough, nasal symptoms, fever, and shortness of breath. However, several groups have reported that SARS-CoV-2 can infect the central nervous system via the olfactory bulb followed by spread throughout the brain and peripheral nervous system. This brief report illustrated a 78-year-old man who presented to the emergency department (ED) on March 22, 2020, with chief complaints of dizziness and unsteadiness while walking. He had no symptoms suggestive of COVID-19 on arrival. SARS-CoV-2 nasopharyngeal swab test performed at that time due to his atypical presentation and lymphocytopenia was positive for virus nucleic acids. The neurological symptoms associated with COVID-19 are frequently non-specific and may emerge several days before the respiratory symptoms; as such, identification of patients presenting with these subtle and seemingly unremarkable COVID-19 symptoms will be quite difficult. Added to this, numerous countries still limit testing for SARS-COV-2 to patients presenting with fever or respiratory symptoms. Frontline physicians should be aware of early, non-specific symptoms associated with SARS-CoV-2 infection.

4.
Minerva Med ; 113(2): 281-290, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1847990

ABSTRACT

BACKGROUND: The efficacy and safety of continuous positive airway pressure and respiratory physiotherapy outside the Intensive Care Unit during a pandemic. METHODS: In this cohort study performed in February-May 2020 in a large teaching hospital in Milan, COVID-19 patients with adult respiratory distress syndrome receiving continuous positive airway pressure (positive end-expiratory pressure =10 cm H2O, FiO2=0.6, daily treatment duration: 4×3h-cycles) and respiratory physiotherapy including pronation outside the Intensive Care Unit were followed-up. RESULTS: Of 90 acute respiratory distress syndrome (ARDS) patients treated with continuous positive airway pressure (45/90, 50% pronated at least once) outside the Intensive Care Unit and with a median (interquartile) follow-up of 37 (11-46) days, 45 (50%) were discharged at home, 28 (31%) were still hospitalized, and 17 (19%) died. Continuous positive airway pressure failure was recorded for 35 (39%) patients. Patient mobilization was associated with reduced failure rates (P=0.033). No safety issues were observed. CONCLUSIONS: Continuous positive airway pressure with patient mobilization (including pronation) was effective and safe in patients with ARDS due to COVID-19 managed outside the Intensive Care Unit setting during the pandemic.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Adult , COVID-19/complications , COVID-19/therapy , Cohort Studies , Continuous Positive Airway Pressure , Humans , Intensive Care Units , Pronation , Respiratory Distress Syndrome/therapy
5.
Nutrients ; 12(6)2020 Jun 08.
Article in English | MEDLINE | ID: covidwho-1725884

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) global pandemic is a devastating event that is causing thousands of victims every day around the world. One of the main reasons of the great impact of coronavirus disease 2019 (COVID-19) on society is its unexpected spread, which has not allowed an adequate preparation. The scientific community is fighting against time for the production of a vaccine, but it is difficult to place a safe and effective product on the market as fast as the virus is spreading. Similarly, for drugs that can directly interfere with viral pathways, their production times are long, despite the great efforts made. For these reasons, we analyzed the possible role of non-pharmacological substances such as supplements, probiotics, and nutraceuticals in reducing the risk of Sars-CoV-2 infection or mitigating the symptoms of COVID-19. These substances could have numerous advantages in the current circumstances, are generally easily available, and have negligible side effects if administered at the already used and tested dosages. Large scientific evidence supports the benefits that some bacterial and molecular products may exert on the immune response to respiratory viruses. These could also have a regulatory role in systemic inflammation or endothelial damage, which are two crucial aspects of COVID-19. However, there are no specific data available, and rigorous clinical trials should be conducted to confirm the putative benefits of diet supplementation, probiotics, and nutraceuticals in the current pandemic.


Subject(s)
Coronavirus Infections/diet therapy , Coronavirus Infections/prevention & control , Diet , Dietary Supplements , Pandemics/prevention & control , Pneumonia, Viral/diet therapy , Pneumonia, Viral/prevention & control , Probiotics/therapeutic use , Ascorbic Acid/therapeutic use , Betacoronavirus , COVID-19 , Humans , SARS-CoV-2 , Vitamin D/therapeutic use
6.
Malays J Med Sci ; 27(3): 53-60, 2020 May.
Article in English | MEDLINE | ID: covidwho-1662979

ABSTRACT

BACKGROUND: Deep brain stimulation (DBS) was pioneered by Neuroscience team of Hospital Universiti Sains Malaysia (HUSM) nearly a decade ago to treat advanced medically refractory idiopathic Parkinson's disease (IPD) patients. OBJECTIVES: Brain volume reduction occurs with age, especially in Parkinson plus syndrome or psychiatric disorders. We searched to define the degree of volume discrepancy in advanced IPD patients and correlate the anatomical volumetric changes to motor symptoms and cognitive function. METHODS: We determined the magnetic resonance imaging (MRI)-based volumetry of deep brain nuclei and brain structures of DBS-IPD group and matched controls. RESULTS: DBS-IPD group had significant deep nuclei atrophy and volume discrepancy, yet none had cognitive or psychobehavioural disturbances. Globus pallidus volume showed positive correlation to higher mental function. CONCLUSION: The morphometric changes and clinical severity discrepancy in IPD may imply a more complex degenerative mechanism involving multiple neural pathways. Such alteration could be early changes before clinical manifestation.

7.
Front Immunol ; 12: 674922, 2021.
Article in English | MEDLINE | ID: covidwho-1607886

ABSTRACT

Since December 2019, the world has been facing an outbreak of a new disease called coronavirus disease 2019 (COVID-19). The COVID-19 pandemic is caused by a novel beta-coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 infection mainly affects the respiratory system. Recently, there have been some reports of extra-respiratory symptoms such as neurological manifestations in COVID-19. According to the increasing reports of Guillain-Barré syndrome following COVID-19, we mainly focused on SARS-CoV-2 infection and Guillain-Barré syndrome in this review. We tried to explain the possibility of a relationship between SARS-CoV-2 infection and Guillain-Barré syndrome and potential pathogenic mechanisms based on current and past knowledge.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/etiology , SARS-CoV-2/pathogenicity , COVID-19/epidemiology , COVID-19/immunology , COVID-19/pathology , Guillain-Barre Syndrome/epidemiology , Guillain-Barre Syndrome/immunology , Guillain-Barre Syndrome/pathology , Humans , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , Nervous System Diseases/immunology , Nervous System Diseases/pathology , Virulence
8.
J Immunotoxicol ; 18(1): 23-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1593522

ABSTRACT

The coronavirus SARS-CoV-2 of 2019 (COVID-19) causes a pandemic that has been diagnosed in more than 70 million people worldwide. Mild-to-moderate COVID-19 symptoms include coughing, fever, myalgia, shortness of breath, and acute inflammatory lung injury (ALI). In contrast, acute respiratory distress syndrome (ARDS) and respiratory failure occur in patients diagnosed with severe COVID-19. ARDS is mediated, at least in part, by a dysregulated inflammatory response due to excessive levels of circulating cytokines, a condition known as the "cytokine-storm syndrome." Currently, there are FDA-approved therapies that attenuate the dysregulated inflammation that occurs in COVID-19 patients, such as dexamethasone or other corticosteroids and IL-6 inhibitors, including sarilumab, tocilizumab, and siltuximab. However, the efficacy of these treatments have been shown to be inconsistent. Compounds that activate the vagus nerve-mediated cholinergic anti-inflammatory reflex, such as the α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuate ARDS/inflammatory lung injury by decreasing the extracellular levels of high mobility group box-1 (HMGB1) in the airways and the circulation. It is possible that HMGB1 may be an important mediator of the "cytokine-storm syndrome." Notably, high plasma levels of HMGB1 have been reported in patients diagnosed with severe COVID-19, and there is a significant negative correlation between HMGB1 plasma levels and clinical outcomes. Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.


Subject(s)
Benzylidene Compounds/pharmacology , COVID-19/drug therapy , Cholinergic Agents/pharmacology , Inflammation/drug therapy , Nicotine/metabolism , Pyridines/pharmacology , SARS-CoV-2/physiology , Tobacco Use Disorder/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Cigarette Smoking/adverse effects , Dexamethasone/therapeutic use , HMGB1 Protein/blood , Humans , Pandemics , alpha7 Nicotinic Acetylcholine Receptor/agonists
9.
Front Immunol ; 12: 631233, 2021.
Article in English | MEDLINE | ID: covidwho-1575223

ABSTRACT

Coronavirus disease-19 caused by the novel RNA betacoronavirus SARS-CoV2 has first emerged in Wuhan, China in December 2019, and since then developed into a worldwide pandemic with >99 million people afflicted and >2.1 million fatal outcomes as of 24th January 2021. SARS-CoV2 targets the lower respiratory tract system leading to pneumonia with fever, cough, and dyspnea. Most patients develop only mild symptoms. However, a certain percentage develop severe symptoms with dyspnea, hypoxia, and lung involvement which can further progress to a critical stage where respiratory support due to respiratory failure is required. Most of the COVID-19 symptoms are related to hyperinflammation as seen in cytokine release syndrome and it is believed that fatalities are due to a COVID-19 related cytokine storm. Treatments with anti-inflammatory or anti-viral drugs are still in clinical trials or could not reduce mortality. This makes it necessary to develop novel anti-inflammatory therapies. Recently, the therapeutic potential of phytocannabinoids, the unique active compounds of the cannabis plant, has been discovered in the area of immunology. Phytocannabinoids are a group of terpenophenolic compounds which biological functions are conveyed by their interactions with the endocannabinoid system in humans. Here, we explore the anti-inflammatory function of cannabinoids in relation to inflammatory events that happen during severe COVID-19 disease, and how cannabinoids might help to prevent the progression from mild to severe disease.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/therapy , Cannabinoids/therapeutic use , Cannabis/immunology , Cytokine Release Syndrome/therapy , Phytotherapy , SARS-CoV-2/physiology , Endocannabinoids/metabolism , Humans , Pandemics
10.
Ann Med ; 53(1): 410-412, 2021 12.
Article in English | MEDLINE | ID: covidwho-1573909

ABSTRACT

OBJECTIVE: Cytokine release syndrome is suggested to be the most important mechanism triggering acute respiratory distress syndrome and end organ damage in COVID-19. The severity of disease may be measured by different biomarkers. METHODS: We studied markers of inflammation and coagulation as recorded in 29 patients on admission to the hospital in order to identify markers of severe COVID-19 and need of ICU. RESULTS: Patients who were eventually admitted to ICU displayed significantly higher serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. No statistical differences were found between the groups in median levels of lymphocytes, D-dimer or ferritin. CONCLUSIONS: IL-6 and CRP were the strongest predictors of severity in hospitalized patients with COVID-19.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Interleukin-6/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Humans , Male , Middle Aged , Severity of Illness Index , Young Adult
11.
Surg Infect (Larchmt) ; 22(9): 948-954, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1522102

ABSTRACT

Background: In trauma, direct pulmonary injury and innate immune response activation primes the lungs for acute respiratory distress syndrome (ARDS). The inflammasome-dependent release of interleukin-18 (IL-18) was recently identified as a key mediator in ARDS pathogenesis, leading us to hypothesize that plasma IL-18 is a diagnostic predictor of ARDS in severe blunt trauma. Patients and Methods: Secondary analysis of the Inflammation and Host Response to Injury database was performed on plasma cytokines collected within 12 hours of severe blunt trauma. Trauma-related cytokines, including IL-18, were compared between patients with and without ARDS and were evaluated for association with ARDS using regression analysis. Threshold cytokine concentrations predictive of ARDS were determined using receiver-operating curve (ROC) analysis. Results: Cytokine analysis of patients without ARDS patients (n = 61) compared with patients with ARDS (n = 19) demonstrated elevated plasma IL-18 concentration in ARDS and IL-18 remained correlated with ARDS on logistic regression after confounder adjustment (p = 0.008). Additionally, ROC analysis revealed IL-18 as a strong ARDS predictor (area under the curve [AUC] = 0.83), with a threshold IL-18 value of 170 pg/mL (Youden index, 0.3). Unlike in patients without ARDS, elevated IL-18 persisted in patients with ARDS during the acute injury phase (p ≤ 0.02). Other trauma-related cytokines did not correlate with ARDS. Conclusions: In severe blunt trauma, IL-18 is a robust predictor of ARDS and remains elevated throughout the acute injury phase. These findings support the use of IL-18 as a key ARDS biomarker, promoting early identification of trauma patients at greater risk of developing ARDS. Timely recognition of ARDS and implementation of advantageous supportive care practices may reduce trauma-related ARDS morbidity and costs.


Subject(s)
Respiratory Distress Syndrome , Wounds, Nonpenetrating , Humans , Interleukin-18 , Logistic Models , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Risk Assessment , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/diagnosis
12.
Pharmacol Res ; 169: 105689, 2021 07.
Article in English | MEDLINE | ID: covidwho-1525917

ABSTRACT

Genome wide association, epidemiological, and clinical studies have established high lipoprotein(a) [Lp(a)] as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is an apoB100 containing lipoprotein covalently bound to apolipoprotein(a) [apo(a)], a glycoprotein. Plasma Lp(a) levels are to a large extent determined by genetics. Its link to cardiovascular disease (CVD) may be driven by its pro-inflammatory effects, of which its association with oxidized phospholipids (oxPL) bound to Lp(a) is the most studied. Various inflammatory conditions, such as rheumatoid arthritis (RA), systemic lupus erythematosus, acquired immunodeficiency syndrome, and chronic renal failure are associated with high Lp(a) levels. In cases of RA, high Lp(a) levels are reversed by interleukin-6 receptor (IL-6R) blockade by tocilizumab, suggesting a potential role for IL-6 in regulating Lp(a) plasma levels. Elevated levels of IL-6 and IL-6R polymorphisms are associated with CVD. Therapies aimed at lowering apo(a) and thereby reducing plasma Lp(a) levels are in clinical trials. Their results will determine if reductions in apo(a) and Lp(a) decrease cardiovascular outcomes. As we enter this new arena of available treatments, there is a need to improve our understanding of mechanisms. This review will focus on the role of Lp(a) in inflammation and CVD.


Subject(s)
Inflammation/metabolism , Lipoprotein(a)/blood , Animals , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Humans , Inflammation/blood , Inflammation/etiology , Lipoprotein(a)/metabolism , Lipoprotein(a)/physiology
13.
J Thromb Thrombolysis ; 52(4): 1043-1046, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1525570

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a complex disease with many clinicopathological aspects, including abnormal immunothrombosis, and the full comprehension of its pathogenetic mechanisms is urgently required. METHODS/RESULTS: By means of a multidisciplinary approach, we here report a catastrophic COVID-19 in a 44-year-old Philippine male patient, discovered lupus anticoagulant (LAC)-positive shortly before death, occurred 8 days after hospitalization in a clinical scenario refractory to standard high acuity care recalling Asherson's syndrome (catastrophic antiphospholipid syndrome). CONCLUSION: A parallelism between this severe form of COVID-19 and Asherson's syndrome can be so drawn. Both the diseases in fact exhibit hypercytokinemia, thrombotic microangiopathy, disseminated intravascular coagulation and multiple organ failure, they show a relationship with viral infections, and they are burdened by a high mortality rate. A genetic predisposition to develop these two overlapping conditions may be supposed.


Subject(s)
Antiphospholipid Syndrome , COVID-19 , Lupus Coagulation Inhibitor/blood , Adult , Fatal Outcome , Humans , Male
14.
Nat Med ; 27(4): 601-615, 2021 04.
Article in English | MEDLINE | ID: covidwho-1517636

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Acute Disease , COVID-19/epidemiology , COVID-19/ethnology , COVID-19/therapy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Humans , Patient Advocacy , Syndrome , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/therapy , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control
15.
Eur Respir J ; 58(1)2021 07.
Article in English | MEDLINE | ID: covidwho-1496128

ABSTRACT

OBJECTIVE: To evaluate pulmonary function and clinical symptoms in coronavirus disease 2019 (COVID-19) survivors within 3 months after hospital discharge, and to identify risk factors associated with impaired lung function. METHODS AND MATERIAL: COVID-19 patients were prospectively followed-up with pulmonary function tests and clinical characteristics for 3 months following discharge from a hospital in Wuhan, China between January and February 2020. RESULTS: 647 patients were included. 87 (13%) patients presented with weakness, 63 (10%) with palpitations and 56 (9%) with dyspnoea. The prevalence of each of the three symptoms were markedly higher in severe patients than nonsevere patients (19% versus 10% for weakness, p=0.003; 14% versus 7% for palpitations, p=0.007; 12% versus 7% for dyspnoea, p=0.014). Results of multivariable regression showed increased odds of ongoing symptoms among severe patients (OR 1.7, 95% CI 1.1-2.6; p=0.026) or patients with longer hospital stays (OR 1.03, 95% CI 1.00-1.05; p=0.041). Pulmonary function test results were available for 81 patients, including 41 nonsevere and 40 severe patients. In this subgroup, 44 (54%) patients manifested abnormal diffusing capacity of the lung for carbon monoxide (D LCO) (68% severe versus 42% nonsevere patients, p=0.019). Chest computed tomography (CT) total severity score >10.5 (OR 10.4, 95% CI 2.5-44.1; p=0.001) on admission and acute respiratory distress syndrome (ARDS) (OR 4.6, 95% CI 1.4-15.5; p=0.014) were significantly associated with impaired D LCO. Pulmonary interstitial damage may be associated with abnormal D LCO. CONCLUSION: Pulmonary function, particularly D LCO, declined in COVID-19 survivors. This decrease was associated with total severity score of chest CT >10.5 and ARDS occurrence. Pulmonary interstitial damage might contribute to the imparied D LCO.


Subject(s)
COVID-19 , Carbon Monoxide , China , Follow-Up Studies , Humans , Lung/diagnostic imaging , SARS-CoV-2
16.
Crit Care Med ; 49(7): 1149-1158, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1494026

ABSTRACT

OBJECTIVES: Circulating nucleosomes and their component histones have been implicated as pathogenic in sepsis and acute respiratory distress syndrome in adults. However, their role in pediatric acute respiratory distress syndrome is unknown. DESIGN: We performed a prospective cohort study in children with acute respiratory distress syndrome, with plasma collection within 24 hours of acute respiratory distress syndrome onset. We associated nucleosome levels with severity of acute respiratory distress syndrome and with nonpulmonary organ failures and tested for association of nucleosomes with PICU mortality and ventilator-free days at 28 days in univariate and multivariable analyses. We also performed proteomics of DNA-bound plasma proteins in a matched case-control study of septic children with and without acute respiratory distress syndrome in order to identify specific histone proteins elevated in acute respiratory distress syndrome. SETTING: Large academic tertiary-care PICU. PATIENTS: Intubated children meeting Berlin criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled 333 children with acute respiratory distress syndrome, with 69 nonsurvivors (21%). Plasma nucleosomes were correlated with acute respiratory distress syndrome severity and with the number of nonpulmonary organ failures at acute respiratory distress syndrome onset. Nucleosomes were higher (p < 0.001) in nonsurvivors (0.40 [interquartile range, 0.20-0.71] arbitrary units) relative to survivors (0.10 [interquartile range, 0.04-0.25] arbitrary units). Nucleosomes were associated with PICU mortality in multivariable analysis (adjusted odds ratio 1.84 per 1 sd increase; 95% CI, 1.38-2.45; p < 0.001). Nucleosomes were also associated with a lower probability of being extubated alive by day 28 after multivariable adjustment (adjusted subdistribution hazard ratio, 0.74; 95% CI, 0.63-0.88; p = 0.001). Proteomic analysis demonstrated higher levels of the core nucleosome histones H2A, H2B, H3, and H4 in septic children with acute respiratory distress syndrome, relative to septic children without acute respiratory distress syndrome. CONCLUSIONS: Plasma nucleosomes are associated with acute respiratory distress syndrome severity, nonpulmonary organ failures, and worse outcomes in pediatric acute respiratory distress syndrome.


Subject(s)
Histones/blood , Nucleosomes/metabolism , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/mortality , Adolescent , Airway Extubation , Case-Control Studies , Child , Child, Preschool , DNA/blood , Female , Hospital Mortality , Humans , Intensive Care Units, Pediatric , Male , Multiple Organ Failure/mortality , Prognosis , Prospective Studies , Proteomics , Respiration, Artificial , Respiratory Distress Syndrome/complications , Sepsis/blood , Sepsis/complications , Severity of Illness Index , Survival Rate
17.
Am J Obstet Gynecol MFM ; 3(3): 100312, 2021 05.
Article in English | MEDLINE | ID: covidwho-1453982

ABSTRACT

OBJECTIVE: This study aimed to evaluate the comparative clinical effectiveness and safety of dexamethasone vs betamethasone for preterm birth. DATA SOURCES: The sources searched were MEDLINE, EMBASE, Cochrane Library, LILACS, ClinicalTrials.gov, and International Clinical Trials Registry Platform without language restrictions until October 2019 in addition to the reference lists of included studies. Field experts were also contacted. STUDY ELIGIBILITY CRITERIA: Randomized or quasi-randomized controlled trials comparing any corticosteroids against each other or against placebo at any dose for preterm birth were included in the study. METHODS: Three researchers independently selected and extracted data and assessed the risk of bias of the included studies by using Early Review Organizing Software and Covidence software. Random-effects pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcomes were chorioamnionitis, endometritis or puerperal sepsis, neonatal death, respiratory distress syndrome, and neurodevelopmental disability. RESULTS: A total of 45 trials (11,227 women and 11,878 infants) were included in the study. No clinical or statistical difference was found between dexamethasone and betamethasone in neonatal death (odds ratio, 1.05; 95% confidence interval, 0.62-1.84; moderate-certainty evidence), neurodevelopmental disability (odds ratio, 1.03; 95% confidence interval, 0.80-1.33; moderate-certainty evidence), intraventricular hemorrhage (odds ratio, 1.04; 95% confidence interval, 0.56-1.78); low-certainty evidence), or birthweight (+5.29 g; 95% confidence interval, -49.79 to 58.97; high-certainty evidence). There was no statistically significant difference, but a potentially clinically important effect was found between dexamethasone and betamethasone in chorioamnionitis (odds ratio, 0.70; 95% confidence interval, 0.45-1.06; moderate-certainty evidence), fetal death (odds ratio, 0.81; 95% confidence interval, 0.24-2.41; low-certainty evidence), puerperal sepsis (odds ratio, 2.04; 95% confidence interval, 0.72-6.06; low-certainty evidence), and respiratory distress syndrome (odds ratio, 1.34; 95% confidence interval, 0.96-2.11; moderate-certainty evidence). Meta-regression, subgroup, and sensitivity analyses did not reveal important changes regarding the main analysis. CONCLUSION: Corticosteroids have proven effective for most neonatal and child-relevant outcomes compared with placebo or no treatment for women at risk of preterm birth. No important difference was found on neonatal death, neurodevelopmental disability, intraventricular hemorrhage, and birthweight between corticosteroids, and there was no statistically significant difference, but a potentially important difference was found in chorioamnionitis, fetal death, endometritis or puerperal sepsis, and respiratory distress syndrome. Further research is warranted to improve the certainty of evidence and inform health policies.


Subject(s)
Premature Birth , Bayes Theorem , Betamethasone , Child , Dexamethasone/therapeutic use , Female , Humans , Infant , Infant, Newborn , Network Meta-Analysis , Pregnancy , Premature Birth/epidemiology
18.
Surg Endosc ; 35(6): 2981-2985, 2021 06.
Article in English | MEDLINE | ID: covidwho-1453742

ABSTRACT

INTRODUCTION: Stray energy transfer from surgical monopolar radiofrequency energy instruments can cause unintended thermal injuries during laparoscopic surgery. Single-incision laparoscopic surgery transfers more stray energy than traditional laparoscopic surgery. There is paucity of published data concerning stray energy during single-incision robotic surgery. The purpose of this study was to quantify stray energy transfer during traditional, multiport robotic surgery (TRS) compared to single-incision robotic surgery (SIRS). METHODS: An in vivo porcine model was used to simulate a multiport or single-incision robotic cholecystectomy (DaVinci Si, Intuitive Surgical, Sunnyvale, CA). A 5 s, open air activation of the monopolar scissors was done on 30 W and 60 W coag mode (ForceTriad, Covidien-Medtronic, Boulder, CO) and Swift Coag effect 3, max power 180 W (VIO 300D, ERBE USA, Marietta, GA). Temperature of the tissue (°C) adjacent to the tip of the assistant grasper or the camera was measured with a thermal camera (E95, FLIR Systems, Wilsonville, OR) to quantify stray energy transfer. RESULTS: Stray energy transfer was greater in the SIRS setup compared to TRS setup at the assistant grasper (11.6 ± 3.3 °C vs. 8.4 ± 1.6 °C, p = 0.013). Reducing power from 60 to 30 W significantly reduced stray energy transfer in SIRS (15.3 ± 3.4 °C vs. 11.6 ± 3.3 °C, p = 0.023), but not significantly for TRS (9.4 ± 2.5 °C vs. 8.4 ± 1.6 °C, p = 0.278). The use of a constant voltage regulating generator also minimized stray energy transfer for both SIRS (0.7 ± 0.4 °C, p < 0.001) and TRS (0.7 ± 0.4 °C, p < 0.001). CONCLUSIONS: More stray energy transfer occurs during single-incision robotic surgery than multiport robotic surgery. Utilizing a constant voltage regulating generator minimized stray energy transfer for both setups. These data can be used to guide robotic surgeons in their use of safe, surgical energy.


Subject(s)
Laparoscopy , Robotic Surgical Procedures , Robotics , Surgical Wound , Animals , Energy Transfer , Swine
19.
Medicine (Baltimore) ; 100(19): e25923, 2021 May 14.
Article in English | MEDLINE | ID: covidwho-1455404

ABSTRACT

ABSTRACT: Blocking IL-6 pathways with sarilumab, a fully human anti-IL-6R antagonist may potentially curb the inflammatory storm of SARS-CoV2. In the present emergency scenario, we used "off-label" sarilumab in 5 elderly patients in life-threatening condition not candidates to further active measures. We suggest that sarilumab can modulate severe COVID-19-associated Cytokine Release Syndrome.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Interleukin-6/antagonists & inhibitors , Aged , Anti-Infective Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/physiopathology , Comorbidity , Critical Illness , Cytokine Release Syndrome/physiopathology , Humans , Hydroxychloroquine/therapeutic use , Male , Middle Aged , RNA, Viral , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2
20.
J Infect Dev Ctries ; 15(3): 353-359, 2021 Mar 31.
Article in English | MEDLINE | ID: covidwho-1444370

ABSTRACT

INTRODUCTION: The early identification of factors that predict the length of hospital stay (HS) in patients affected by coronavirus desease (COVID-19) might assist therapeutic decisions and patient flow management. METHODOLOGY: We collected, at the time of admission, routine clinical, laboratory, and imaging parameters of hypoxia, lung damage, inflammation, and organ dysfunction in a consecutive series of 50 COVID-19 patients admitted to the Respiratory Disease and Infectious Disease Units of the University Hospital of Sassari (North-Sardinia, Italy) and alive on discharge. RESULTS: Prolonged HS (PHS, >21 days) patients had significantly lower PaO2/FiO2 ratio and lymphocytes, and significantly higher Chest CT severity score, C-reactive protein (CRP) and lactic dehydrogenase (LDH) when compared to non-PHS patients. In univariate logistic regression, Chest CT severity score (OR = 1.1891, p = 0.007), intensity of care (OR = 2.1350, p = 0.022), PaO2/FiO2 ratio (OR = 0.9802, p = 0.007), CRP (OR = 1.0952, p = 0.042) and platelet to lymphocyte ratio (OR = 1.0039, p = 0.036) were significantly associated with PHS. However, in multivariate logistic regression, only the PaO2/FiO2 ratio remained significantly correlated with PHS (OR = 0.9164; 95% CI 0.8479-0.9904, p = 0.0275). In ROC curve analysis, using a threshold of 248, the PaO2/FiO2 ratio predicted PHS with sensitivity and specificity of 60% and 91%, respectively (AUC = 0.780, 95% CI 0.637-0.886 p = 0.002). CONCLUSIONS: The PaO2/FiO2 ratio on admission is independently associated with PHS in COVID-19 patients. Larger prospective studies are needed to confirm this finding.


Subject(s)
COVID-19/diagnosis , COVID-19/physiopathology , Hypoxia/diagnosis , Length of Stay/statistics & numerical data , Aged , Aged, 80 and over , COVID-19/epidemiology , Female , Humans , Hypoxia/virology , Italy/epidemiology , Male , Middle Aged , Prospective Studies , Retrospective Studies
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