Publications by authors named "Domenico Grieco"

110 Publications

Lung ultrasound predicts non-invasive ventilation outcome in COVID-19 acute respiratory failure: a pilot study.

Minerva Anestesiol 2021 Jul 14. Epub 2021 Jul 14.

Intensive Care Unit, Department of Emergency, Anesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background: To determine relationships between lung aeration assessed by lung ultrasound (LUS) with Non-Invasive Ventilation (NIMV) outcome, intensive care unit (ICU) admission and mechanical ventilation (MV) needs in COVID-19 respiratory failure.

Methods: A cohort of adult patients with COVID-19 respiratory failure underwent LUS during initial assessment. A simplified LUS protocol consisting in scanning six areas, three for each side, was adopted. A score from 0 to 3 was assigned to each area. Comprehensive LUS score (LUSsc) was calculated as the sum of the score in all areas. LUSsc, the amount of involved sonographic lung areas (LUSq), the number of lung quadrants radiographically infiltrated and the degree of oxygenation impairment at admission (SpO2/FiO2 ratio) were compared to NIMV Outcome, MV needs and ICU admission.

Results: Among 85 patients prospectively included in the analysis, 49 of 61 needed MV. LUSsc and LUSq were higher in patients who required MV (median 12 [IQR 8-14] and median 6 [IQR 4-6], respectively) than in those who did not (6 [IQR 2-9] and 3 [IQR 1-5], respectively), both p < 0.001. NIMV trial failed in 26 patients out 36. LUSsc and LUSq were significantly higher in patients who failed NIMV than in those who did not. From ROC analysis, LUSsc ≧ 12 and LUSq ≧5 gave the best cut-off values for NIMV failure prediction (AUC=0.95, 95%CI 0.83-0.99 and AUC=0.81, 95%CI 0.65-0.91, respectively).

Conclusions: Our data suggest LUS as a possible tool for identifying patients who are likely to require MV and ICU admission or to fail a NIMV trial.
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http://dx.doi.org/10.23736/S0375-9393.21.15188-0DOI Listing
July 2021

Non-invasive ventilatory support and high-flow nasal oxygen as first-line treatment of acute hypoxemic respiratory failure and ARDS.

Intensive Care Med 2021 Aug 7;47(8):851-866. Epub 2021 Jul 7.

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

The role of non-invasive respiratory support (high-flow nasal oxygen and noninvasive ventilation) in the management of acute hypoxemic respiratory failure and acute respiratory distress syndrome is debated. The oxygenation improvement coupled with lung and diaphragm protection produced by non-invasive support may help to avoid endotracheal intubation, which prevents the complications of sedation and invasive mechanical ventilation. However, spontaneous breathing in patients with lung injury carries the risk that vigorous inspiratory effort, combined or not with mechanical increases in inspiratory airway pressure, produces high transpulmonary pressure swings and local lung overstretch. This ultimately results in additional lung damage (patient self-inflicted lung injury), so that patients intubated after a trial of noninvasive support are burdened by increased mortality. Reducing inspiratory effort by high-flow nasal oxygen or delivery of sustained positive end-expiratory pressure through the helmet interface may reduce these risks. In this physiology-to-bedside review, we provide an updated overview about the role of noninvasive respiratory support strategies as early treatment of hypoxemic respiratory failure in the intensive care unit. Noninvasive strategies appear safe and effective in mild-to-moderate hypoxemia (PaO/FiO > 150 mmHg), while they can yield delayed intubation with increased mortality in a significant proportion of moderate-to-severe (PaO/FiO ≤ 150 mmHg) cases. High-flow nasal oxygen and helmet noninvasive ventilation represent the most promising techniques for first-line treatment of severe patients. However, no conclusive evidence allows to recommend a single approach over the others in case of moderate-to-severe hypoxemia. During any treatment, strict physiological monitoring remains of paramount importance to promptly detect the need for endotracheal intubation and not delay protective ventilation.
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http://dx.doi.org/10.1007/s00134-021-06459-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261815PMC
August 2021

Diaphragm thickening fraction predicts noninvasive ventilation outcome: a preliminary physiological study.

Crit Care 2021 06 26;25(1):219. Epub 2021 Jun 26.

Department of Anesthesiology, Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.

Background: A correlation between unsuccessful noninvasive ventilation (NIV) and poor outcome has been suggested in de-novo Acute Respiratory Failure (ARF) patients. Consequently, it is of paramount importance to identify accurate predictors of NIV outcome. The aim of our preliminary study is to evaluate the Diaphragmatic Thickening Fraction (DTF) and the respiratory rate/DTF ratio as predictors of NIV outcome in de-novo ARF patients.

Methods: Over 36 months, we studied patients admitted to the emergency department with a diagnosis of de-novo ARF and requiring NIV treatment. DTF and respiratory rate/DTF ratio were measured by 2 trained operators at baseline, at 1, 4, 12, 24, 48, 72 and 96 h of NIV treatment and/or until NIV discontinuation or intubation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of DTF and respiratory rate/DTF ratio to distinguish between patients who were successfully weaned and those who failed.

Results: Eighteen patients were included. We found overall good repeatability of DTF assessment, with Intra-class Correlation Coefficient (ICC) of 0.82 (95% confidence interval 0.72-0.88). The cut-off values of DTF for prediction of NIV failure were < 36.3% and < 37.1% for the operator 1 and 2 (p < 0.0001), respectively. The cut-off value of respiratory rate/DTF ratio for prediction of NIV failure was > 0.6 for both operators (p < 0.0001).

Conclusion: DTF and respiratory rate/DTF ratio may both represent valid, feasible and noninvasive tools to predict NIV outcome in patients with de-novo ARF. Trial registration ClinicalTrials.gov Identifier: NCT02976233, registered 26 November 2016.
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http://dx.doi.org/10.1186/s13054-021-03638-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233594PMC
June 2021

Staphylococcus aureus ventilator-associated pneumonia in patients with COVID-19: clinical features and potential inference with lung dysbiosis.

Crit Care 2021 06 7;25(1):197. Epub 2021 Jun 7.

Dipartimento Di Scienze Biotecnologiche Di Base, Cliniche Intensivologiche E Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy.

Background: Hospitalized patients with COVID-19 admitted to the intensive care unit (ICU) and requiring mechanical ventilation are at risk of ventilator-associated bacterial infections secondary to SARS-CoV-2 infection. Our study aimed to investigate clinical features of Staphylococcus aureus ventilator-associated pneumonia (SA-VAP) and, if bronchoalveolar lavage samples were available, lung bacterial community features in ICU patients with or without COVID-19.

Methods: We prospectively included hospitalized patients with COVID-19 across two medical ICUs of the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy), who developed SA-VAP between 20 March 2020 and 30 October 2020 (thereafter referred to as cases). After 1:2 matching based on the simplified acute physiology score II (SAPS II) and the sequential organ failure assessment (SOFA) score, cases were compared with SA-VAP patients without COVID-19 (controls). Clinical, microbiological, and lung microbiota data were analyzed.

Results: We studied two groups of patients (40 COVID-19 and 80 non-COVID-19). COVID-19 patients had a higher rate of late-onset (87.5% versus 63.8%; p = 0.01), methicillin-resistant (65.0% vs 27.5%; p < 0.01) or bacteremic (47.5% vs 6.3%; p < 0.01) infections compared with non-COVID-19 patients. No statistically significant differences between the patient groups were observed in ICU mortality (p = 0.12), clinical cure (p = 0.20) and microbiological eradication (p = 0.31). On multivariable logistic regression analysis, SAPS II and initial inappropriate antimicrobial therapy were independently associated with ICU mortality. Then, lung microbiota characterization in 10 COVID-19 and 16 non-COVID-19 patients revealed that the overall microbial community composition was significantly different between the patient groups (unweighted UniFrac distance, R 0.15349; p < 0.01). Species diversity was lower in COVID-19 than in non COVID-19 patients (94.4 ± 44.9 vs 152.5 ± 41.8; p < 0.01). Interestingly, we found that S. aureus (log fold change, 29.5), Streptococcus anginosus subspecies anginosus (log fold change, 24.9), and Olsenella (log fold change, 25.7) were significantly enriched in the COVID-19 group compared to the non-COVID-19 group of SA-VAP patients.

Conclusions: In our study population, COVID-19 seemed to significantly affect microbiological and clinical features of SA-VAP as well as to be associated with a peculiar lung microbiota composition.
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http://dx.doi.org/10.1186/s13054-021-03623-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182737PMC
June 2021

Simple electrophysiological predictor of QRS change induced by cardiac resynchronization therapy: A novel marker of complete left bundle branch block.

Heart Rhythm 2021 Jun 23. Epub 2021 Jun 23.

Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2(nd) Department of Internal Cardiovascular Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Background: QRS complex shortening by cardiac resynchronization therapy (CRT) has been associated with improved outcomes.

Objective: We hypothesized that the absence of QRS duration (QRSd) prolongation by right ventricular mid-septal pacing (RVP) may indicate complete left bundle branch block (cLBBB).

Methods: We prospectively collected 12-lead surface electrocardiograms (ECGs) and intracardiac electrograms during CRT implant procedures. Digital recordings were edited and manually measured. The outcome measure was a change in QRSd induced by CRT (delta CRT). Several outcome predictors were investigated: native QRSd, cLBBB (by using Strauss criteria), interval between the onset of the QRS complex and the local left ventricular electrogram (Q-LV), and a newly proposed index defined by the difference between RVP and native QRSd (delta RVP).

Results: One hundred thirty-three consecutive patients were included in the study. Delta RVP was 27 ± 25 ms, and delta CRT was -14 ± 28 ms. Delta CRT correlated with native QRSd (r = -0.65), with the presence of ECG-based cLBBB (r = -0.40), with Q-LV (r = -0.68), and with delta RVP (r = 0.72) (P < .00001 for all correlations). In multivariable analysis, delta CRT was most strongly associated with delta RVP (P < .00001), followed by native QRSd and Q-LV, while ECG-based cLBBB became a nonsignificant factor.

Conclusion: Baseline QRSd, delta RVP, and LV electrical lead position (Q-LV) represent strong independent predictors of ECG response to CRT. The absence of QRSd prolongation by RVP may serve as an alternative and more specific marker of cLBBB. Delta RVP correlates strongly with the CRT effect on QRSd and outperforms the predictive value of ECG-based cLBBB.
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http://dx.doi.org/10.1016/j.hrthm.2021.05.033DOI Listing
June 2021

Immune Modulation in Critically Ill Septic Patients.

Medicina (Kaunas) 2021 May 31;57(6). Epub 2021 May 31.

Dipartimento di Scienze dell' Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Sepsis is triggered by infection-induced immune alteration and may be theoretically improved by pharmacological and extracorporeal immune modulating therapies. Pharmacological immune modulation may have long lasting clinical effects, that may even worsen patient-related outcomes. On the other hand, extracorporeal immune modulation allows short-term removal of inflammatory mediators from the bloodstream. Although such therapies have been widely used in clinical practice, the role of immune modulation in critically ill septic patients remains unclear and little evidence supports the role of immune modulation in this clinical context. Accordingly, further research should be carried out by an evidence-based and personalized approach in order to improve the management of critically ill septic patients.
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http://dx.doi.org/10.3390/medicina57060552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226671PMC
May 2021

Abnormal venous return: Still a challenge for electrophysiology procedures? A case report.

J Cardiol Cases 2021 May 1;23(5):202-205. Epub 2020 Dec 1.

Cardiology Unit, Policlinico Casilino, Rome, Italy.

Catheter ablation of cardiac arrhythmias is usually performed through the femoral venous approach. Systemic venous return anomalies such as interruption of the inferior vena cava may represent a challenge during electrophysiological procedures. A 55-year-old patient with previous surgical correction of abnormal pulmonary venous return was admitted for poorly tolerated atrial flutter recurrences. He also had an interrupted inferior vena cava continuing as azygos vein and left superior vena cava draining via coronary sinus into the right atrium. Cavotricuspid isthmus radiofrequency ablation was successfully performed through the persistent left superior vena cava using a three-dimensional (3D) electroanatomical mapping system. Despite systemic venous abnormalities may potentially have important implications during electrophysiological procedures, arrhythmias can be successfully ablated with the aid of 3D electroanatomical mapping systems. < Congenital venous return anomalies can represent significant difficulties in accessing catheters to the cardiac chambers during electrophysiological procedures, which may be facilitated by three-dimensional mapping systems. Radiofrequency ablation of the cavotricuspid isthmus can be successfully performed using the femoral approach and introducing catheters into the right atrium sequentially through the femoral-iliac venous axis, the azygos vein, the persistent left superior vena cava, and the coronary sinus.>.
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http://dx.doi.org/10.1016/j.jccase.2020.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103316PMC
May 2021

COVID-19 influences lung microbiota dynamics and favors the emergence of rare infectious diseases: A case report of Hafnia Alvei pneumonia.

J Crit Care 2021 08 18;64:173-175. Epub 2021 Apr 18.

Dipartimento di Scienze dell' Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Facoltà di medicina e chirurgia "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.

The coronavirus disease 2019 causes a wide degree of organ dysfunction and is associated with bacterial secondary infections. We reported lung microbiota dynamics in a critically ill patient with coronavirus disease 2019, who developed severe Hafnia alvei ventilator-associated pneumonia and required extracorporeal membrane oxygenation support.
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http://dx.doi.org/10.1016/j.jcrc.2021.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053226PMC
August 2021

Impact of His bundle pacing on right ventricular performance in patients undergoing permanent pacemaker implantation.

Pacing Clin Electrophysiol 2021 Jun 7;44(6):986-994. Epub 2021 May 7.

Department of Cardiology, Policlinico Casilino of, Rome, Rome, Italy.

Background: His-Bundle pacing (HBP) is an emerging technique for physiological pacing. However, its effects on right ventricle (RV) performance are still unknown.

Methods: We enrolled consecutive patients with an indication for pacemaker (PM) implantation to compare HBP versus RV pacing (RVP) effects on RV performance. Patients were evaluated before implantation and after 6 months by a transthoracic echocardiogram.

Results: A total of 84 patients (age 75.1±7.9 years, 64% male) were enrolled, 42 patients (50%) underwent successful HBP, and 42 patients (50%) apical RVP. At follow up, we found a significant improvement in RV-FAC (Fractional Area Change)% [baseline: HBP 34 IQR (31-37) vs. RVP 33 IQR (29.7-37.2),p = .602; 6-months: HBP 37 IQR (33-39) vs. RVP 30 IQR (27.7-35), p < .0001] and RV-GLS (Global Longitudinal Strain)% [baseline: HBP -18 IQR (-20.2 to -15) vs. RVP -16 IQR (-18.7 to -14), p = .150; 6-months: HBP -20 IQR(-23 to -17) vs. RVP -13.5 IQR (-16 to -11), p < .0001] with HBP whereas RVP was associated with a significant decline in both parameters. RVP was also associated with a significant worsening of tricuspid annular plane systolic excursion (TAPSE) (p < .0001) and S wave velocity (p < .0001) at follow up. Conversely from RVP, HBP significantly improved pulmonary artery systolic pressure (PASP) [baseline: HBP 38 IQR (32-42) mmHg vs. RVP 34 IQR (31.5-37) mmHg,p = .060; 6-months: HBP 32 IQR (26-38) mmHg vs. RVP 39 IQR (36-41) mmHg, p < .0001] and tricuspid regurgitation (p = .005) irrespectively from lead position above or below the tricuspid valve.

Conclusions: In patients undergoing PM implantation, HBP ensues a beneficial and protective impact on RV performance compared with RVP.
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http://dx.doi.org/10.1111/pace.14249DOI Listing
June 2021

Dyspnea and respiratory muscles ultrasound to predict extubation failure.

Eur Respir J 2021 Apr 19. Epub 2021 Apr 19.

AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université, site Pitié-Salpêtrière, Service de Pneumologie, Médecine intensive Réanimation (Département R3S), Paris, France.

This study investigated dyspnea intensity and respiratory muscles ultrasound early after extubation to predict extubation failure.It was conducted prospectively in two intensive care units in France and Canada. Patients intubated for at least 48 h were studied within 2 h after an extubation following a successful spontaneous breathing trial. Dyspnea was evaluated by the Dyspnea-Visual Analog Scale from 0 to 10 cm (VAS) and the Intensive Care - Respiratory Distress Observational Scale (range 0-10). The ultrasound thickening fraction of the parasternal intercostal and the diaphragm were measured; limb muscle strength was evaluated using the Medical Research Council score (MRC) (range 0-60).Extubation failure occurred in 21 of the 122 enrolled patients (17%). Dyspnea-VAS and Intensive Care - Respiratory Distress Observational scale were higher in patients with extubation failure success: 7 (5-9) cm 3 (1-5) cm respectively (p<0.001) and 4.4 (2.5-6.5) 2.4 (2.1-2.8) respectively (p<0.001). The ratio of intercostal muscle to diaphragm thickening fraction was significantly higher and MRC was lower in patients with failure (0.9 [0.4-3.0] 0.3 [0.2-0.5], p<0.001, and 45 [36-50] 52 [44-60], p=0.012). The thickening fraction of the intercostal and its ratio to diaphragm thickening showed the highest area under the receiver operating characteristic curves for an early prediction of extubation failure (0.81). Areas under the receiver operating characteristic curves of Dyspnea-VAS and Intensive Care - Respiratory Distress Observational scale reached 0.78 and 0.74 respectively.Respiratory muscle ultrasound and dyspnea measured within 2 h after extubation predict subsequent extubation failure.
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http://dx.doi.org/10.1183/13993003.00002-2021DOI Listing
April 2021

Atrial fibrillation and autonomic nervous system: A translational approach to guide therapeutic goals.

J Arrhythm 2021 Apr 9;37(2):320-330. Epub 2021 Feb 9.

Department of Cardiology Policlinico Casilino Rome Italy.

The autonomic nervous system (ANS) is known to play an important role in the genesis and maintenance of atrial fibrillation (AF). Biomolecular and genetic mechanisms, anatomical knowledges with recent diagnostic techniques acquisitions, both invasive and non-invasive, have enabled greater therapeutic goals in patients affected by AF related to ANS imbalance. Catheter ablation of ganglionated plexi (GP) in the left and right atrium has been proposed in varied clinical conditions. Moreover interesting results arise from renal sympathetic denervation and vagal nerve stimulation. Despite all this, in the scenario of ANS modulation translational strategies we necessary must consider the treatment or correction of dynamic factors such as obesity, obstructive sleep apnea, lifestyle, food, and stress. Finally, new antiarrhythmic drugs, gene therapy and "ablatogenomic" could be represent exciting future therapeutic perspectives.
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http://dx.doi.org/10.1002/joa3.12512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022002PMC
April 2021

Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients.

Crit Care 2021 04 6;25(1):128. Epub 2021 Apr 6.

Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.

Background: Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave.

Methods: Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO/FiO ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position.

Results: Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p < 0.001). Overall, prone position induced a significant increase in PaO/FiO ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively).

Conclusions: During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching.

Trial Registration: clinicaltrials.gov number: NCT04388670.
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http://dx.doi.org/10.1186/s13054-021-03552-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022297PMC
April 2021

Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial.

JAMA 2021 05;325(17):1731-1743

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario AGemelli IRCCS, Rome, Italy.

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19.

Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone.

Design, Setting, And Participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200).

Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55).

Main Outcomes And Measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay.

Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99).

Conclusions And Relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation.

Trial Registration: ClinicalTrials.gov Identifier: NCT04502576.
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http://dx.doi.org/10.1001/jama.2021.4682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995134PMC
May 2021

Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure: Guidance from an International Group of Healthcare Workers.

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

1Department of Intensive Care, Amsterdam University Medical Centers, Location 'AMC', Amsterdam, The Netherlands.

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.
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http://dx.doi.org/10.4269/ajtmh.20-1445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103477PMC
March 2021

High Failure Rate of Noninvasive Oxygenation Strategies in Critically Ill Subjects With Acute Hypoxemic Respiratory Failure Due to COVID-19.

Respir Care 2021 05 2;66(5):705-714. Epub 2021 Mar 2.

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS; Rome, Italy.

Background: The efficacy of noninvasive oxygenation strategies (NIOS) in treating COVID-19 disease is unknown. We conducted a prospective observational study to assess the rate of NIOS failure in subjects treated in the ICU for hypoxemic respiratory failure due to COVID-19.

Methods: Patients receiving first-line treatment NIOS for hypoxemic respiratory failure due to COVID-19 in the ICU of a university hospital were included in this study; laboratory data were collected upon arrival, and 28-d outcome was recorded. After propensity score matching based on Simplified Acute Physiology (SAPS) II score, age, [Formula: see text] and [Formula: see text] at arrival, the NIOS failure rate in subjects with COVID-19 was compared to a previously published cohort who received NIOS during hypoxemic respiratory failure due to other causes.

Results: A total of 85 subjects received first-line treatment with NIOS. The most frequently used methods were helmet noninvasive ventilation and high-flow nasal cannula; of these, 52 subjects (61%) required endotracheal intubation. Independent factors associated with NIOS failure were SAPS II score ( = .009) and serum lactate dehydrogenase at enrollment ( = .02); the combination of SAPS II score ≥ 33 with serum lactate dehydrogenase ≥ 405 units/L at ICU admission had 91% specificity in predicting the need for endotracheal intubation. In the propensity-matched cohorts (54 pairs), subjects with COVID-19 showed higher risk of NIOS failure than those with other causes of hypoxemic respiratory failure (59% vs 35%, = .02), with an adjusted hazard ratio of 2 (95% CI 1.1-3.6, = .01).

Conclusions: As compared to hypoxemic respiratory failure due to other etiologies, subjects with COVID-19 who were treated with NIOS in the ICU were burdened by a 2-fold higher risk of failure. Subjects with a SAPS II score ≥ 33 and serum lactate dehydrogenase ≥ 405 units/L represent the population with the greatest risk.
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http://dx.doi.org/10.4187/respcare.08622DOI Listing
May 2021

Respiratory mechanics heterogeneity is related to inflammatory biomarkers in acute respiratory distress syndrome due to COVID-19.

Minerva Anestesiol 2021 06 16;87(6):740-744. Epub 2021 Feb 16.

Department of Emergency, Intensive Care Medicine and Anesthesia, IRCCS A. Gemelli University Polyclinic Foundation, Rome, Italy.

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http://dx.doi.org/10.23736/S0375-9393.21.15289-7DOI Listing
June 2021

Instrumental dead space in ventilator management.

Lancet Respir Med 2021 03 29;9(3):e22. Epub 2021 Jan 29.

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Anesthesiology and Intensive Care Medicine, Catholic University of The Sacred Heart, Rome, Italy.

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http://dx.doi.org/10.1016/S2213-2600(21)00024-2DOI Listing
March 2021

Noninvasive ventilation and high-flow oxygen therapy for severe community-acquired pneumonia.

Curr Opin Infect Dis 2021 04;34(2):142-150

Dipartimento di Scienza dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8.

Purpose Of Review: We review the evidence on the use of noninvasive respiratory supports (noninvasive ventilation and high-flow nasal cannula oxygen therapy) in patients with acute respiratory failure because of severe community-acquired pneumonia.

Recent Findings: Noninvasive ventilation is strongly advised for the treatment of hypercapnic respiratory failure and recent evidence justifies its use in patients with hypoxemic respiratory failure when delivered by helmet. Indeed, such interface allows alveolar recruitment by providing high level of positive end-expiratory pressure, which improves hypoxemia. On the other hand, high-flow nasal cannula oxygen therapy is effective in patients with hypoxemic respiratory failure and some articles support its use in patients with hypercapnia. However, early identification of noninvasive respiratory supports treatment failure is crucial to prevent delayed orotracheal intubation and protective invasive mechanical ventilation.

Summary: Noninvasive ventilation is the first-line therapy in patients with acute hypercapnic respiratory failure because of pneumonia. Although an increasing amount of evidence investigated the application of noninvasive respiratory support to hypoxemic respiratory failure, the optimal ventilatory strategy in this setting is uncertain. Noninvasive mechanical ventilation delivered by helmet and high-flow nasal cannula oxygen therapy appear as promising tools but their role needs to be confirmed by future research.
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http://dx.doi.org/10.1097/QCO.0000000000000715DOI Listing
April 2021

Hemadsorption.

Curr Opin Anaesthesiol 2021 Apr;34(2):113-118

Unità Operativa Complessa di Anestesia, Rianimazione, Terapia Intensiva e Tossicologia Clinica; Dipartimento di Scienze dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Purpose Of Review: To review pathophysiological pathways of immune system response to infections, which may justify mediators removal by extracorporeal blood purification therapies (EBPTs) in critically ill septic patients. Moreover, we presented an overview of the EBPTs mostly used in clinical practice with the aim to modulate immune system dysfunction in sepsis.

Recent Findings: Sepsis is a life-threatening disease and recent findings showed that its pathophysiology relies on dysregulated immune system response to pathogen invasion of the body. In the light of this view, EBPTs have been demonstrated effective to remove specific mediators and foster balance between pro- and anti-inflammatory pathways.

Summary: EBPTs have been widely used in clinical practice, with the aim to modulate immune system dysfunction by the removal of pathogens and inflammatory mediators in critically ill patients with sepsis. Such therapies are characterised by specific structural features, which allow selective and nonselective removal of mediators by adsorption. However, few evidences support their role in the management of critically ill patients with sepsis. Accordingly, an evidence-based and personalized approach to EBPTs in sepsis is strongly advocated, in order to solve controversies in this field and optimise the management of critically ill septic patients.
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http://dx.doi.org/10.1097/ACO.0000000000000953DOI Listing
April 2021

Extracorporeal immune modulation in COVID-19 induced immune dysfunction and secondary infections: the role of oXiris® membrane.

Minerva Anestesiol 2021 03 17;87(3):384-385. Epub 2020 Dec 17.

Unit of Anesthesia, Intensive Care and Clinical Toxicology, Department of Emergency Science, Anesthesiology and Intensive Care, IRCCS A. Gemelli University Polyclinic Foundation, Rome, Italy.

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http://dx.doi.org/10.23736/S0375-9393.20.15124-1DOI Listing
March 2021

Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial.

Chest 2021 Apr 13;159(4):1426-1436. Epub 2020 Nov 13.

Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anesthesiology and Critical Care, Pitié-Salpêtrière Hospital, Paris, France.

Background: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant.

Research Question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible?

Study Design And Methods: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm HO for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days.

Results: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group.

Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk.

Trial Registry: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2020.10.079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664474PMC
April 2021

(1,3)-β-D-Glucan-based empirical antifungal interruption in suspected invasive candidiasis: a randomized trial.

Crit Care 2020 09 5;24(1):550. Epub 2020 Sep 5.

Dipartimento di Scienza dell'Emergenza, Anestesiologiche e della Rianimazione - UOC di Anestesia, Rianimazione, Terapia Intensiva e Tossicologia Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy.

Background: (1,3)-β-D-Glucan has been widely used in clinical practice for the diagnosis of invasive Candida infections. However, such serum biomarker showed potential to guide antimicrobial therapy in order to reduce the duration of empirical antifungal treatment in critically ill septic patients with suspected invasive candidiasis.

Methods: This was a single-centre, randomized, open-label clinical trial in which critically ill patients were enrolled during the admission to the intensive care unit (ICU). All septic patients who presented invasive Candida infection risk factors and for whom an empirical antifungal therapy was commenced were randomly assigned (1:1) in those stopping antifungal therapy if (1,3)-β-D-glucan was negative ((1,3)-β-D-glucan group) or those continuing the antifungal therapy based on clinical rules (control group). Serum 1,3-β-D-glucan was measured at the enrolment and every 48/72 h over 14 days afterwards. The primary endpoint was the duration of antifungal treatment in the first 30 days after enrolment.

Results: We randomized 108 patients into the (1,3)-β-D-glucan (n = 53) and control (n = 55) groups. Median [IQR] duration of antifungal treatment was 2 days [1-3] in the (1,3)-β-D-glucan group vs. 10 days [6-13] in the control group (between-group absolute difference in means, 6.29 days [95% CI 3.94-8.65], p < 0.001). Thirty-day mortality was similar (28.3% [(1,3)-β-D-glucan group] vs. 27.3% [control group], p = 0.92) as well as the overall rate of documented candidiasis (11.3% [(1,3)-β-D-glucan group] vs. 12.7% [control group], p = 0.94), the length of mechanical ventilation (p = 0.97) and ICU stay (p = 0.23).

Conclusions: In critically ill septic patients admitted to the ICU at risk of invasive candidiasis, a (1,3)-β-D-glucan-guided strategy could reduce the duration of empirical antifungal therapy. However, the safety of this algorithm needs to be confirmed in future, multicentre clinical trial with a larger population.

Trial Registration: ClinicalTrials.gov, NCT03117439 , retrospectively registered on 18 April 2017.
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http://dx.doi.org/10.1186/s13054-020-03265-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487510PMC
September 2020

Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study.

Lancet Respir Med 2020 12 27;8(12):1201-1208. Epub 2020 Aug 27.

Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, Alma Mater Studiorum-Università di Bologna, Bologna, Italy. Electronic address:

Background: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19.

Methods: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed.

Findings: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm HO (33-52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm HO [25-43]; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32-1·95] vs 1·90 [1·50-2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001).

Interpretation: Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates.

Funding: None.
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http://dx.doi.org/10.1016/S2213-2600(20)30370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834127PMC
December 2020

Respiratory physiology of COVID-19-induced respiratory failure compared to ARDS of other etiologies.

Crit Care 2020 08 28;24(1):529. Epub 2020 Aug 28.

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background: Whether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes.

Methods: Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmHO. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO/FiO, FiO, PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study.

Results: Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th-75th percentiles] PaO/FiO in the two groups was 119 mmHg [101-142] and 116 mmHg [87-154]. Average compliance (41 ml/cmHO [32-52] vs. 36 ml/cmHO [27-42], p = 0.045) and ventilatory ratio (2.1 [1.7-2.3] vs. 1.6 [1.4-2.1], p = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO/FiO was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO/FiO in both cohorts, but more remarkably in COVID-19 patients (p = 0.005). Recruitability was not different between cohorts (p = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP.

Conclusions: Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small.
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http://dx.doi.org/10.1186/s13054-020-03253-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453378PMC
August 2020

Contact-force monitoring increases accuracy of right ventricular voltage mapping avoiding "false scar" detection in patients with no evidence of structural heart disease.

Indian Pacing Electrophysiol J 2020 Nov - Dec;20(6):243-249. Epub 2020 Aug 6.

Cardiology Unit, Policlinico Casilino, Rome, Italy.

Purpose: Electroanatomical mapping (EAM) could increase cardiac magnetic resonance imaging (CMR) sensitivity in detecting ventricular scar. Possible bias may be scar over-estimation due to inadequate tissue contact. Aim of the study is to evaluate contact-force monitoring influence during EAM, in patients with idiopathic right ventricular arrhythmias.

Methods: 20 pts (13 M; 43 ± 12 y) with idiopathic right ventricular outflow tract (RVOT) arrhythmias and no structural abnormalities were submitted to Smarttouch catheter Carto3 EAM. Native maps included points collected without considering contact-force. EAM scar was defined as area ≥1 cm including at least 3 adjacent points with signal amplitude (bipolar <0.5 mV, unipolar 3,5 mV), surrounded by low-voltage border zone. EAM were re-evaluated offline, removing points collected with contact force <5 g. Finally, contact force-corrected maps were compared to the native ones.

Results: An EAM was created for each patient (345 ± 85 points). After removing poor contact points, a mean of 149 ± 60 points was collected. The percentage of false scar, collected during contact force blinded mapping compared to total volume, was 6.0 ± 5.2% for bipolar scar and 7.1 ± 5.9% for unipolar scar, respectively. No EAM scar was present after poor contact points removal. Right ventricular areas analysis revealed a greater number of points with contact force < 5 g acquired in free wall, where reduced mean bipolar and unipolar voltage were recorded.

Conclusions: To date this is the first work conducted on structurally normal hearts in which contact-force significantly increases EAM accuracy, avoiding "false scar" related to non-adequate contact between catheter and tissue.
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http://dx.doi.org/10.1016/j.ipej.2020.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691776PMC
August 2020

Catheter ablation of right atrial ganglionated plexi to treat cardioinhibitory neurocardiogenic syncope: a long-term follow-up prospective study.

J Interv Card Electrophysiol 2020 Aug 6. Epub 2020 Aug 6.

Division of Cardiology, Policlinico Casilino, Via Casilina 1049, 00169, Rome, Italy.

Purpose: Several reports have focused on biatrial ganglionated plexi (GP) transcatheter ablation to treat cardioinhibitory neurocardiogenic syncope (CNS). Considering that anatomical studies showed a significant number of GP in the right atrium (RA), we hypothesized that RA "cardioneuroablation" could be an effective treatment for CNS.

Methods: Eighteen consecutive patients (mean age: 36.9 ± 11.2 years) with severe CNS were submitted to transcatheter ablation of GPs in the RA alone using an anatomical approach. Head up tilt test evaluation was performed during the follow-up period at 6, 12, and 24 months and in case of significant symptoms, while heart rate variability parameters were evaluated at patients discharge at 1, 3, 6, 12, 24, and 36 months after ablation.

Results: At a mean follow-up of 34.1 ± 6.1 months, 3 (16.6%) patients experienced syncopal episodes and 5 patients (27.7%) only prodromal episodes. Syncopal and prodromal recurrences were significantly decreased both in overall population (P = 0.001) and in symptomatic patients after ablation (P = 0.003). Heart rate variability analysis showed the loss of autonomic balance secondary to a reincrease of sympathetic tone after the acute phase faster than vagal tone more evident at 12 months (LF/HF vs preablation, P < 0.001) and persistent until 24 months. Finally, a good correlation was observed between symptomatic events and the extension of RF lesions in supero-, middle-, and infero-posterior RA areas (r = 0.73, P = 0.03; r = 0.85, P = 0.02; r = 0.87, P = 0.004, respectively).

Conclusions: Cardioneuroablation in the RA can be considered safe and an effective technique to treat CNS episodes.
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http://dx.doi.org/10.1007/s10840-020-00840-9DOI Listing
August 2020

Clinical characteristics of challenging catheter ablation procedures in patients with WPW syndrome: A 10 year single-center experience.

J Cardiol 2020 10 9;76(4):420-426. Epub 2020 Jun 9.

Division of Cardiology, Policlinico Casilino, Roma, Italy.

Background: Catheter ablation is the established treatment for patients with symptomatic Wolff-Parkinson-White syndrome (WPW). However, some patients undergo a challenging ablation or have recurrences during the early post-ablation phase. The aim of this study was to evaluate the clinical factors associated with an unsuccessful ablation outcome or repeated sessions.

Methods: Four hundred seventy-five symptomatic consecutive WPW patients (38.2±16.2 years old, 61% men, 69% with pre-excitation) who underwent an accessory pathway (AP) ablation from August 2005 to December 2015 were enrolled. When APs recurred, a redo ablation procedure was performed according to the patients' desire.

Results: Four hundred thirty-nine patients (92.4%) were cured by ablation, but it failed in 36 (7.6%) after the first procedure. Seventeen patients had AP recurrences during the acute phase within 36h post-ablation. On the other hand, 4 were identified after more than one year. In a multivariate logistic regression analysis, multiple, parahisian, and broad APs were significant independent predictors of recurrences after the 1st procedure, with odds ratios of 14.88 (p<0.001), 10.14 (p<0.001), and 6.88 (p<0.001), respectively. Finally, 468 patients (98.5%) received a successful ablation during a mean follow-up of 8.3±3.0 years. However, after the final procedure no significant predictors were recognized. Out of 508 total procedures, three major (0.6%) complications occurred.

Conclusions: Symptomatic WPW patients with multiple, parahisian, and broad APs had a significantly higher risk of recurrence. In half of the recurrence patients, AP recurrences were confirmed during the acute phase, but were rarely recorded in the very late phase.
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http://dx.doi.org/10.1016/j.jjcc.2020.05.003DOI Listing
October 2020

Microbiologic surveillance through subglottic secretion cultures during invasive mechanical ventilation: a prospective observational study.

J Crit Care 2020 10 26;59:42-48. Epub 2020 May 26.

Dipartimento di Scienze dell'Emergenza, Anestesiologiche e della Rianimazione, UOC di Anestesia, Rianimazione, Terapia Intensiva e Tossicologia Clinica; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Istituto di Anestesia e Rianimazione; Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address:

Purpose: Whether subglottic secretions (SS) culture during invasive mechanical ventilation may aid microbiological surveillance is unknown. We conducted a prospective study to assess SS cultures predictivity of endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) isolates.

Materials And Methods: 109 patients receiving mechanical ventilation for ≥48 hours underwent SS and ETA surveillance cultures twice weekly; blind BAL was performed in case of clinically suspected pneumonia.

Results: SS and ETA cultures were fully concordant in 170 (81%-overall accuracy) of 211 sample pairs. As compared to ETA, SS culture global sensitivity and specificity were 84% [95%CI: 77 to 91] and 74% [95%CI: 66 to 82]; negative and positive predictive values were 82% and 77%. Forty-four episodes of clinically suspected pneumonia were observed. Compared to BAL, SS culture global sensitivity and specificity were 68% [95%CI: 45 to 81] and 63% [95%CI: 44 to 82]; negative and positive predictive values were both 65%. SS sensitivity, specificity, positive and negative predictive values in anticipating BAL isolates were comparable to ETA (all p > 0.20).

Conclusions: SS cultures show worthy accuracy in identifying ETA isolates, with excellent sensitivity and good negative predictivity. SS cultures may be not inferior to ETA in predicting BAL results in case of ventilator-associated pneumonia.

Trial Registration: ClinicalTrials.gov, NCT03153241. Registered on 15 May 2017, https://clinicaltrials.gov/ct2/show/NCT03153241.
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http://dx.doi.org/10.1016/j.jcrc.2020.05.013DOI Listing
October 2020

Lung- and Diaphragm-Protective Ventilation.

Am J Respir Crit Care Med 2020 10;202(7):950-961

Dipartimento di Medicina d'Urgenza e di Terapia Intensiva e Anestesia, Fondazione Policlinico Universitario, A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.
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http://dx.doi.org/10.1164/rccm.202003-0655CPDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710325PMC
October 2020

Exploiting immune-dependent effects of microtubule-targeting agents to improve efficacy and tolerability of cancer treatment.

Cell Death Dis 2020 05 12;11(5):361. Epub 2020 May 12.

CEINGE Biotecnologie Avanzate, Naples, Italy.

Microtubule-targeting agents (MTAs), like taxanes and vinca alkaloids, are tubulin-binding drugs that are very effective in the treatment of various types of cancers. In cell cultures, these drugs appear to affect assembly of the mitotic spindle and to delay progression through mitosis and this correlates with their ability to induce cell death. Their clinical efficacy is, however, limited by resistance and toxicity. For these reasons, other spindle-targeting drugs, affecting proteins such as certain kinesins like Eg5 and CENP-E, or kinases like Plk1, Aurora A and B, have been developed as an alternative to MTAs. However, these attempts have disappointed in the clinic since these drugs show poor anticancer activity and toxicity ahead of positive effects. In addition, whether efficacy of MTAs in cancer treatment is solely due to their ability to delay mitosis progression remains controversial. Here we discuss recent findings indicating that the taxane paclitaxel can promote a proinflammatory response by activation of innate immunity. We further describe how this can help adaptive antitumor immune response and suggest, on this basis and on the recent success of immune checkpoint inhibitors in cancer treatment, that a combination therapy based on low doses of taxanes and immune checkpoint inhibitors may be of high clinical advantage in terms of wide applicability, reduced toxicity, and increased antitumor response.
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http://dx.doi.org/10.1038/s41419-020-2567-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217828PMC
May 2020
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