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Clinical trials and observational studies have established cyclophosphamide (CY) or rituximab plus glucocorticoid (GC) as standard remission induction therapies in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, because these regimens are associated with serious adverse drug reactions, the development of drugs with novel mechanisms of actions are needed. Progress in basic and clinical research has identified novel candidate targeting molecules, including B-cell activating factor (BAF), C5a receptor, and interleukin-6. The combination of rituximab and BAF blockade in patients with MPA and GPA is under investigation in an effort to strike a better benefit-risk balance. Phase II clinical trials of avacopan (CCX168), an orally administered C5a receptor antagonist, have suggested a reduction in the dosage of concomitant GC or the replacement of GC in patients with MPA and GPA. The results from a currently ongoing phase III trial are awaited. Anecdotal case reports and an open-label pilot study have indicated the effectiveness of tocilizumab in patients with MPA and GPA. A randomized clinical trial comparing tocilizumab and intravenous CY in combination with GC is currently in progress. Molecular targeted therapy is expected to transform the treatment strategy for MPA and GPA to allow GC-free or at least less GC-dependent forms of therapy.

Smoking in young adulthood is a risk factor for future health-related disabilities and a cause of expanding health inequalities. Education and smoking are inversely associated. Using population-based representative data, this study aimed to clarify how the presence of household smokers during childhood related to both current smoking status and educational attainment among young adults. Surveys were distributed to young adults (19–20 years) invited to coming-of-age ceremonies in 2014–2017 in a rural area in Japan. Data were collected on low educational attainment (defined as ≤ 12 years of education), current smoking status, and childhood household smoking status. We used logistic regression models to calculate odds ratios (ORs) of low educational attainment for household smoking status. A total of 17.6% of men (n = 1077) and 3.8% of women (n = 1021) were current smokers. Current smoking was more common among participants from households with smokers (P

Hybrid Assistive Neuromuscular Dynamic Stimulation (HANDS) therapy is one of the neurorehabilitation therapeutic approaches that facilitates the use of the paretic upper extremity (UE) in daily life by combining closed-loop electromyography- (EMG-) controlled neuromuscular electrical stimulation (NMES) with a wrist-hand splint. This closed-loop EMG-controlled NMES can change its stimulation intensity in direct proportion to the changes in voluntary generated EMG amplitudes recorded with surface electrodes placed on the target muscle. The stimulation was applied to the paretic finger extensors. Patients wore a wrist-hand splint and carried a portable stimulator in an arm holder for 8 hours during the daytime. The system was active for 8 hours, and patients were instructed to use their paretic hand as much as possible. HANDS therapy was conducted for 3 weeks. The patients were also instructed to practice bimanual activities in their daily lives. Paretic upper extremity motor function improved after 3 weeks of HANDS therapy. Functional improvement of upper extremity motor function and spasticity with HANDS therapy is based on the disinhibition of the affected hemisphere and modulation of reciprocal inhibition. HANDS therapy may offer a promising option for the management of the paretic UE in patients with stroke.

BACKGROUND: Many genome-wide association studies pointed out that SLC2A9 gene, which encodes a voltage-driven urate transporter, SLC2A9/GLUT9 (a.k.a. URATv1), as one of the most influential genes for serum urate levels. SLC2A9 is reported to encode two splice variants: SLC2A9-S (512 amino acids) and SLC2A9-L (540 amino acids), only difference being at their N-termini. We investigated isoform-specific localization of SLC2A9 in the human kidney and role of N-terminal amino acids in differential sorting in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Isoform specific antibodies against SLC2A9 were developed and human kidney sections were stained. SLC2A9-S was expressed in the apical side of the collecting duct while SLC2A9-L was expressed in the basolateral side of the proximal tubule. GFP fused SLC2A9s were expressed in MDCK cells and intracellular localization was observed. SLC2A9-S was expressed at both apical and basolateral membranes, whereas SLC2A9-L was expressed only at the basolateral membrane. Although SLC2A9-L has a putative di-leucine motif at 33th and 34th leucine, deletion of the motif or replacement of leucine did not affect its subcellular localization. When up to 16 amino acids were removed from the N-terminal of SLC2A9-S or when up to 25 amino acids were removed from the N-terminal of SLC2A9-L, there was no change in their sorting. Deletion of 20 amino acids from SLC2A9-S was not expressed in the cell. More than 30 amino acids deletion from SLC2A9-L resulted in expression at both apical and basolateral membranes as well as in the lysosome. When amino acids from 25th and 30th were changed to alanine in SLC2A9-L, expression pattern was the same as wild-type. CONCLUSIONS/SIGNIFICANCE: SLC2A9-L was expressed in the basolateral membrane of kidney proximal tubules in humans and this isoform is likely to responsible for urate reabsorption. N-terminal amino acids unique to each isoform played an important role in protein stability and trafficking.

Acute hypercapnic respiratory failure is a life-threatening condition caused by alveolar hypoventilation. It is mostly caused by an acute exacerbation of chronic obstructive pulmonary disease or conditions yielding muscle dysfunction. Noninvasive ventilation through a facemask is the cornerstone first-line strategy to support hypercapnic patients with acidemia, and current guidelines strongly recommend this intervention to improve survival and long-term clinical outcomes. Because of its benefits related to carbon dioxide washout from the upper airways and the enhanced comfort, high-flow nasal oxygen has been proposed as a respiratory support strategy in patients with hypercapnic respiratory failure, both as an alternative to and in combination with noninvasive ventilation. When compared to noninvasive ventilation as a first-line intervention, high-flow nasal oxygen shows a higher rate of failure. Hence, if not contraindicated, the use of noninvasive ventilation should be preferred. After the resolution of acidemia with noninvasive ventilation, high-flow nasal oxygen showed promising physiological effects compared to conventional oxygen. During weaning from mechanical ventilation in patients with or at risk of developing hypercapnia, high-flow nasal oxygen showed encouraging results, especially when applied alternating with sessions of noninvasive ventilation. Optimal settings of high-flow nasal oxygen in hypercapnic patients include the use of a smaller-size cannula, flows ranging between 30 and 40 L/min, and FiO 2 adjusted to obtain SpO 2 between 88% and 92%. Specific interfaces, such as asymmetric cannulas, may further enhance the benefits of a high flow in terms of carbon dioxide clearance. In this narrative review, we provide an updated overview of the physiological rationale and clinical evidence concerning the use of high-flow nasal oxygen in patients with acute hypercapnic respiratory failure.

The management of patients with life-threatening respiratory disease in the ICU and at home has become increasingly of interest over the past decades. Growing knowledge supports the use of NRS, aimed at improving patient comfort and improving quality of life. However, its role during palliative care is not well defined, and evidence of support remains limited. The aim of this narrative review is to examine the recent evidence relating to the use of non-invasive respiratory support at the end of life, in order to clarify who benefits and when. The literature research was conducted on PubMed, using MeSH words. A review of the relevant literature showed that non-invasive respiratory support techniques for patients with life-limiting respiratory disease vary (from high-flow oxygen therapy to conventional oxygen therapy, from CPAP to NPPV) and each has precise indications. To date, from the hospital to the home setting, the monitoring and application of these respiratory support techniques have varied widely. In conclusion, the choice of respiratory support in this category of patients should be based on the technique that will optimize the comfort of the patient and improve the quality of their life. On the other hand, regarding monitoring, both telemedicine and ultrasound diagnostics help to satisfy the patient's wish to spend the last period of his life in the home environment, to avoid inappropriately aggressive diagnostic interventions, and to reduce the high costs of hospitalized procedures in this category of patients.

In acute respiratory distress syndrome, the role of positive end-expiratory pressure (PEEP) to prevent ventilator-induced lung injury is controversial. Randomized trials comparing higher versus lower PEEP strategies failed to demonstrate a clinical benefit. This may depend on the inter-individually variable potential for lung recruitment (i.e. recruitability), which would warrant PEEP individualization to balance alveolar recruitment and the unavoidable baby lung overinflation produced by high pressure. Many techniques have been used to assess recruitability, including lung imaging, multiple pressure-volume curves and lung volume measurement. The Recruitment-to-Inflation ratio (R/I) has been recently proposed to bedside assess recruitability without additional equipment. R/I assessment is a simplified technique based on the multiple pressure-volume curve concept: it is measured by monitoring respiratory mechanics and exhaled tidal volume during a 10-cmH2O one-breath derecruitment maneuver after a short high-PEEP test. R/I scales recruited volume to respiratory system compliance, and normalizes recruitment to a proxy of actual lung size. With modest R/I (<0.3-0.4), setting low PEEP (5-8 cmH2O) may be advisable; with R/I>0.6-0.7, high PEEP (≥15 cmH2O) can be considered, provided that airway and/or transpulmonary plateau pressure do not exceed safety limits. In case of intermediate R/I (≈0.5), a more granular assessment of recruitability may be needed. This could be accomplished with advanced monitoring tools, like sequential lung volume measurement with granular R/I assessment or electrical impedance tomography monitoring during a decremental PEEP trial. In this review, we discuss R/I rationale, applications and limits, providing insights on its clinical use for PEEP selection in moderate-to-severe acute respiratory distress syndrome.

Background: Positive end-expiratory pressure (PEEP) can potentially modulate inspiratory effort (ΔPes), which is the major determinant of self-inflicted lung injury., Research Question: Does high PEEP reduce ΔPes in patients with moderate-to-severe ARDS on assisted ventilation?, Study Design and Methods: Sixteen patients with Pao 2 /Fio 2  ≤ 200 mm Hg and ΔPes ≥ 10 cm H 2 O underwent a randomized sequence of four ventilator settings: PEEP = 5 cm H 2 O or PEEP = 15 cm H 2 O + synchronous (pressure support ventilation [PSV]) or asynchronous (pressure-controlled intermittent mandatory ventilation [PC-IMV]) inspiratory assistance. ΔPes and respiratory system, lung, and chest wall mechanics were assessed with esophageal manometry and occlusions. PEEP-induced alveolar recruitment and overinflation, lung dynamic strain, and tidal volume distribution were assessed with electrical impedance tomography., Results: ΔPes was not systematically different at high vs low PEEP (pressure support ventilation: median, 20 cm H 2 O; interquartile range (IQR), 15-24 cm H 2 O vs median, 15 cm H 2 O; IQR, 13-23 cm H 2 O; P = .24; pressure-controlled intermittent mandatory ventilation: median, 20; IQR, 18-23 vs median, 19; IQR, 17-25; P = .67, respectively). Similarly, respiratory system and transpulmonary driving pressures, tidal volume, lung/chest wall mechanics, and pendelluft extent were not different between study phases. High PEEP resulted in lower or higher ΔPes, respiratory system driving pressure, and transpulmonary driving pressure according to whether this increased or decreased respiratory system compliance (r = -0.85, P < .001; r = -0.75, P < .001; r = -0.80, P < .001, respectively). PEEP-induced changes in respiratory system compliance were driven by its lung component and were dependent on the extent of PEEP-induced alveolar overinflation (r = -0.66, P = .006). High PEEP caused variable recruitment and systematic redistribution of tidal volume toward dorsal lung regions, thereby reducing dynamic strain in ventral areas (pressure support ventilation: median, 0.49; IQR, 0.37-0.83 vs median, 0.96; IQR, 0.62-1.56; P = .003; pressure-controlled intermittent mandatory ventilation: median, 0.65; IQR, 0.42-1.31 vs median, 1.14; IQR, 0.79-1.52; P = .002). All results were consistent during synchronous and asynchronous inspiratory assistance., Interpretation: The impact of high PEEP on ΔPes and lung stress is interindividually variable according to different effects on the respiratory system and lung compliance resulting from alveolar overinflation. High PEEP may help mitigate the risk of self-inflicted lung injury solely if it increases lung/respiratory system compliance., Trial Registration: ClinicalTrials.gov; No.: NCT04241874; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: D. L. G. has received speaking fees from Gilead, Intersurgical, MSD, and GE; and reports having received travel accommodation by Fisher and Paykel, outside the submitted work. M. A. has received personal fees by Maquet and a research grant by Toray, outside the submitted work. D. L. G. and M. A. disclose a research grant by GE, outside the submitted work. None declared (G. B., V. G., A. B., L. D. C., T. R., L. S. M., L. M., T. M., G. S., G. D. P., M. A. P., R. R. D. S. S., L. B.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Intensive Care Unit (ICU)-Acquired Weakness (ICU-AW) is a generalized muscle weakness that is clinically detected in critical patients and has no plausible etiology other than critical illness. ICU-AW is uncommon in patients undergoing orthotopic liver transplantation (OLT). Our report sheds light on the highest number of ICU-AW cases observed in a single center on OLT patients with early allograft dysfunction. Out of 282 patients who underwent OLT from January 2015 to June 2023, 7 (2.5%) developed generalized muscle weakness in the ICU and underwent neurophysiological investigations. The neurologic examination showed preserved extraocular, flaccid quadriplegia with the absence of deep tendon reflexes in all patients. Neurophysiological studies, including electromyography and nerve conduction studies, showed abnormalities with fibrillation potentials and the rapid recruitment of small polyphasic motor units in the examined muscles, as well as a reduced amplitude of the compound muscle action potential and sensory nerve action potential, with an absence of demyelinating features. Pre-transplant clinical status was critical in all patients. During ICU stay, early allograft dysfunction, acute kidney injury, prolonged mechanical ventilation, sepsis, hyperglycemia, and high blood transfusions were observed in all patients. Two patients were retransplanted. Five patients were alive at 90 days; two patients died. In non-cooperative OLT patients, neurophysiological investigations are essential for the diagnosis of ICU-AW. In this setting, the high number of red blood cell transfusions is a potential risk factor for ICU-AW.

Background: The effects of awake prone position on the breathing pattern of hypoxemic patients need to be better understood. We conducted a crossover trial to assess the physiological effects of awake prone position in patients with acute hypoxemic respiratory failure., Methods: Fifteen patients with acute hypoxemic respiratory failure and PaO 2 /FiO 2  < 200 mmHg underwent high-flow nasal oxygen for 1 h in supine position and 2 h in prone position, followed by a final 1-h supine phase. At the end of each study phase, the following parameters were measured: arterial blood gases, inspiratory effort (ΔP ES ), transpulmonary driving pressure (ΔP L ), respiratory rate and esophageal pressure simplified pressure-time product per minute (sPTP ES ) by esophageal manometry, tidal volume (V T ), end-expiratory lung impedance (EELI), lung compliance, airway resistance, time constant, dynamic strain (V T /EELI) and pendelluft extent through electrical impedance tomography., Results: Compared to supine position, prone position increased PaO 2 /FiO 2 (median [Interquartile range] 104 mmHg [76-129] vs. 74 [69-93], p < 0.001), reduced respiratory rate (24 breaths/min [22-26] vs. 27 [26-30], p = 0.05) and increased ΔP ES (12 cmH 2 O [11-13] vs. 9 [8-12], p = 0.04) with similar sPTP ES (131 [75-154] cmH 2 O s min -1 vs. 105 [81-129], p > 0.99) and ΔP L (9 [7-11] cmH 2 O vs. 8 [5-9], p = 0.17). Airway resistance and time constant were higher in prone vs. supine position (9 cmH 2 O s arbitrary units -3 [4-11] vs. 6 [4-9], p = 0.05; 0.53 s [0.32-61] vs. 0.40 [0.37-0.44], p = 0.03). Prone position increased EELI (3887 arbitrary units [3414-8547] vs. 1456 [959-2420], p = 0.002) and promoted V T distribution towards dorsal lung regions without affecting V T size and lung compliance: this generated lower dynamic strain (0.21 [0.16-0.24] vs. 0.38 [0.30-0.49], p = 0.004). The magnitude of pendelluft phenomenon was not different between study phases (55% [7-57] of V T in prone vs. 31% [14-55] in supine position, p > 0.99)., Conclusions: Prone position improves oxygenation, increases EELI and promotes V T distribution towards dependent lung regions without affecting V T size, ΔP L , lung compliance and pendelluft magnitude. Prone position reduces respiratory rate and increases ΔP ES because of positional increases in airway resistance and prolonged expiratory time. Because high ΔP ES is the main mechanistic determinant of self-inflicted lung injury, caution may be needed in using awake prone position in patients exhibiting intense ΔP ES . Clinical trail registeration: The study was registered on clinicaltrials.gov (NCT03095300) on March 29, 2017., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Acute respiratory distress syndrome (ARDS) is a leading cause of disability and mortality worldwide, and while no specific etiologic interventions have been shown to improve outcomes, noninvasive and invasive respiratory support strategies are life-saving interventions that allow time for lung recovery. However, the inappropriate management of these strategies, which neglects the unique features of respiratory, lung, and chest wall mechanics may result in disease progression, such as patient self-inflicted lung injury during spontaneous breathing or by ventilator-induced lung injury during invasive mechanical ventilation. ARDS characteristics are highly heterogeneous; therefore, a physiology-based approach is strongly advocated to titrate the delivery and management of respiratory support strategies to match patient characteristics and needs to limit ARDS progression. Several tools have been implemented in clinical practice to aid the clinician in identifying the ARDS sub-phenotypes based on physiological peculiarities (inspiratory effort, respiratory mechanics, and recruitability), thus allowing for the appropriate application of personalized supportive care. In this narrative review, we provide an overview of noninvasive and invasive respiratory support strategies, as well as discuss how identifying ARDS sub-phenotypes in daily practice can help clinicians to deliver personalized respiratory support and potentially improve patient outcomes.

Background: Long-term outcomes of patients treated with helmet noninvasive ventilation (NIV) are unknown: safety concerns regarding the risk of patient self-inflicted lung injury and delayed intubation exist when NIV is applied in hypoxemic patients. We assessed the 6-month outcome of patients who received helmet NIV or high-flow nasal oxygen for COVID-19 hypoxemic respiratory failure., Methods: In this prespecified analysis of a randomized trial of helmet NIV versus high-flow nasal oxygen (HENIVOT), clinical status, physical performance (6-min-walking-test and 30-s chair stand test), respiratory function and quality of life (EuroQoL five dimensions five levels questionnaire, EuroQoL VAS, SF36 and Post-Traumatic Stress Disorder Checklist for the DSM) were evaluated 6 months after the enrollment., Results: Among 80 patients who were alive, 71 (89%) completed the follow-up: 35 had received helmet NIV, 36 high-flow oxygen. There was no inter-group difference in any item concerning vital signs (N = 4), physical performance (N = 18), respiratory function (N = 27), quality of life (N = 21) and laboratory tests (N = 15). Arthralgia was significantly lower in the helmet group (16% vs. 55%, p = 0.002). Fifty-two percent of patients in helmet group vs. 63% of patients in high-flow group had diffusing capacity of the lungs for carbon monoxide < 80% of predicted (p = 0.44); 13% vs. 22% had forced vital capacity < 80% of predicted (p = 0.51). Both groups reported similar degree of pain (p = 0.81) and anxiety (p = 0.81) at the EQ-5D-5L test; the EQ-VAS score was similar in the two groups (p = 0.27). Compared to patients who successfully avoided invasive mechanical ventilation (54/71, 76%), intubated patients (17/71, 24%) had significantly worse pulmonary function (median diffusing capacity of the lungs for carbon monoxide 66% [Interquartile range: 47-77] of predicted vs. 80% [71-88], p = 0.005) and decreased quality of life (EQ-VAS: 70 [53-70] vs. 80 [70-83], p = 0.01)., Conclusions: In patients with COVID-19 hypoxemic respiratory failure, treatment with helmet NIV or high-flow oxygen yielded similar quality of life and functional outcome at 6 months. The need for invasive mechanical ventilation was associated with worse outcomes. These data indicate that helmet NIV, as applied in the HENIVOT trial, can be safely used in hypoxemic patients. Trial registration Registered on clinicaltrials.gov NCT04502576 on August 6, 2020., (© 2023. The Author(s).)

Rationale: The respective effects of positive end-expiratory pressure (PEEP) and pressure support delivered through the helmet interface in patients with hypoxemia need to be better understood. Objectives: To assess the respective effects of helmet pressure support (noninvasive ventilation [NIV]) and continuous positive airway pressure (CPAP) compared with high-flow nasal oxygen (HFNO) on effort to breathe, lung inflation, and gas exchange in patients with hypoxemia (Pa O 2 /Fi O 2  ⩽ 200). Methods: Fifteen patients underwent 1-hour phases (constant Fi O 2 ) of HFNO (60 L/min), helmet NIV (PEEP = 14 cm H 2 O, pressure support = 12 cm H 2 O), and CPAP (PEEP = 14 cm H 2 O) in randomized sequence. Measurements and Main Results: Inspiratory esophageal (ΔP ES ) and transpulmonary pressure (ΔP L ) swings were used as surrogates for inspiratory effort and lung distension, respectively. Tidal Volume (Vt) and end-expiratory lung volume were assessed with electrical impedance tomography. ΔP ES was lower during NIV versus CPAP and HFNO (median [interquartile range], 5 [3-9] cm H 2 O vs. 13 [10-19] cm H 2 O vs. 10 [8-13] cm H 2 O; P  = 0.001 and P  = 0.01). ΔP L was not statistically different between treatments. Pa O 2 /Fi O 2 ratio was significantly higher during NIV and CPAP versus HFNO (166 [136-215] and 175 [158-281] vs. 120 [107-149]; P  = 0.002 and P  = 0.001). NIV and CPAP similarly increased Vt versus HFNO (mean change, 70% [95% confidence interval (CI), 17-122%], P  = 0.02; 93% [95% CI, 30-155%], P  = 0.002) and end-expiratory lung volume (mean change, 198% [95% CI, 67-330%], P  = 0.001; 263% [95% CI, 121-407%], P  = 0.001), mostly due to increased aeration/ventilation in dorsal lung regions. During HFNO, 14 of 15 patients had pendelluft involving >10% of Vt; pendelluft was mitigated by CPAP and further by NIV. Conclusions: Compared with HFNO, helmet NIV, but not CPAP, reduced ΔP ES . CPAP and NIV similarly increased oxygenation, end-expiratory lung volume, and Vt, without affecting ΔP L . NIV, and to a lesser extent CPAP, mitigated pendelluft. Clinical trial registered with clinicaltrials.gov (NCT04241861).

Introduction: Non-invasive ventilation (NIV) represents an effective strategy for managing acute respiratory failure. Facemask NIV is strongly recommended in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with hypercapnia and acute cardiogenic pulmonary edema (ACPE). Its role in managing acute hypoxemic respiratory failure (AHRF) remains a debated issue. NIV and continuous positive airway pressure (CPAP) delivered through the helmet are recently receiving growing interest for AHRF management., Areas Covered: In this narrative review, we discuss the clinical applications of helmet support compared to the other available noninvasive strategies in the different phenotypes of acute respiratory failure., Expert Opinion: Helmets enable the use of high positive end-expiratory pressure, which may protect from self-inflicted lung injury: in AHRF, the possible superiority of helmet support over other noninvasive strategies in terms of clinical outcome has been hypothesized in a network metanalysis and a randomized trial, but has not been confirmed by other investigations and warrants confirmation. In AECOPD patients, helmet efficacy may be inferior to that of face masks, and its use prompts caution due to the risk of CO 2 rebreathing. Helmet support can be safely applied in hypoxemic patients with ACPE, with no advantages over facemasks.

Optimal initial non-invasive management of acute hypoxemic respiratory failure (AHRF), of both coronavirus disease 2019 (COVID-19) and non-COVID-19 etiologies, has been the subject of significant discussion. Avoidance of endotracheal intubation reduces related complications, but maintenance of spontaneous breathing with intense respiratory effort may increase risks of patients' self-inflicted lung injury, leading to delayed intubation and worse clinical outcomes. High-flow nasal oxygen is currently recommended as the optimal strategy for AHRF management for its simplicity and beneficial physiological effects. Non-invasive ventilation (NIV), delivered as either pressure support or continuous positive airway pressure via interfaces like face masks and helmets, can improve oxygenation and may be associated with reduced endotracheal intubation rates. However, treatment failure is common and associated with poor outcomes. Expertise and knowledge of the specific features of each interface are necessary to fully exploit their potential benefits and minimize risks. Strict clinical and physiological monitoring is necessary during any treatment to avoid delays in endotracheal intubation and protective ventilation. In this narrative review, we analyze the physiological benefits and risks of spontaneous breathing in AHRF, and the characteristics of tools for delivering NIV. The goal herein is to provide a contemporary, evidence-based overview of this highly relevant topic., Competing Interests: Domenico Luca Grieco has received payments for travel expenses by Getinge and Air Liquide; speaking fees by Intersurgical, Gilead, Pfizer, General Electric Healthcare, and Fisher & Paykel; and a research grant by General Electric Healthcare. All other authors declare that they have no conflicts of interests., (© 2022 The Author(s). Published by Elsevier B.V. on behalf of Chinese Medical Association.)

Introduction: Helmet noninvasive support may provide advantages over other noninvasive oxygenation strategies in the management of acute hypoxemic respiratory failure. In this narrative review based on a systematic search of the literature, we summarize the rationale, mechanism of action and technicalities for helmet support in hypoxemic patients., Main Results: In hypoxemic patients, helmet can facilitate noninvasive application of continuous positive-airway pressure or pressure-support ventilation via a hood interface that seals at the neck and is secured by straps under the arms. Helmet use requires specific settings. Continuous positive-airway pressure is delivered through a high-flow generator or a Venturi system connected to the inspiratory port of the interface, and a positive end-expiratory pressure valve place at the expiratory port of the helmet;  alternatively, pressure-support ventilation is delivered by connecting the helmet to a mechanical ventilator through a bi-tube circuit. The helmet interface allows continuous treatments with high positive end-expiratory pressure with good patient comfort. Preliminary data suggest that helmet noninvasive ventilation (NIV) may provide physiological benefits compared to other noninvasive oxygenation strategies (conventional oxygen, facemask NIV, high-flow nasal oxygen) in non-hypercapnic patients with moderate-to-severe hypoxemia (PaO 2 /FiO 2  ≤ 200 mmHg), possibly because higher positive end-expiratory pressure (10-15 cmH 2 O) can be applied for prolonged periods with good tolerability. This improves oxygenation, limits ventilator inhomogeneities, and may attenuate the potential harm of lung and diaphragm injury caused by vigorous inspiratory effort. The potential superiority of helmet support for reducing the risk of intubation has been hypothesized in small, pilot randomized trials and in a network metanalysis., Conclusions: Helmet noninvasive support represents a promising tool for the initial management of patients with severe hypoxemic respiratory failure. Currently, the lack of confidence with this and technique and the absence of conclusive data regarding its efficacy render helmet use limited to specific settings, with expert and trained personnel. As per other noninvasive oxygenation strategies, careful clinical and physiological monitoring during the treatment is essential to early identify treatment failure and avoid delays in intubation., (© 2022. The Author(s).)

Machine learning and cluster analysis applied to the clinical setting of an intensive care unit can be a valuable aid for clinical management, especially with the increasing complexity of clinical monitoring. Providing a method to measure clinical experience, a proxy for that automatic gestalt evaluation that an experienced clinician sometimes effortlessly, but often only after long, hard consideration and consultation with colleagues, relies upon for decision making, is what we wanted to achieve with the application of machine learning to antibiotic therapy and clinical monitoring in the present work. This is a single-center retrospective analysis proposing methods for evaluation of vitals and antimicrobial therapy in intensive care patients. For each patient included in the present study, duration of antibiotic therapy, consecutive days of treatment and type and combination of antimicrobial agents have been assessed and considered as single unique daily record for analysis. Each parameter, composing a record was normalized using a fuzzy logic approach and assigned to five descriptive categories (fuzzy domain sub-sets ranging from "very low" to "very high"). Clustering of these normalized therapy records was performed, and each patient/day was considered to be a pertaining cluster. The same methodology was used for hourly bed-side monitoring. Changes in patient conditions (monitoring) can lead to a shift of clusters. This can provide an additional tool for assessing progress of complex patients. We used Fuzzy logic normalization to descriptive categories of parameters as a form nearer to human language than raw numbers.

Background: There is growing interest towards the use of helmet noninvasive ventilation (NIV) for the management of acute hypoxemic respiratory failure. Gas conditioning through heat and moisture exchangers (HME) or heated humidifiers (HHs) is needed during facemask NIV to provide a minimum level of humidity in the inspired gas (15 mg H 2 O/L). The optimal gas conditioning strategy during helmet NIV remains to be established., Methods: Twenty patients with acute hypoxemic respiratory failure (PaO 2 /FiO 2  < 300 mmHg) underwent consecutive 1-h periods of helmet NIV (PEEP 12 cmH 2 O, pressure support 12 cmH 2 O) with four humidification settings, applied in a random order: double-tube circuit with HHs and temperature set at 34 °C (HH34) and 37 °C (HH37); Y-piece circuit with HME; double-tube circuit with no humidification (NoH). Temperature and humidity of inhaled gas were measured through a capacitive hygrometer. Arterial blood gases, discomfort and dyspnea through visual analog scales (VAS), esophageal pressure swings (ΔP ES ) and simplified pressure-time product (PTP ES ), dynamic transpulmonary driving pressure (ΔP L ) and asynchrony index were measured in each step., Results: Median [IqR] absolute humidity, temperature and VAS discomfort were significantly lower during NoH vs. HME, HH34 and HH37: absolute humidity (mgH 2 O/L) 16 [12-19] vs. 28 [23-31] vs. 28 [24-31] vs. 33 [29-38], p < 0.001; temperature (°C) 29 [28-30] vs. 30 [29-31] vs. 31 [29-32] vs 32. [31-33], p < 0.001; VAS discomfort 4 [2-6] vs. 6 [2-7] vs. 7 [4-8] vs. 8 [4-10], p = 0.03. VAS discomfort increased with higher absolute humidity (p < 0.01) and temperature (p = 0.007). Higher VAS discomfort was associated with increased VAS dyspnea (p = 0.001). Arterial blood gases, respiratory rate, ΔP ES , PTP ES and ΔP L were similar in all conditions. Overall asynchrony index was similar in all steps, but autotriggering rate was lower during NoH and HME (p = 0.03)., Conclusions: During 1-h sessions of helmet NIV in patients with hypoxemic respiratory failure, a double-tube circuit with no humidification allowed adequate conditioning of inspired gas, optimized comfort and improved patient-ventilator interaction. Use of HHs or HME in this setting resulted in increased discomfort due to excessive heat and humidity in the interface, which was associated with more intense dyspnea. Trail Registration Registered on clinicaltrials.gov (NCT02875379) on August 23rd, 2016., (© 2021. The Author(s).)

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 cmH 2 O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO 2 /FiO 2 , FiO 2 , 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 2 /FiO 2 in the two groups was 119 mmHg [101-142] and 116 mmHg [87-154]. Average compliance (41 ml/cmH 2 O [32-52] vs. 36 ml/cmH 2 O [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 2 /FiO 2 was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO 2 /FiO 2 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.