A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Assessment of cephalometric parameters and correlation with the severity of the obstructive sleep apnea syndrome.

BACKGROUND: In individuals diagnosed with obstructive sleep apnea syndrome (OSAS), variations in craniofacial structure have been inconsistently documented, showing differing degrees of alteration between obese and nonobese patients. In addition, sleep disturbance has also been shown to induce disequilibrium in this population of patients. This pilot observational study aimed to assess craniofacial values in obese and nonobese subpopulations of patients with OSAS and their correlation and association with the severity of OSAS. We also assessed whether OSAS patients are characterized by an impaired equilibrium in relation to and associated with the severity of OSAS. METHODS: We included all consecutive adult patients with OSAS. Through cephalometry, we assessed the upper (UPa-UPp) and lower (LPa-LPp) pharynx diameters, superior anterior facial height (Sor-ANS), anterior facial height (ANS-Me), anterior vertical dimension (Sor-Me), posterior facial height (S-Go) and craniovertebral angle (CVA). Furthermore, we analyzed postural equilibrium through a stabilometric examination. RESULTS: Forty consecutive OSAS patients (45% female with a mean age of 56 ± 8.2 years) were included. The subgroup of nonobese patients had a reduced UPa-UPp (p = 0.02). Cephalometric measurements were correlated with the severity of OSAS in nonobese patients, whereas only Sor-ANS was correlated with the severity of OSAS in the obese subpopulation. In the overall population, altered craniofacial values are associated with severe OSAS. Although there are differences in equilibrium between obese and nonobese OSAS patients, the stabilometric measurements were not correlated or associated with OSAS severity. CONCLUSION: Altered craniofacial values and compromised equilibrium in OSAS patients are linked to OSAS severity. Therefore, the management of OSAS should be tailored not only to weight management but also to craniofacial and postural rehabilitation to enhance patient outcomes.

Persistence of SARS-CoV-2 infection and viral intra- and inter-host evolution in COVID-19 hospitalized patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) persistence in COVID-19 patients could play a key role in the emergence of variants of concern. The rapid intra-host evolution of SARS-CoV-2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID-19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID-19 patients with persistent SARS-CoV-2 infection, from January 2022 to March 2023, was conducted. To characterize the intra- and inter-host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS-CoV-2 intra-host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host-based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro-active genomic surveillance of persistent SARS-CoV-2 infected patients is recommended to identify genetically divergent lineages before their diffusion.

Retrospective ANalysis of multi-drug resistant Gram-nEgative bacteRia on veno-venous extracorporeal membrane oxygenation. The multicenter RANGER STUDY.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no mention of microbiological history, especially related to multi-drug resistant (MDR) bacteria isolated before V-V ECMO placement. Our study aims to investigate: (i) the prevalence and incidence of MDR Gram-negative (GN) bacteria in a cohort of V-V ECMOs; (ii) the risk of 1-year mortality, especially in the case of predetected MDR GN bacteria; and (iii) the impact of annual hospital V-V ECMO volume on the probability of acquiring MDR GN bacteria. METHODS: All consecutive adults admitted to the Intensive Care Units of 5 Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records, survival < 24 h after V-V ECMO. A standard protocol of microbiological surveillance was applied and MDR profiles were identified using in vitro susceptibility tests. Cox-proportional hazards models were applied for investigating mortality. RESULTS: Two hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall MDR GN bacteria percentage was 50%: 21% (n.59) detected before and 29% (n.80) after V-V ECMO placement. The overall 1-year mortality was 42%, with a higher risk observed in predetected patients (aHR 2.14 [1.33-3.47], p value 0.002), while not in 'V-V ECMO-acquired MDR GN bacteria' group (aHR 1.51 [0.94-2.42], p value 0.090), as compared to 'non-MDR GN bacteria' group (reference). Same findings were found considering only infections. A larger annual hospital V-V ECMO volume was associated with a lower probability of acquiring MDR GN bacteria during V-V ECMO course (aOR 0.91 [0.86-0.97], p value 0.002). CONCLUSIONS: 21% of MDR GN bacteria were detected before; while 29% after V-V ECMO connection. A history of MDR GN bacteria, isolated before V-V ECMO, was an independent risk factor for mortality. The annual hospital V-V ECMO volume affected the probability of acquiring MDR GN bacteria. Trial Registration ClinicalTrial.gov Registration Number NCTNCT06199141, date 12.26.2023.

Benefits of secretion clearance with high frequency percussive ventilation in tracheostomized critically ill patients: a pilot study.

Clearance of secretions remains a challenge in ventilated patients. Despite high-frequency percussive ventilation (HFPV) showing benefits in patients with cystic fibrosis and neuromuscular disorders, very little is known about its effects on other patient categories. Therefore, we designed a physiological pilot study investigating the effects on lung aeration and gas exchange of short HFPV cycles in tracheostomized patients undergoing mechanical ventilation. Electrical impedance tomography (EIT) was recorded at baseline (T0) by a belt wrapped around the patient's chest, followed by the HFPV cycle lasting 10 min. EIT data was collected again after the HFPV cycle (T1) as well as after 1 h (T2) and 3 h (T3) from T0. Variation from baseline of end-expiratory lung impedance (∆EELI), tidal variation (TIV) and global inhomogeneity index (GI) were computed. Arterial blood was also taken for gas analysis. HFPV cycle significantly improved the ∆EELI at T1, T2 and T3 when compared to baseline (p < 0.05 for all comparisons). The ratio between arterial partial pressure and inspired fraction of oxygen (PaO2/FiO2) also increased after the treatment (p < 0.001 for all comparison) whereas TIV (p = 0.132) and GI (p = 0.114) remained unchanged. Short cycles of HFPV superimposed to mechanical ventilation promoted alveolar recruitment, as suggested by improved ∆EELI, and improved oxygenation in tracheostomized patients with high load of secretion.Trial Registration Prospectively registered on www.clinicaltrials.gov (NCT05200507; dated 6th January 2022).

High-flow nasal cannula oxygen therapy for outpatients undergoing flexible bronchoscopy: a randomised controlled trial.

INTRODUCTION: High-flow nasal cannula (HFNC) provides benefits to patients undergoing flexible bronchoscopy (FOB). We compared the effects of HFNC versus standard therapy (ST) on gas exchange, lung volume and diaphragm function in patients undergoing FOB for bronchoalveolar lavage (BAL). METHODS: 36 outpatients were randomised to ST or HFNC. Arterial blood gases, episodes of severe desaturation, changes of end-expiratory lung impedance (ΔEELI), diaphragm ultrasound were recorded. Measurements were done at baseline (T0), after bronchoscope insertion (T1), at the end of the procedure (T2) and 10 min afterwards (T3). RESULTS: Arterial partial oxygen pressure (PaO2) was not different between T0 (10.8 (95% CI 8.7 to 12.0) kPa and T2 (11.1 (95% CI 10.4 to 12.0) kPa) with HFNC, while decreased from 11.1 (95% CI 10.5 to 12.1) to 9.1 (95% CI 8.4 to 9.8) kPa with ST. At T2, PaO2 was significantly higher with HFNC than with ST (p<0.001). Also, with HFNC, compared with ST, fewer desaturations occurred (11% vs 56%; p<0.01). ΔEELI was no different at the different time points with HFNC, while with ST there was a significant decrease at T1 (-170 (95% CI -382 to -32) mL, p=0.003), T2 (-211 (95% CI -425 to -148) mL, p<0.001) and T3 (-213 (95% CI -398 to -81) mL, p<0.001), as opposed to T0. EELI was lower with ST than HFNC at T1 (p=0.006), T2 (p=0.001) and T3 (p=0.002). Diaphragm displacement was no different between groups (p=0.748), while the thickening fraction significantly increased at T1 and T2 with ST only (p<0.01). CONCLUSIONS: During FOB for BAL, HFNC improves gas exchange, avoiding loss of end-expiratory lung volume and preventing increase of diaphragm activation. TRIAL REGISTRATION NUMBER: NCT04016480.

Inappropriate Citation of Retracted Articles in Anesthesiology and Intensive Care Medicine Publications.

BACKGROUND: Retracted articles represent research withdrawn from the existing body of literature after publication. Research articles may be retracted for several reasons ranging from honest errors to intentional misconduct. They should not be used as reliable sources, and it is unclear why they are cited occasionally by other articles. This study hypothesized that several mechanisms may contribute to citing retracted literature and aimed to analyze the characteristics of articles citing retracted literature in anesthesiology and critical care. METHODS: Using the Retraction Watch database, we retrieved retracted articles on anesthesiology and intensive care medicine up to August 16, 2021, and identified the papers citing these retracted articles. A survey designed to investigate the reasons for citing these articles was sent to the corresponding authors of the citing papers. RESULTS: We identified 478 retracted articles, 220 (46%) of which were cited at least once. We contacted 1297 corresponding authors of the papers that cited these articles, 417 (30%) of whom responded to our survey and were included in the final analysis. The median number of authors in the analyzed articles was five, and the median elapsed time from retraction to citation was 3 yr. Most of the corresponding authors (372, 89%) were unaware of the retracted status of the cited article, mainly because of inadequate notification of the retraction status in journals and/or databases and the use of stored copies. CONCLUSIONS: The corresponding authors were generally unaware of the retraction of the cited article, usually because of inadequate identification of the retracted status in journals and/or web databases and the use of stored copies. Awareness of this phenomenon and rigorous control of the cited references before submitting a paper are of fundamental importance in research.

Role of the T2Dx magnetic resonance assay in patients with suspected bloodstream infection: a single-centre real-world experience.

BACKGROUND: T2Dx was approved by the US Food and Drug Administration for the rapid detection of a modified panel of ESKAPE bacterial species or Candida spp. causing bloodstream infection (BSI). PATIENTS AND METHODS: We performed a retrospective, observational study from January 1, 2018 to December 31, 2019 of all hospitalised patients with suspected BSI who underwent assessment using T2Dx in addition to standard blood culture (BC). T2-positive patients (cases) were compared to a matched group of patients with BSI documented only by BC (1:2 ratio) to investigate the possible impact of T2Dx on the appropriateness of empirical antimicrobial therapy and 21-day mortality. RESULTS: In total, 78 T2Dx-analysed samples (49 patients) were analysed. The T2Dx assay result was positive for18 patients and negative for 31 patients. The concordance rates of the T2Bacteria Panel and T2Candida Panel results with those of standard BC were 74.4% and 91.4%, respectively. In the matched analysis, inappropriate empiric antimicrobial therapy administration was significantly less frequent in cases than in comparators (5.5% vs. 38.8%). The 21-day mortality rate was twofold lower in cases than in comparators (22.2% vs. 44.4%), although the difference was not significant. No other analysed variables were significantly different between the two groups. CONCLUSIONS: This study illustrated that T2Dx might be associated with an increase in the appropriateness of empiric antimicrobial therapy in patients with BSI. Further studies are needed to evaluate whether the T2Dx assay can improve patient outcomes.

Platelet aggregometry for hip fracture surgery in patients treated with clopidogrel: a pilot study.

Surgery for hip fractures should be performed within 48 h from patient's admission. However, several factors including chronic antiplatelet therapy could delay operation. Among the totality of patients taking clopidogrel, up to 30% are resistant to the drug and have a normal platelets reactivity. We propose thromboelastography (TEG) with an ADP Platelet Mapping assay kit to assess platelet aggregation, a safe tool that could help to avoid surgery delay in those patients treated with antiplatelet therapy. A patient's blood sample was collected for aggregometry. If MA-ADP and platelets aggregation (%) were within normal values, the patient was fit for immediate surgery with neuraxial anesthesia and ultrasound-guided nerve block. If one of the two parameters or both were deranged, a mortality risk assessment was estimated. In the low risk category, the patients waited till normalization of the parameters, whereas in the high-risk group a general anesthesia and peripheral antalgic block was carried out. Nine patients were enrolled. Four of them showed normal aggregometry and surgery was performed within 24 h from admission. Two patients were classified as high mortality risk and surgery was carried out under general anesthesia. Three patients awaited operation till normalization of parameters. No peri or post-operative complications were reported. An aggregometry-guided protocol can safely expedite hip fracture surgery in patients taking clopidogrel. Nonetheless, in presence of a normal platelets function, clinician can opt for a neuraxial instead of general anesthesia reducing the incidence of postoperative delirium and cognitive dysfunction.Trial registration: prospectively registered at clinicaltrials.gov (NCT04642209; date of registration: 23rd November 2020).

Oxygenation strategies during flexible bronchoscopy: a review of the literature.

During flexible fiberoptic bronchoscopy (FOB) the arterial partial pressure of oxygen can drop, increasing the risk for respiratory failure. To avoid desaturation episodes during the procedure several oxygenation strategies have been proposed, including conventional oxygen therapy (COT), high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV). By a review of the current literature, we merely describe the clinical practice of oxygen therapies during FOB. We also conducted a pooled data analysis with respect to oxygenation outcomes, comparing HFNC with COT and NIV, separately. COT showed its benefits in patients undergoing FOB for broncho-alveolar lavage (BAL) or brushing for cytology, in those with peripheral arterial oxyhemoglobin saturation < 93% prior to the procedure or affected by obstructive disorder. HFNC is preferable over COT in patients with mild to moderate acute respiratory failure (ARF) undergoing FOB, by improving oxygen saturation and decreasing the episodes of desaturation. On the opposite, CPAP and NIV guarantee improved oxygenation outcomes as compared to HFNC, and they should be preferred in patients with more severe hypoxemic ARF during FOB.

Respiratory Drive in Patients with Sepsis and Septic Shock: Modulation by High-flow Nasal Cannula.

BACKGROUND: Experimental and pilot clinical data suggest that spontaneously breathing patients with sepsis and septic shock may present increased respiratory drive and effort, even in the absence of pulmonary infection. The study hypothesis was that respiratory drive and effort may be increased in septic patients and correlated with extrapulmonary determinant and that high-flow nasal cannula may modulate drive and effort. METHODS: Twenty-five nonintubated patients with extrapulmonary sepsis or septic shock were enrolled. Each patient underwent three consecutive steps: low-flow oxygen at baseline, high-flow nasal cannula, and then low-flow oxygen again. Arterial blood gases, esophageal pressure, and electrical impedance tomography data were recorded toward the end of each step. Respiratory effort was measured as the negative swing of esophageal pressure (ΔPes); drive was quantified as the change in esophageal pressure during the first 500 ms from start of inspiration (P0.5). Dynamic lung compliance was calculated as the tidal volume measured by electrical impedance tomography, divided by ΔPes. The results are presented as medians [25th to 75th percentile]. RESULTS: Thirteen patients (52%) were in septic shock. The Sequential Organ Failure Assessment score was 5 [4 to 9]. During low-flow oxygen at baseline, respiratory drive and effort were elevated and significantly correlated with arterial lactate (r = 0.46, P = 0.034) and inversely with dynamic lung compliance (r = -0.735, P < 0.001). Noninvasive support by high-flow nasal cannula induced a significant decrease of respiratory drive (P0.5: 6.0 [4.4 to 9.0] vs. 4.3 [3.5 to 6.6] vs. 6.6 [4.9 to 10.7] cm H2O, P < 0.001) and effort (ΔPes: 8.0 [6.0 to 11.5] vs. 5.5 [4.5 to 8.0] vs. 7.5 [6.0 to 12.6] cm H2O, P < 0.001). Oxygenation and arterial carbon dioxide levels remained stable during all study phases. CONCLUSIONS: Patients with sepsis and septic shock of extrapulmonary origin present elevated respiratory drive and effort, which can be effectively reduced by high-flow nasal cannula.

Low-Dose of Rocuronium During Thyroid Surgery: Effects on Intraoperative Nerve-Monitoring and Intubation.

BACKGROUND: Intraoperative Neurophysiological Monitoring (IONM) reduces the incidence of Recurrent Laryngeal Nerve (RLN) injuries during thyroid surgery. To preserve nerve function, long acting neuromuscular blocking agents (NMBA) should be avoided. However, NMBA are necessary for laryngoscopy and endotracheal intubation. We designed this double-blinded, randomized, placebo-controlled trial to assess if a low-dose of rocuronium given at intubation would affect the IONM data recorded before the thyroid dissection. METHODS: Hundred patients undergoing elective thyroid surgery were randomized to receive either 0.3 mg kg-1 of low dose rocuronium (intervention) or no-NMBA (control). Intubation was performed with video-laryngoscopy. IONM was placed on RLN and nerve stimulation was performed before and after thyroid dissection. The presence of a valid amplitude prior to dissection was defined when the IONM signal was >100 µV. Occurrence of difficult laryngoscopy was reported together with intubation details including time, difficulty and failure. The lowest peripheral saturation (SpO2) and the number of desaturation episodes during the intubation were also registered. RESULTS: No patients showed impaired IONM signal before dissection in both groups. Cormack-Lehane grade was higher in the intervention group (11;2) compared to control one (11;1; P = 0.046). No-NMBA patients had increased number of difficult laryngoscopies (21% versus 6%, P = 0.041) and intubations (34% versus 8%; P = 0.003) as well as a longer time to intubation (78 [55; 175] versus 55 [31; 110] sec; P = 0.006). Lower values of peripheral SpO2 during intubation attempt were registered in the no NMBA group (99 [97; 100] versus 99 [99; 100] %; P = 0.020). However, the number of intubation failure was similar between groups (p=0.495). CONCLUSIONS: Low-dose of rocuronium does not compromise pre-dissection IONM signal and improves intubation condition when compared to a relaxant free strategy.

Intraoperative protective ventilation in patients undergoing major neurosurgical interventions: a randomized clinical trial.

BACKGROUND: Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. METHODS: This single-centre, pilot randomized clinical trial was conducted at the University Hospital "Maggiore della Carità" (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6-8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. RESULTS: A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. CONCLUSIONS: LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. TRIAL REGISTRATION: registered on the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ), registration number ACTRN12615000707561.

Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence.

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab's therapeutic effects in patients with life-threatening SARS-CoV-2 infection.

New treatments for asthma: From the pathogenic role of prostaglandin D2 to the therapeutic effects of fevipiprant.

Prostaglandin D2 (PGD2) is a pleiotropic mediator, significantly involved in the pathogenesis of type 2 (T2) asthma because of its biologic actions exerted on both immune/inflammatory and airway structural cells. In particular, the pro-inflammatory and pro-remodelling effects of PGD2 are mainly mediated by stimulation of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). This receptor is the target of the oral competitive antagonist fevipiprant, which on the basis of recent phase II studies is emerging as a potential very promising anti-asthma drug. Indeed, fevipiprant appears to be safe and effective, especially in consideration of its ability to inhibit eosinophilic bronchial inflammation and improve forced expiratory volume in one second (FEV1). Further ongoing phase III trials will definitely clarify if fevipiprant can prospectively become a valid option for an efficacious add-on treatment of moderate-to-severe T2-high asthma.

Chest physiotherapy improves lung aeration in hypersecretive critically ill patients: a pilot randomized physiological study.

BACKGROUND: Besides airway suctioning, patients undergoing invasive mechanical ventilation (iMV) benefit of different combinations of chest physiotherapy techniques, to improve mucus removal. To date, little is known about the clearance effects of oscillating devices on patients with acute respiratory failure undergoing iMV. This study aimed to assess (1) the effects of high-frequency chest wall oscillation (HFCWO) on lung aeration and ventilation distribution, as assessed by electrical impedance tomography (EIT), and (2) the effect of the association of HFCWO with recruitment manoeuvres (RM). METHODS: Sixty critically ill patients, 30 classified as normosecretive and 30 as hypersecretive, who received ≥ 48 h of iMV, underwent HFCWO; patients from both subgroups were randomized to receive RM or not, according to two separated randomization sequences. We therefore obtained four arms of 15 patients each. After baseline record (T0), HFCWO was applied for 10 min. At the end of the treatment (T1) or after 1 (T2) and 3 h (T3), EIT data were recorded. At the beginning of each step, closed tracheobronchial suctioning was performed. In the RM subgroup, tracheobronchial suctioning was followed by application of 30 cmH2O to the patient's airway for 30 s. At each step, we assessed the change in end-expiratory lung impedance (ΔEELI) and in tidal impedance variation (ΔTIV), and the center of gravity (COG) through EIT. We also analysed arterial blood gases (ABGs). RESULTS: ΔTIV and COG did not differ between normosecretive and hypersecretive patients. Compared to T0, ΔEELI significantly increased in hypersecretive patients at T2 and T3, irrespective of the RM; on the contrary, no differences were observed in normosecretive patients. No differences of ABGs were recorded. CONCLUSIONS: In hypersecretive patients, HFCWO significantly improved aeration of the dorsal lung region, without affecting ABGs. The application of RM did not provide any further improvements. TRIAL REGISTRATION: Prospectively registered at the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ; number of registration: ACTRN12615001257550; date of registration: 17th November 2015).

High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial.

BACKGROUND: The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO2 clearance after 2 h of treatment. METHODS: We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25-7.35, PaCO2 ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. RESULTS: Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO2 reduction from baseline to 2 h were - 6.8 mmHg (± 8.7) in the HFNT and - 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. CONCLUSIONS: HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. TRIAL REGISTRATION: The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

Diaphragmatic Dysfunction After Elective Cardiac Surgery: A Prospective Observational Study.

OBJECTIVES: To determine the incidence of postoperative diaphragm dysfunction as diagnosed by ultrasonography. DESIGN: Explorative prospective observational study. SETTING: University intensive care unit. PARTICIPANTS: One hundred consecutive patients undergoing elective cardiac surgery. INTERVENTIONS: Diaphragm ultrasound was performed the day before surgery during unassisted breath (D-1), at the first spontaneous breathing trial attempt (DSBT), 24 hours after surgery (D+1), and at intensive care unit (ICU) discharge (DICU). Diaphragm displacement, inspiratory and expiratory thickness, and the thickening fraction were measured at all timepoints. MEASUREMENTS AND MAIN RESULTS: Primary outcome was assessing the rate of postoperative diaphragm dysfunction, defined as a thickening fraction <20% at DSBT. Secondary outcomes were the number of difficult-to-wean patients, the need for rescue noninvasive ventilation, the reintubation rate, and the ICU length of stay. Thirty-eight patients showed diaphragm dysfunction at DSBT, which resolved over time. No differences in preoperative characteristics and comorbidities were found between patients who developed postoperative diaphragm dysfunction and patients without postoperative disorders. The duration of cardiopulmonary bypass (103 ± 34 v 55 ± 34 min; P < 0.001) was significantly associated with the development of postoperative diaphragm dysfunction. When compared with patients without postoperative diaphragm disorders, patients with diaphragm dysfunction were characterized by a higher rate of difficult weaning (32% v 5%; P < 0.001), lower extubation rate at 24 hours after surgery (50% v 92%; P < 0.001), and longer ICU length of stay (19 [16; 88] v 16 [15; 18] hours; P < 0.001). CONCLUSIONS: The incidence of postoperative diaphragm dysfunction after elective cardiac surgery is high and might contribute to prolonging ICU length of stay.

Effects of listening to music in digestive endoscopy: A prospective intervention study led by nursing.

AIMS: To explore whether music can reduce anxiety and pain in patients who underwent diagnostic endoscopic examinations in conscious and deep sedation and to assess degree of satisfaction and willingness to repeat the procedure. DESIGN: Prospective study led by nursing. METHODS: Between March 2019-June 2019, consecutive outpatients undergoing endoscopic examinations were simple matched into four groups: Group 1: conscious sedation with music; Group 2: conscious sedation without music; Group 3: deep sedation with music and Group 4: deep sedation without music. Ten minutes before the procedure, two trainee nurses applied music. State-Trait Anxiety Inventory was used to evaluate anxiety. RESULTS: Before and at the end of the procedure, patients who listened to music had a lower level anxiety than those who did not listen and, also, reported lower pain intensity during procedure. Only within Group 1 median anxiety, measured after the procedure, is lower than that measured before. In the bivariate logistic regression model, pain and listening to music were independent factors for satisfaction and willingness to repeat procedure. CONCLUSION: music in digestive endoscopy reduce pain and anxiety in conscious sedation, thus could be used to reduce anxiety in support to conscious sedation leading to lower usage of deep sedation and consequently reduction of costs and adverse events. IMPACT: Anxiety in digestive endoscopy limits patients' satisfaction. Music in digestive endoscopy as a specific nursing intervention could reduce anxiety of patients. This nursing intervention study confirms positive effect of music in digestive endoscopy. As part of nursing management, the addition of music to daily care practice in digestive endoscopy may reduce anxiety and increase the patient's degree of satisfaction. Use of music could limit deep sedation use in digestive endoscopy with consequent reduction of risks for patients, execution times, and costs of procedures.

Oesophageal balloon calibration during pressure support ventilation: a proof of concept study.

Oesophageal balloon calibration improves the oesophageal pressure (Pes) assessment during invasive controlled mechanical ventilation. The primary aim of the present investigation was to ascertain the feasibility of oesophageal balloon calibration during pressure support ventilation (PSV). Secondarily, the calibrated Pes (Pescal) was compared to uncalibrated one acquired at 4 ml-filling volume (PesV4), as per manufacturer recommendation. After a naso-gastric tube equipped with oesophageal balloon was correctly positioned in 21 adult patients undergoing invasive volume-controlled ventilation (VCV) for acute hypoxemic respiratory failure, the balloon was progressively inflated, applying a series of end-inspiratory and end-expiratory holds at each filling volume during VCV and PSV. Upon optimal balloon filling volume (Vbest) was identified, Pescal was computed by correcting the Pes measured at Vbest for the oesophageal wall pressure elicited at same filling volume. Finally, end-expiratory and end-inspiratory PesV4 were recorded too. A total of 42 calibrations, 21 per ventilatory mode, were performed. Vbest was 1.9 ± 1.6 ml in VCV and 1.7 ± 1.6 ml in PSV (p = 0.5217). PesV4 was overestimated compared to Pescal at end-expiration and end-inspiration (p <0.0001 for all comparisons) in both VCV (13.4 ± 3.4 cmH2O and 15.4 ± 3 cmH2O vs. 8.5 ± 2.9 cmH2O and 11.4 ± 3 cmH2O) and PSV (14.7 ± 4.2 cmH2O and 17 ± 3.9 cmH2O vs. 8.9 ± 3.4 cmH2O and 12.4 ± 3.9 cmH2O). In PSV, oesophageal balloon calibration is feasible and allows to obtain a reliable Pes assessment compared to uncalibrated approach.