Publications by authors named "Paolo Pelosi"

588 Publications

Molecular Epidemiological Investigation of a Nosocomial Cluster of : Evidence of Recent Emergence in Italy and Ease of Transmission during the COVID-19 Pandemic.

J Fungi (Basel) 2021 Feb 15;7(2). Epub 2021 Feb 15.

Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genoa, Italy.

is an emerging MDR pathogen raising major concerns worldwide. In Italy, it was first and only identified in July 2019 in our hospital (San Martino Hospital, Genoa), where infection or colonization cases have been increasingly recognized during the following months. To gain insights into the introduction, transmission dynamics, and resistance traits of this fungal pathogen, consecutive isolates collected from July 2019 to May 2020 ( = 10) were subjected to whole-genome sequencing (WGS) and antifungal susceptibility testing (AST); patients' clinical and trace data were also collected. WGS resolved all isolates within the genetic clade I (South Asian) and showed that all but one were part of a cluster likely stemming from the index case. Phylogenetic molecular clock analyses predicted a recent introduction (May 2019) in the hospital setting and suggested that most transmissions were associated with a ward converted to a COVID-19-dedicated ICU during the pandemic. All isolates were resistant to amphotericin B, voriconazole, and fluconazole at high-level, owing to mutations in (K143R) and (A640V). Present data demonstrated that the introduction of MDR in Italy was a recent event and suggested that its spread could have been facilitated by the COVID-19 pandemic. Continued efforts to implement stringent infection prevention and control strategies are warranted to limit the spread of this emerging pathogen within the healthcare system.
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http://dx.doi.org/10.3390/jof7020140DOI Listing
February 2021

Early Percutaneous Tracheostomy in the Coronavirus Disease 2019 Era: Shining New Light on Old Questions.

Crit Care Med 2021 Mar 3. Epub 2021 Mar 3.

Global Tracheostomy Collaborative, Raleigh, NC Department of Otolaryngology-Head & Neck Surgery, University of Michigan Medical School, Ann Arbor, MI UK National Tracheostomy Safety Project, NHS England, London, United Kingdom Department of Anaesthesia & Intensive Care Medicine, Manchester University NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy Department of Anesthesiology and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy.

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http://dx.doi.org/10.1097/CCM.0000000000004884DOI Listing
March 2021

Early Detection of Sepsis With Machine Learning Techniques: A Brief Clinical Perspective.

Front Med (Lausanne) 2021 12;8:617486. Epub 2021 Feb 12.

Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS for Oncology and Neurosciences, Genoa, Italy.

Sepsis is a major cause of death worldwide. Over the past years, prediction of clinically relevant events through machine learning models has gained particular attention. In the present perspective, we provide a brief, clinician-oriented vision on the following relevant aspects concerning the use of machine learning predictive models for the early detection of sepsis in the daily practice: (i) the controversy of sepsis definition and its influence on the development of prediction models; (ii) the choice and availability of input features; (iii) the measure of the model performance, the output, and their usefulness in the clinical practice. The increasing involvement of artificial intelligence and machine learning in health care cannot be disregarded, despite important pitfalls that should be always carefully taken into consideration. In the long run, a rigorous multidisciplinary approach to enrich our understanding in the application of machine learning techniques for the early recognition of sepsis may show potential to augment medical decision-making when facing this heterogeneous and complex syndrome.
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http://dx.doi.org/10.3389/fmed.2021.617486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906970PMC
February 2021

Novel Synthetic and Natural Therapies for Traumatic Brain Injury.

Curr Neuropharmacol 2021 Feb 25. Epub 2021 Feb 25.

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Genoa. Italy.

Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by a dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage-such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in inhibition of secondary brain injury can result as potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies basing on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.
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http://dx.doi.org/10.2174/1570159X19666210225145957DOI Listing
February 2021

Computed tomography assessment of PEEP-induced alveolar recruitment in patients with severe COVID-19 pneumonia.

Crit Care 2021 02 24;25(1):81. Epub 2021 Feb 24.

Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV 16, Genoa, Italy.

Background: There is a paucity of data concerning the optimal ventilator management in patients with COVID-19 pneumonia; particularly, the optimal levels of positive-end expiratory pressure (PEEP) are unknown. We aimed to investigate the effects of two levels of PEEP on alveolar recruitment in critically ill patients with severe COVID-19 pneumonia.

Methods: A single-center cohort study was conducted in a 39-bed intensive care unit at a university-affiliated hospital in Genoa, Italy. Chest computed tomography (CT) was performed to quantify aeration at 8 and 16 cmHO PEEP. The primary endpoint was the amount of alveolar recruitment, defined as the change in the non-aerated compartment at the two PEEP levels on CT scan.

Results: Forty-two patients were included in this analysis. Alveolar recruitment was median [interquartile range] 2.7 [0.7-4.5] % of lung weight and was not associated with excess lung weight, PaO/FiO ratio, respiratory system compliance, inflammatory and thrombophilia markers. Patients in the upper quartile of recruitment (recruiters), compared to non-recruiters, had comparable clinical characteristics, lung weight and gas volume. Alveolar recruitment was not different in patients with lower versus higher respiratory system compliance. In a subgroup of 20 patients with available gas exchange data, increasing PEEP decreased respiratory system compliance (median difference, MD - 9 ml/cmHO, 95% CI from - 12 to - 6 ml/cmHO, p < 0.001) and the ventilatory ratio (MD - 0.1, 95% CI from - 0.3 to - 0.1, p = 0.003), increased PaO with FiO = 0.5 (MD 24 mmHg, 95% CI from 12 to 51 mmHg, p < 0.001), but did not change PaO with FiO = 1.0 (MD 7 mmHg, 95% CI from - 12 to 49 mmHg, p = 0.313). Moreover, alveolar recruitment was not correlated with improvement of oxygenation or venous admixture.

Conclusions: In patients with severe COVID-19 pneumonia, higher PEEP resulted in limited alveolar recruitment. These findings suggest limiting PEEP strictly to the values necessary to maintain oxygenation, thus avoiding the use of higher PEEP levels.
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http://dx.doi.org/10.1186/s13054-021-03477-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903929PMC
February 2021

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study.

Eur J Anaesthesiol 2021 02 16. Epub 2021 Feb 16.

From the Department of Intensive Care (SGN, LH, PS, ASN, JMB, MJS), Department of Anaesthesiology, Amsterdam UMC, location AMC, Amsterdam, The Netherlands (SGN, LH, SNTH, MWH), Department of Critical Care Medicine, Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Monash University, Melbourne, Victoria, Australia (ASN), Hedenstierna Laboratory, Department of Clinical Physiology, Uppsala University Hospital, Uppsala, Sweden (GH), Intensive Care Unit, University Hospital of Montpellier and Saint Eloi Hospital, Montpellier University, Montpellier, France (SJ), Division of Cardiac, Thoracic, Vascular Anaesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria (MH, WS), Operating Services, Critical Care and Anaesthesia, Sheffield Teaching Hospitals, Sheffield and University of Sheffield, Sheffield, UK (GHM), Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA (MFVM), Department of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany (CP), Department of Biotechnology and Life Sciences, ASST Sette Laghi Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy (PS), Department of Anaesthesiology, Intensive Care Medicine and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, Halle (HW), Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany (MG de A), Dipartimento di Scienze Chirurgiche e Diagnostiche Integrate, Università degli Studi di Genova (PP), IRCCS, Ospedale Policlinico San Martino, Genova, Italy (PP), Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand (MJS) and Nuffield Department of Medicine, University of Oxford, Oxford, UK (MJS).

Background: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.

Objectives: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.

Design, Patients And Setting: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.

Main Outcome Measures: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.

Results: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.

Conclusion: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.

Trial Registration: The study was registered at Clinicaltrials.gov, NCT01601223.
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http://dx.doi.org/10.1097/EJA.0000000000001476DOI Listing
February 2021

Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies.

Front Physiol 2021 28;12:593223. Epub 2021 Jan 28.

Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Severe acute respiratory disease coronavirus 2 (SARS-CoV-2, formerly 2019-nCoV) is a novel coronavirus that has rapidly disseminated worldwide, causing the coronavirus disease 2019 (COVID-19) pandemic. As of January 6th, 2021, there were over 86 million global confirmed cases, and the disease has claimed over 1.87 million lives (a ∼2.2% case fatality rate). SARS-CoV-2 is able to infect human cells by binding its spike (S) protein to angiotensin-conversing enzyme 2 (ACE2), which is expressed abundantly in several cell types and tissues. ACE2 has extensive biological activities as a component of the renin-angiotensin-aldosterone system (RAAS) and plays a pivotal role as counter-regulator of angiotensin II (Ang II) activity by converting the latter to Ang (1-7). Virion binding to ACE2 for host cell entry leads to internalization of both via endocytosis, as well as activation of ADAM17/TACE, resulting in downregulation of ACE2 and loss of its protective actions in the lungs and other organs. Although COVID-19 was initially described as a purely respiratory disease, it is now known that infected individuals can rapidly progress to a multiple organ dysfunction syndrome. In fact, all human structures that express ACE2 are susceptible to SARS-CoV-2 infection and/or to the downstream effects of reduced ACE2 levels, namely systemic inflammation and injury. In this review, we aim to summarize the major features of SARS-CoV-2 biology and the current understanding of COVID-19 pathogenesis, as well as its clinical repercussions in the lung, heart, kidney, bowel, liver, and brain. We also highlight potential therapeutic targets and current global efforts to identify safe and effective therapies against this life-threatening condition.
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http://dx.doi.org/10.3389/fphys.2021.593223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876335PMC
January 2021

Impact of positive biphasic pressure during low and high inspiratory efforts in Pseudomonas aeruginosa-induced pneumonia.

PLoS One 2021 12;16(2):e0246891. Epub 2021 Feb 12.

Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.

Background: During pneumonia, normal alveolar areas coexist adjacently with consolidated areas, and high inspiratory efforts may predispose to lung damage. To date, no study has evaluated different degrees of effort during Biphasic positive airway pressure (BIVENT) on lung and diaphragm damage in experimental pneumonia, though largely used in clinical setting. We aimed to evaluate lung damage, genes associated with ventilator-induced lung injury (VILI) and diaphragmatic injury, and blood bacteria in pressure-support ventilation (PSV), BIVENT with low and high inspiratory efforts in experimental pneumonia.

Material And Methods: Twenty-eight male Wistar rats (mean ± SD weight, 333±78g) were submitted Pseudomonas aeruginosa-induced pneumonia. After 24-h, animals were ventilated for 1h in: 1) PSV; 2) BIVENT with low (BIVENTLow-Effort); and 3) BIVENT with high inspiratory effort (BIVENTHigh-Effort). BIVENT was set at Phigh to achieve VT = 6 ml/kg and Plow at 5 cmH2O (n = 7/group). High- and low-effort conditions were obtained through anaesthetic infusion modulation based on neuromuscular drive (P0.1). Lung mechanics, histological damage score, blood bacteria, and expression of genes related to VILI in lung tissue, and inflammation in diaphragm tissue.

Results: Transpulmonary peak pressure and histological damage score were higher in BIVENTHigh-Effort compared to BIVENTLow-Effort and PSV [16.1 ± 1.9cmH2O vs 12.8 ± 1.5cmH2O and 12.5 ± 1.6cmH2O, p = 0.015, and p = 0.010; median (interquartile range) 11 (9-13) vs 7 (6-9) and 7 (6-9), p = 0.021, and p = 0.029, respectively]. BIVENTHigh-Effort increased interleukin-6 expression compared to BIVENTLow-Effort (p = 0.035) as well as expressions of cytokine-induced neutrophil chemoattractant-1, amphiregulin, and type III procollagen compared to PSV (p = 0.001, p = 0.001, p = 0.004, respectively). Tumour necrosis factor-α expression in diaphragm tissue and blood bacteria were higher in BIVENTHigh-Effort than BIVENTLow-Effort (p = 0.002, p = 0.009, respectively).

Conclusion: BIVENT requires careful control of inspiratory effort to avoid lung and diaphragm damage, as well as blood bacteria. P0.1 might be considered a helpful parameter to optimize inspiratory effort.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246891PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880436PMC
February 2021

Incidence and Prognosis of Ventilator-Associated Pneumonia in Critically Ill Patients with COVID-19: A Multicenter Study.

J Clin Med 2021 Feb 3;10(4). Epub 2021 Feb 3.

Infectious Diseases Unit, San Martino Polyclinic Hospital-IRCCS for Oncology and Neurosciences, 16132 Genoa, Italy.

The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16-21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were (27/77, 35%) and (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43-7.61, = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05-57.26, < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases.
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http://dx.doi.org/10.3390/jcm10040555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913191PMC
February 2021

Association between perioperative fluid administration and postoperative outcomes: a 20-year systematic review and a meta-analysis of randomized goal-directed trials in major visceral/noncardiac surgery.

Crit Care 2021 02 1;25(1):43. Epub 2021 Feb 1.

Humanitas Clinical and Research Center - IRCCS, Rozzano, MI, Italy.

Background: Appropriate perioperative fluid management is of pivotal importance to reduce postoperative complications, which impact on early and long-term patient outcome. The so-called perioperative goal-directed therapy (GDT) approach aims at customizing perioperative fluid management on the individual patients' hemodynamic response. Whether or not the overall amount of perioperative volume infused in the context of GDT could influence postoperative surgical outcomes is unclear.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of GDT approach between study population and control group in reducing postoperative complications and perioperative mortality, using MEDLINE, EMBASE and the Cochrane Controlled Clinical trials register. The enrolled studies were grouped considering the amount infused intraoperatively and during the first 24 h after the admission in the critical care unit (perioperative fluid).

Results: The metanalysis included 21 RCTs enrolling 2729 patients with a median amount of perioperative fluid infusion of 4500 ml. In the studies reporting an overall amount below or above this threshold, the differences in postoperative complications were not statically significant between controls and GDT subgroup [43.4% vs. 34.2%, p value = 0.23 and 54.8% vs. 39.8%; p value = 0.09, respectively]. Overall, GDT reduced the overall rate of postoperative complications, as compared to controls [pooled risk difference (95% CI) = - 0.10 (- 0.14, - 0.07); Chi = 30.97; p value < 0.0001], but not to a reduction of perioperative mortality [pooled risk difference (95%CI) = - 0.016 (- 0.0334; 0.0014); p value = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal (p value = 0.52) nor cardiovascular (p value = 0.86) or pulmonary (p value = 0.14) or neurological (p value = 0.44) or infective (p value = 0.12) complications.

Conclusions: Irrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality.

Trial Registration: CRD42020168866; Registration: February 2020 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=168866.
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http://dx.doi.org/10.1186/s13054-021-03464-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849093PMC
February 2021

Nebulised heparin for patients on ventilation: implications for COVID-19 pneumonia.

Lancet Respir Med 2021 Jan 22. Epub 2021 Jan 22.

Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy; Anesthesia and Intensive Care, Ospedale Policlinico San Martino, IRCCS per l'Oncologia e le Neuroscienze, Genoa, Italy. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(20)30513-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826131PMC
January 2021

Turning tables: a war-like approach to neurosurgical emergencies in the Covid-19.

J Neurosurg Sci 2021 Jan 22. Epub 2021 Jan 22.

Department of Neurosurgery, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy.

Background: During the Coronavirus-disease-2019 (COVID-19) pandemic emergency, neurosurgeons may have to decide to prioritize treatments to patients with the best chance of survival, as in a war setting triage. We discuss factors that should be taken into account in the perioperative period and neurocritical care management of neurosurgical patients during a pandemic emergency; in particular, we will focus on the decision on whether to operate or not a patient during the COVID-19 pandemic and where and how to provide neurointensive care treatment.

Methods: A multidisciplinary expert panel composed by specialists with direct experience in COVID-19 management discussed and reviewed the criteria that should be taken into account in the decision to operate or not a patient during the COVID-19 pandemic.

Results: Disease-related factors should be first taken into account in order to precisely know the enemy we are facing. Patient-related factors should be then evaluated to understand the battleground on which we are facing the enemy. After these considerations, we must ascertain costs and expected outcomes of our surgical intervention by evaluation of surgery-related factors. Finally, the last factor that need to be evaluated before surgery is the availability of resources, staff and ward availability for perioperative care in particular. All these considerations will lead to the optimal organization and management of neurosurgical emergencies during pandemic times, taking into account the community and not only the single patient.

Conclusions: We provided schematic preoperative considerations that we hope will help neurosurgeons to guide their decisions in these challenging times.
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http://dx.doi.org/10.23736/S0390-5616.21.05226-7DOI Listing
January 2021

Responses of the Pheromone-Binding Protein of the Silk Moth on a Graphene Biosensor Match Binding Constants in Solution.

Sensors (Basel) 2021 Jan 12;21(2). Epub 2021 Jan 12.

CEST Competence Centre for Electrochemical Surface Technology, 2700 Wiener Neustadt, Austria.

An electronic biosensor for odors was assembled by immobilizing the silk moth pheromone binding protein (BmorPBP1) on a reduced graphene oxide surface of a field-effect transistor. At physiological pH, the sensor detects the pheromones, bombykol and bombykal, with good affinity and specificity. Among the other odorants tested, only eugenol elicited a strong signal, while terpenoids and other odorants (linalool, geraniol, isoamyl acetate, and 2-isobutyl-3-methoxypyrazine) produced only very weak responses. Parallel binding assays were performed with the same protein and the same ligands, using the common fluorescence approach adopted for similar proteins. The results are in good agreement with the sensor's responses: bombykol and bombykal, together with eugenol, proved to be strong ligands, while the other compounds showed only poor affinity. When tested at pH 4, the protein failed to bind bombykol both in solution and when immobilized on the sensor. This result further indicates that the BmorPBP1 retains its full activity when immobilized on a surface, including the conformational change observed in acidic conditions. The good agreement between fluorescence assays and sensor responses suggests that ligand-binding assays in solution can be used to screen mutants of a binding protein when selecting the best form to be immobilized on a biosensor.
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http://dx.doi.org/10.3390/s21020499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827809PMC
January 2021

Epidemiological Characteristics, Ventilator Management, and Clinical Outcome in Patients Receiving Invasive Ventilation in Intensive Care Units from 10 Asian Middle-Income Countries (PRoVENT-iMiC): An International, Multicenter, Prospective Study.

Am J Trop Med Hyg 2021 Jan 11. Epub 2021 Jan 11.

Laboratory of Experimental Intensive Care and Anaesthesiology (L·E·I·C·A) Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands.

Epidemiology, ventilator management, and outcome in patients receiving invasive ventilation in intensive care units (ICUs) in middle-income countries are largely unknown. PRactice of VENTilation in Middle-income Countries is an international multicenter 4-week observational study of invasively ventilated adult patients in 54 ICUs from 10 Asian countries conducted in 2017/18. Study outcomes included major ventilator settings (including tidal volume [] and positive end-expiratory pressure [PEEP]); the proportion of patients at risk for acute respiratory distress syndrome (ARDS), according to the lung injury prediction score (LIPS), or with ARDS; the incidence of pulmonary complications; and ICU mortality. In 1,315 patients included, median was similar in patients with LIPS < 4 and patients with LIPS ≥ 4, but lower in patients with ARDS (7.90 [6.8-8.9], 8.0 [6.8-9.2], and 7.0 [5.8-8.4] mL/kg Predicted body weight; = 0.0001). Median PEEP was similar in patients with LIPS < 4 and LIPS ≥ 4, but higher in patients with ARDS (five [5-7], five [5-8], and 10 [5-12] cmHO; < 0.0001). The proportions of patients with LIPS ≥ 4 or with ARDS were 68% (95% CI: 66-71) and 7% (95% CI: 6-8), respectively. Pulmonary complications increased stepwise from patients with LIPS < 4 to patients with LIPS ≥ 4 and patients with ARDS (19%, 21%, and 38% respectively; = 0.0002), with a similar trend in ICU mortality (17%, 34%, and 45% respectively; < 0.0001). The capacity of the LIPS to predict development of ARDS was poor (ROC AUC of 0.62, 95% CI: 0.54-0.70). In Asian middle-income countries, where two-thirds of ventilated patients are at risk for ARDS according to the LIPS and pulmonary complications are frequent, setting of is globally in line with current recommendations.
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http://dx.doi.org/10.4269/ajtmh.20-1177DOI Listing
January 2021

Keeping an Open Mind: tracheostomy for patients with COVID-19.

Anesth Analg 2021 Jan 8;Publish Ahead of Print. Epub 2021 Jan 8.

Michael J. Brenner, MD, FACS Associate Professor and Co-Director of Branch Science, Medical School President, Global Tracheostomy Collaborative, Raleigh NC Chair, Centralized Otolaryngology Research Efforts, American Academy of Otolaryngology - Head & Neck Surgery, Alexandria, VA Department of Otolaryngology - Head & Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States

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http://dx.doi.org/10.1213/ANE.0000000000005419DOI Listing
January 2021

Anxiety among front-line health-care workers supporting patients with COVID-19: A global survey.

Gen Hosp Psychiatry 2021 Jan-Feb;68:90-96. Epub 2020 Dec 20.

Department of Anaesthesia Critical Care Emergency and Pain Medicine, University Hospital of Nimes, Montpellier University, Nimes, France; Clinical Research and Epidemiology in Pneumonia and Sepsis, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.

Objective: We aimed to explore anxiety status across a broad range of HCWs supporting patients with COVID-19 in different global regions.

Method: This was an international online survey in which participation was on voluntary basis and data were submitted via Google Drive, across a two-week period starting from March 18, 2020. The Beck Anxiety Inventory was used to quantify the level of anxiety.

Results: 1416 HCWs (70.8% medical doctors, 26.2% nurses) responded to the survey from 75 countries. The distribution of anxiety levels was: normal/minimal (n = 503, 35.5%), low (n = 390, 27.5%); moderate (n = 287, 20.3%), and severe (n = 236, 16.7%). According to multiple generalized linear model, female gender (p = 0.001), occupation (ie, being a nurse dealing directly with patients with COVID-19 [p = 0.017]), being younger (p = 0.001), reporting inadequate knowledge on COVID-19 (p = 0.005), having insufficient personal protective equipment (p = 0.001) and poor access to hand sanitizers or liquid soaps (p = 0.008), coexisting chronic disorders (p = 0.001) and existing mental health problems (p = 0.001), and higher income of countries where HCWs lived (p = 0.048) were significantly associated with increased anxiety.

Conclusions: Front-line HCWs, regardless of the levels of COVID-19 transmission in their country, are anxious when they do not feel protected. Our findings suggest that anxiety could be mitigated ensuring sufficient levels of protective personal equipment alongside greater education and information.
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http://dx.doi.org/10.1016/j.genhosppsych.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749993PMC
February 2021

Prevalence and Clinical Significance of Persistent Viral Shedding in Hospitalized Adult Patients with SARS-CoV-2 Infection: A Prospective Observational Study.

Infect Dis Ther 2021 Jan 8. Epub 2021 Jan 8.

Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS for Oncology and Neurosciences, Genoa, Italy.

Background: The goal of this study was to investigate the prevalence and factors associated with persistent viral shedding (PVS) in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: This was a prospective observational study including all consecutive adults hospitalized with SARS-CoV-2 infection. When the first nasopharyngeal swab was positive for SARS-CoV-2 RNA (day 0), additional samples were obtained on days + 3, + 5, + 7 and then once every 7 days until virus detection was negative. PVS was defined as the duration of shedding of at least 21 days after diagnosis. The primary endpoint of this study was the prevalence of PVS.

Results: Data were obtained regarding 121 consecutive hospitalized patients with SARS-CoV-2 infection (median age 66 years, male sex 65.3%). Overall, the prevalence of PVS was 38% (46/121 patients). According to univariate analysis, factors associated with PVS were immunosuppression (6.7% vs 21.7%, p = 0.02), increased interleukin-6 (IL-6) levels (≥ 35 ng/ml) at the time of diagnosis (43.4% vs 67.3%, p = 0.02), time from onset of symptoms to diagnosis (median days 7.0 vs 3.5, p = 0.001), intensive care unit admission (22.7% vs 43.5%, p = 0.02), and need for invasive mechanical ventilation (20.0% vs 41.3%, p = 0.01). The multivariate analysis indicated that immunosuppression, increased IL-6 levels at the time of diagnosis, time from onset of symptoms to diagnosis, and need for mechanical ventilation were independent factors associated with PVS.

Conclusions: PVS was detected in up to 38% of hospitalized patients with SARS-CoV-2 infection and was strongly associated with immunosuppression, increased IL-6 levels, and the need for mechanical ventilation.
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http://dx.doi.org/10.1007/s40121-020-00381-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791162PMC
January 2021

Ketamine in acute phase of severe traumatic brain injury "an old drug for new uses?"

Crit Care 2021 01 6;25(1):19. Epub 2021 Jan 6.

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy.

Maintaining an adequate level of sedation and analgesia plays a key role in the management of traumatic brain injury (TBI). To date, it is unclear which drug or combination of drugs is most effective in achieving these goals. Ketamine is an agent with attractive pharmacological and pharmacokinetics characteristics. Current evidence shows that ketamine does not increase and may instead decrease intracranial pressure, and its safety profile makes it a reliable tool in the prehospital environment. In this point of view, we discuss different aspects of the use of ketamine in the acute phase of TBI, with its potential benefits and pitfalls.
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http://dx.doi.org/10.1186/s13054-020-03452-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788834PMC
January 2021

Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review.

J Clin Med 2021 Jan 3;10(1). Epub 2021 Jan 3.

Department of Anesthesia and Intensive Care, Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, 16132 Genoa, Italy.

In critically ill patients with acute respiratory distress syndrome (ARDS) coronavirus disease 2019 (COVID-19), a high incidence of thromboembolic and hemorrhagic events is reported. COVID-19 may lead to impairment of the coagulation cascade, with an imbalance in platelet function and the regulatory mechanisms of coagulation and fibrinolysis. Clinical manifestations vary from a rise in laboratory markers and subclinical microthrombi to thromboembolic events, bleeding, and disseminated intravascular coagulation. After an inflammatory trigger, the mechanism for activation of the coagulation cascade in COVID-19 is the tissue factor pathway, which causes endotoxin and tumor necrosis factor-mediated production of interleukins and platelet activation. The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia. The variety of clinical presentations of the coagulopathy confronts the clinician with the difficult questions of whether and how to provide optimal supportive care. In addition to coagulation tests, advanced laboratory tests such as protein C, protein S, antithrombin, tissue factor pathway inhibitors, D-dimers, activated factor Xa, and quantification of specific coagulation factors can be useful, as can thromboelastography or thromboelastometry. Treatment should be tailored, focusing on the estimated risk of bleeding and thrombosis. The aim of this review is to explore the pathophysiology and clinical evidence of coagulation disorders in severe ARDS-related COVID-19 patients.
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http://dx.doi.org/10.3390/jcm10010140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795033PMC
January 2021

Spread of Carbapenem-Resistant Gram-Negatives and during the COVID-19 Pandemic in Critically Ill Patients: One Step Back in Antimicrobial Stewardship?

Microorganisms 2021 Jan 3;9(1). Epub 2021 Jan 3.

Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, 16132 Genoa, Italy.

The possible negative impact of severe adult respiratory distress caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19) on antimicrobial stewardship and infection control has been postulated, but few real-life data are available. The aim of this study was to report our experience with colonization/infection of carbapenem-resistant (CRPA), carbapenem-resistant (CR-Kp) and among critically ill COVID-19 patients admitted to the intensive care unit (ICU). All COVID-19 patients admitted to the ICUs at San Martino Policlinico Hospital-IRCCS in Genoa, Italy, were screened from 28 February to 31 May 2020. One-hundred and eighteen patients admitted to COVID-19 ICUs were included in the study. Among them, 12 (10.2%) became colonized/infected with CRPA, 6 (5.1%) with and 2 (1.6%) with CR-Kp. All patients with CRPA received prior treatment with meropenem, and in 11 (91.7%) infection was not preceded by colonization. Four patients (66.7%) developed candidemia. A significant spread of resistant pathogens was observed among critically ill COVID-19 patients. Dedicated strategies are warranted to prevent horizontal spread and maintain effective antimicrobial stewardship programs in the setting of COVID-19 care.
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http://dx.doi.org/10.3390/microorganisms9010095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823370PMC
January 2021

The effects of preoperative moderate to severe anaemia on length of hospital stay: A propensity score-matched analysis in non-cardiac surgery patients.

Eur J Anaesthesiol 2021 Jan 4;Publish Ahead of Print. Epub 2021 Jan 4.

From the Department of Anaesthesiology, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands (CSE-B, CB), Department of Intensive Care and Laboratory of Experimental Intensive Care and Anaesthesia (L·E·I·C·A), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands (SNT-H, AS-N, JM-B, MJS), Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands (SNT-H, MW-H), Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paolo, Brazil (AS-N), Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden (GH), Montpellier University Hospital, Saint Eloi Intensive Care Unit and PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France (SJ), Division of Cardiac, Thoracic, Vascular Anaesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria (MH, WS), Operating Services, Critical Care and Anaesthesia, Sheffield Teaching Hospitals, Sheffield and University of Sheffield, Sheffield, UK (GH-M), Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Bostan, MA, USA (MF-VM), Queen Mary University of London, London, UK (RM-P), Department of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany (CP), Department of Biotechnology and Sciences of Life, ASST Sette Laghi Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy (PS), Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany (HW), Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (MGD-A), Dipartimento di Scienze Chirurgiche e Diagnostiche Integrate, Università degli Studi di Genova, Genova, Italy (PP), IRCCS Ospedale Policlinico San Martino, Genova, Italy (PP), Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand (MJS), Nuffield Department of Medicine, University of Oxford, Oxford, UK (MJS).

Background: Anaemia is frequently recorded during preoperative screening and has been suggested to affect outcomes after surgery negatively.

Objectives: The objectives were to assess the frequency of moderate to severe anaemia and its association with length of hospital stay.

Design: Post hoc analysis of the international observational prospective 'Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study.

Patients And Setting: The current analysis included adult patients requiring general anaesthesia for non-cardiac surgery. Preoperative anaemia was defined as a haemoglobin concentration of 11 g dl-1 or lower, thus including moderate and severe anaemia according to World Health Organisation criteria.

Main Outcome Measures: The primary outcome was length of hospital stay. Secondary outcomes included hospital mortality, intra-operative adverse events and postoperative pulmonary complications (PPCs).

Results: Haemoglobin concentrations were available for 8264 of 9864 patients. Preoperative moderate to severe anaemia was present in 7.7% of patients. Multivariable analysis showed that preoperative moderate to severe anaemia was associated with an increased length of hospital stay with a mean difference of 1.3 ((95% CI 0.8 to 1.8) days; P < .001). In the propensity-matched analysis, this association remained present, median 4.0 [IQR 1.0 to 5.0] vs. 2.0 [IQR 0.0 to 5.0] days, P = .001. Multivariable analysis showed an increased in-hospital mortality (OR 2.9 (95% CI 1.1 to 7.5); P  = .029), and higher incidences of intra-operative hypotension (36.3 vs. 25.3%; P < .001) and PPCs (17.1 vs. 10.5%; P = .001) in moderately to severely anaemic patients. However, this was not confirmed in the propensity score-matched analysis.

Conclusions: In this international cohort of non-cardiac surgical patients, preoperative moderate to severe anaemia was associated with a longer duration of hospital stay but not increased intra-operative complications, PPCs or in-hospital mortality.

Trial Registration: The LAS VEGAS study was registered at Clinicaltrials.gov, number NCT01601223.
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http://dx.doi.org/10.1097/EJA.0000000000001412DOI Listing
January 2021

Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial.

Eur Respir J 2021 Jan 14. Epub 2021 Jan 14.

Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Nitazoxanide is widely available and exerts broad-spectrum antiviral activity However, there is no evidence of its impact on SARS-CoV-2 infection.In a multicenter, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of Covid-19 symptoms (dry cough, fever, and/or fatigue) were enrolled. After confirmation of SARS-CoV2 infection by RT-PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, TID, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation, and hospitalisation rate. Adverse events were also assessed.From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median time from symptom onset to first dose of study drug was 5 (4-5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm 18.2% in the placebo arm (p=0.009). Viral load was also reduced after nitazoxanide compared to placebo (p=0.006). The percent viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed.In patients with mild Covid-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.
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http://dx.doi.org/10.1183/13993003.03725-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758778PMC
January 2021

Modeling intra-abdominal volume and respiratory driving pressure during pneumoperitoneum insufflation - a patient-level data meta-analysis.

J Appl Physiol (1985) 2020 Dec 24. Epub 2020 Dec 24.

Research Group in Perioperative Medicine, Hospital Universitario y Politecnico la Fe, Spain.

During pneumoperitoneum, intra-abdominal pressure (IAP) is usually kept at 12-14 mmHg. There is no clinical benefit in IAP increments if they do not increase intra-abdominal volume IAV. We aimed to estimate IAV (ΔIAV) and respiratory driving pressure changes (ΔP) in relation to changes in IAP (ΔIAP). We carried out a patient-level meta-analysis of 204 adult patients with available data on IAV and ΔP during pneumoperitoneum from three trials assessing the effect of IAP on postoperative recovery and airway pressure during laparoscopic surgery under general anesthesia. The primary endpoint was ΔIAV, and the secondary endpoint was ΔP. The endpoints' response to ΔIAP was modeled using mixed multivariable Bayesian regression to estimate which mathematical function best fitted it. IAP values on the pressure-volume (PV) curve where the endpoint rate of change according to IAP decreased were identified. Abdomino-thoracic transmission (ATT) rate, i.e., the rate ΔP changeto ΔIAP, was also estimated. The best-fitting function was sigmoid logistic and linear for IAV and ΔP response, respectively. Increments in IAV reached a plateau at 6.0 [95%CI 5.9 to 6.2] L. ΔIAV for each ΔIAP decreased at IAP ranging from 9.8 [95%CI 9.7 to 9.9], to 12.2 [12.0 to12.3] mmHg. ATT rate was 0.65 [95%CI 0.62 to 0.68]. One mmHg of IAP raised ΔP 0.88 cmHO. During pneumoperitoneum, IAP has a non-linear relationship with IAV and a linear one with ΔP. IAP should be set below the point where IAV gains diminish.
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http://dx.doi.org/10.1152/japplphysiol.00814.2020DOI Listing
December 2020

Effects of higher PEEP and recruitment manoeuvres on mortality in patients with ARDS: a systematic review, meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials.

Intensive Care Med Exp 2020 Dec 18;8(Suppl 1):39. Epub 2020 Dec 18.

Department of Surgical Sciences and Integrated Diagnostics, University of Genova, Largo Rosanna Benzi 8, 16131, Genova, Italy.

Purpose: In patients with acute respiratory distress syndrome (ARDS), lung recruitment could be maximised with the use of recruitment manoeuvres (RM) or applying a positive end-expiratory pressure (PEEP) higher than what is necessary to maintain minimal adequate oxygenation. We aimed to determine whether ventilation strategies using higher PEEP and/or RMs could decrease mortality in patients with ARDS.

Methods: We searched MEDLINE, EMBASE and CENTRAL from 1996 to December 2019, included randomized controlled trials comparing ventilation with higher PEEP and/or RMs to strategies with lower PEEP and no RMs in patients with ARDS. We computed pooled estimates with a DerSimonian-Laird mixed-effects model, assessing mortality and incidence of barotrauma, population characteristics, physiologic variables and ventilator settings. We performed a trial sequential analysis (TSA) and a meta-regression.

Results: Excluding two studies that used tidal volume (V) reduction as co-intervention, we included 3870 patients from 10 trials using higher PEEP alone (n = 3), combined with RMs (n = 6) or RMs alone (n = 1). We did not observe differences in mortality (relative risk, RR 0.96, 95% confidence interval, CI [0.84-1.09], p = 0.50) nor in incidence of barotrauma (RR 1.22, 95% CI [0.93-1.61], p = 0.16). In the meta-regression, the PEEP difference between intervention and control group at day 1 and the use of RMs were not associated with increased risk of barotrauma. The TSA reached the required information size for mortality (n = 2928), and the z-line surpassed the futility boundary.

Conclusions: At low V, the routine use of higher PEEP and/or RMs did not reduce mortality in unselected patients with ARDS.

Trial Registration: PROSPERO CRD42017082035 .
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http://dx.doi.org/10.1186/s40635-020-00322-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746429PMC
December 2020

Ischaemic stroke-induced distal organ damage: pathophysiology and new therapeutic strategies.

Intensive Care Med Exp 2020 Dec 18;8(Suppl 1):23. Epub 2020 Dec 18.

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Largo Rosanna Benzi 10, 16100, Genoa, Italy.

Acute ischaemic stroke is associated with a high risk of non-neurological complications, which include respiratory failure, cardiovascular dysfunction, kidney and liver injury, and altered immune and endocrine function. The aim of this manuscript is to provide an overview of the main forms of stroke-induced distal organ damage, providing new pathophysiological insights and recommendations for clinical management.Non-neurological complications of stroke can affect outcomes, with potential for serious short-term and long-term consequences. Many of these complications can be prevented; when prevention is not feasible, early detection and proper management can still be effective in mitigating their adverse impact. The general care of stroke survivors entails not only treatment in the acute setting but also prevention of secondary complications that might hinder functional recovery. Acute ischaemic stroke triggers a cascade of events-including local and systemic activation of the immune system-which results in a number of systemic consequences and, ultimately, may cause organ failure. Understanding the pathophysiology and clinical relevance of non-neurological complications is a crucial component in the proper treatment of patients with acute stroke.Little evidence-based data is available to guide management of these complications. There is a clear need for improved surveillance and specific interventions for the prevention, early diagnosis, and proper management of non-neurological complications during the acute phase of ischaemic stroke, which should reduce morbidity and mortality.
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http://dx.doi.org/10.1186/s40635-020-00305-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746424PMC
December 2020

Pathophysiology and clinical consequences of arterial blood gases and pH after cardiac arrest.

Intensive Care Med Exp 2020 Dec 18;8(Suppl 1):19. Epub 2020 Dec 18.

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, University of Genoa, Largo Rosanna Benzi, 15, 16100, Genoa, Italy.

Post cardiac arrest syndrome is associated with high morbidity and mortality, which is related not only to a poor neurological outcome but also to respiratory and cardiovascular dysfunctions. The control of gas exchange, and in particular oxygenation and carbon dioxide levels, is fundamental in mechanically ventilated patients after resuscitation, as arterial blood gases derangement might have important effects on the cerebral blood flow and systemic physiology.In particular, the pathophysiological role of carbon dioxide (CO) levels is strongly underestimated, as its alterations quickly affect also the changes of intracellular pH, and consequently influence metabolic energy and oxygen demand. Hypo/hypercapnia, as well as mechanical ventilation during and after resuscitation, can affect CO levels and trigger a dangerous pathophysiological vicious circle related to the relationship between pH, cellular demand, and catecholamine levels. The developing hypocapnia can nullify the beneficial effects of the hypothermia. The aim of this review was to describe the pathophysiology and clinical consequences of arterial blood gases and pH after cardiac arrest.According to our findings, the optimal ventilator strategies in post cardiac arrest patients are not fully understood, and oxygen and carbon dioxide targets should take in consideration a complex pattern of pathophysiological factors. Further studies are warranted to define the optimal settings of mechanical ventilation in patients after cardiac arrest.
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http://dx.doi.org/10.1186/s40635-020-00307-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746422PMC
December 2020

Effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of airway secretions in endotracheal tubes: substudy of a randomized clinical trial.

Intensive Care Med Exp 2020 Dec 18;8(Suppl 1):71. Epub 2020 Dec 18.

Department of Intensive Care, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands.

Background: Accumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the 'Preventive Nebulization of Mucolytic Agents and Bronchodilating Drugs in Intubated and Ventilated Intensive Care Unit Patients trial' (NEBULAE) was to compare the effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of secretions in endotracheal tubes in critically ill patients.

Results: In this single-center substudy of a national multicenter trial, patients were randomized to a strategy of routine nebulizations of acetylcysteine with salbutamol every 6 h until end of invasive ventilation, or to a strategy with on-demand nebulizations of acetylcysteine or salbutamol applied on strict clinical indications only. The primary endpoint, the maximum reduction in cross-sectional area (CSA) of the endotracheal tube was assessed with high-resolution computed tomography. Endotracheal tubes were collected from 72 patients, 36 from patients randomized to the routine nebulization strategy and 36 of patients randomized to the on-demand nebulization strategy. The maximum cross-sectional area (CSA) of the endotracheal tube was median 12 [6 to 15]% in tubes obtained from patients in the routine nebulization group, not different from median 9 [6 to 14]% in tubes obtained from patients in the on-demand nebulization group (P = 0.33).

Conclusion: In adult critically ill patients under invasive ventilation, routine nebulization of mucolytics and bronchodilators did not affect accumulation of airway secretions in the endotracheal tube. Trial registration Clinicaltrials.gov Identifier: NCT02159196.
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http://dx.doi.org/10.1186/s40635-020-00351-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746420PMC
December 2020

Fluids in ARDS: more pros than cons.

Intensive Care Med Exp 2020 Dec 18;8(Suppl 1):32. Epub 2020 Dec 18.

Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Avenida Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.

In acute respiratory distress syndrome (ARDS), increased pulmonary vascular permeability makes the lung vulnerable to edema. The use of conservative as compared to liberal fluid strategies may increase the number of ventilator-free days and survival, as well as reduce organ dysfunction. Monitoring the effects of fluid administration is of the utmost importance; dynamic indexes, such as stroke volume and pulse pressure variations, outperform static ones, such as the central venous pressure. The passive leg raise and end-expiratory occlusion tests are recommended for guiding fluid management decisions. The type of intravenous fluids should also be taken into consideration: crystalloids, colloids, and human albumin have all been used for fluid resuscitation. Recent studies have also shown differences in outcome between balanced and non-balanced intravenous solutions. In preclinical studies, infusion of albumin promotes maintenance of the glycocalyx layer, reduces inflammation, and improves alveolar-capillary membrane permeability. Fluids in ARDS must be administered cautiously, considering hemodynamic and perfusion status, oncotic and hydrostatic pressures, ARDS severity, fluid type, volume and infusion rate, and cardiac and renal function. Of note, no guideline to date has recommended a specific fluid composition for use in ARDS; most physicians currently follow recommendations for sepsis.
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http://dx.doi.org/10.1186/s40635-020-00319-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746428PMC
December 2020

Neurological Complications and Noninvasive Multimodal Neuromonitoring in Critically Ill Mechanically Ventilated COVID-19 Patients.

Front Neurol 2020 27;11:602114. Epub 2020 Nov 27.

Anesthesia and Intensive Care, San Martino Policlinico Hospital, Istituto di Ricovero e Cura a Carattere Scientifico for Oncology and Neurosciences, Genoa, Italy.

The incidence and the clinical presentation of neurological manifestations of coronavirus disease-2019 (COVID-19) remain unclear. No data regarding the use of neuromonitoring tools in this group of patients are available. This is a retrospective study of prospectively collected data. The primary aim was to assess the incidence and the type of neurological complications in critically ill COVID-19 patients and their effect on survival as well as on hospital and intensive care unit (ICU) length of stay. The secondary aim was to describe cerebral hemodynamic changes detected by noninvasive neuromonitoring modalities such as transcranial Doppler, optic nerve sheath diameter (ONSD), and automated pupillometry. Ninety-four patients with COVID-19 admitted to an ICU from February 28 to June 30, 2020, were included in this study. Fifty-three patients underwent noninvasive neuromonitoring. Neurological complications were detected in 50% of patients, with delirium as the most common manifestation. Patients with neurological complications, compared to those without, had longer hospital (36.8 ± 25.1 vs. 19.4 ± 16.9 days, < 0.001) and ICU (31.5 ± 22.6 vs. 11.5±10.1 days, < 0.001) stay. The duration of mechanical ventilation was independently associated with the risk of developing neurological complications (odds ratio 1.100, 95% CI 1.046-1.175, = 0.001). Patients with increased intracranial pressure measured by ONSD (19% of the overall population) had longer ICU stay. Neurological complications are common in critically ill patients with COVID-19 receiving invasive mechanical ventilation and are associated with prolonged ICU length of stay. Multimodal noninvasive neuromonitoring systems are useful tools for the early detection of variations in cerebrovascular parameters in COVID-19.
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http://dx.doi.org/10.3389/fneur.2020.602114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729072PMC
November 2020

Escalate and De-Escalate Therapies for Intracranial Pressure Control in Traumatic Brain Injury.

Front Neurol 2020 24;11:564751. Epub 2020 Nov 24.

Department of Neurosurgery, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) for Oncology and Neuroscience, Genoa, Italy.

Severe traumatic brain injury (TBI) is frequently associated with an elevation of intracranial pressure (ICP), followed by cerebral perfusion pressure (CPP) reduction. Invasive monitoring of ICP is recommended to guide a step-by-step "staircase approach" which aims to normalize ICP values and reduce the risks of secondary damage. However, if such monitoring is not available clinical examination and radiological criteria should be used. A major concern is how to taper the therapies employed for ICP control. The aim of this manuscript is to review the criteria for escalating and withdrawing therapies in TBI patients. Each step of the staircase approach carries a risk of adverse effects related to the duration of treatment. Tapering of barbiturates should start once ICP control has been achieved for at least 24 h, although a period of 2-12 days is often required. Administration of hyperosmolar fluids should be avoided if ICP is normal. Sedation should be reduced after at least 24 h of controlled ICP to allow neurological examination. Removal of invasive ICP monitoring is suggested after 72 h of normal ICP. For patients who have undergone surgical decompression, cranioplasty represents the final step, and an earlier cranioplasty (15-90 days after decompression) seems to reduce the rate of infection, seizures, and hydrocephalus.
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http://dx.doi.org/10.3389/fneur.2020.564751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724991PMC
November 2020