Evidence of SARS-CoV-2 in nasal brushings and olfactory mucosa biopsies of COVID-19 patients

The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy

IMPORTANCE Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. OBJECTIVE To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. EXPOSURES COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). MAIN OUTCOMES AND MEASURES The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. RESULTS Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] agewas 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dosewas 0.03 (95% CI, 0.03-0.04; P <.001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P <.001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P <.001), primarily male individuals (110 patients [ 79.1%] vs 252 patients [60.9%]; P <.001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P <.001) and had higher ratio of arterial partial pressure of oxygen (PaO2) and fraction of inspiratory oxygen (FiO(2)) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P =.007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower PaO2/FiO(2) at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. CONCLUSIONS AND RELEVANCE In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status.These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people

Neurally Adjusted Ventilatory Assist in Acute Respiratory Failure—A Narrative Review

Maintaining spontaneous breathing has both potentially beneficial and deleterious consequences in patients with acute respiratory failure, depending on the balance that can be obtained between the protecting and damaging effects on the lungs and the diaphragm. Neurally adjusted ventilatory assist (NAVA) is an assist mode, which supplies the respiratory system with a pressure proportional to the integral of the electrical activity of the diaphragm. This proportional mode of ventilation has the theoretical potential to deliver lung- and respiratory-muscle-protective ventilation by preserving the physiologic defense mechanisms against both lung overdistention and ventilator overassistance, as well as reducing the incidence of diaphragm disuse atrophy while maintaining patient–ventilator synchrony. This narrative review presents an overview of NAVA technology, its basic principles, the different methods to set the assist level and the findings of experimental and clinical studies which focused on lung and diaphragm protection, machine–patient interaction and preservation of breathing pattern variability. A summary of the findings of the available clinical trials which investigate the use of NAVA in acute respiratory failure will also be presented and discussed

Utilizzo di Etest nell’antibiogramma diretto da emocoltura su bacilli Gram negativi a crescita rapida e Staphylococcus spp.

The objective of this study was to compare E test antibiotic gradient performed directly from positive blood coltures with Vitek 2 System for rapid susceptibility testing.A total of 47 strains of Gram negative rapid growers and 37 strains of Staphylococcus spp. (10 strains S. aureus and 27 coagulase negative) were investigated. Direct testing of susceptibility to amikacin, imipenem, piperacillin-tazobactam, and ciprofloxacin was evaluated for Gram negative strains, and to oxacillin,ofloxacin, and imipenem for Gram positive. The rate of correlation resulted 99.4% for Gram negative strains (187/188) and 97% for Gram positive strains (144/148).Major errors (i.e. reported as resistant by the Etest but shown to be sensible by the Vitek) were observed and regarding one strain of P. aeruginosa for imipenem and two strains of Staphylococcus coagulase negative for oxacillin and imipenem. Etest resulted useful for direct testing susceptibility from blood and may lead to cost reducttion

A High Respiratory Drive Is Associated with Weaning Failure in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome: The Role of the Electrical Activity of the Diaphragm

Background: Mechanical ventilation is the main supportive treatment of severe cases of COVID-19-associated ARDS (C-ARDS). Weaning failure is common and associated with worse outcomes. We investigated the role of respiratory drive, assessed by monitoring the electrical activity of the diaphragm (EAdi), as a predictor of weaning failure. Methods: Consecutive, mechanically ventilated patients admitted to the ICU for C-ARDS with difficult weaning were enrolled. Blood gas, ventilator, and respiratory mechanic parameters, as well as EAdi, were recorded at the time of placement of EAdi catheter, and then after 1, 2, 3, 7, and 10 days, and compared between patients with weaning success and weaning failure. Results: Twenty patients were enrolled: age 66 (60–69); 85% males; PaO2/FiO2 at admission 148 (126–177) mmHg. Thirteen subjects (65%) were classified as having a successful weaning. A younger age (OR(95%CI): 0.02 (0.01–0.11) per year), a higher PaO2/FiO2 ratio (OR(95%CI): 1.10 (1.01–1.21) per mmHg), and a lower EAdi (OR(95%CI): 0.16 (0.08–0.34) per μV) were associated with weaning success. Conclusion: In critically ill patients with moderate–severe C-ARDS and difficult weaning from mechanical ventilation, a successful weaning was associated with a lower age, a higher oxygenation, and a lower respiratory drive, as assessed at the bedside via EAdi monitoring

Relation between peak and integral of the diaphragm electromyographic activity at different levels of support during weaning from mechanical ventilation: A physiologic study

Purpose: To investigate the relationship between peak (EAdipeak) and area under the curve (EAdiAUC) of diaphragm electrical activity, and to evaluate the validity of their ratio (P/I index) as a measure of the imbalance between drive and sustainability of effort demand at different support levels. Materials: Prospective physiological study on 18 ready-to-wean patients ventilated with neurally adjusted ventilatory assist (NAVA) undergoing 2 levels of NAVA (NAVA100%and NAVA50%) followed by a weaning trial with continuous positive airway pressure, according to which patients were classified as success or failure. Tidal volume (VT), respiratory rate, EAdipeak, EAdiAUC, rapid shallow breathing index (respiratory rate/VT), neuroventilatory index (VT/EAdipeak), and P/I index were obtained at the end of each step. Results: The slopes of regression line between EAdipeakand EAdiAUC(a mathematical equivalent of P/I index) and P/I index were significantly higher in failures. At variance with other variables, P/I index did not vary with level of support. P/I index was inversely correlated with inspiratory time at all support levels. Conclusions: The relationship between EAdipeakand EAdiAUCand the P/I index may give important information on the balance between respiratory drive and inspiratory demand sustainability

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients from 29 Countries

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality. Results: Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance: In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events - in particular cardiovascular instability - were observed frequently

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates