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Background: Postoperative hypoxemia and pulmonary complications remain a frequent event after on-pump cardiac surgery and mostly characterized by pulmonary atelectasis. Surfactant dysfunction or hyposecretion happens prior to atelectasis formation, and sigh represents the strongest stimulus for surfactant secretion. The role of sigh breaths added to conventional lung protective ventilation in reducing postoperative hypoxemia and pulmonary complications among cardiac surgery is unknown., Methods: The perioperative sigh ventilation in cardiac surgery (E-SIGHT) trial is a single-center, two-arm, randomized controlled trial. In total, 192 patients scheduled for elective cardiac surgery with cardiopulmonary bypass (CPB) and aortic cross-clamp will be randomized into one of the two treatment arms. In the experimental group, besides conventional lung protective ventilation, sigh volumes producing plateau pressures of 35 cmH 2 O (or 40 cmH 2 O for patients with body mass index > 35 kg/m 2 ) delivered once every 6 min from intubation to extubation. In the control group, conventional lung protective ventilation without preplanned recruitment maneuvers is used. Lung protective ventilation (LPV) consists of low tidal volumes (6-8 mL/kg of predicted body weight) and positive end-expiratory pressure (PEEP) setting according to low PEEP/FiO 2 table for acute respiratory distress syndrome (ARDS). The primary endpoint is time-weighted average SpO 2 /FiO 2 ratio during the initial post-extubation hour. Main secondary endpoint is the severity of postoperative pulmonary complications (PPCs) computed by postoperative day 7., Discussion: The E-SIGHT trial will be the first randomized controlled trial to evaluate the impact of perioperative sigh ventilation on the postoperative outcomes after on-pump cardiac surgery. The trial will introduce and assess a novel perioperative ventilation approach to mitigate the risk of postoperative hypoxemia and PPCs in patients undergoing cardiac surgery. Also provide the basis for a future larger trial aiming at verifying the impact of sigh ventilation on postoperative pulmonary complications., Trial Registration: ClinicalTrials.gov NCT06248320. Registered on January 30, 2024. Last updated February 26, 2024., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest The author declares no conflicts of interest

Background: Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs., Methods: We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence., Results: Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56-0.87, P=0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48-0.77, P< 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67-1.10, P=0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies., Conclusions: Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery., Systematic Review Protocol: INPLASY 202410068., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: This study compares the effect of positive end-expiratory pressure (PEEP) on postoperative pulmonary complications (PPCs) in patients with obesity undergoing laparoscopic bariatric surgery (LBS) under general anesthesia with mechanical ventilation., Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Internet, Wanfang database, and Google Scholar for studies published up to July 29, 2023, without time or language restrictions. The search terms included "PEEP," "laparoscopic," and "bariatric surgery." Randomized controlled trials comparing different levels of PEEP or PEEP with zero-PEEP (ZEEP) in patients with obesity undergoing LBS were included. The primary outcome was a composite of PPCs, and the secondary outcomes were intraoperative oxygenation, respiratory compliance, and mean arterial pressure (MAP). A fixed-effect or random-effect model was selected for meta-analysis based on the heterogeneity of the included studies., Results: Thirteen randomized controlled trials with a total of 708 participants were included for analysis. No statistically significant difference in PPCs was found between the PEEP and ZEEP groups (risk ratio = 0.27, 95% CI: 0.05-1.60; p = 0.15). However, high PEEP ≥ 10 cm H 2 O significantly decreased PPCs compared with low PEEP < 10 cm H 2 O (risk ratio = 0.20, 95% CI: 0.05-0.89; p = 0.03). The included studies showed no significant heterogeneity (I 2  = 20% & 0%). Compared with ZEEP, PEEP significantly increased intraoperative oxygenation and respiratory compliance (WMD = 74.97 mm Hg, 95% CI: 41.74-108.21; p < 0.001 & WMD = 9.40 ml cm H 2 O - 1 , 95% CI: 0.65-18.16; p = 0.04). High PEEP significantly improved intraoperative oxygenation and respiratory compliance during pneumoperitoneum compared with low PEEP (WMD = 66.81 mm Hg, 95% CI: 25.85-107.78; p = 0.001 & WMD = 8.03 ml cm H 2 O - 1 , 95% CI: 4.70-11.36; p < 0.001). Importantly, PEEP did not impair hemodynamic status in LBS., Conclusions: In patients with obesity undergoing LBS, high PEEP ≥ 10 cm H 2 O could decrease PPCs compared with low PEEP < 10 cm H 2 O, while there was a similar incidence of PPCs between PEEP (8-10 cm H 2 O) and the ZEEP group. The application of PEEP in ventilation strategies increased intraoperative oxygenation and respiratory compliance without affecting intraoperative MAP. A PEEP of at least 10 cm H 2 O is recommended to reduce PPCs in patients with obesity undergoing LBS., Registration Number: CRD42023391178 in PROSPERO., (© 2024. The Author(s).)

Background: Systematic reviews have reported conflicting evidence on whether macrolide antibiotics reduce rates of chronic lung disease of prematurity (CLD) in at-risk preterm infants born at less than 30 weeks' gestation, including in those colonised with pulmonary Ureaplasma spp. Since an adequately powered trial has been lacking, we aimed to assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate or severe CLD in preterm infants., Methods: AZTEC was a multicentre, double-blind, randomised, placebo-controlled trial conducted in 28 tertiary neonatal intensive care units in the UK. Infants were eligible if they were born at less than 30 weeks' gestation and had received at least 2 h of either non-invasive (continuous positive airway pressure or humidified high flow nasal cannula therapy) or invasive respiratory support (via endotracheal tube) within 72 h of birth. Eligible infants were randomly allocated in a 1:1 ratio using random permuted blocks of four to receive either intravenous azithromycin at 20 mg/kg per day for 3 days followed by 10 mg/kg for 7 days, or to placebo. Allocation was stratified by centre and gestational age at birth (<28 weeks vs ≥28 weeks). Azithromycin and placebo vials were encased in tamper-evident custom cardboard cartons to ensure masking for clinicians, parents, and the research team. The primary outcome was survival without development of physiologically defined moderate or severe CLD at 36 weeks' postmenstrual age. Outcomes and safety were analysed on an intention-to-treat basis (all randomly allocated infants, regardless of any post-randomisation events). The study was registered with ISRCRN (11650227) and is closed., Findings: Infants were recruited between Oct 9, 2019, and March 22, 2022. 799 (53·1%) of 1505 eligible infants underwent random allocation; three infants were withdrawn, including consent to use their data, leaving 796 infants for analysis. Survival without moderate or severe CLD occurred in 166 (42%) of 394 infants in the intervention group and 179 (45%) of 402 in the placebo group (three-level adjusted OR [aOR] 0·84, 95% CI 0·55-1·29, p=0·43). Pulmonary Ureaplasma spp colonisation did not influence treatment effect. Overall, seven serious adverse events were reported for the azithromycin group (five graded as severe, two as moderate), and six serious adverse events were reported in the placebo group (two severe, two moderate, and two mild), as assessed by the local principal investigators., Interpretation: Since prophylactic use of azithromycin did not improve survival without development of physiologically-defined CLD, regardless of Ureaplasma spp colonisation, it cannot be recommended in clinical practice., Funding: UK National Institute for Health and Care Research., Competing Interests: Declaration of interests SK, JL, DG, KH, NK, ET-J, MT, JM, and JB received funding from NIHR HTA as coapplicants for this project. JM reports payments or honoraria for lectures from Institut Biochimique SA, support for attending meetings from Fred Hutchinson Cancer Centre, and patents issued and pending. SK reports receiving grant funding outside of this work from the Medical Research Council, Aspire Pharma, and Moulton Foundation; and consultancy fees from Aspire Pharma during the past 36 months. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: AR declares research funding from Monash University and the Lions Cord Blood Foundation, outside of the submitted work.

Introduction: Lung-protective ventilation strategies (LPVS) for one-lung ventilation (OLV) in paediatric patients pose greater challenges than in adults. Optimising LPVS for paediatric OLV to mitigate postoperative pulmonary complications (PPCs) has emerged as a current research focal point. However, there remains a divergence of opinions concerning the individualised setting and application of positive end-expiratory pressure (PEEP). Lung dynamic compliance (Cdyn) can serve as a reflection of the lung's physiological state in children during OLV and is a readily obtainable parameter. This study protocol is formulated to assess the effectiveness of Cdyn-guided PEEP titration on PPCs during paediatric OLV., Methods and Analysis: This study constitutes a single-centre, prospective, double-blind, randomised controlled trial. The trial aims to recruit 60 paediatric patients scheduled for video-assisted thoracoscopic surgery. These eligible patients will be randomly assigned to either the Cdyn-guided PEEP group or the conventional PEEP group during general anaesthesia for OLV. The primary outcome will involve assessing the incidence of PPCs at 7 days after surgery. Secondary outcomes will encompass the evaluation of the modified lung ultrasound score following surgery, as well as monitoring the oxygenation index, driving pressure and Cdyn during mechanical ventilation. Data collection will be performed by investigators who are kept blinded to the interventions., Ethics and Dissemination: The Clinical Trial Ethics Committee at Shenzhen Children's Hospital has conferred ethical approvals for this trial (approval number: 2022076). Results from this trial will be disseminated in peer-reviewed journals and presented at professional symposiums., Trail Registration Number: NCT05386901., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Postoperative pulmonary complications (PPCs) after one-lung ventilation (OLV) significantly impact patient prognosis and quality of life., Objective: To study the impact of an optimal inspiratory flow rate on PPCs in thoracic surgery patients., Methods: One hundred eight elective thoracic surgery patients were randomly assigned to 2 groups in this consort study (control group: n = 53 with a fixed inspiratory expiratory ratio of 1:2; and experimental group [flow rate optimization group]: n = 55). Measurements of Ppeak, Pplat, PETCO 2 , lung dynamic compliance (Cdyn), respiratory rate, and oxygen concentration were obtained at the following specific time points: immediately after intubation (T0); immediately after starting OLV (T1); 30 min after OLV (T2); and 10 min after 2-lung ventilation (T4). The PaO 2 :FiO 2 ratio was measured using blood gas analysis 30 min after initiating one-lung breathing (T2) and immediately when OLV ended (T3). The lung ultrasound score (LUS) was assessed following anesthesia and resuscitation (T5). The occurrence of atelectasis was documented immediately after the surgery. PPCs occurrences were noted 3 days after surgery., Results: The treatment group had a significantly lower total prevalence of PPCs compared to the control group (3.64% vs. 16.98%; P = 0.022). There were no notable variations in peak airway pressure, airway plateau pressure, dynamic lung compliance, PETCO 2 , respiratory rate, and oxygen concentration between the two groups during intubation (T0). Dynamic lung compliance and the oxygenation index were significantly increased at T1, T2, and T4 (P < 0.05), whereas the CRP level and number of inflammatory cells decreased dramatically (P < 0.05)., Conclusion: Optimizing inspiratory flow rate and utilizing pressure control ventilation -volume guaranteed (PCV-VG) mode can decrease PPCs and enhance lung dynamic compliance in OLV patients., (© 2024. The Author(s).)

Aims: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine., Methods: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis., Results: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011., Conclusion: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Questions: Among patients having elective abdominal surgery, how much does preoperative physiotherapy education with breathing exercise training reduce the incidence of postoperative pulmonary complications (PPCs), hospital length of stay and 12-month mortality? How stable are the treatment effects across different PPC definitions, including pneumonia? How much do the treatment effects on PPC, hospital length of stay and mortality vary within clinically relevant subgroups?, Design: Individual participant-level meta-analysis (n = 800) from two randomised controlled trials analysed with multivariable regression., Participants: Adults undergoing major elective abdominal surgery., Interventions: Experimental participants received a single preoperative session with a physiotherapist within 4 weeks of surgery and educated on PPC prevention with breathing exercises and early mobilisation. They were taught breathing exercises and instructed to start them immediately on waking from surgery. The control group received no preoperative or postoperative physiotherapy, or early ambulation alone., Outcome Measures: PPC, hospital length of stay and 12-month mortality., Results: Participants who received preoperative physiotherapy had 47% lower odds of developing a PPC (adjusted OR 0.53, 95% CI 0.34 to 0.85). This effect was stable regardless of PPC definition. Effects were greatest in participants who smoked, were aged ≤ 45 years, had abnormal body weight, had multiple comorbidities, or were undergoing bariatric or upper gastrointestinal surgery. Participants having operations ≤ 3 hours in duration were least responsive to preoperative physiotherapy. Participants with multiple comorbidities were more likely to have a shorter hospital stay if provided with preoperative physiotherapy (adjusted MD -3.2 days, 95% CI -6.2 to -0.3). Effects on mortality were uncertain., Conclusion: There is strong evidence to support preoperative physiotherapy in preventing PPCs after elective abdominal surgery., (Copyright © 2024 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.)

Purpose: To identify tidal volume (V T ) and positive end-expiratory pressure (PEEP) associated with the lowest incidence and severity of postoperative pulmonary complications (PPCs) for each phenotype based on preoperative characteristics., Methods: The subjects of this retrospective observational cohort study were 34,910 adults who underwent surgery, using general anesthesia with mechanical ventilation. Initially, the least absolute shrinkage and selection operator regression was employed to select relevant preoperative characteristics. Then, the classification and regression tree (CART) was built to identify phenotypes. Finally, we computed the area under the receiver operating characteristic curves from logistic regressions to identify V T and PEEP associated with the lowest incidence and severity of PPCs for each phenotype., Results: CARTs classified seven phenotypes for each outcome. A probability of the development of PPCs ranged from the lowest (3.51%) to the highest (68.57%), whereas the probability of the development of the highest level of PPC severity ranged from 3.3% to 91.0%. Across all phenotypes, the V T and PEEP associated with the most desirable outcomes were within a small range of V T 7-8 ml/kg predicted body weight with PEEP of between 6 and 8 cmH 2 O., Conclusions: The ranges of optimal V T and PEEP were small, regardless of the phenotypes, which had a wide range of risk profiles., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Timely detection of modifiable risk factors for postoperative pulmonary complications (PPCs) could inform ventilation strategies that attenuate lung injury. We sought to develop, validate, and internally test machine learning models that use intraoperative respiratory features to predict PPCs., Methods: We analysed perioperative data from a cohort comprising patients aged 65 yr and older at an academic medical centre from 2019 to 2023. Two linear and four nonlinear learning models were developed and compared with the current gold-standard risk assessment tool ARISCAT (Assess Respiratory Risk in Surgical Patients in Catalonia Tool). The Shapley additive explanation of artificial intelligence was utilised to interpret feature importance and interactions., Results: Perioperative data were obtained from 10 284 patients who underwent 10 484 operations (mean age [range] 71 [65-98] yr; 42% female). An optimised XGBoost model that used preoperative variables and intraoperative respiratory variables had area under the receiver operating characteristic curves (AUROCs) of 0.878 (0.866-0.891) and 0.881 (0.879-0.883) in the validation and prospective cohorts, respectively. These models outperformed ARISCAT (AUROC: 0.496-0.533). The intraoperative dynamic features of respiratory dynamic system compliance, mechanical power, and driving pressure were identified as key modifiable contributors to PPCs. A simplified model based on XGBoost including 20 variables generated an AUROC of 0.864 (0.852-0.875) in an internal testing cohort. This has been developed into a web-based tool for further external validation (https://aorm.wchscu.cn/)., Conclusions: These findings suggest that real-time identification of surgical patients' risk of postoperative pulmonary complications could help personalise intraoperative ventilatory strategies and reduce postoperative pulmonary complications., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Intraoperative lung-protective ventilation, including low tidal volume and positive end-expiratory pressure, reduces postoperative pulmonary complications. However, the effect and specific alveolar recruitment maneuver method are controversial. We investigated whether the intraoperative intermittent recruitment maneuver further reduced postoperative pulmonary complications while using a lung-protective ventilation strategy. Adult patients undergoing elective laparoscopic colorectal surgery were randomly allocated to the recruitment or control groups. Intraoperative ventilation was adjusted to maintain a tidal volume of 6-8 mL kg-1 and positive end-expiratory pressure of 5 cmH2O in both groups. The alveolar recruitment maneuver was applied at three time points (at the start and end of the pneumoperitoneum, and immediately before extubation) by maintaining a continuous pressure of 30 cmH2O for 30 s in the recruitment group. Clinical and radiological evidence of postoperative pulmonary complications was investigated within 7 days postoperatively. A total of 125 patients were included in the analysis. The overall incidence of postoperative pulmonary complications was not significantly different between the recruitment and control groups (28.1% vs. 31.1%, P = 0.711), while the mean ± standard deviation intraoperative peak inspiratory pressure was significantly lower in the recruitment group (10.7 ± 3.2 vs. 13.5 ± 3.0 cmH2O at the time of CO2 gas-out, P < 0.001; 9.8 ± 2.3 vs. 12.5 ± 3.0 cmH2O at the time of recovery, P < 0.001). The alveolar recruitment maneuver with a pressure of 30 cmH2O for 30 s did not further reduce postoperative pulmonary complications when a low tidal volume and 5 cmH2O positive end-expiratory pressure were applied to patients undergoing laparoscopic colorectal surgery and was not associated with any significant adverse events. However, the alveolar recruitment maneuver significantly reduced intraoperative peak inspiratory pressure. Further study is needed to validate the beneficial effect of the alveolar recruitment maneuver in patients at increased risk of postoperative pulmonary complications. Trial registration: Clinicaltrials.gov (NCT03681236)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bae et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) research program, supported by the National Heart, Lung, and Blood Institute (NHLBI), focuses on developing and testing sustainable interventions to reduce heart and lung disease disparities. This perspective piece reflects on lessons learned during the planning phase (UG3) and outlines the accomplishments of the DECIPHeR Alliance. The article emphasizes the importance of a biphasic (UG3/UH3) funding mechanism, technical assistance, and collaborative subcommittees in achieving success. As DECIPHeR enters phase 2 (UH3), the article anticipates rigorously planned studies addressing social determinants of health and emphasizes the need for effective implementation strategies and equitable research frameworks. The Alliance's contributions, such as the IM4Equity framework, offer novel approaches to community-engaged health equity and implementation science research. The article explores future opportunities, including dissemination strategies, community engagement, and collaboration with diverse partners, to maximize DECIPHeR's impact on health disparities beyond cardiovascular and pulmonary health., Competing Interests: Conflict of Interest: No conflicts of interest reported by authors.

NHLBI funded seven projects as part of the Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) Initiative. They were expected to collaborate with community partners to (1) employ validated theoretical or conceptual implementation research frameworks, (2) include implementation research study designs, (3) include implementation measures as primary outcomes, and (4) inform our understanding of mediators and mechanisms of action of the implementation strategy. Several projects focused on late-stage implementation strategies that optimally and sustainably delivered two or more evidence-based multilevel interventions to reduce or eliminate cardiovascular and/or pulmonary health disparities and to improve population health in high-burden communities. Projects that were successful in the three-year planning phase transitioned to a 4-year execution phase. NHLBI formed a Technical Assistance Workgroup during the planning phase to help awardees refine study aims, strengthen research designs, detail analytic plans, and to use valid sample size methods. This paper highlights methodological and study design challenges encountered during this process. Important lessons learned included (1) the need for greater emphasis on implementation outcomes, (2) the need to clearly distinguish between intervention and implementation strategies in the protocol, (3) the need to address clustering due to randomization of groups or clusters, (4) the need to address the cross-classification that results when intervention agents work across multiple units of randomization in the same arm, (5) the need to accommodate time-varying intervention effects in stepped-wedge designs, and (6) the need for data-based estimates of the parameters required for sample size estimation.

Despite several ambitious national health initiatives to eliminate health disparities, spanning more than 4 decades, health disparities remain pervasive in the United States. In an attempt to bend the curve in disparities elimination, the National Heart, Lung, and Blood Institute (NHLBI) issued a funding opportunity on Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) in March 2019. Seven implementation research centers and 1 research coordinating center were funded in September 2020 to plan, develop, and test effective implementation strategies for eliminating disparities in heart and lung disease risk. In the 16 articles presented in this issue of Ethnicity & Disease , the DECIPHeR Alliance investigators and their NHLBI program staff address the work accomplished in the first phase of this biphasic research endeavor. Included in the collection are an article on important lessons learned during technical assistance sessions designed to ensure scientific rigor in clinical study designs, and 2 examples of clinical study process articles. Several articles show the diversity of clinical and public health settings addressed including schools, faith-based settings, federally qualified health centers, and other safety net clinics. All strategies for eliminating disparities tackle a cardiovascular or pulmonary disease and related risk factors. In an additional article, NHLBI program staff address expectations in phase 2 of the DECIPHeR program, strategies to ensure feasibility of scaling and spreading promising strategies identified, and opportunities for translating the DECIPHeR research model to other chronic diseases for the elimination of related health disparities., Competing Interests: Conflict of Interest: No conflicts of interest reported by authors.

Background: The translation of evidence-based interventions into practice settings remains challenging. Implementation science aims to bridge the evidence-to-practice gap by understanding multilevel contexts and tailoring evidence-based interventions accordingly. Engaging community partners who possess timely, local knowledge is crucial for this process to be successful. The Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) Alliance aims to address cardiopulmonary health disparities by engaging diverse community partners to improve the implementation of evidence-based interventions. The goal of the Community Engagement Subcommittee is to strengthen community engagement practice across DECIPHeR. This paper presents the subcommittee's "Why We Engage Communities" statement that outlines why community engagement is critical for implementation science. The paper also provides case examples of DECIPHeR community engagement activities., Methods: To develop the "Why We Engage Communities" statement, we conducted a literature review, surveyed subcommittee members to assess the importance of community engagement in their work, and integrated community partner feedback. We synthesize the findings into three key themes and present examples of community engagement activities and their impact across DECIPHeR projects., Results: The statement presents three themes that illustrate why community engagement increases the impact of implementation and health equity research. Community engagement (1) engages local knowledge and expertise, (2) promotes authentic relationships, and (3) builds community and researcher capacity. The statement provides a guiding framework for strengthening DECIPHeR research and enhancing community partnerships., Conclusion: Community engagement can improve the implementation of evidence-based interventions across diverse settings, improving intervention effectiveness in underserved communities and furthering health equity., Competing Interests: Conflict of Interest: All authors have no conflicts of interest to report.

Background: Chronic lung disease (CLD) occurs frequently in preterm infants and is associated with respiratory morbidity. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased compliance and tidal volume, and decreased airway resistance, have been documented with the use of bronchodilators in infants with CLD. Therefore, bronchodilators are widely considered to have a role in the prevention and treatment of CLD, but there remains uncertainty as to whether they improve clinical outcomes. This is an update of the 2016 Cochrane review., Objectives: To determine the effect of inhaled bronchodilators given as prophylaxis or as treatment for chronic lung disease (CLD) on mortality and other complications of preterm birth in infants at risk for or identified as having CLD., Search Methods: An Information Specialist searched CENTRAL, MEDLINE, Embase, CINAHL and three trials registers from 2016 to May 2023. In addition, the review authors undertook reference checking, citation searching and contact with trial authors to identify additional studies., Selection Criteria: We included randomised and quasi-randomised controlled trials involving preterm infants less than 32 weeks old that compared bronchodilators to no intervention or placebo. CLD was defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age. Initiation of bronchodilator therapy for the prevention of CLD had to occur within two weeks of birth. Treatment of infants with CLD had to be initiated before discharge from the neonatal unit. The intervention had to include administration of a bronchodilator by nebulisation or metered dose inhaler. The comparator was no intervention or placebo., Data Collection and Analysis: We used the standard methodological procedures expected by Cochrane. Critical outcomes included: mortality within the trial period; CLD (defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age); adverse effects of bronchodilators, including hypokalaemia (low potassium levels in the blood), tachycardia, cardiac arrhythmia, tremor, hypertension and hyperglycaemia (high blood sugar); and pneumothorax. We used the GRADE approach to assess the certainty of the evidence for each outcome., Main Results: We included two randomised controlled trials in this review update. Only one trial provided useable outcome data. This trial was conducted in six neonatal intensive care units in France and Portugal, and involved 173 participants with a gestational age of less than 31 weeks. The infants in the intervention group received salbutamol for the prevention of CLD. The evidence suggests that salbutamol may result in little to no difference in mortality (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.50 to 2.31; risk difference (RD) 0.01, 95% CI -0.09 to 0.11; low-certainty evidence) or CLD at 28 days (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17; low-certainty evidence), when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax. The one trial with usable data reported that there were no relevant differences between groups, without providing the number of events (very low-certainty evidence). Investigators in this study did not report if side effects occurred. We found no eligible trials that evaluated the use of bronchodilator therapy for the treatment of infants with CLD. We identified no ongoing studies., Authors' Conclusions: Low-certainty evidence from one trial showed that inhaled bronchodilator prophylaxis may result in little or no difference in the incidence of mortality or CLD in preterm infants, when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax, and neither included study reported on the incidence of serious adverse effects. We identified no trials that studied the use of bronchodilator therapy for the treatment of CLD. Additional clinical trials are necessary to assess the role of bronchodilator agents in the prophylaxis or treatment of CLD. Researchers studying the effects of inhaled bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose of Review: The present review summarizes the current knowledge and the barriers encountered when implementing tailoring lung-protective ventilation strategies to individual patients based on advanced monitoring systems., Recent Findings: Lung-protective ventilation has become a pivotal component of perioperative care, aiming to enhance patient outcomes and reduce the incidence of postoperative pulmonary complications (PPCs). High-quality research has established the benefits of strategies such as low tidal volume ventilation and low driving pressures. Debate is still ongoing on the most suitable levels of positive end-expiratory pressure (PEEP) and the role of recruitment maneuvers. Adapting PEEP according to patient-specific factors offers potential benefits in maintaining ventilation distribution uniformity, especially in challenging scenarios like pneumoperitoneum and steep Trendelenburg positions. Advanced monitoring systems, which continuously assess patient responses and enable the fine-tuning of ventilation parameters, offer real-time data analytics to predict and prevent impending lung complications. However, their impact on postoperative outcomes, particularly PPCs, is an ongoing area of research., Summary: Refining protective lung ventilation is crucial to provide patients with the best possible care during surgery, reduce the incidence of PPCs, and improve their overall surgical journey., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pulmonary complications after thoracic surgery are common and associated with significant morbidity and high cost of care. Goal-directed fluid therapy (GDFT) could reduce the incidence of postoperative pulmonary complications (PPCs) and facilitate recovery in patients undergoing major abdominal surgery. However, whether GDFT could reduce the incidence of PPCs in patients undergoing thoracic surgery was unclear. The present meta-analysis was designed to assess the impact of Goal-directed Fluid Therapy on PPCs in patients undergoing thoracic surgery., Methods: Randomized controlled trials (RCTs) comparing GDFT with other conventional fluid management strategies in adult patients undergoing thoracic surgery were identified. Databases searched included PubMed, Web of Science, Embase, and Cochrane Library databases. Review Manager 5.4 (The Cochrane Collaboration, Oxford, UK) software was used for statistical analysis. Heterogeneity was analyzed using I 2 statistics, and a standardized mean difference with 95% CI and P value was used to calculate the treatment effect for outcome variables. The primary study outcomes were the incidence of PPCs. Secondary outcomes were the total volume infused, the length of hospitalization, the incidence of cardiac complications, and the incidence of renal dysfunction. Subgroup analysis was planned to verify the definite role of GDFT., Results: A total of 6 RCTs consisting of 680 patients were included in this meta-analysis, which revealed that GDFT did not reduce the incidence of PPCs in patients undergoing thoracic surgery (RR, 0.57; 95% CI 0.29-1.14). However, GDFT decreased the total intra-operative fluid input (MD, - 244.40 ml; 95% CI - 397.06 to - 91.74). There was no statistical difference in the duration of hospitalization (MD; - 1.31, 95% CI - 3.00 to 0.38), incidence of renal dysfunction (RR, 0.62; 95% CI 0.29-1.35), and incidence of cardiac complications (RR, 0.62; 95% CI 0.27-1.40)., Conclusions: The results of this meta-analysis indicate that GDFT did not reduce the postoperative incidence of pulmonary complications in individuals undergoing thoracic surgery. However, considering the small number of contributing studies, these results should be interpreted with caution., (© 2024. The Author(s).)

Background: Inadequate postoperative analgesia may cause postoperative complications, such as pulmonary complications. This study evaluated the analgesic effectiveness of a single preoperative injection of dinalbuphine sebacate (DS) in patients undergoing video-assisted thoracoscopic wedge resection and assessed whether it can reduce the incidence of postoperative pulmonary complications (PPCs)., Methods: In this study, the data of 757 patients who underwent VATS wedge resection at a medical center were retrospectively reviewed. The patients were divided into the DS group and the conventional analgesia (CA) group. The following parameters were analyzed: analgesic consumption during hospitalization, the incidence of PPCs, and the postoperative use of oxygen therapy., Results: Compared with the CA group, the DS group had lower nalbuphine, tramadol, parecoxib, acetaminophen, diclofenac, and utraphen consumption during the postoperative period; higher morphine and ketorolac consumption; and comparable fentanyl consumption. Nonetheless, the frequency of requesting pain relief was significantly lower in the DS group. No significant between-group differences were noted in the incidence of PPCs. However, the DS group had fewer requirements for oxygen therapy in the ward, early removal of chest tubes, and shorter length of hospital stay., Conclusion: A single preoperative injection of DS reduced the frequency of salvage analgesic administration and total consumption of certain postoperative analgesics, suggesting the effective pain relief of DS, and it did not increase the incidence of PPCs. Additionally, it reduced the need for postoperative oxygen therapy, which may suggest a better prognosis and smoother postoperative pulmonary recovery for patients.

Climate change adversely impacts global health. Increasingly, temperature variability, inclement weather, declining air quality, and growing food and clean water supply insecurities threaten human health. Earth's temperature is projected to increase up to 6.4 °C by the end of the 21st century, exacerbating the threat. Public and health care professionals, including pulmonologists, perceive the detrimental effects of climate change and air pollution and support efforts to mitigate its effects. In fact, evidence is strong that premature cardiopulmonary death is associated with air pollution exposure via inhalation through the respiratory system, which functions as a portal of entry. However, little guidance is available for pulmonologists in recognizing the effects of climate change and air pollution on the diverse range of pulmonary disorders. To educate and mitigate risk for patients competently, pulmonologists must be armed with evidence-based findings of the impact of climate change and air pollution on specific pulmonary diseases. Our goal is to provide pulmonologists with the background and tools to improve patients' health and to prevent adverse outcomes despite climate change-imposed threats. In this review, we detail current evidence of climate change and air pollution impact on a diverse range of pulmonary disorders. Knowledge enables a proactive and individualized approach toward prevention strategies for patients, rather than merely treating ailments reactively., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

As the public health burden of air pollution continues to increase, new strategies to mitigate harmful health effects are needed. Dietary antioxidants have previously been explored to protect against air pollution-induced lung injury producing inconclusive results. Inhaled (pulmonary or nasal) administration of antioxidants presents a more promising approach as it could directly increase antioxidant levels in the airway surface liquid (ASL), providing protection against oxidative damage from air pollution. Several antioxidants have been shown to exhibit antioxidant, anti-inflammatory, and anti-microbial properties in in vitro and in vivo models of air pollution exposure; however, little work has been done to translate these basic research findings into practice. This narrative review summarizes these findings and data from human studies using inhaled antioxidants in response to air pollution, which have produced positive results, indicating further investigation is warranted. In addition to human studies, cell and murine studies should be conducted using more relevant models of exposure such as air-liquid interface (ALI) cultures of primary cells and non-aqueous apical delivery of antioxidants and pollutants. Inhalation of antioxidants shows promise as a protective intervention to prevent air pollution-induced lung injury and exacerbation of existing lung disease., (© 2023. The Author(s).)

Postoperative pulmonary complications (PPCs) are associated with poor patient outcomes, increased costs and prolonged hospitalizations. Incentive spirometry (IS) reduces PPC incidence, but patient IS adherence is often suboptimal. Thus, the purpose of this study was to explore patients' beliefs about, and knowledge of PPCs and IS. We observed IS technique and conducted interviews guided by qualitative descriptive methodologies and the Health Belief Model. Verbatim transcripts of interviews were analyzed using inductive and deductive content analytic methods. Twenty postoperative spinal surgery patients at a single tertiary hospital were enrolled. Five categories related to PPC and IS beliefs and knowledge were identified: (1) social support, (2) preventing a PPC, (3) learning about PPCs, (4) reminders, and (5) lack of IS knowledge. Understanding why patients do not adhere to IS protocols is crucial for minimizing the risk of iatrogenic PPCs and developing strategies to improve adherence to IS.

Background: Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery., Methods: Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (≥2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1-2 through POD 7; PPC grades 3-4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery., Discussion: Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery., Trial Registration: ClinicalTrial.gov NCT04108130., Competing Interests: AFB reports additional research funding from the US Department of Defense, the Merck Investigator-initiated Studies Program and the Institute for Healthcare Quality, Safety and Efficiency for projects unrelated to the discussed work. The rest of authors report no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Fernandez-Bustamante et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: Crocin has been reported to have multiple bioactivities. However, the effect of crocin administration on caecal ligation and puncture (CLP)-induced sepsis remains unknown., Objective: We investigated the effects of crocin on CLP-induced sepsis in mice and the underlying mechanism of action., Materials and Methods: Five experimental groups ( n  = 10) of BALB/c mice were used: control, CLP (normal saline) and CLP + crocin (50, 100 and 250 mg/kg, 30 min prior to CLP). Mice were sacrificed 24 h after CLP. Liver, kidney and lung histopathology, indicator levels, apoptotic status, pro-inflammatory cytokines and relative protein levels were evaluated., Results: Compared to the CLP group, crocin treatment significantly increased the survival rate (70%, 80%, 90% vs. 30%). Crocin groups exhibited protection against liver, kidney and lung damage with mild-to-moderate morphological changes and lower indicator levels: liver (2.80 ± 0.45, 2.60 ± 0.55, 1.60 ± 0.55 vs. 5.60 ± 0.55), kidney (3.00 ± 0.71, 2.60 ± 0.55, 1.40 ± 0.55 vs. 6.20 ± 0.84) and lungs (8.00 ± 1.59, 6.80 ± 1.64, 2.80 ± 0.84 vs. 14.80 ± 1.79). The proinflammatory cytokines (IL-1β, TNF-α, IL-6 and IL-10 levels in the crocin groups) were distinctly lower and the apoptotic index showed a significant decrease. Crocin administration significantly suppressed p38 MAPK phosphorylation and inhibited NF-κB/IκBα and Bcl-2/Bax activation., Discussion and Conclusions: Pre-treatment with crocin confers protective effects against CLP-induced liver, kidney and lung injury, implying it to be a potential therapeutic agent.

Competing Interests: AA gave presentations at symposia for, served on scientific advisory boards for, received research funds from, or did a combination thereof for AstraZeneca, Chiesi, GlaxoSmithKline, Menarini, MSD, Nuvaira, Orion, Sanofi, and Zambon. CFV gave presentations at symposia, served on scientific advisory boards, or did both for Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Grifols, Insmed, Menarini, Novartis, Nuvaira, and MedUpdate. DMGH received sponsorship to attend international meetings and honoraria for lecturing, attending advisory boards, and preparing educational materials from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Inogen, Menarini, MedUpdate, Novartis, Pfizer, Sandoz, and Sanofi.

Post-tuberculosis lung disease (PTLD) refers to a group of lung diseases with chronic respiratory abnormalities, with or without clinical symptoms, partly or entirely caused by pulmonary tuberculosis. PTLD has high morbidity, disability rate and mortality, and has a serious impact on individuals, families and society. It is of great significance to fully understand its harm, explore its mechanism, and conduct in-depth research on its prevention, treatment, and rehabilitation.

Introduction: Despite the growing evidence on efficacy, little is known regarding the efficiency of Vitamin A supplementation to decrease the probability of chronic lung disease (CLD) in preterm infants. This study aims to determine the cost-utility of Vitamin A to prevent CLD in preterm infants in Colombia., Methods: A decision tree model was used to estimate the cost and quality-adjusted life-years (QALYs) of Vitamin A supplementation in preterm infants. Multiple sensitivity analyses were conducted to evaluate the robustness of the model. Cost-effectiveness was evaluated at a willingness-to-pay value of US$5180., Results: Vitamin A was associated with lower costs and higher QALYs. The expected annual cost per patient with Vitamin A was US$1579 (95% CI US$1555-US$1585) and without Vitamin A was US$1913 (95% CI US$1891-US$1934). The QALYs per person estimated with Vitamin A was 0.66 (95% CI 0.66-0.67) and without Vitamin A was 0.61 (95% CI 0.60-0.61). This position of absolute dominance (Vitamin A has lower costs and higher QALYs than without Vitamin A) is unnecessary to estimate the incremental cost-effectiveness ratio., Conclusion: Our economic evaluation shows that Vitamin A is cost-effective to reduce the incidence rate of CLD in premature infants in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines., (© 2022 Wiley Periodicals LLC.)

Background: Prolonged spinal surgery in the prone position may lead to postoperative pulmonary complications (PPCs). We aimed to compare the effects of driving pressure-guided ventilation versus conventional protective ventilation on postoperative pulmonary complications in patients undergoing spinal surgery in the prone position. We hypothesized that driving pressure-guided ventilation would be associated with a decreased incidence of PPC., Methods: We enrolled 78 patients into this single-center, double-blind, randomized controlled trial. The driving pressure (DP) group (n = 40) received a tidal volume of 6 ml/kg of predicted body weight, individualized positive end-expiratory pressure (PEEP) which produced the lowest driving pressure (plateau pressure-PEEP), and a recruitment maneuver. The protective ventilation (PV) group (n = 38) received the same tidal volume and recruitment maneuver but with a fixed PEEP of 5 cm H 2 O. Our primary outcome was postoperative pulmonary complications based on Lung Ultrasound Scores (LUS) at the end of the surgery and the simplified Clinical Pulmonary Infection Score (sCPIS) on postoperative days (POD) 1 and 3., Results: DP patients had lower LUS and POD1 sCPIS than the PV group ( p  < 0.01). DP patients had lower driving pressure during the surgery than PV patients ( p  < 0.01). Perioperative arterial blood gases and hemodynamic parameters were comparable between the two groups ( p  > 0.05). The visual pain score (VAS) in postoperative days, drainage, and lengths of stay (LOS) were also similar between the two groups ( p  > 0.05)., Conclusions: Driving pressure-guided ventilation during spinal surgery with a prolonged prone patient position may reduce the incidence of early postoperative pulmonary complications, compared with conventional protective ventilation.

Aim: To determine whether the injection of haemocoagulase into the biopsy tract can reduce pneumothorax and pulmonary haemorrhage after computed tomography (CT)-guided percutaneous transthoracic lung biopsy (PTLB)., Materials and Methods: A retrospective study was performed involving patients with undiagnosed pulmonary lesions scheduled for PTLB between January 2020 and March 2021. Patients were assigned to the haemocoagulase group or the non-haemocoagulase group. After CT-guided biopsies were performed with a 17 G coaxial system, patients in the haemocoagulase group received a haemocoagulase injection (0.2-0.5 units) in the biopsy tract as the sheath was withdrawn. Postoperative image studies were performed to evaluate complications, including pneumothorax and pulmonary haemorrhage. Factors, including the patient's position, lesion location, and pathological results, were evaluated to determine their associations with the complications., Results: A total of 100 patients were included, with 44 men and a mean age of 53 years old. The overall incidences of pneumothorax and pulmonary haemorrhage were 15% and 13%, respectively. The incidences of pneumothorax and pulmonary haemorrhage were statistically significantly lower in the haemocoagulase group (8% and 6%, respectively) than in the non-haemocoagulase group (22% and 20%, respectively; p=0.04 and 0.03, respectively). There was no statistically significant difference in haemoptysis between the haemocoagulase (6%) and non-haemocoagulase (2%) groups (p=0.23). There were also no statistically significant associations of pneumothorax or pulmonary haemorrhage with the patients' positions, lesion location, or pathological results., Conclusion: Biopsy tract haemocoagulase injection reduced the incidences of postoperative pneumothorax and pulmonary haemorrhage after PTLB., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The AZTEC trial is a multi-centre, randomised, placebo-controlled trial of azithromycin to improve survival without development of chronic lung disease of prematurity (CLD) in preterm infants. The statistical analysis plan for the clinical outcomes of the AZTEC trial is described., Methods and Design: A double-blind, randomised, placebo-controlled trial of a 10-day course of intravenous azithromycin (20 mg/kg for 3 days; 10 mg/kg for 7 days) administered to preterm infants born at < 30 weeks' gestational age across UK tertiary neonatal units. Following parental consent, infants are randomly allocated to azithromycin or placebo, with allocated treatment starting within 72 h of birth. The primary outcome is survival without moderate/severe CLD at 36 weeks' postmenstrual age (PMA). Serial respiratory fluid and stool samples are being collected up to 21 days of life. The target sample size is 796 infants, which is based on detecting a 12% absolute difference in survival without moderate/severe CLD at 36 weeks' PMA (90% power, two-sided alpha of 0.05) and includes 10% loss to follow-up., Results: Baseline demographic and clinical characteristics will be summarised by treatment arm and in total. Categorical data will be summarised by numbers and percentages. Continuous data will be summarised by mean, standard deviation, if data are normal, or median, interquartile range, if data are skewed. Tests of statistical significance will not be undertaken for baseline characteristics. The primary analysis, on the intention to treat (ITT) population, will be analysed using multilevel logistic regression, within a multiple imputation framework. Adjusted odds ratios, 95% confidence intervals, and p-values will be presented. For all other analyses, the analysis population will be based on the complete case population, which is a modified ITT population. All analyses will be adjusted for gestational age and treatment arm and account for any clustering by centre and/or multiple births as a random effect., Conclusion: We describe the statistical analysis plan for the AZTEC trial, including the analysis principles, definitions of the key clinical outcomes, methods for primary analysis, pre-specified subgroup analysis, sensitivity analysis, and secondary analysis. The plan has been finalised prior to the completion of recruitment., Trial Registration: ISRCTN registry ISRCTN11650227. Registered on 31 July 2018., (© 2022. The Author(s).)

Exposure to particulate matter (PM)2.5 in air pollution is a serious health issue worldwide. At present, effective prevention measures and modalities of treatment for PM2.5-caused lung toxicity are lacking. This study elucidated the protective effect of astragaloside IV (Ast), a natural product from Astragalus membranaceous Bunge, against PM2.5-caused lung toxicity and its possible molecular mechanisms. The mice model of lung toxicity was performed by intratracheal instillation of PM2.5 dust suspension. The investigation was performed with Ast or in combination with nigericin, which is a NOD-like receptor protein 3 (NLRP3) activator. The results revealed that PM2.5 lead significant lung inflammation and promoted the pyroptosis pattern of cell death by upregulating pro-inflammatory cytokines and causing oxidative stress related to the NLRP3 inflammasome-mediated pyroptosis pathway. Ast protected against PM2.5 resulted lung toxicity via suppressing NLRP3 inflammasome-mediated pyroptosis via NLRP3/caspase-1 axis inhibition, thereby protecting the lung against PM2.5-induced lung inflammation and oxidative damage, eventually resulting in prolonged survival in mice. Nigericin partially reversed the protective effects of Ast. The present research provides new insights into the therapeutic potential of Ast, demonstrating that it might be a possible candidate for the prevention of PM2.5-caused respiratory diseases. Targeting the NLRP3 inflammasome might be a novel therapeutic tactic for PM2.5-caused respiratory diseases., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To describe the National Heart Lung and Blood Institute (NHLBI) sponsored Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease (DECIPHeR) Alliance to support late-stage implementation research aimed at reducing disparities in communities with high burdens of cardiovascular and/or pulmonary disease., Study Setting: NHBLI funded seven DECIPHeR studies and a Coordinating Center. Projects target high-risk diverse populations including racial and ethnic minorities, urban, rural, and low-income communities, disadvantaged children, and persons with serious mental illness. Two projects address multiple cardiovascular risk factors, three focus on hypertension, one on tobacco use, and one on pediatric asthma., Study Design: The initial phase supports planning activities for sustainable uptake of evidence-based interventions in targeted communities. The second phase tests late-stage evidence-based implementation strategies., Data Collection/extraction Methods: Not applicable., Principal Findings: We provide an overview of the DECIPHeR Alliance and individual study designs, populations, and settings, implementation strategies, interventions, and outcomes. We describe the Alliance's organizational structure, designed to promote cross-center partnership and collaboration., Conclusions: The DECIPHeR Alliance represents an ambitious national effort to develop sustainable implementation of interventions to achieve cardiovascular and pulmonary health equity., (© 2022 The Authors. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Objectives: Cyclophosphamide (CPA) is highly effective in treating several human tumours and autoimmune disorders; but, it triggers deleterious side effects. Avocado, Persea americana (Mill.), is a widely consumed fruit with pronounced nutritional and medicinal value. Though many studies examined the protective mechanisms of natural products against CPA toxicity, almost none investigated the modulation of CPA metabolism as a potential underlying mechanism for protection. Here, we investigated the modulating effect of avocado extract (AE) on certain CPA metabolizing enzymes and its correlation with the extent of CPA-induced pulmonary toxicity and urotoxicity., Methods: Rats received oral AE (0.9 g/kg body weight/day) 7 days before a single CPA injection (150 mg/kg body weight) and continued AE intake for 2, 7 or 28 days to study three phases of CPA-induced urotoxicity and pulmonary toxicity., Key Findings: CPA acutely elevated then reduced hepatic microsomal cytochrome P450 2B6 (CYP2B6) content and significantly suppressed bladder and lung glutathione-S-transferase activity. Furthermore, CPA elevated lung myeloperoxidase activity, DNA content and hydroxyproline level and bladder blood content. AE ameliorated CPA-induced derangements through suppression of CYP2B6 and myeloperoxidase and augmentation of glutathione-S-transferase activity in CPA-treated rats., Conclusions: AE modulation of CPA metabolizing enzymes and potential anti-inflammatory effect may mitigate CPA-induced toxicity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nutraceuticals are dietary supplements that are used to improve health, postpone aging, prevent illnesses, and maintain the human body's correct functioning. Nutraceuticals are now garnering a lot of interest because of their nutritional and therapeutic benefits. The research indicating the relevance of nutraceuticals as a possible therapeutic candidate against inflammatory lung disease was covered in this review. Nowadays, inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, pneumonia, lung cancer, becoming highly dreadful because of their associated fatality. Inflammation is one of the cores and common factors of these diseases which is mainly associated with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, NF-κB p65 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation, and initiation of the signaling pathway of the NF-κB. The secondary metabolites from natural sources are the active component that attenuates NF-κB and the associated pathway that inhibits inflammation in lung diseases. Nutraceuticals belonging to the chemical category polyphenols, alkaloids, terpenoids, flavonoids, tannins have the potential to combat the NF-κB pathway. Accordingly, this review discusses the medical value of nutraceuticals briefly and their ability to mitigate various inflammatory lung diseases through targeting inhibition of NF-κB., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Typical lung diseases are pneumonia, asthma, sleep apnea syndrome (SA), interstitial pneumonia (IP), lung cancer, and chronic obstructive pulmonary disease (COPD). Coronavirus disease 2019 (COVID-19) is a type of viral pneumonia. Many researchers have reported that phytochemicals (chemical compounds produced by plants) and vitamin D are useful in stimulating our immunity. This review discusses the alleviation of lung diseases by grape phytochemicals and vitamin D., Discussion: Pneumonia is an acute inflammation caused by the infection of pathogens; the worst case is a fatal cytokine storm in the lung. In asthma, allergens, tobacco smoke, or air pollution may cause seizures. Lung diseases caused by lung fibrosis may manifest chronic inflammation, progress into alveolar fibrosis, and cause respiratory malfunction. SA is a lifestyle disease related to obesity and metabolic syndrome. To alleviate these symptoms, changing the eating habit is one of the strategies. Improvement in the daily lifestyle reduces the risk of lung cancer. Self-management, including nutritional management and exercise, is very important for COPD patients in addition to pharmacotherapy., Conclusion: The intake of grape phytochemicals and vitamin D prevents the progress of lung diseases. Both phytochemicals and vitamin D prevent the production of proinflammatory cytokine, TNF-α, that is responsible for inflammation and lung diseases. Daily intake of grape phytochemicals is important. The optimum vitamin D level in serum is > 30 ng/mL. For the prevention of lung diseases, upregulating immunity and maintaining good gut microbiota are important because gut microbiota change depending on what we eat., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs)., Objectives: This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy., Methods: In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC 025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR)., Results: The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC 025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC 025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%., Conclusions: In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients., Competing Interests: Funding Support and Author Disclosures This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. This study was supported in part by NIH/NCI grant RO1-CA 233610 (Dr Herrmann). Dr Perales has received personal fees from Abbvie, Bellicum, Bristol Myers Squibb, Celgene, Cidara Theraputics, Incyte, Kite/Gilead, Medigene, Miltenyi, MolMed, Nektar Therapeutics, NexImmune, Novartis, Omeros, Merck, Servier, and Tekeda; has served on data safety and monitoring boards for Cidara Therapeutics, Medigene, and Servier; and has received clinical trial support from Incyte, Kite/Gilead, and Miltenyi. Data presented in this study do not represent the opinion of the United States Food and Drug Administration (FDA). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The outbreak of Coronavirus disease 2019 (COVID-19) made imperative the use of protective devices as a source control tool. As there is no definite antiviral treatment and effective vaccine, the only efficient means of protecting and mitigating infectious contagion has been the use of personal protective equipment, especially by healthcare workers. However, masks affect the humidification process of inhaled air, possibly leading to a basal inflammatory state of the upper airways., Study Design: This is a single-center observational study conducted at the University Hospital of Catania from April 1, 2020, to June 31, 2020., Methods: We analyzed the role of protective masks on the elimination of upper airways complaints in healthcare workers of the University Hospital of Catania. We evaluated 277 subjects through a self-administered 17 item questionnaire based on respiratory, work performance and health-related quality of life domains., Results: A higher prevalence of nasal and ocular symptoms, perceived reduced work performance, difficulty in concentrating, and sleep disorders were found. After two weeks adhering to a list of good practices that we recommended, significant reversibility of the symptoms investigated and work performance enhancement were observed., Conclusions: Despite clinical complaints related to personal protective equipment, effective amelioration through usage rules is easily obtained. Given the essential use of protective masks, healthcare workers have to adhere to appropriate work and safety prevention rules.

Background: Pulmonary nontuberculous mycobacterial (pNTM) infection is mainly acquired through the inhalation of bioaerosols. Nevertheless, behavioural restrictions are rarely given by clinicians to susceptible populations, in part because the available guidelines for pNTM management emphasize more diagnosis and treatment than prevention. Aim of this review is to clarify if pNTM prevention should routinely include recommendations about risk reducing behaviors., Methods: We used PubMed as biomedical database. We limited our search to the publication period 2000 to 2020 with selected keyword combinations including "nontuberculous mycobacteria", "water", "soil", and "exposure". Titles and abstract of selected articles were systematically screened. Articles were included in the analysis if they were published under free access through the digital library of the University of Brescia (Italy), and provided full text either in English, French, German or Italian. Articles were excluded if the topic was beyond the aim of our study. Finally, we selected 20 articles., Results: Studies disagree in identifying the type of aerosol posing the highest risk for the development of pNTM infection. In the retrieved publications the colonization of household niches has been associated with a higher risk of pNTM disease, such as in the exposure to shower aerosols. Considering the non-household settings, the exposure to aerosols in indoor swimming and the higher soil exposure (>2 h/week) seem to correlate with a higher risk to develop pNTM disease. According to our findings, randomized behavioural intervention studies are missing., Conclusions: Stringent scientific evidence is missing to formulate recommendations on behavioural risk reduction for pNTM., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Along with surging threats and antibiotic resistance of Pseudomonas aeruginosa in health care settings, it is imperative to develop effective vaccines against P. aeruginosa infection. In this study, we used an Asd (aspartate-semialdehyde dehydrogenase)-based balanced-lethal host-vector system of a recombinant Yersinia pseudotuberculosis mutant to produce self-adjuvanting outer membrane vesicles (OMVs). The OMVs were used as a carrier to deliver the heterologous PcrV-HitA T (PH) fusion antigen of P. aeruginosa for vaccine evaluation. Intramuscular vaccination with OMVs carrying the PH antigen (referred to rOMV-PH) afforded 73% protection against intranasal challenge with 5 × 10 6 (25 50% lethal doses) of the cytotoxic PA103 strain and complete protection against a noncytotoxic PAO1 strain. In contrast, vaccination with the PH-deficient OMVs or PH antigen alone failed to offer effective protection against the same challenge. Immune analysis showed that the rOMV-PH vaccination induced potent humoral and Th1/Th17 responses compared to the PH vaccination. The rOMV-PH vaccination rapidly cleared P. aeruginosa burdens with coordinated production of proinflammatory cytokines in mice. Moreover, antigen-specific CD4 + and CD8 + T cells and their producing cytokines (tumor necrosis factor alpha and interleukin-17A), rather than antibodies, were essential for protection against pneumonic P. aeruginosa infection. Our studies demonstrated that the recombinant Y. pseudotuberculosis OMVs delivering heterologous P. aeruginosa antigens could be a new promising vaccine candidate for preventing the spread of drug-resistant P. aeruginosa. IMPORTANCE Hospital- and community-acquired infections with Pseudomonas aeruginosa cause a high rate of morbidity and mortality in patients who have underlying medical conditions. The spread of multidrug-resistant P. aeruginosa strains is becoming a great challenge for treatment using antibiotics. Thus, a vaccine as one of the alternative strategies is urgently required to prevent P. aeruginosa infection.

Background: Despite progress in perioperative care standards, there has not been a significant risk reduction in morbidity and mortality rates of lower extremity amputations, an intermediate risk surgery performed on high risk patients. The single-shot peripheral nerve block has shown equivocal impact on postoperative course following lower extremity amputation. Hence, we assessed the potential of preemptive use of continuous catheter-based peripheral nerve block in lower extremity amputations for reduction in pulmonary complications, acute post-operative pain scores, and opioid use in post-operative period., Methods: A retrospective review of a quality improvement project initiated in 2018 was conducted to compare outcomes amongst general anesthesia in combination with a catheter-based peripheral nerve block (catheter group) and general anesthesia alone in patients receiving lower extremity amputation. The rate of postoperative pulmonary complications was identified as a primary endpoint. The secondary outcomes assessed were acute post-operative pain scores and opioid consumption up to 48 hours. Our analysis was adjusted for potential confounding variables inclusive of demographics, medical comorbidities, type of surgical procedure and smoking status., Results: Ninety-six patients were included in the study (61 in the general anesthesia group, 35 in the catheter group). After adjusting for baseline demographics, comorbidities, surgical technique and smoking status, the odds of postoperative pulmonary complications were significantly lower with catheter-based peripheral nerve block in comparison to general anesthesia alone, OR 0.11 [95% CI, 0.01- 0.88] (P = 0.048). The decrease in acute pain scores was also observed in the catheter group when compared to general anesthesia alone, OR 0.72 [95% CI, 0.56 - 0.93] (P = 0.012). Similarly, the opioid consumption was also lower in the catheter group in comparison to general anesthesia alone, OR 0.97 [95% CI, 0.95 - 0.99] (P = 0.025)., Conclusion: Preemptive use of continuous peripheral nerve block in patients undergoing lower extremity amputation reduces the incidence of pulmonary complications, acute postoperative pain scores and narcotic use in post-operative period., (Copyright © 2021. Published by Elsevier Inc.)

Background: The effect of general anesthetics (propofol and volatile anesthetics) on pulmonary outcome after lung resection surgery with one-lung ventilation (OLV) is yet undetermined. We evaluated the effect of intravenous anesthesia (propofol) and volatile anesthesia (sevoflurane or desflurane) regimens on postoperative pulmonary complications (PPCs) in patients undergoing lung resection surgery., Methods: This prospective, randomized controlled trial enrolled 555 adult patients scheduled for lung resection surgery with OLV. Participants were randomized to 1 of 3 general anesthetic regimens (propofol, sevoflurane, or desflurane). Standard anesthesia and ventilation protocols were followed in all groups. The primary outcome was a composite of PPCs in the first 7 postoperative days. Secondary outcomes included the severity of PPCs and major postoperative complications classification. Intergroup difference in the primary outcome was assessed for significance using the Pearson χ2 test., Results: Of 837 patients who were assessed for eligibility, 555 were randomized and 545 were analyzed. One hundred and seventy-nine patients were assigned to the propofol group, 182 in the sevoflurane group, and 184 in the desflurane group. The incidence of PPCs did not differ between the combined volatile anesthetics (sevoflurane and desflurane) group and the propofol group (21.9% vs 24.0%; odds ratio, 0.89; 95% confidence interval, 0.58-1.35; P = .570). The PPCs grade and Clavien-Dindo scores did not differ significantly across groups., Conclusions: In patients undergoing lung resection surgery with OLV, general anesthesia with volatile anesthetics (sevoflurane or desflurane) did not reduce PPCs compared with propofol. No difference in secondary outcomes was observed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Primary prevention and interception of chronic lung disease are essential in the effort to reduce the morbidity and mortality caused by respiratory conditions. In this review, we apply a life course approach that examines exposures across the life span to identify risk factors that are associated with not only chronic lung disease but also an intermediate phenotype between ideal lung health and lung disease, termed "impaired respiratory health." Notably, risk factors such as exposure to tobacco smoke and air pollution, as well as obesity and physical fitness, affect respiratory health across the life course by being associated with both abnormal lung growth and lung function decline. We then discuss the importance of disease interception and identifying those at highest risk of developing chronic lung disease. This work begins with understanding and detecting impaired respiratory health, and we review several promising molecular biomarkers, predictive symptoms, and early imaging findings that may lead to a better understanding of this intermediate phenotype., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

This narrative review provides a summary of the impact of tobacco smoking on the respiratory system and the benefits of smoking cessation. Tobacco smoking is one of the leading preventable causes of death world-wide and a major risk factor for lung cancer and chronic obstructive pulmonary disease. Smoking is also associated with an increased risk of respiratory infections and appears to be related to poorer outcomes among those with COVID-19. Non-smokers with second-hand smoke exposure also experience significant adverse respiratory effects. Smoking imposes enormous health- and non-health-related costs to societies. The benefits of smoking cessation, in both prevention and management of respiratory disease, have been known for decades and, to this day, cessation support remains one of the most important cost-effective interventions that health professionals can provide to people who smoke. Cessation at any age confers substantial health benefits, even in smokers with established morbidities. As other treatments for chronic respiratory disease advance and survival rates increase, smoking cessation treatment will become even more relevant. While smoking cessation interventions are available, the offer of these by clinicians and uptake by patients remain limited., (© 2020 Society for the Study of Addiction.)

Electronic cigarettes (e-cigarettes) or vaping use in adolescents has emerged as a public health crisis that impacts the perioperative care of this vulnerable population. E-cigarettes have become the most commonly used tobacco products among youth in the United States. Fruit and mint flavors and additives such as marijuana have enticed children and adolescents. E-cigarette, or vaping, product use-associated lung injury (EVALI) is a newly identified lung disease linked to vaping. Clinical presentation of EVALI can be varied, but most commonly includes the respiratory system, gastrointestinal (GI) tract, and constitutional symptoms. Clinical management of EVALI has consisted of vaping cessation and supportive therapy, including supplemental oxygen, noninvasive ventilation, mechanical ventilation, glucocorticoids, and empiric antibiotics, until infectious causes are eliminated, and in the most severe cases, extracorporeal membrane oxygenation (ECMO). Currently, although there is an insufficient evidence to determine the safety and the efficacy of e-cigarettes for perioperative smoking cessation, EVALI clearly places these patients at an increased risk of perioperative morbidity. Given the relatively recent introduction of e-cigarettes, the long-term impact on adolescent health is unknown. As a result, the paucity of postoperative outcomes in this potentially vulnerable population does not support evidence-based recommendations for the management of these patients. Clinicians should identify "at-risk" individuals during preanesthetic evaluations and adjust the risk stratification accordingly. Our societies encourage continued education of the public and health care providers of the risks associated with vaping and nicotine use and encourage regular preoperative screening and postoperative outcome studies of patients with regard to smoking and vaping use., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Herein, we report a new technique of middle lobe fixation using Hemopatch after thoracoscopic right upper lobectomy. A 3-0 atraumatic polypropylene suture is passed first through the Hemopatch, then two not-inflated lobes, and then again patch. The lung is half-inflated, and the Hemopatch is placed onto the surface of the two half-inflated lobes in a bridging manner over the fissure. The suture is then tied by a clip. This procedure was successfully applied in five consecutive patients after thoracoscopic right upper lobectomy for cancer. No complications occurred during and after operation., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Fast-track anesthesia in liver transplantation (LT) has been discussed over the past few decades; however, factors associated with immediate extubation after LT surgery are not well defined. This study aimed to identify predictive factors and examine impacts of immediate extubation on post-LT outcomes., Methods: A total of 279 LT patients between January 2014 and May 2017 were included. Primary outcome was immediate extubation after LT. Other postoperative outcomes included reintubation, intensive care unit stay and cost, pulmonary complications within 90 days, and 90-day graft survival. Logistic regression was performed to identify factors that were predictive for immediate extubation. A matched control was used to study immediate extubation effect on the other postoperative outcomes., Results: Of these 279 patients, 80 (28.7%) underwent immediate extubation. Patients with anhepatic time >75 minutes and with total intraoperative blood transfusion ≥12 units were less likely to be immediately extubated (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = 0.02; OR, 0.11; 95% CI, 0.05-0.21; P < 0.001). The multivariable analysis showed immediate extubation significantly decreased the risk of pulmonary complications (OR, 0.34; 95% CI, 0.15-0.77; P = 0.01). According to a matched case-control model (immediate group [n = 72], delayed group [n = 72]), the immediate group had a significantly lower rate of pulmonary complications (11.1% versus 27.8%; P = 0.012). Intensive care unit stay and cost were relatively lower in the immediate group (2 versus 3 d; P = 0.082; $5700 versus $7710; P = 0.11). Reintubation rates (2.8% versus 2.8%; P > 0.9) and 90-day graft survival rates (95.8% versus 98.6%; P = 0.31) were similar., Conclusions: Immediate extubation post-LT in appropriate patients is safe and may improve patient outcomes and resource allocation., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)