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2.
Pharmacol Res Perspect ; 9(5): e00873, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34632734

RESUMO

We hypothesized whether propofol or active propofol component (2,6-diisopropylphenol [DIPPH] and lipid excipient [LIP-EXC]) separately may alter inflammatory mediators expressed by macrophages and neutrophils in lean and obese rats. Male Wistar rats (n = 10) were randomly assigned to receive a standard (lean) or obesity-inducing diet (obese) for 12 weeks. Animals were euthanized, and alveolar macrophages and neutrophils from lean and obese animals were exposed to propofol (50 µM), active propofol component (50 µM, 2,6-DIPPH), and lipid excipient (soybean oil, purified egg phospholipid, and glycerol) for 1 h. The primary outcome was IL-6 expression after propofol and its components exposure by alveolar macrophages extracted from bronchoalveolar lavage fluid. The secondary outcomes were the production of mediators released by macrophages from adipose tissue, and neutrophils from lung and adipose tissues, and neutrophil migration. IL-6 increased after the exposure to both propofol (median [interquartile range] 4.14[1.95-5.20]; p = .04) and its active component (2,6-DIPPH) (4.09[1.67-5.91]; p = .04) in alveolar macrophages from obese animals. However, only 2,6-DIPPH increased IL-10 expression (7.59[6.28-12.95]; p = .001) in adipose tissue-derived macrophages. Additionally, 2,6-DIPPH increased C-X-C chemokine receptor 2 and 4 (CXCR2 and CXCR4, respectively) in lung (10.08[8.23-29.01]; p = .02; 1.55[1.49-3.43]; p = .02) and adipose tissues (8.78[4.15-11.57]; p = .03; 2.86[2.17-3.71]; p = .01), as well as improved lung-derived neutrophil migration (28.00[-3.42 to 45.07]; p = .001). In obesity, the active component of propofol affected both the M1 and M2 markers as well as neutrophils in both alveolar and adipose tissue cells, suggesting that lipid excipient may hinder the effects of active propofol.

3.
Ann Med ; 53(1): 1779-1786, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637370

RESUMO

BACKGROUND: An unexpected high prevalence of enterococcal bloodstream infection (BSI) has been observed in critically ill patients with COVID-19 in the intensive care unit (ICU). MATERIALS AND METHODS: The primary objective was to describe the characteristics of ICU-acquired enterococcal BSI in critically ill patients with COVID-19. A secondary objective was to exploratorily assess the predictors of 30-day mortality in critically ill COVID-19 patients with ICU-acquired enterococcal BSI. RESULTS: During the study period, 223 patients with COVID-19 were admitted to COVID-19-dedicated ICUs in our centre. Overall, 51 episodes of enterococcal BSI, occurring in 43 patients, were registered. 29 (56.9%) and 22 (43.1%) BSI were caused by Enterococcus faecalis and Enterococcus faecium, respectively. The cumulative incidence of ICU-acquired enterococcal BSI was of 229 episodes per 1000 ICU admissions (95% mid-p confidence interval [CI] 172-298). Most patients received an empirical therapy with at least one agent showing in vitro activity against the blood isolate (38/43, 88%). The crude 30-day mortality was 42% (18/43) and 57% (4/7) in the entire series and in patients with vancomycin-resistant E. faecium BSI, respectively. The sequential organ failure assessment (SOFA) score showed an independent association with increased mortality (odds ratio 1.32 per one-point increase, with 95% confidence interval 1.04-1.66, p = .021). CONCLUSIONS: The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19. Our results suggest a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.KEY MESSAGESThe cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19.The crude 30-day mortality of enterococcal BSI in critically ill patients with COVID-19 may be higher than 40%.There could be a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34479782

RESUMO

The novel coronavirus pandemic has radically changed the landscape of normal surgical practice. Lifesaving cancer surgery, however, remains a clinical priority, and there is an increasing need to fully define the optimal oncologic management of patients with varying stages of lung cancer, allowing prioritization of which thoracic procedures should be performed in the current era. Healthcare providers and managers should not ignore the risk of a bimodal peak of mortality in patients with lung cancer; an imminent spike due to mortality from acute coronavirus disease 2019 (COVID-19) infection, and a secondary peak reflecting an excess of cancer-related mortality among patients whose treatments were deemed less urgent, delayed, or cancelled. The European Association of Cardiothoracic Anaesthesiology and Intensive Care Thoracic Anesthesia Subspecialty group has considered these challenges and developed an updated set of expert recommendations concerning the infectious period, timing of surgery, vaccination, preoperative screening and evaluation, airway management, and ventilation of thoracic surgical patients during the COVID-19 pandemic.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34480392

RESUMO

Odorant-binding proteins (OBPs) of vertebrates belong to the lipocalin superfamily and perform a dual function: solubilizing and ferrying volatile pheromones to the olfactory receptors, and complexing the same molecules in specialized glands and assisting their release into the environment. Within vertebrates, to date they have been reported only in mammals, apart from two studies on amphibians. Based on the small number of OBPs expressed in each species, on their sites of production outside the olfactory area and their presence in biological fluids known to be pheromone carriers, such as urine, saliva and sexual secretions, we conclude that OBPs of mammals are specifically dedicated to pheromonal communication. This assumption is further supported by the observation that some OBPs present in biological secretions are endowed with their own pheromonal activity, adding renewed interest to these proteins. Another novel piece of evidence is the recent discovery that glycosylation and phosphorylation can modulate the binding activity of these proteins, improving their affinity to pheromones and narrowing their specificity. A comparison with insects and other arthropods shows a completely different scenario. While mammalian OBPs are specifically tuned to pheromones, those of insects, which are completely different in sequence and structure, include carriers for general odorants in addition to those dedicated to pheromones. Additionally, whereas mammals adopted a single family of carrier proteins for chemical communication, insects and other arthropods are endowed with several families of semiochemical-binding proteins. Here, we review the literature on the structural and functional properties of vertebrate OBPs, summarize the most interesting new findings and suggest possible exciting future developments.

6.
Eur J Intern Med ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34511338

RESUMO

OBJECTIVES: The hypothesis of this study is that tocilizumab should affect common signs of infection due to its immunosuppressive properties. Primary aim of the study was to investigate whether the administration of tocilizumab to critically ill patients with COVID-19, led to a different clinical presentation of infectious complications compared to patients who did not receive tocilizumab. Secondary aim was investigating differences in laboratory parameters between groups. METHODS: Single-centre retrospective study, enrolling COVID-19 patients who developed a microbiologically confirmed infectious complication [ventilator associated pneumonia or bloodstream infection] after intensive care unit [ICU] admission and either treated with tocilizumab or not [controls]. RESULTS: A total of 58 patients were included, 25 treated with tocilizumab and 33 controls. Median time from tocilizumab administration to infection onset was 10 days [range 2-26]. Patients were 78% male, with median age 65 years [range 45-79]. At first clinical presentation of the infectious event, the frequency of hypotension [11/25, 44% vs. 11/33, 33%], fever [8/25, 32% vs. 10/33, 30%] or hypothermia [0/25,0%, vs. 2/33, 6%], and oxygen desaturation [6/25, 28% vs 4/33, 12%], as well as the frequency of SOFA score increase of ≥ 2 points [4/25, 16%,vs. 4/33, 12%] was similar in tocilizumab treated patients and controls [p>0.1 for all comparisons]. Among laboratory parameters, C-Reactive Protein elevation was reduced in tocilizumab treated patients compared to controls [8/25, 32% vs. 22/33, 67%, p=0.009]. CONCLUSION: The clinical features of infectious complications in critically ill patients with COVID-19 admitted to ICU were not affected by tocilizumab.

7.
Ultrasound Med Biol ; 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34551862

RESUMO

Chest computed tomography (CT) may provide insights into the pathophysiology of coronavirus disease 2019 (COVID-19), although it is not suitable for a timely bedside dynamic assessment of patients admitted to intensive care unit (ICU); therefore, lung ultrasound (LUS) has been proposed as a complementary diagnostic tool. The aims of this study were to investigate different lungs phenotypes in patients with COVID-19 and to assess the differences in CT and LUS scores between ICU survivors and non-survivors. We also explored the association between CT and LUS, and oxygenation (arterial partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2]) and clinical parameters. The study included 39 patients with COVID-19. CT scans revealed types 1, 2 and 3 phenotypes in 62%, 28% and 10% of patients, respectively. Among survivors, pattern 1 was prevalent (p < 0.005). Chest CT and LUS scores differed between survivors and non-survivors both at ICU admission and 10 days after and were associated with ICU mortality. Chest CT score was positively correlated with LUS findings at ICU admission (r = 0.953, p < 0.0001) and was inversely correlated with PaO2/FiO2 (r = -0.375, p = 0.019) and C-reactive protein (r = 0.329, p = 0.041). LUS score was inversely correlated with PaO2/FiO2 (r = -0.345, p = 0.031). COVID-19 presents distinct phenotypes with differences between survivors and non-survivors. LUS is a valuable monitoring tool in an ICU setting because it may correlate with CT findings and mortality, although it cannot predict oxygenation changes.

9.
Acta Biomed ; 92(4): e2021092, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34487082

RESUMO

Advance healthcare directives are legal documents, in which the patient, foreseeing a potential loss of capacity and autonomy, makes in advance decisions regarding future care and, in particular, end-of-life arrangements. In Italy, advance healthcare directives  are regulated by the Law 219 of 22 December 2017. Objectives of the study were: i) to develop and validate a questionnaire dedicated to evaluate the knowledge of the Law in a sample of 98 anesthesiologists, and ii) to shed light on the process of health-related decision-making and its determinants (age, gender, doctor/training resident, religious beliefs). A second part of the survey  not analyzed  in the present study, aimed to assess, through two simulated clinical scenarios, how patient' directives, relatives and the medical staff could influence physicians' clinical decision. Overall Cronbach's alpha coefficient of the questionnaire resulted 0.83. Three factors explaining up to 38.4% of total variance (communication and relationship with the patient; critical life-threatening situations and binding nature of the advance directive for the physician; and involvement of patients). Most of the doctors (58.7%) did not fully know the recent legislative provision. The lack of knowledge is critical in view of the specificity of the clinical area investigated (anesthesiology and intensive care), which has to cope with ethical issues. An adequate revision and implementation of the traditional curricula could help medical students and trainees develop the aptitudes and skills needed in their future profession.


Assuntos
Anestesiologia , Conhecimentos, Atitudes e Prática em Saúde , Diretivas Antecipadas , Pessoal de Saúde , Humanos , Itália , Projetos Piloto , Inquéritos e Questionários
10.
PLoS One ; 16(8): e0256021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34415935

RESUMO

BACKGROUND: We hypothesized that a decrease in frequency of controlled breaths during biphasic positive airway pressure (BIVENT), associated with an increase in spontaneous breaths, whether pressure support (PSV)-assisted or not, would mitigate lung and diaphragm damage in mild experimental acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 hours, animals were randomly assigned to: 1) BIVENT-100+PSV0%: airway pressure (Phigh) adjusted to VT = 6 mL/kg and frequency of controlled breaths (f) = 100 bpm; 2) BIVENT-50+PSV0%: Phigh adjusted to VT = 6 mL/kg and f = 50 bpm; 3) BIVENT-50+PSV50% (PSV set to half the Phigh reference value, i.e., PSV50%); or 4) BIVENT-50+PSV100% (PSV equal to Phigh reference value, i.e., PSV100%). Positive end-expiratory pressure (Plow) was equal to 5 cmH2O. Nonventilated animals were used for lung and diaphragm histology and molecular biology analysis. RESULTS: BIVENT-50+PSV0%, compared to BIVENT-100+PSV0%, reduced the diffuse alveolar damage (DAD) score, the expression of amphiregulin (marker of alveolar stretch) and muscle atrophy F-box (marker of diaphragm atrophy). In BIVENT-50 groups, the increase in PSV (BIVENT-50+PSV50% versus BIVENT-50+PSV100%) yielded better lung mechanics and less alveolar collapse, interstitial edema, cumulative DAD score, as well as gene expressions associated with lung inflammation, epithelial and endothelial cell damage in lung tissue, and muscle ring finger protein 1 (marker of muscle proteolysis) in diaphragm. Transpulmonary peak pressure (Ppeak,L) and pressure-time product per minute (PTPmin) at Phigh were associated with lung damage, while increased spontaneous breathing at Plow did not promote lung injury. CONCLUSION: In the ARDS model used herein, during BIVENT, the level of PSV and the phase of the respiratory cycle in which the inspiratory effort occurs affected lung and diaphragm damage. Partitioning of inspiratory effort and transpulmonary pressure in spontaneous breaths at Plow and Phigh is required to minimize VILI.

11.
BMJ Open ; 11(8): e047100, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380722

RESUMO

INTRODUCTION: Mechanical ventilatory is a crucial element of acute brain injured patients' management. The ventilatory goals to ensure lung protection during acute respiratory failure may not be adequate in case of concomitant brain injury. Therefore, there are limited data from which physicians can draw conclusions regarding optimal ventilator management in this setting. METHODS AND ANALYSIS: This is an international multicentre prospective observational cohort study. The aim of the 'multicentre observational study on practice of ventilation in brain injured patients'-the VENTIBRAIN study-is to describe the current practice of ventilator settings and mechanical ventilation in acute brain injured patients. Secondary objectives include the description of ventilator settings among different countries, and their association with outcomes. Inclusion criteria will be adult patients admitted to the intensive care unit (ICU) with a diagnosis of traumatic brain injury or cerebrovascular diseases (intracranial haemorrhage, subarachnoid haemorrhage, ischaemic stroke), requiring intubation and mechanical ventilation and admission to the ICU. Exclusion criteria will be the following: patients aged <18 years; pregnant patients; patients not intubated or not mechanically ventilated or receiving only non-invasive ventilation. Data related to clinical examination, neuromonitoring if available, ventilator settings and arterial blood gases will be recorded at admission and daily for the first 7 days and then at day 10 and 14. The Glasgow Outcome Scale Extended on mortality and neurological outcome will be collected at discharge from ICU, hospital and at 6 months follow-up. ETHICS AND DISSEMINATION: The study has been approved by the Ethic committee of Brianza at the Azienda Socio Sanitaria Territoriale-Monza. Data will be disseminated to the scientific community by abstracts submitted to the European Society of Intensive Care Medicine annual conference and by original articles submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04459884.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Adulto , Encéfalo , Humanos , Unidades de Terapia Intensiva , Pulmão , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Estudos Prospectivos , Respiração Artificial
12.
BMC Pulm Med ; 21(1): 267, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404383

RESUMO

BACKGROUND: The aim of the study is to estimate the prevalence of atelectasis assessed with computer tomography (CT) in SARS-CoV-2 pneumonia and the relationship between the amount of atelectasis with oxygenation impairment, Intensive Care Unit admission rate and the length of in-hospital stay. PATIENTS AND METHODS: Two-hundred thirty-seven patients admitted to the hospital with SARS-CoV-2 pneumonia diagnosed by clinical, radiology and molecular tests in the nasopharyngeal swab who underwent a chest computed tomography because of a respiratory worsening from Apr 1 to Apr 30, 2020 were included in the study. Patients were divided into three groups depending on the presence and amount of atelectasis at the computed tomography: no atelectasis, small atelectasis (< 5% of the estimated lung volume) or large atelectasis (> 5% of the estimated lung volume). In all patients, clinical severity, oxygen-therapy need, Intensive Care Unit admission rate, the length of in-hospital stay and in-hospital mortality data were collected. RESULTS: Thirty patients (19%) showed small atelectasis while eight patients (5%) showed large atelectasis. One hundred and seventeen patients (76%) did not show atelectasis. Patients with large atelectasis compared to patients with small atelectasis had lower SatO2/FiO2 (182 vs 411 respectively, p = 0.01), needed more days of oxygen therapy (20 vs 5 days respectively, p = 0,02), more frequently Intensive Care Unit admission (75% vs 7% respectively, p < 0.01) and a longer period of hospitalization (40 vs 14 days respectively p < 0.01). CONCLUSION: In patients with SARS-CoV-2 pneumonia, atelectasis might appear in up to 24% of patients and the presence of larger amount of atelectasis is associated with worse oxygenation and clinical outcome.


Assuntos
COVID-19 , Hipóxia , Pneumonia Viral , Atelectasia Pulmonar , Tomografia Computadorizada por Raios X/métodos , Idoso , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/fisiopatologia , Teste para COVID-19/métodos , Feminino , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Pulmão/diagnóstico por imagem , Medidas de Volume Pulmonar/métodos , Masculino , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Prevalência , Atelectasia Pulmonar/diagnóstico por imagem , Atelectasia Pulmonar/epidemiologia , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/fisiopatologia , Respiração Artificial/métodos , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Espanha/epidemiologia , Tomografia Computadorizada por Raios X/estatística & dados numéricos
13.
Artigo em Inglês | MEDLINE | ID: mdl-34404594

RESUMO

OBJECTIVES: To determine whether driving pressure and expiratory flow limitation are associated with the development of postoperative pulmonary complications (PPCs) in cardiac surgery patients. DESIGN: Prospective cohort study. SETTING: University Hospital San Raffaele, Milan, Italy. PARTICIPANTS: Patients undergoing elective cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the occurrence of a predefined composite of PPCs. The authors determined the association among PPCs and intraoperative ventilation parameters, mechanical power and energy load, and occurrence of expiratory flow limitation (EFL) assessed with the positive end-expiratory pressure test. Two hundred patients were enrolled, of whom 78 (39%) developed one or more PPCs. Patients with PPCs, compared with those without PPCs, had similar driving pressure (mean difference [MD] -0.1 [95% confidence interval (CI), -1.0 to 0.7] cmH2O, p = 0.561), mechanical power (MD 0.5 [95% CI, -0.3 to 1.1] J/m, p = 0.364), and total energy load (MD 95 [95% CI, -78 to 263] J, p = 0.293), but they had a higher incidence of EFL (51% v 38%, p = 0.005). Only EFL was associated independently with the development of PPCs (odds ratio 2.46 [95% CI, 1.28-4.80], p = 0.007). CONCLUSIONS: PPCs occurred frequently in this patient population undergoing cardiac surgery. PPCs were associated independently with the presence of EFL but not with driving pressure, total energy load, or mechanical power.

15.
Br J Anaesth ; 127(4): 648-659, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34340836

RESUMO

Mechanical ventilation induces a number of systemic responses for which the brain plays an essential role. During the last decade, substantial evidence has emerged showing that the brain modifies pulmonary responses to physical and biological stimuli by various mechanisms, including the modulation of neuroinflammatory reflexes and the onset of abnormal breathing patterns. Afferent signals and circulating factors from injured peripheral tissues, including the lung, can induce neuronal reprogramming, potentially contributing to neurocognitive dysfunction and psychological alterations seen in critically ill patients. These impairments are ubiquitous in the presence of positive pressure ventilation. This narrative review summarises current evidence of lung-brain crosstalk in patients receiving mechanical ventilation and describes the clinical implications of this crosstalk. Further, it proposes directions for future research ranging from identifying mechanisms of multiorgan failure to mitigating long-term sequelae after critical illness.

16.
Respir Care ; 66(9): 1389-1397, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34230215

RESUMO

BACKGROUND: This was a pilot study to analyze the effects of tracheostomy on patient-ventilator asynchronies and respiratory system mechanics. Data were extracted from an ongoing prospective, real-world database that stores continuous output from ventilators and bedside monitors. Twenty adult subjects were on mechanical ventilation and were tracheostomized during an ICU stay: 55% were admitted to the ICU for respiratory failure and 35% for neurologic conditions; the median duration of mechanical ventilation before tracheostomy was 12 d; and the median duration of mechanical ventilation was 16 d. METHODS: We compared patient-ventilator asynchronies (the overall asynchrony index and the rates of specific asynchronies) and respiratory system mechanics (respiratory-system compliance and airway resistance) during the 24 h before tracheostomy versus the 24 h after tracheostomy. We analyzed possible differences in these variables among the subjects who underwent surgical versus percutaneous tracheostomy. To compare longitudinal changes in the variables, we used linear mixed-effects models for repeated measures along time in different observation periods. A total of 920 h of mechanical ventilation were analyzed. RESULTS: Respiratory mechanics and asynchronies did not differ significantly between the 24-h periods before and after tracheostomy: compliance of the respiratory system median (IQR) (47.9 [41.3 - 54.6] mL/cm H2O vs 47.6 [40.9 - 54.3] mL/cm H2O; P = .94), airway resistance (9.3 [7.5 - 11.1] cm H2O/L/s vs 7.0 [5.2 - 8.8] cm H2O/L/s; P = .07), asynchrony index (2.0% [1.1 - 3.6%] vs 4.1% [2.3 - 7.6%]; P = .09), ineffective expiratory efforts (0.9% [0.4 - 1.8%] vs 2.2% [1.0 - 4.4%]; P = .08), double cycling (0.5% [0.3 - 1.0%] vs 0.9% [0.5 - 1.9%]; P = .24), and percentage of air trapping (7.6% [4.2 - 13.8%] vs 10.6% [5.9 - 19.2%]; P = .43). No differences in respiratory mechanics or patient-ventilator asynchronies were observed between percutaneous and surgical procedures. CONCLUSIONS: Tracheostomy did not affect patient-ventilator asynchronies or respiratory mechanics within 24 h before and after the procedure.


Assuntos
Traqueostomia , Ventiladores Mecânicos , Adulto , Humanos , Pulmão , Projetos Piloto , Estudos Prospectivos , Respiração Artificial , Mecânica Respiratória
17.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202019

RESUMO

Spider mites are one of the major agricultural pests, feeding on a large variety of plants. As a contribution to understanding chemical communication in these arthropods, we have characterized a recently discovered class of odorant-binding proteins (OBPs) in Tetranychus urticae. As in other species of Chelicerata, the four OBPs of T. urticae contain six conserved cysteines paired in a pattern (C1-C6, C2-C3, C4-C5) differing from that of insect counterparts (C1-C3, C2-C5, C4-C6). Proteomic analysis uncovered a second family of OBPs, including twelve members that are likely to be unique to T. urticae. A three-dimensional model of TurtOBP1, built on the recent X-ray structure of Varroa destructor OBP1, shows protein folding different from that of insect OBPs, although with some common features. Ligand-binding experiments indicated some affinity to coniferyl aldehyde, but specific ligands may still need to be found among very large molecules, as suggested by the size of the binding pocket.


Assuntos
Receptores Odorantes/metabolismo , Tetranychidae/metabolismo , Sequência de Aminoácidos , Animais , Ligantes , Modelos Moleculares , Estrutura Molecular , Odorantes , Filogenia , Ligação Proteica , Conformação Proteica , Proteoma , Proteômica/métodos , Receptores Odorantes/química , Receptores Odorantes/genética , Tetranychidae/genética
18.
Crit Care ; 25(1): 236, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229735

RESUMO

Infectious diseases may affect brain function and cause encephalopathy even when the pathogen does not directly infect the central nervous system, known as infectious disease-associated encephalopathy. The systemic inflammatory process may result in neuroinflammation, with glial cell activation and increased levels of cytokines, reduced neurotrophic factors, blood-brain barrier dysfunction, neurotransmitter metabolism imbalances, and neurotoxicity, and behavioral and cognitive impairments often occur in the late course. Even though infectious disease-associated encephalopathies may cause devastating neurologic and cognitive deficits, the concept of infectious disease-associated encephalopathies is still under-investigated; knowledge of the underlying mechanisms, which may be distinct from those of encephalopathies of non-infectious cause, is still limited. In this review, we focus on the pathophysiology of encephalopathies associated with peripheral (sepsis, malaria, influenza, and COVID-19), emerging therapeutic strategies, and the role of neuroinflammation.


Assuntos
Encefalopatias/imunologia , COVID-19/complicações , Citocinas/imunologia , Influenza Humana/complicações , Malária/complicações , Sepse/complicações , Barreira Hematoencefálica/imunologia , Encefalopatias/prevenção & controle , COVID-19/imunologia , Humanos , Influenza Humana/imunologia , Malária/imunologia , Sepse/imunologia
19.
Br J Anaesth ; 127(3): 353-364, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34217468

RESUMO

COVID-19 pneumonia is associated with hypoxaemic respiratory failure, ranging from mild to severe. Because of the worldwide shortage of ICU beds, a relatively high number of patients with respiratory failure are receiving prolonged noninvasive respiratory support, even when their clinical status would have required invasive mechanical ventilation. There are few experimental and clinical data reporting that vigorous breathing effort during spontaneous ventilation can worsen lung injury and cause a phenomenon that has been termed patient self-inflicted lung injury (P-SILI). The aim of this narrative review is to provide an overview of P-SILI pathophysiology and the role of noninvasive respiratory support in COVID-19 pneumonia. Respiratory mechanics, vascular compromise, viscoelastic properties, lung inhomogeneity, work of breathing, and oesophageal pressure swings are discussed. The concept of P-SILI has been widely investigated in recent years, but controversies persist regarding its mechanisms. To minimise the risk of P-SILI, intensivists should better understand its underlying pathophysiology to optimise the type of noninvasive respiratory support provided to patients with COVID-19 pneumonia, and decide on the optimal timing of intubation for these patients.


Assuntos
Lesão Pulmonar Aguda/epidemiologia , Lesão Pulmonar Aguda/terapia , Anestesiologistas , COVID-19 , Ventilação não Invasiva , Respiração Artificial , Lesão Pulmonar Induzida por Ventilação Mecânica/epidemiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/terapia , Humanos , Ventilação não Invasiva/efeitos adversos , Respiração com Pressão Positiva/efeitos adversos , Insuficiência Respiratória , Mecânica Respiratória
20.
Crit Care ; 25(1): 250, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271958

RESUMO

A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume (VT) is a standard of care, further individualization of VT may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust VT and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.


Assuntos
Medicina de Precisão/métodos , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Humanos , Medicina de Precisão/tendências , Respiração Artificial/tendências , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/fisiopatologia , Mecânica Respiratória/fisiologia
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