Safety and Diagnostic Yield of Medical Pleuroscopy (MP) Performed under Balanced Analgosedation by a Pneumological Team Compared to Video-Assisted Thoracic Surgery (VATS): A Retrospective Controlled Real-Life Study (TORAPO).

INTRODUCTION: Medical pleuroscopy (MP) is an invasive technique that provides access to the pleural space with a rigid or semi-rigid work instrument, allowing for visualization and the obtaining of bioptic pleural samples. Using pulmonologist-based analgosedation to perform pleuroscopy is still debated for safety reasons. The aim of this real-life study is to demonstrate the safety and diagnostic yield of MP performed under balanced analgosedation by a pulmonologist team with expertise in the management of critically ill patients in the respiratory intensive care unit (RICU) and interventional pulmonology unit as compared to video-assisted thoracic surgery (VATS) performed by a thoracic surgeon team under anesthesiologist-based analgosedation. METHODS: In this multicentric retrospective controlled study, the inclusion criteria were patients older than 18 years old with pleural effusion of unknown diagnosis consecutively admitted in the years 2017-2022 to the pulmonology unit and RICU of San Donato Hospital in Arezzo (Italy, Tuscany) and to the thoracic surgery unit of Santa Maria Le Scotte in Siena (Italy, Tuscany) to undergo, respectively, MP under balanced propofol-based analgosedation on spontaneous breathing with local anesthesia provided by a pulmonologist team (Group A), and VATS provided by a surgeon team under propofol-based analgosedation managed by an anesthesiologist using invasive mechanical ventilation (IMV) via endotracheal intubation (ETI) (Group B). The primary endpoints were (1) a comparison between the two groups in terms of the diagnostic yield of pleural effusion, and (2) major and minor complications of pleuroscopic procedures. The secondary endpoints were (1) the length of the pleuroscopic procedure; (2) the duration of hospitalization; (3) propofol doses; and (4) the patient's comfort after the procedure assessed using the Visual Analogue Scale (VAS). RESULTS: We enrolled 91 patients in Group A and 116 patients in Group B. A conclusive diagnosis was obtained in 97.8% of Group A vs. 100% of Group B (p = 0.374). Malignant effusion was diagnosed in 59.3% of Group A and in 55.1% of Group B; p = 0.547. No intraoperative or postoperative mortality events or major complications were observed in Group A. The major complications observed in Group B were three major bleeding events (p = 0.079) and one exitus (p = 0.315) not related to the interventional procedure. No significant difference emerged between the two groups in terms of minor complications. The duration of the intervention was significantly lower in Group A (40.0 min ± 12.6 versus 51.5 ± 31.0; p = 0.001). Pain control and, therefore, patient comfort were better in Group A, with an average VAS of 0.34 ± 0.65 versus 2.58 ± 1.26, p < 0.001. The duration of hospitalization was lower in Group B (5.1 ± 2.6 vs. 15.5 ± 8.0, p < 0.001). The average overall dose of propofol administered was significantly lower in Group A (65.6 ± 35.8 mg versus 280 ± 20.0 mg; p < 0.001). CONCLUSIONS: This real-life study shows that the MP performed under propofol-based analgosedation by an independent pneumologist team is a safe and well-tolerated procedure with a diagnostic yield and complication rates similar to those obtained with VATS.

Prone positioning during CPAP therapy in SARS-CoV-2 pneumonia: a concise clinical review.

During the COVID-19 pandemic, the number of patients with hypoxemic acute respiratory failure (ARF) due to SARS-CoV-2 pneumonia threatened to overwhelm intensive care units. To reduce the need for invasive mechanical ventilation (IMV), clinicians tried noninvasive strategies to manage ARF, including the use of awake prone positioning (PP) with continuous positive airway pressure (CPAP). In this article, we review the patho-physiologic rationale, clinical effectiveness and practical issues of the use of PP during CPAP in non-intubated, spontaneously breathing patients affected by SARS-CoV-2 pneumonia with ARF. Use of PP during CPAP appears to be safe and feasible and may have a lower rate of adverse events compared to IMV. A better response to PP is observed among patients in early phases of acute respiratory distress syndrome. While PP during CPAP may improve oxygenation, the impact on the need for intubation and mortality remains unclear. It is possible to speculate on the role of PP during CPAP in terms of improvement of ventilation mechanics and reduction of strain stress.

The use of non-invasive respiratory assistance to facilitate bronchofiberoscopy performance in patients with hypoxemic (type one) respiratory failure - Study protocol.

PURPOSE: Bronchofiberoscopy (FOB) is a procedure routinely performed for: lung cancer, obstruction, interstitial diseases, foreign bodies' removal, airway clearance, and hemoptysis. It causes acute airway narrowing leading to respiratory and cardiovascular stress. Due to increasing number of ill patients with respiratory failure (RF), conventional oxygen therapy (COT) is frequently insufficient to assure accurate oxygenation and prevent RF in patients requiring FOB. In this clinical scenario, patients may be intubated and supported with invasive mechanical ventilation (IMV) with the specific aim of allowing a safe FOB. However, this invasive strategy is associated with an increased risk of IMV-associated complications. MATERIALS AND METHODS: Our study is a planned prospective multicenter three-arm randomized controlled trial (RCT). The target number of 300 patients was calculated based on the intubation risk in RF patients, which is 0.2-2%. The patients will be assigned to each arm based on Horowitz index. In each arm, the patients will be randomly assigned to one out of two dedicated respiratory support methods in each group i.e. COT/high flow nasal cannula (HFNC), HFNC/non-invasive ventilation (NIV) and NIV/IMV. In the manuscript the current state of art in the area of respiratory support is discussed. We have underlined knowledge gaps in medical evidence which we are planning to reveal with our results. RESULTS: The results of our study are clinically crucial, because they address current gaps concerning COT/HFNC/NIV/IMV. CONCLUSION: The expected findings of this study would allow for careful selection of respiratory support method to safely perform FOB in patients with hypoxemic RF.

May noninvasive mechanical ventilation and/ or continuous positive airway pressure increase the bronchoalveolar lavage salvage in patients with pulmonary diseases? Randomized clinical trial - Study protocol.

PURPOSE: Bronchoalveolar lavage (BAL) procedure is a useful tool in the diagnosis of patients with interstitial lung disease (ILD) and is helpful in clinical research of chronic obstructive pulmonary disease (COPD) patients. Still little is known about predictors of poor BAL salvage. The trial aims to find the most efficient way to improve BAL recovery. MATERIAL AND METHODS: Our study is a prospective, multicenter, international, two-arm randomized controlled trial. We aim to obtain BAL samples from a total number of 300 patients: 150 with ILD and 150 with COPD to achieve a statistical power of 80 â€‹%. Patients with initial BAL salvage <60 â€‹% will be randomized into the non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) arm. The NIV and CPAP will be set according to the study protocol. The influence on BAL salvage will be assessed in terms of BAL volume and content. Multivariable analysis of the additional test results to determine predictors for low BAL recovery will be conducted. In a study subgroup of approximately 20 patients per specific disease, a metabolomic assessment of exhaled air condensate will be performed. All procedures will be assessed in terms of the patient's safety. The trial was registered on clinicaltrials.gov (ID# NCT05631132). Interested experienced centers are invited to join the research group by writing to the corresponding author. CONCLUSION: The results of our prospective study will address the currently unsolved problem of how to increase BAL salvage in patients with pulmonary diseases without increasing the risk of respiratory failure exacerbation.

Associations of Awake Prone Positioning-Induced Changes in Physiology with Intubation: An International Prospective Observational Study in Patients with Acute Hypoxemic Respiratory Failure Related to COVID-19.

INTRODUCTION: Awake prone positioning has the potential to improve oxygenation and decrease respiratory rate, potentially reducing the need for intubation in patients with acute hypoxemic respiratory failure. We investigated awake prone positioning-induced changes in oxygenation and respiratory rate, and the prognostic capacity for intubation in patients with COVID-19 pneumonia. METHODS: International multicenter prospective observation study in critically ill adult patients with COVID-19 receiving supplemental oxygen. We collected data on oxygenation and respiratory rate at baseline, and at 1 h after being placed in prone positioning. The combined primary outcome was oxygenation and respiratory rate at 1 h. The secondary endpoint was treatment failure, defined as need for intubation within 24 h of start of awake prone positioning. RESULTS: Between March 27th and November 2020, 101 patients were enrolled of which 99 were fully analyzable. Awake prone positioning lasted mean of 3 [2-4] h. In 77 patients (77.7%), awake prone positioning improved oxygenation, and in 37 patients (54.4%) it decreased respiratory rate. Twenty-nine patients (29.3%) were intubated within 24 h. An increase in SpO2/FiO2 of < 10 (OR 5.1, 95% CI 1.4-18.5, P = 0.01), a failure to increase PaO2/FiO2 to > 116 mmHg (OR 3.6, 95% CI 1.2-10.8, P = 0.02), and a decrease in respiratory rate of < 2 breaths/min (OR 3.6, 95% CI 1.3-9.5, P = 0.01) were independent variables associated with need for intubation. The AUC-ROC curve for intubation using a multivariable model was 0.73 (95% CI 0.62-0.84). CONCLUSIONS: Awake prone positioning improves oxygenation in the majority of patients, and decreases respiratory rate in more than half of patients with acute hypoxemic respiratory failure caused by COVID-19. One in three patients need intubation within 24 h. Awake prone position-induced changes in oxygenation and respiratory rate have prognostic capacity for intubation within 24 h.

A pragmatic, open-label, multi-center, randomized controlled clinical trial on the rotational use of interfaces vs standard of care in patients treated with noninvasive positive pressure ventilation for acute hypercapnic respiratory failure: the ROTAtional-USE of interface STUDY (ROTA-USE STUDY).

BACKGROUND: In the last decades, noninvasive ventilation (NIV) has been increasingly used to support patients with hypercapnic and hypoxemic acute respiratory failure. Pressure ulcers are a frequently observed NIV-related adverse effect, directly related to interface type and exposure time. Switching to a different interface has been proposed as a solution to improve patient comfort. However, large studies investigating the benefit of this strategy are not available. Thus, the aim of the ROTAtional-USE of interface STUDY (ROTA-USE STUDY) is to investigate whether a protocolized rotational use of interfaces during NIV is effective in reducing the incidence of pressure ulcers. METHODS: The ROTA-USE STUDY is a pragmatic, parallel arm, open-label, multicenter, spontaneous, non-profit, randomized controlled trial requiring non-significant risk medical devices, with the aim to determine whether a rotational strategy of NIV interfaces is associated with a lower incidence of pressure ulcers compared to the standard of care. In the intervention group, NIV mask will be randomly chosen and rotated every 6 h. In the control group, mask will be chosen according to the standard of care of the participating centers and changed in case of discomfort or in the presence of new pressure sores. In both groups, the skin underneath the mask will be inspected every 12 h for any possible damage by blinded assessors. The primary outcome is the proportion of patients developing new pressure sores at 36 h from randomization. The secondary outcomes are (i) onset of pressure sores measured at different time points, i.e., 12, 24, 36, 48, 60, 72, 84, and 96 h; (ii) number and stage of pressure sores and comfort measured at 12, 24, 36, 48, 60, 72, 84, and 96 h; and (iii) the economic impact of the protocolized rotational use of interfaces. A sample size of 239 subjects per group (intervention and control) is estimated to detect a 10% absolute difference in the proportion of patients developing pressure sores at 36 h. DISCUSSION: The development of pressure ulcers is a common side effect of NIV that negatively affects the patients' comfort and tolerance, often leading to NIV failure and adverse outcomes. The ROTA-USE STUDY will determine whether a protocolized rotational approach can reduce the incidence, number, and severity of pressure ulcers in NIV-treated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05513508. Registered on August 24, 2022.

BL-MOL-AR Project, Preliminary Results about Liquid Biopsy: Molecular Approach Experience and Research Activity in Oncological Settings.

Background Liquid biopsy is mainly used to identify tumor cells in pulmonary neoplasms. It is more often used in research than in clinical practice. The BL-MOL-AR study aims to investigate the efficacy of next-generation sequencing (NGS) and clinical interpretation of the circulating free DNA (cfDNA) levels. This study reports the preliminary results from the first samples analyzed from patients affected by various neoplasms: lung, intestinal, mammary, gastric, biliary, and cutaneous. Methods The Biopsia Liquida-Molecolare-Arezzo study aims to enroll cancer patients affected by various malignancies, including pulmonary, intestinal, advanced urothelial, biliary, breast, cutaneous, and gastric malignancies. Thirty-nine patients were included in this preliminary report. At time zero, a liquid biopsy is executed, and two types of NGS panels are performed, comprising 17 genes in panel 1, which is already used in the routine tissue setting, and 52 genes in panel 2. From the 7th month after enrollment, 10 sequential liquid biopsies are performed up to the 17th month. The variant allele frequency (%) and cfDNA levels (ng/mL) are measured in every plasmatic sample. Results The NGS results obtained by different panels are similar even though the number of mutations is more concordant for lung pathologies. There are no significant differences in the actionability levels of the identified variants. Most of the molecular profiles of liquid biopsies reflect tissue data. Conclusions Preliminary data from this study confirm the need to clarify the limitations and potential of liquid biopsy beyond the lung setting. Overall, parameters related to cfDNA levels and variant allele frequency could provide important indications for prognosis and disease monitoring.

A Strange Case of Traumatic Pleural Effusion: Pleural Empyema Due to Actinomyces meyeri, a Case Report.

BACKGROUND: Actinomycosis by Actinomyces meyeri is rare and scarcely reported in the literature. The lung is the main organ involved. Penicillin and amoxicillin are the first-choice treatments. Surgery is indicated when empyema and abscesses are resistant to medical treatment. CASE PRESENTATION: We report an underdiagnosed case of pleural empyema due to A. meyeri in a patient with closed chest trauma. The patient, a male, 47 years old, presented with a dry cough, thoracic pain, and dyspnea a month after the trauma. A chest X-ray showed a left lower lobe pleural effusion, so he was subjected to a thoracentesis, leading to a partial re-expansion of the left lung. The patient also complained about gum discomfort; thus, a dental x-ray scan was taken, which showed the presence of vertical bone resorption in a periodontal pocket. The patient was treated with levofloxacin 500 mg orally once a day, which was continued for 15 days after discharge. Two months after the accident, he presented again with intermittent fever, a worsening cough, and dyspnea. A CT scan showed thickening of the left pleura and a loculated pleural effusion with partial collapse of the left lower lobe. A decision was made to refer the patient to the Thoracic Unit to undergo surgery via a left thoracoscopic uniportal approach. The lung was thoroughly decorticated, and the purulent fluid was aspirated. The postoperative course was uneventful. Cultures showed the growth of Actinomyces meyeri, which is sensitive to imipenem and amoxicillin. The patient started a proper antibiotic regimen and, whenever possible, was discharged. At 12 months follow-up, a chest X-ray showed a complete resolution of the left pleural effusion with complete re-expansion of the left lung. CONCLUSIONS: Although rare, Actinomycetes infections must be considered especially in front of non-solving empyema or severe pneumonia of unknown cause because in the majority of cases, with the proper treatment, the restitutio ad integrum is possible.

Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline.

This rapid practice guideline provides evidence-based recommendations for the use of awake proning in adult patients with acute hypoxemic respiratory failure due to COVID-19. The panel included 20 experts from 12 countries, including one patient representative, and used a strict conflict of interest policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the guidelines in intensive care, development, and evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation (GRADE) method we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. We conducted an electronic vote, requiring >80% agreement amongst the panel for a recommendation to be adopted. The panel made a strong recommendation for a trial of awake proning in adult patients with COVID-19 related hypoxemic acute respiratory failure who are not invasively ventilated. Awake proning appears to reduce the risk of tracheal intubation, although it may not reduce mortality. The panel judged that most patients would want a trial of awake proning, although this may not be feasible in some patients and some patients may not tolerate it. However, given the high risk of clinical deterioration amongst these patients, awake proning should be conducted in an area where patients can be monitored by staff experienced in rapidly detecting and managing clinical deterioration. This RPG panel recommends a trial of awake prone positioning in patients with acute hypoxemic respiratory failure due to COVID-19.

High-flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxaemia: a randomised controlled trial.

RATIONALE: In patients with COVID-19 pneumonia and mild hypoxaemia, the clinical benefit of high-flow nasal oxygen (HFNO) remains unclear. We aimed to examine whether HFNO compared with conventional oxygen therapy (COT) could prevent escalation of respiratory support in this patient population. METHODS: In this multicentre, randomised, parallel-group, open-label trial, patients with COVID-19 pneumonia and peripheral oxygen saturation (SpO2) ≤92% who required oxygen therapy were randomised to HFNO or COT. The primary outcome was the rate of escalation of respiratory support (ie, continuous positive airway pressure, non-invasive ventilation or invasive mechanical ventilation) within 28 days. Among secondary outcomes, clinical recovery was defined as the improvement in oxygenation (SpO2 ≥96% with fractional inspired oxygen (FiO2) ≤30% or partial pressure of arterial carbon dioxide/FiO2 ratio >300 mm Hg). RESULTS: Among 364 randomised patients, 55 (30.3%) of 181 patients assigned to HFNO and 70 (38.6%) of 181 patients assigned to COT underwent escalation of respiratory support, with no significant difference between groups (absolute risk difference -8.2% (95% CI -18% to +1.4%); RR 0.79 (95% CI 0.59 to 1.05); p=0.09). There was no significant difference in clinical recovery (69.1% vs 60.8%; absolute risk difference 8.2% (95% CI -1.5% to +18.0%), RR 1.14 (95% CI 0.98 to 1.32)), intensive care unit admission (7.7% vs 11.0%, absolute risk difference -3.3% (95% CI -9.3% to +2.6%)), and in hospital length of stay (11 (IQR 8-17) vs 11 (IQR 7-20) days, absolute risk difference -1.0% (95% CI -3.1% to +1.1%)). CONCLUSIONS: Among patients with COVID-19 pneumonia and mild hypoxaemia, the use of HFNO did not significantly reduce the likelihood of escalation of respiratory support. TRIAL REGISTRATION NUMBER: NCT04655638.

Sex differences in excessive oral corticosteroid exposure in poor adherent adult asthmatics overusing short-acting ß-2 agonists.

BACKGROUND: We know that excessive short-acting ß2-agonists (SABA) use in asthma may be associated to high exacerbation risks. We studied whether such excessive SABA consumption is connected with different higher oral corticosteroid (OC) prescriptions in the two sexes. METHODS: In our prescribing database, we searched subjects aged 18-40 years that were prescribed at least one SABA package/year and/or at least two ICS or two ICS/LABA boxes/year to identify asthmatics. Their OC prescriptions/year were also examined. Subjects were divided into 4 groups according to SABA packages/year prescribed (0, 1-2,3-6 and ≥7), considering sexes separately. RESULTS: Individuals recruited were 9,102. Subjects with at least one OC prescription were higher in each group and were females (P<0.001). The OC packages/year number was also more elevated in women especially those with >7 SABA prescriptions/year (0.96 in males vs. 2.64 in females, P<0.001). 94.7%/93.6% males/females, who never used SABA, took at least one ICS/LABA (mean 5.84/5.48 packages/year), while the subject percentage adhering to ICS/LABA dropped to 28-47% (mean 0.94-3.82 packages/year) in those who used SABA (P<0.001). Higher SABA prescriptions were associated with an increasing OC dispensation (ß=0.057, P<0.0001). We observed also a greater risk of using >3 OC packages/year in subjects with 3-6 (OR: 2.98 [95% CI: 2.19-4.06], P<0.001) and ≥7 (OR: 3.49 [95% CI: 2.39-5.10], P<0.001) SABA prescriptions compared to those that never used SABA. Besides, we found that using ICS (OR:0.51 [95% CI: 0.35-0.75], P<0.001) or ICS/LABA (OR:0.07 [95% CI: 0.05-0.09], P<0.001) may significantly reduce SABA prescriptions. CONCLUSIONS: Poor adherence to maintenance treatment appears to associated with excessive SABA prescriptions that may lead to a higher OC consumption particularly noticeable in women.

Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS).

BACKGROUND: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. METHODS: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. RESULTS: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. CONCLUSION: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.

Long-term home noninvasive ventilation (LTHNIV) in restrictive thoracic diseases: the Italian snapshot.

Long-term home noninvasive ventilation (LTHNIV) in restrictive thoracic diseases was explored via the recently published international REINVENT ERS survey. The Italian subset of respondents (ITA-r), the highest above all participating nations, was analyzed and compared to non-Italian respondents (NO-ITA-r). The ITA-r represented 20% of the total answers examined. Ninety-four percent were physicians, whose half worked in a respiratory ICU (RICU). ITA-r mainly worked in community hospitals vs NO-ITA-r who are largely affiliated with university hospitals (p<0.0001). Amyotrophic lateral sclerosis (ALS) was considered the most common medical condition leading to NIV indication by both ITA-r and NO-ITA-r (93% vs 78%, p>0.5). A greater proportion of ITA-r considered MIP/MEP the most important test for NIV initiation as compared to NO-ITA-r (p<0.05). There was no significant difference for both ITA-r and NO-ITA-r as regards the other questions. This study illustrates Italian LTHNIV practices in patients with NMD and it shows some important differences with the other countries' practices but agreement in terms of goals to achieve, reasons to initiate NIV, and practices among the two communities.

A 35-Year-Old Man With Fever, Cough, and Erythematous-Erosive Mucous Membrane Lesions Accompanied by a Generalized Cutaneous Rash.

CASE PRESENTATION: A 35-year-old man presented to the ED with a 7-day history of fever, asthenia, and cough. He had previously received a 3-day course of amoxicillin and clavulanic acid (1 g tid po) and then ceftriaxone (1 g IM once per day) prescribed by his general practitioner with no substantial benefit. He was an active smoker (11.2 pack/y), without known allergy-related syndromes and any important reports in his medical history.

Pulmonologist-Administered Balanced Propofol Analgosedation during Interventional Procedures: An Italian Real-Life Study on Comfort and Safety.

Propofol-based sedation provides faster recovery than midazolam-based regimens with similar safety and comfort during video flexible bronchoscope (VFB) procedures. Pulmonologist-administered propofol "balanced" analgosedation (PAP-BAS) is still debated in Italy. In this real-life study, PAP-BAS safety and comfort during VFB procedures were investigated. We analysed prospectively the subjects undergoing elective VFB procedures in the Pulmonology and RICU of Arezzo Hospital between February and July 2019. PAP-BAS combined low propofol and meperidine doses titrated to achieve an RASS score between 0 and -3. The primary end-point was the complications' rate. Secondary end-points were as follows: the relation between propofol's dose and a subject's comfort assessed with a VAS, recovery time according to a modified Aldrete score ≥9, RASS, and subjects' will of undergoing the procedure again. We collected postprocedure symptoms' intensity too. Our 158 study patients (67 years; SD ± 14; 64% males) incurred in 25% of complication, fully resolved with medical therapy. Neither recourse to ventilator support nor death was reported. Intraprocedural comfort was good (94% of VAS score ≤2). Among postprocedural symptoms, cough was the most frequently reported, in 36% of the cases. Although half of subjects remembered the procedure, 90% of them would have repeated it, if necessary. 85% of them recovered from procedures within 10 minutes. Complications, VAS, and recovery time were not correlated with propofol dose. To our knowledge, this is the first Italian study showing that PAP-BAS to perform a VFB procedure is safe, well tolerated with a quick recovery. Randomised controlled trials are warranted to confirm these preliminary results.

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial.

RATIONALE: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus disease 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with COVID-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for three consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need for supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. RESULTS: Overall, 112 (75.4%) out of 151 patients in the pulse methylprednisolone arm and 111 (75.2%) of 150 in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups (15 days, 95% CI 13.0-17.0 days and 16 days, 95% CI 13.8-18.2 days, respectively; hazard ratio (HR) 0.92, 95% CI 0.71-1.20; p=0.528). No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to intensive care unit with orotracheal intubation or death (20.0% versus 16.1%; HR 1.26, 95% CI 0.74-2.16; p=0.176) or overall mortality (10.0% versus 12.2%; HR 0.83, 95% CI 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. CONCLUSIONS: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia.

The Italian Version of the Severe Respiratory Insufficiency Questionnaire.

BACKGROUND: The Severe Respiratory Insufficiency Questionnaire (SRI) is a multidimensional instrument for health-related quality of life (HRQL) assessment in patients with chronic respiratory failure (CRF). The SRI has originally been developed in German in 2003, but 15 translated versions have been created during the last 18 years with the exclusion of the Italian translation. AIMS OF THE STUDY: The present project was aimed at creating an Italian version of the SRI. METHODS: Professional forward-translation and back-translation procedures have been provided based on the original German version by independent translators, and this was followed by final reconciliation. RESULTS: The Italian SRI contains 49 items covering 7 different subscales which can summarize to one Summary Score. CONCLUSIONS: The Italian SRI is a multidimensional instrument, which can be used for HRQL assessment in Italian-speaking patients with CRF. Validation of the Italian version of the questionnaire is formally required in the future.

The role of Monocyte Distribution Width (MDW) in the prognosis and monitoring of COVID-19 patients.

The new parameter derived from the standard deviation of the monocyte distribution width (MDW) has shown a good diagnostic efficacy in COVID-19 patients. In this study, we propose MDW as a prognostic and monitoring parameter in patients with severe forms of COVID-19. Sixty SARS-CoV-2-positive patients admitted to the San Donato Hospital in Arezzo were enrolled. A blood sample taken to measure the complete blood count was used for the determination of MDW using a UniCel DxH 900 instrument (Beckman Coulter). For each patient, a mean of 6 ± 2 measurements of MDW were taken. The difference between the last and first MDW results was reported as the ΔMDW variable. The ΔMDW and age were significantly correlated to the outcome. In non-survivors patients, the difference in the mean of the MDW between the first and other points was not significant, while in survivors, the first point was higher than the other points (p < 0.005), with the exception of the mean of the second point (p-value = NS). The ΔMDW area under the curve (AUC) was 0.84, and with a cut-off lower than 0.00 the sensitivity and specificity were 88% and 81%, respectively. The most important result of this study is the ΔMDW calculated on the basis of the difference between the first and third measurement, after approximately the 5-7th day of hospitalisation. A ΔMDW less than one was indicative of an unfavourable prognosis. The data reported suggest that MDW could be used to support monitoring and surveillance, alongside other tests such as procalcitonin, in critically ill patients in the ICU.

Post-tracheostomy complications: respiratory failure caused by authologic foreign body-case report.

Tracheostomy is performed frequently as a palliative treatment in patients with end-stage respiratory failure (RF). However, in patients requiring prolonged mechanical ventilation it may be difficult to recognize and can often lead to life-threatening RF. We present two cases of acute-on-chronic respiratory failure (ACRF) occurring in patients who had undergone tracheostomy [one with percutaneous dilatational tracheostomy (PDT) and the second with surgical tracheostomy (ST)]. The first case was admitted due to ACRF several months after previous successful decannulation and the second case after failure of several attempts of weaning from tracheal cannula. In both cases, noninvasive mechanical ventilation assisted flexible bronchoscopy (NIV-FB) was able to identify and solve the tracheal stenosis secondary to stiff banana-shaped whitish foreign bodies. Histology sampling and genetic testing confirmed autologous foreign body formation-tracheal cartilage calcification. NIV-FB was found to be safe and effective in both diagnosis and treatment of the tracheal stenosis. Life-threatening RF connected with tracheal stenosis may be caused by rupture of tracheal cartilage ossification in patients with a history of ST and PDT. Bronchofiberoscopy performed with NIV will be a useful procedure to evaluate and treat the respiratory tract in patients with RF with suspected tracheal stenosis.

ERS clinical practice guidelines: high-flow nasal cannula in acute respiratory failure.

BACKGROUND: High-flow nasal cannula (HFNC) has become a frequently used noninvasive form of respiratory support in acute settings; however, evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF). MATERIALS AND METHODOLOGY: The European Respiratory Society task force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The task force used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and noninvasive ventilation (NIV) for the management of adults in acute settings with ARF. RESULTS: The task force developed eight conditional recommendations, suggesting the use of 1) HFNC over COT in hypoxaemic ARF; 2) HFNC over NIV in hypoxaemic ARF; 3) HFNC over COT during breaks from NIV; 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications; 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications; 6) HFNC over COT in nonsurgical patients at low risk of extubation failure; 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV; and 8) trialling NIV prior to use of HFNC in patients with COPD and hypercapnic ARF. CONCLUSIONS: HFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of noninvasive respiratory support to provide to patients in different acute settings.