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Background: Identification of hypoxaemia and hypercapnia is essential for the diagnosis and treatment of acute respiratory failure. While arterial blood gas (ABG) analysis is standard for PO2 and PCO2 measurement, venous blood gas (VBG) analysis is increasingly used as an alternative. Previous systematic reviews established that VBG reporting of PO2 and PCO2 is less accurate, but the impacts on clinical management and patient outcomes are unknown. Aims: This study aimed to systematically review available evidence of the clinical impacts of using ABGs or VBGs and examine the arteriovenous difference in blood gas parameters. Methods: A comprehensive search of the MEDLINE, Embase and Cochrane Library databases since inception was conducted. Included studies were prospective or cross‐sectional studies comparing peripheral ABG to peripheral VBG in adult non‐critical care inpatients presenting with respiratory symptoms. Results: Of 15 119 articles screened, 15 were included. No studies were found that examined clinical impacts resulting from using VBG compared to ABG. Included studies focused on the agreement between ABG and VBG measurements of pH, PO2, PCO2 and HCO3−. Due to the heterogeneity of the included studies, qualitative evidence synthesis was performed. While the arteriovenous difference in pH and HCO3− was generally predictable, the difference in PO2 and PCO2 was more significant and less predictable. Conclusions: Our study reinforces the notion that VBG is not comparable to ABG for physiological measurements. However, a key revelation from our research is the significant lack of data regarding the clinical implications of using VBG instead of ABG, a common scenario in clinical practice. This highlights a critical knowledge gap. [ABSTRACT FROM AUTHOR]

Objectives: To investigate temporal changes in the association between SARS‐CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. Methods: Serial oropharyngeal and blood samples were obtained from hospitalized COVID‐19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission). Results: Elevated admission levels of IL (interleukin)‐6, IL‐33, IL‐8, monocyte chemoattractant protein‐1 (MCP‐1), interferon‐γ‐induced protein 10 (IP‐10), IL‐1β, and IL‐1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP‐10 and MCP‐1 at days 3–5, accompanied by IL‐8 and IL‐6 at days 7–10. Finally, there was a seemingly additive effect of IP‐10, MCP‐1, and IL‐6 in predicting severe outcomes when combined with high VL at baseline. Conclusions: An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high‐risk patients. [ABSTRACT FROM AUTHOR]

Background Objective(s) Design Setting Patients Intervention(s) Main Outcome Measure(s) Results Conclusions Minor but painful medical procedures are often handled at the operating room. If safe and effective treatment options are available many procedures may be performed outside of the operating room.The objective of this study is to assess the adverse events of intranasal s‐ketamine and/or sufentanil alone or as part of a multimodal analgesic regime for medical procedures outside of the operating room. Secondary outcomes included analgesic effect, doses and indications for use.Retrospective observational study.Tertiary care paediatric hospital.Children 1 year up till 18 years.Intranasal (IN) sufentanil (S), intranasal s‐ketamine (K) or the free combination of the two drugs (SK).The frequency of adverse events including serious adverse events reported by intervention.Between 2004 and 2014, 2185 medical procedures were registered, including 652 procedures with IN SK, 1469 procedures with IN S and 64 procedures with IN K. The children's median age was 5.6 years (range 1.0–17.9). Medical procedures with at least one adverse event were 18% with IN SK, 25% with IN K and 18% with IN S. Common adverse events included episodes of vomiting (9%), nausea (8%) and dizziness (3%). In two patients receiving IN S, serious adverse events occurred. One patient had respiratory depression and bronchospasm and another patient with cerebral palsy had a seizure. Both were handled immediately and did not result in any sequelae. The median doses of intranasal sufentanil were 38% lower when combined with s‐ketamine (IN SK free combination: sufentanil dose 0.5 μg/kg (range 0.2–1.3) and s‐ketamine dose 0.5 mg/kg (range 0.2–1.5). IN S monotherapy, sufentanil dose 0.8 μg/kg (range 0.2–2.7)). Similar analgesic effect was reported for S and SK.Intranasal sufentanil and/or s‐ketamine are feasible for the treatment of procedural pain in an ambulatory setting with appropriate per‐ and post‐procedural observations and trained staff. [ABSTRACT FROM AUTHOR]

The article describes the case of a seven-day old neonate with prenatal diagnosis of congenital pulmonary airway malformation and was diagnosed with anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA), a rate congenital heart disease. It describes the patient's echocardiographic results and cites possible complications from extracorporeal membrane exygenation (ECMO). It refers to coronary reimplantation as the most common surgical strategy for ARCAPA.

Extracorporeal membrane oxygenation (ECMO) is a type of circulatory life support for patients with severe lung failure. The use of ECMO has increased worldwide since the pandemic of H1N1 in 2009 and more recently SARS‐CoV‐2 in 2020 both of which caused severe respiratory failure. ECMO patients experience both increased risk of bleeding and thrombosis. This is due to the pathological insult that damages the lungs, the ECMO circuit, coagulopathy, inflammation and anticoagulation. ECMO presents unique demands on the coagulation laboratory both in tests required to manage the patients and result interpretation. This is a personal opinion of 20 years ECMO experience as a clinical scientist and a short current review of the literature. It will focus on the laboratory coagulation tests used to manage ECMO patients, including different anticoagulants used, testing frequency and interpretation of the results. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine if extended‐release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly‐d,l‐Lactic Acid (PDLLA) and/or Polycaprolactone (PCL‐1 or PCL‐2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97–100 days after implantation. Following the administration of a 30 μg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre‐dose respiratory rate (RR). The BIOPIN NTX‐implanted dogs were exposed to escalating doses of intravenous fentanyl (30 μg/kg, 60 μg/kg, 90 μg/kg, and 120 μg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 μg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 μg/kg and especially at 120 μg/kg. Bioabsorbable, extended‐release BIOPIN naltrexone implants are effective in mitigating fentanyl‐induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl‐induced respiratory depression in humans. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Adverse events reviews are a fundamental component of trauma quality improvement (QI) that facilitate the correction of systemic issues in care. Although injury‐related mortality in Cameroon is substantial, to our knowledge, opportunities for QI have not been formally assessed. Thus, a formal review of adverse events in Cameroonian trauma patients was implemented as a first step toward identifying targets for systems modification.A QI committee composed of multidisciplinary experts at four hospitals in Cameroon was formed to review adverse events including deaths among trauma patients from 2019 to 2021. Events were discussed at newly established morbidity and mortality conferences and committee meetings to identify contributing factors and overall preventability.During 50 meetings, 95 adverse events were reviewed, including 58 deaths (61%). Other adverse events were delays in diagnosis/treatment (22%) and surgical site infections (17%). Overall, 34 deaths (59%) were classified as preventable, 21% potentially preventable, and 21% not preventable. Over half (52%) of the 46 preventable or potentially preventable deaths occurred in the emergency department (ED); while brain injury (57%), respiratory failure (41%), and hemorrhage (39%) were the most frequent physiologic factors associated with mortality. Contributory factors identified include lack of a structured approach to patient management, absence of continuous training for personnel, and locally adapted protocols.Basic improvements in evaluation and management of life‐threatening issues in the ED can significantly reduce the high rate of preventable trauma‐related deaths across Cameroon. Formal trauma QI methods can be utilized in low‐resource environments to determine mortality root causes and identify intervention targets. [ABSTRACT FROM AUTHOR]

Inflammation may contribute to postoperative cardiac complications and ketorolac, an anti‐inflammatory agent inhibiting cyclooxygenase (COX), shows promise in enhancing cardiac graft patency by suppressing endothelial cell proliferation in animal studies. However, the safety of postoperative ketorolac use remains controversial. This study investigates the association between early ketorolac application and complications following cardiac surgery. Data from the Medical Information Mart for Intensive Care‐IV (MIMIC‐IV) database fueled this retrospective cohort study. The primary outcome is a composite of mortality, pulmonary insufficiency, severe acute kidney injury (AKI), hemorrhage or hematoma, infection, cardiogenic shock, and cerebrovascular infarction postcardiac surgery. Propensity score matching (PSM; 1:1 match, caliper 0.2), multivariate logistic regression, interaction stratification analysis, pairwise algorithmic, and overlap weight model analyses were employed. Following inclusion and exclusion criteria, 7143 patients who underwent valvular surgery or coronary artery bypass grafting (CABG) were included. PSM created a balanced cohort of 3270 individuals (1635 in the ketorolac group). The matched cohort exhibited an 8.1% overall rate of postoperative complications, with a lower composite outcome rate in patients receiving ketorolac within 48 h of surgery compared with those without (PSM, OR 0.70 [95% CI, 0.54–0.90]). Consistent associations were observed in total cohort analyses, sensitivity, and subgroup analyses. Early ketorolac use within 48 h post‐CABG or valvular procedures in adults is independently associated with a lower incidence of composite postoperative adverse events. Prospective trials are warranted to assess causality. [ABSTRACT FROM AUTHOR]

Introduction: The cardiac pacemaker is indicated for treating various types of bradyarrhythmia, providing lifelong cardiovascular benefits. Recent data showed that COVID‐19 has impacted procedure numbers and led to adverse long‐term outcomes in patients with cardiac pacemakers. However, the impact of COVID‐19 infection on the in‐hospital outcome of patients undergoing conventional pacemaker implantation remains unclear. Method: Patients aged above 18 years who were hospitalized for conventional pacemaker implantation in the Nationwide In‐patient Sample (NIS) 2020 were identified using relevant ICD‐10 CM and PCS codes. Multivariable logistic and linear regression models were used to analyze pre‐specified outcomes, with the primary outcome being in‐patient mortality and secondary outcomes including system‐based and procedure‐related complications. Results: Of 108 020 patients hospitalized for conventional pacemaker implantation, 0.71% (765 out of 108 020) had a concurrent diagnosis of COVID‐19 infection. Individuals with COVID‐19 infection exhibited a lower mean age (73.7 years vs. 75.9 years, p =.027) and a lower female proportion (39.87% vs. 47.60%, p =.062) than those without COVID‐19. In the multivariable logistic and linear regression models, adjusted for patient and hospital factors, COVID‐19 infection was associated with higher in‐hospital mortality (aOR 4.67; 95% CI 2.02 to 10.27, p <.001), extended length of stay (5.23 days vs. 1.04 days, p <.001), and linked with various in‐hospital complications, including sepsis, acute respiratory failure, post‐procedural pneumothorax, and venous thromboembolism. Conclusion: Our study suggests that COVID‐19 infection is attributed to higher in‐hospital mortality, extended hospital stays, and increased adverse in‐hospital outcomes in patients undergoing conventional pacemaker implantation. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation (AF) and heart failure (HF) commonly coexist, resulting in adverse health and economic consequences such as declining ventricular function, heightened mortality, and reduced quality of life. However, limited information exists on the impact of COVID‐19 on AF patients that hospitalized for HF. Methods: We analyzed the 2020 U.S. National Inpatient Sample to investigate the effects of COVID‐19 on AF patients that primarily hospitalized for HF. Participants aged 18 and above were identified using relevant ICD‐10 CM codes. Adjusted odds ratios for outcomes were calculated through multivariable logistic regression. The primary outcome was inpatient mortality, with secondary outcomes including system‐based complications. Results: We identified 322,090 patients with primary discharge diagnosis of HF with comorbid AF. Among them, 0.73% (2355/322,090) also had a concurrent diagnosis of COVID‐19. In a survey multivariable logistic and linear regression model adjusting for patient and hospital factors, COVID‐19 infection was associated with higher in‐hospital mortality (aOR 3.17; 95% CI 2.25, 4.47, p < 0.001), prolonged length of stay (βLOS 2.82; 95% CI 1.71, 3.93, p < 0.001), acute myocarditis (aOR 6.64; 95% CI 1.45, 30.45, p 0.015), acute kidney injury (AKI) (aOR 1.48; 95% CI 1.21, 1.82, p < 0.001), acute respiratory failure (aOR 1.24; 95% CI 1.01, 1.52, p 0.045), and mechanical ventilation (aOR 2.00; 95% CI 1.28, 3.13, p 0.002). Conclusion: Our study revealed that COVID‐19 is linked to higher in‐hospital mortality and increased adverse outcomes in AF patients hospitalized for HF. [ABSTRACT FROM AUTHOR]

Opioid overdose is the leading cause of drug overdose lethality, posing an urgent need for investigation. The key brain region for inspiratory rhythm regulation and opioid‐induced respiratory depression (OIRD) is the preBötzinger Complex (preBötC) and current knowledge has mainly been obtained from animal systems. This study aims to establish a protocol to generate human preBötC neurons from induced pluripotent cells (iPSCs) and develop an opioid overdose and recovery model utilizing these iPSC‐preBötC neurons. A de novo protocol to differentiate preBötC‐like neurons from human iPSCs is established. These neurons express essential preBötC markers analyzed by immunocytochemistry and demonstrate expected electrophysiological responses to preBötC modulators analyzed by patch clamp electrophysiology. The correlation of the specific biomarkers and function analysis strongly suggests a preBötC‐like phenotype. Moreover, the dose‐dependent inhibition of these neurons' activity is demonstrated for four different opioids with identified IC50's comparable to the literature. Inhibition is rescued by naloxone in a concentration‐dependent manner. This iPSC‐preBötC mimic is crucial for investigating OIRD and combating the overdose crisis and a first step for the integration of a functional overdose model into microphysiological systems. [ABSTRACT FROM AUTHOR]

Purpose: Echocardiography is considered essential during cannulation placement and manipulations. Literature evaluating transthoracic echocardiography (TTE) usage during pediatric VV‐ECMO is scant. The purpose of this study is to describe the use of echocardiography during VV‐ECMO at a large, quaternary children's hospital. Methods: A retrospective, single‐year cohort study was performed of pediatric patients on VV‐ECMO via dual‐lumen cannula at our institution from January 2019 through December 2019. For each echocardiogram, final cannula component (re‐infusion port (ReP), distal tip, proximal port and distal port) positions were evaluated by one echocardiographer. For TTEs with ReP in the right atrium, two echocardiographers independently evaluated ReP direction using 2‐point (Yes/No) and 4‐point scales, which were semi‐quantitative protocols using color Doppler images to estimate ReP jet direction to the tricuspid valve. Cohen's kappa or weighted kappa was used to measure interrater agreement. Results: During study period, 11 patients (64% male) received VV‐ECMO with 49 TTEs and one transesophageal echocardiogram performed. The median patient age was 4.3 years [IQR: 1.1–11.5] and median VV‐ECMO run time of 192 h [90–349]. The median time between TTEs on VV‐ECMO was 34 h [8.3–65]. Most common position for the ReP was the right atrium (n = 33, 67%), and ReP location was not identified in five TTEs (10%). For ReP flow direction, echocardiographers agreed on 82% of TTEs using 2‐point evaluation. There was only moderate agreement between echocardiographers on the 2‐point and 4‐point assessments (k =.54, kw =.46 respectively). Conclusions: TTE is the predominant cardiac ultrasound modality used during VV‐ECMO for pediatric respiratory failure. Subjective evaluation of VV‐ECMO ReP jet direction in the right atrium is challenging, regardless of assessment method. [ABSTRACT FROM AUTHOR]

Background: Time‐resolved magnetic resonance fingerprinting (MRF), or 4D‐MRF, has been demonstrated its feasibility in motion management in radiotherapy (RT). However, the prohibitive long acquisition time is one of challenges of the clinical implementation of 4D‐MRF. The shortening of acquisition time causes data insufficiency in each respiratory phase, leading to poor accuracies and consistencies of the predicted tissues' properties of each phase. Purpose: To develop a technique for the reconstruction of multi‐phase parametric maps in four‐dimensional magnetic resonance fingerprinting (4D‐MRF) through the optimization of local T1 and T2 sensitivities. Methods: The proposed technique employed an iterative optimization to tailor the data arrangement of each phase by manipulation of inter‐phase frames, such that the T1 and T2 sensitivities, which were quantified by the modified Minkowski distance, of the truncated signal evolution curve was maximized. The multi‐phase signal evolution curves were modified by sliding window reconstruction and inter‐phase frame sharing (SWIFS). Motion correction (MC) and dot product matching were sequentially performed on the modified signal evolution and dictionary to reconstruct the multi‐parametric maps. The proposed technique was evaluated by numerical simulations using the extended cardiac‐torso (XCAT) phantom with regular and irregular breathing patterns, and by in vivo MRF data of three health volunteers and six liver cancer patients acquired at a 3.0 T scanner. Results: In simulation study, the proposed SWIFS approach achieved the overall mean absolute percentage error (MAPE) of 8.62% ± 1.59% and 16.2% ± 3.88% for the eight‐phases T1 and T2 maps, respectively, in the sagittal view with irregular breathing patterns. In contrast, the overall MAPE of T1 and T2 maps generated by the conventional approach with multiple MRF repetitions were 22.1% ± 11.0% and 30.8% ± 14.9%, respectively. For in‐vivo study, the predicted mean T1 and T2 of liver by the proposed SWIFS approach were 795 ms ± 38.9 ms and 58.3 ms ± 11.7 ms, respectively. Conclusions: Both simulation and in vivo results showed that the approach empowered by T1 and T2 sensitivities optimization and sliding window under the shortened acquisition of MRF had superior performance in the estimation of multi‐phase T1 and T2 maps as compared to the conventional approach with oversampling of MRF data. [ABSTRACT FROM AUTHOR]

An open‐label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil‐induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT 04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed a hypercapnic gas mixture through a tight‐fitting mask for an initial period of 46 min prior to a series of mask "holidays" introduced to reduce subject discomfort and encourage study completion. Ten minutes after initiating the hypercapnic gas mixture, a remifentanil bolus was administered, and an infusion continued for the study duration. Subjects were administered either naloxone or nalmefene 15 min after initiating the remifentanil infusion and MV monitored for 21 min followed by a mask holiday. Both nalmefene and naloxone produced a time‐dependent reversal of remifentanil‐induced reductions in MV measured 2.5–20 min post administration. At the primary endpoint (5 min post administration), nalmefene increases in MV (5.75 L/min) were nearly twice that produced by naloxone (3.01 L/min) (P <.0009); the point estimate favors nalmefene, demonstrating non‐inferiority and superiority. In this model of opioid‐induced respiratory depression, nalmefene has a more rapid onset of action than naloxone, which required 20 min to achieve a comparable reversal of respiratory depression. Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose. [ABSTRACT FROM AUTHOR]

The clinical spectrum of COVID‐19 includes a wide range of manifestations, from mild symptoms to severe pneumonia. HLA system plays a pivotal role in immune responses to infectious diseases. The purpose of our study was to investigate the association between HLA and COVID‐19 severity in a Japanese population. The study included 209 Japanese COVID‐19 patients aged ≥20 years. Saliva samples were collected and used to determine the HLA genotype by HLA imputation through genome‐wide association analyses. The association between HLA genotype and COVID‐19 severity was then evaluated. The allele frequency was compared between patients with respiratory failure (severe group: 91 cases) and those without respiratory failure (non‐severe group: 118 cases), categorising the data into three time periods: pre‐Omicron epidemic period, Omicron epidemic period, and total period of this study (from January 2021 to May 2023). In comparing the severe and non‐severe groups, the frequencies of the HLA‐DQA1*01:03 (35.1% vs. 10.5%, odds ratio [OR] = 4.57, corrected p [pc] = 0.041) and ‐DQB1*06:01 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) alleles were significantly higher in the severe group during the pre‐Omicron epidemic period. During the Omicron epidemic period, HLA‐DQB1*06 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) was significantly higher in the severe group. During total period of this study, HLA‐DQA1*01:03 (30.2% vs. 14.4%, OR = 2.57, corrected pc = 0.0013) and ‐DQB1*06:01 (44.5% vs. 26.7%, OR = 2.20, pc = 0.013) alleles were significantly higher in the severe group. HLA‐DQB1*06:01 and ‐DQA1*01:03 were in strong linkage disequilibrium with each other (r2 = 0.91) during total period of this study, indicating that these two alleles form a haplotype. The frequency of the HLA‐DQA1*01:03–DQB1*06:01 in the severe group was significantly higher than in the non‐severe group during pre‐Omicron epidemic period (32.4% vs. 7.9%, OR = 5.59, pc = 0.00072), and total period of this study (28.6% vs. 13.1%, OR = 2.63, pc = 0.0013). During Omicron epidemic period, the haplotype did not demonstrate statistical significance, although the odds ratio indicated a value greater 1. Frequencies of the HLA‐DQA1*01:03 and ‐DQB1*06:01 alleles were significantly higher in severe COVID‐19 patients, suggesting that these alleles are risk factors for severe COVID‐19 pneumonia in the Japanese population. [ABSTRACT FROM AUTHOR]

Trimethoprim‐sulfamethoxazole (TMP‐SMX) acute respiratory distress syndrome (ARDS) is a rare, but severe complication of a commonly prescribed antibiotic. TMP‐SMX typically affects young, otherwise well patients with a specific human leukocyte antigen type (HLA‐B*07:02 and HLA‐C*07:02). The condition is poorly understood with a unique pathological appearance and mechanism that remains unclear. Mortality rate is greater than one third. We describe the case of a previously well 18‐year‐old woman treated with a prolonged course of TMP‐SMX for a complex urinary tract infection who developed rapidly progressive respiratory failure requiring prolonged intensive care admission, extra‐corporeal membranous oxygenation, and eventual lung transplantation. No targeted treatment exists, further research is required to better understand disease pathogenetic mechanisms and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Acute exacerbation of idiopathic interstitial pneumonias (AE‐IIPs) is a disease associated with a poor prognosis in patients with IIPs. However, the specific characteristics of fluorine‐18 2‐fluoro‐2‐deoxy‐d‐glucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) imaging for AE‐IIPs remain unclear. Herein, we present the case of a patient with lung cancer combined with IIPs who underwent 18F‐FDG PET/CT at the early onset of AE‐IIPs. The scan, conducted 18 days post‐bronchoscopy for lung cancer evaluation, revealed AE‐IIPs before the onset of respiratory failure. New ground‐glass opacities appeared, accompanied by significant 18F‐FDG accumulation extending beyond these regions. To the best of our knowledge, this report represents the first assessment of 18F‐FDG PET/CT images at the early onset of AE‐IIPs before respiratory failure in humans. The observed features in this PET image could potentially contribute to our understanding of the pathophysiology of AE‐IIPs. [ABSTRACT FROM AUTHOR]

Background: As the pandemic progressed, the use of extracorporeal membrane oxygenation (ECMO) for COVID‐19‐related acute respiratory distress syndrome increased, and patient triage and transfer to ECMO centers became important to optimize patient outcomes. Our objectives are to identify predictors of patient transfer for veno‐venous extracorporeal membrane oxygenation (V‐V ECMO) evaluation as well as to describe the outcomes of accepted patients. Methods: This is a single‐center, retrospective analysis of V‐V ECMO transfer requests for adult patients with known or suspected COVID‐19 and respiratory failure from March 2020 until March 2021. Data were collected prospectively during the triage process for transfer requests as part of clinical patient care at our institution. Results: Of 341 referred patients, 112 (33%) were accepted for transfer to our facility, whereas 229 (67%) patients were declined for transfer. The Classification and Regression Tree analysis showed that patients' high pressure during airway pressure release ventilation (APRV) and age were the variables most significantly associated with the decision to accept or decline patients for transfer. Conclusions: Our triage process enabled one‐third of referred patients to be transferred for evaluation, with nearly 70% of those patients ultimately receiving ECMO support. High ventilator settings on APRV and young age were associated with acceptance for transfer. Accepted patients also had a higher incidence of adjunctive therapies (proning and paralysis) prior to transfer request, less cardiac or renal dysfunction, and a shorter duration of mechanical ventilation. Further research is warranted to investigate the outcomes of nontransferred patients. [ABSTRACT FROM AUTHOR]

Introduction: For the Veterans Health Administration (VHA) to continue to perform complex cardiothoracic surgery, there must be an established pathway for providing urgent/emergent extracorporeal life support (ECLS). Partnership with a nearby tertiary care center with such expertise may be the most resource‐efficient way to provide ECLS services to patients in post‐cardiotomy cardiogenic shock or respiratory failure. The goal of this project was to assess the efficiency, safety, and outcomes of surgical patients who required transfer for perioperative ECLS from a single stand‐alone Veterans Affairs Medical Center (VAMC) to a separate ECLS center. Methods: Cohort consisted of all cardiothoracic surgery patients who experienced cardiogenic shock or refractory respiratory failure at the local VAMC requiring urgent or emergent institution of ECLS between 2019 and 2022. The primary outcomes are the safety and timeliness of transport. Results: Mean time from the initial shock call to arrival at the ECLS center was 2.8 h. There were no complications during transfer. Six patients (86%) survived to decannulation. Conclusion: These results suggest that complex cardiothoracic surgery can be performed within the VHA system and when there is an indication for ECLS, those services can be safely and effectively provided at an affiliated, properly equipped center. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a rare X‐linked recessive disorder characterized by loss‐of‐function mutations in the gene encoding dystrophin. These mutations lead to progressive functional deterioration including muscle weakness, respiratory insufficiency, and musculoskeletal deformities. Three‐dimensional gait analysis (3DGA) has been used as a tool to analyze gait pathology through the quantification of altered joint kinematics, kinetics, and muscle activity patterns. Among 3DGA indices, the Gait Profile Score (GPS), has been used as a sensitive overall measure to detect clinically relevant changes in gait patterns in children with DMD. To enhance our understanding of the clinical translation of 3DGA, we report here the development of a population nonlinear mixed‐effect model that jointly describes the disease progression of the 3DGA index, GPS, and the functional endpoint, North Star Ambulatory Assessment (NSAA). The final model consists of a quadratic structure for GPS progression and a linear structure for GPS‐NSAA correlation. Our model was able to capture the improvement in function in GPS and NSAA in younger subjects, as well as the decline of function in older subjects. Furthermore, the model predicted NSAA (CFB) at 1 year reasonably well for DMD subjects ≤7 years old at baseline. The model tended to slightly underpredict the decline in NSAA after 1 year for those >7 years old at baseline, but the prediction summary statistics were well maintained within the standard deviation of observed data. Quantitative models such as this may help answer clinically relevant questions to facilitate the development of novel therapies in DMD. [ABSTRACT FROM AUTHOR]

Background: Loss of airway patency has been reported during initiation of palliative sedation. In present guidelines the loss of airway patency during initiation of palliative sedation is not addressed. Airway patency can be restored by jaw thrust/chin lift or placing the patient in the recovery position. Aim: A structured ethical analysis of how respiratory depression and loss of airway patency during initiation of palliative sedation should be handled. The essence of the dilemma is whether it is appropriate to apply simple non‐invasive methods to restore airway patency in order to avoid the patient's immediate death. Design: A structured analysis based on the four principles of healthcare ethics and stakeholders' interests. Results: Beneficence and autonomy support a decision not to regain airway patency whereas non‐maleficence lends weight to a decision to restore airway patency. Whether the proportionality criterion of the principle of double effect is met depends on the features of the individual case. The ethical problem appears to be a genuine dilemma where important values and arguments point to different conclusions. Conclusion: Whether to restore airway patency when the airway is obstructed during initiation of palliative sedation will ultimately be based on clinical judgment taking into account both any known patient preferences and relevant clinical information. There are strong arguments favoring both options in this clinical and ethical dilemma. The fact that a clear and universal recommendation cannot be made does not imply indifference regarding what is the clinically and ethically best option for each individual patient. [ABSTRACT FROM AUTHOR]

Adaptation of humans to challenging environmental conditions, such as extreme temperature, malnutrition, or hypoxia, is an interesting phenomenon for both basic and applied research. Identification of the genetic factors contributing to human adaptation to these conditions enhances our understanding of the underlying molecular and physiological mechanisms. In our study, we analyzed the exomes of 22 high altitude mountaineers to uncover genetic variants contributing to hypoxic adaptation. To our surprise, we identified two putative loss‐of‐function variants, rs1385101139 in RTEL1 and rs1002726737 in COL6A1 in two extremely high altitude (personal record of more than 8500 m) professional climbers. Both variants can be interpreted as pathogenic according to medical geneticists' guidelines, and are linked to inherited conditions involving respiratory failure (late‐onset pulmonary fibrosis and severe Ullrich muscular dystrophy for rs1385101139 and rs1002726737, respectively). Our results suggest that a loss of gene function may act as an important factor of human adaptation, which is corroborated by previous reports in other human subjects. [ABSTRACT FROM AUTHOR]

Pleuroperitoneal communication poses a respiratory failure risk due to pleural fluid accumulation with thoracic migration of ascites. Here, we discuss the following cases: Case 1: A woman was diagnosed with a ruptured ovarian tumor with right pleural fluid and ascites, without respiratory failure. Ovarian cystectomy was performed with inadequate removal of ascites. Postoperatively, respiratory failure occurred, and thoracentesis detected pleural fluid resembling ascites. Case 2: A woman was diagnosed with a ruptured ectopic pregnancy with right pleural fluid and ascites without respiratory failure. A diagnosis of clinical pleuroperitoneal communication was considered based on computed tomography findings. During laparoscopic salpingectomy, high‐pressure ventilation was performed to push the pleural fluid back into the abdominal cavity; a negative‐pressure drain was inserted, and the ascites was completely removed. Postoperative radiography revealed the absence of pleural fluid. Therefore, a preoperative diagnosis of clinical pleuroperitoneal communication and appropriate intraoperative techniques can prevent postoperative respiratory failure. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) incidence is decreasing in the Northern Territory (NT) but still exceeds rates elsewhere in Australia. Deaths and morbidity from advanced TB continue, with delay in diagnosis a contributor to adverse outcomes. Aims: We aimed to describe the delay in diagnosis of TB, identify risk factors for delay and examine the associations between delay and clinical outcomes. Methods: We conducted a historical cohort analysis which included adult inpatients diagnosed with TB at the Royal Darwin Hospital from 2010 to 2020. Patient delay was measured as time from symptom onset to first seeking care, and health system delay was quantified as time from first relevant clinical contact to diagnosis. The sum of these two periods was the total delay. Ethics approval was granted by NT HREC (2020‐3852). Results: Eighty‐four cases were included; the median total delay was 90 days (interquartile range (IQR): 60–121), patient delay was 53 days (IQR: 30–90), and health system delay was 21 days (IQR: 12–45). Patient delay was longer among patients with extrapulmonary (median: 100 days (IQR: 90–105) compared with pulmonary TB patients (39 days (IQR: 27–54), P < 0.0001). Health system delay was longer in those aged ≥45 years (30 days (IQR: 16–51) vs younger patients (14 days (IQR: 8–30), P = 0.007) and among non‐smokers (31 days (IQR: 21–55) vs 21 days (IQR: 10–40), P = 0.048). Median delay was longer among patients with non‐drug‐related complications of disease (P < 0.0001), those admitted to critical care (P < 0.0001), and those with respiratory failure (P = 0.001). Conclusion: The patient delays we report are longer than reported elsewhere in Australia. The next steps will require concerted efforts to improve community awareness of TB and strategies to strengthen health systems through better resourcing and healthcare provider support. [ABSTRACT FROM AUTHOR]

Despite a rapid increase in pediatric mortality rate from prescription and illicit opioids, there is limited research on the dose‐dependent impact of opioids on respiratory depression in children, the leading cause of opioid‐associated death. In this article, we extend a previously developed translational model to cover pediatric populations by incorporating age‐dependent pharmacokinetic, pharmacodynamic, and physiological changes compared to adults. Our model reproduced previous perioperative clinical findings that adults and children have similar risk of respiratory depression at the same plasma fentanyl concentration when specific endpoints (minute ventilation, CO2 tension in the blood) were used. However, our model points to a potential caveat that, in a perioperative setting, routine use of mechanical ventilation and supplemental oxygen maintained the blood and tissue oxygen partial pressures in patients and prevented the use of oxygen‐related endpoints to evaluate the consequences of respiratory depression. In a community setting when such oxygenation procedures are not immediately available, our model suggests that the higher oxygen demand and reduced cerebrovascular reactivity could make children more susceptible to severe hypoxemia and brain hypoxia, even with the same plasma fentanyl concentration as adults. Our work indicates that when developing intervention strategies to protect children from opioid overdose in a community setting, these pediatric‐specific factors may need to be considered. [ABSTRACT FROM AUTHOR]

Introduction: Acute presentations and emergencies in neuromuscular disorders (NMDs) often challenge clinical acumen. The objective of this review is to refine the reader's approach to history taking, clinical localization and early diagnosis, as well as emergency management of neuromuscular emergencies. Methods: An extensive literature search was performed to identify relevant studies. We prioritized meta‐analysis, systematic reviews, and position statements where possible to inform any recommendations. Summary: The spectrum of clinical presentations and etiologies ranges from neurotoxic envenomation or infection to autoimmune disease such as Guillain–Barré Syndrome (GBS) and myasthenia gravis (MG). Delayed diagnosis is not uncommon when presentations occur "de novo," respiratory failure is dominant or isolated, or in the case of atypical scenarios such as GBS variants, severe autonomic dysfunction, or rhabdomyolysis. Diseases of the central nervous system, systemic and musculoskeletal disorders can mimic presentations in neuromuscular disorders. Conclusions: Fortunately, early diagnosis and management can improve prognosis. This article provides a comprehensive review of acute presentations in neuromuscular disorders relevant for the emergency physician. [ABSTRACT FROM AUTHOR]

The authors discuss the extent of the problem regarding chronic obstructive pulmonary disease (COPD) among heroin users, its implications for heroin overdose risk, and strategies to address this issue. Topics include how common is early onset COPD among heroin users, evidence that COPD progresses at an accelerated rate among heroin users, and clinical implications of such high rates of COPD.

The article focuses on the usage of sugammadex in emergency departments (EDs) within a large regional health system. Topics include the demographic and clinical characteristics of patients receiving sugammadex, the primary indications for its use (especially for neurological examination post-intubation), and the variation in administration practices between academic and community hospitals.

Background: To date there remains much ambiguity in the literature regarding the immunological interplay between SARS‐CoV‐2 and HIV and the true risk posed to coinfected individuals. There has been little conclusive data regarding the use of CD4 cell count and HIV viral load stratification as predictors of COVID‐19 severity in this cohort. Methods: We performed a retrospective, observational cohort study on people living with HIV (PLWH) who contracted COVID‐19 in central and eastern Europe. We enrolled 536 patients from 16 countries using an online survey. We evaluated patient demographics, HIV characteristics and COVID‐19 presentation and outcomes. Statistical analysis was performed using SPSS 20.1. Results: The majority of the study cohort were male (76.4%) and 152 (28.3%) had a significant medical comorbidity. Median CD4 cell count at COVID‐19 diagnosis was 605 cells/μL [interquartile range (IQR) 409–824]. The majority of patients on antiretroviral therapy (ART) were virally suppressed (92%). In univariate analysis, CD4 cell count <350 cells/μL was associated with higher rates of hospitalization (p < 0.0001) and respiratory failure (p < 0.0001). Univariate and multivariate analyses found that an undetectable HIV VL was associated with a lower rate of hospitalization (p < 0.0001), respiratory failure (p < 0.0001), ICU admission or death (p < 0.0001), and with a higher chance of full recovery (p < 0.0001). Conclusion: We can conclude that detectable HIV viral load was an independent risk factor for severe COVID‐19 illness and can be used as a prognostic indicator in this cohort. [ABSTRACT FROM AUTHOR]

Objective: ACTN2, encoding alpha‐actinin‐2, is essential for cardiac and skeletal muscle sarcomeric function. ACTN2 variants are a known cause of cardiomyopathy without skeletal muscle involvement. Recently, specific dominant monoallelic variants were reported as a rare cause of core myopathy of variable clinical onset, although the pathomechanism remains to be elucidated. The possibility of a recessively inherited ACTN2‐myopathy has also been proposed in a single series. Methods: We provide clinical, imaging, and histological characterization of a series of patients with a novel biallelic ACTN2 variant. Results: We report seven patients from five families with a recurring biallelic variant in ACTN2: c.1516A>G (p.Arg506Gly), all manifesting with a consistent phenotype of asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness. None of the patients have cardiomyopathy or respiratory insufficiency. Notably, all patients report Palestinian ethnicity, suggesting a possible founder ACTN2 variant, which was confirmed through haplotype analysis in two families. Muscle biopsies reveal an underlying myopathic process with disruption of the intermyofibrillar architecture, Type I fiber predominance and atrophy. MRI of the lower extremities demonstrate a distinct pattern of asymmetric muscle involvement with selective involvement of the hamstrings and adductors in the thigh, and anterior tibial group and soleus in the lower leg. Using an in vitro splicing assay, we show that c.1516A>G ACTN2 does not impair normal splicing. Interpretation: This series further establishes ACTN2 as a muscle disease gene, now also including variants with a recessive inheritance mode, and expands the clinical spectrum of actinopathies to adult‐onset progressive muscle disease. [ABSTRACT FROM AUTHOR]

Background: Pulmonary calcification (PC) is a rare clinical entity observed following liver transplantation (LT). Most often identified in adults or in patients with concomitant renal failure, PC is rarely reported in children. While the clinical course of PC is largely benign, cases of progressive respiratory failure and death have been reported. Additionally, PC may mimic several other disease processes making diagnosis and management challenging. Currently, little is reported regarding the diagnosis, management, and long‐term outcomes of children with PC following LT. Methods: We performed a retrospective chart review of patients undergoing LT at our institution between 2006 and 2023. We identified two patients who developed PC following LT. Their diagnosis, clinical course, and long‐term outcomes are reported. A literature review of the presentation, diagnosis, management, and outcomes of adult and pediatric patients with PC post‐LT was also performed. Conclusions: Pulmonary calcifications are a rare but notable complication after pediatric liver transplantation. Our case series adds to the limited literature on this clinical entity in children but also highlights the fact that effective diagnosis and treatment may be safely accomplished without the use of lung biopsy. [ABSTRACT FROM AUTHOR]

Immediate extubation (IE) following liver transplantation (LT) has become the standard practice, even for pediatric patients. However, no preoperative or postoperative case selection protocols for IE are currently available. We have developed selection criteria for IE following pediatric LT. The aim of this study is to assess the safety and effectiveness of these selection criteria and anesthetic management protocol implemented in our hospital for IE after pediatric LT. Method: This was a retrospective study. The records of all cases undergoing LT in our center from January 2016 to December 2020 were collected. We excluded cases > 18 years old at the time of LT. Enrolled cases were divided into two groups: cases with immediate extubation (IE) or without immediate extubation (NIE). We compared preoperative conditions, intraoperative management, and postoperative courses. Finally, we classified NIE group patients into cases extubated at postoperative day 1 (early; E‐NIE) and others (delayed; D‐NIE) and compared their underlying diseases and postoperative courses. Results: In the IE group, there were 81 cases, while the NIE group consisted of 185 cases. All patients in the IE group were successfully extubated without any instances of re‐intubation due to respiratory failure. Within the E‐NIE group, comprising 130 cases, all patients were ultimately extubated without the need for tracheostomy. However, in the D‐NIE group, which encompassed 53 cases, seven patients required tracheostomy. Conclusion: In our center, the implementation of our anesthesia management protocol and the use of pre/postoperative case selection criteria have allowed for the safe practice of IE following pediatric LT. However, it should be noted that patients who cannot be extubated by Postoperative Day 1 (POD1) may be at an increased risk of requiring a tracheostomy. When contemplating IE, it is crucial to take into account the disease‐specific physiological aspects and surgical site situations. [ABSTRACT FROM AUTHOR]

Background and purpose: The study aimed to identify predictors of respiratory failure leading to mechanical ventilation (MV) and tracheostomy in Guillain−Barré syndrome (GBS). Methods: Two hundred and thirty adult cases admitted to the Neurology Unit of Modena, Italy, between January 2000 and December 2021 were studied. A cut‐off of MV starting within 8 weeks from onset of weakness was used. Univariable, multivariable logistic and Cox regression analyses were used to determine which pre‐specified clinical and diagnostic characteristics were capable of predicting MV and tracheostomy, due to weaning failure. The model was internally validated within the full cohort. The Erasmus GBS Respiratory Insufficiency Score was retrospectively applied. Results: One hundred and seventy‐six cases (76.5%) were classified as classical sensorimotor GBS and 54 (23.4%) as variants. Thirty‐two patients (13.9%) needed MV: 84.3% required respiratory support within 7 days. Independent predictors of respiratory failure and MV were older age, facial, bulbar, neck flexor weakness, dysautonomia, axonal electrophysiological subtype, cardiovascular comorbidities and higher disability score at entry. There was no association with abnormal spinal fluid parameters nor with positive serology for recent infections. Twenty‐two patients (68.7%) were ventilated for more than 7 days; 4.7% died within 8 weeks. The patients who required MV were treated more often with plasma exchange. Independent predictors of tracheostomy due to weaning trial failure were facial, bulbar, neck flexor weakness, autonomic dysfunction, associated cardiovascular morbidities and axonal electrophysiological subtype on nerve conduction study. Conclusions: Our study indicates distinct predictors of MV and tracheostomy in GBS patients. [ABSTRACT FROM AUTHOR]

Background: INTELLiVENT‐adaptive support ventilation (ASV) is an automated closed‐loop mode of invasive ventilation for use in critically ill patients. INTELLiVENT‐ASV automatically adjusts, without the intervention of the caregiver, ventilator settings to achieve the lowest work and force of breathing. Aims: The aim of this case series is to describe the specific adjustments of INTELLiVENT‐ASV in patients with acute hypoxemic respiratory failure, who were intubated for invasive ventilation. Study design: We describe three patients with severe acute respiratory distress syndrome (ARDS) because of COVID‐19 who received invasive ventilation in our intensive care unit (ICU) in the first year of the COVID‐19 pandemic. Results: INTELLiVENT‐ASV could be used successfully, but only after certain adjustments in the settings of the ventilator. Specifically, the high oxygen targets that are automatically chosen by INTELLiVENT‐ASV when the lung condition 'ARDS' is ticked had to be lowered, and the titration ranges for positive end expiratory pressure (PEEP) and inspired oxygen fraction (FiO2) had to be narrowed. Conclusions: The challenges taught us how to adjust the ventilator settings so that INTELLiVENT‐ASV could be used in successive COVID‐19 ARDS patients, and we experienced the benefits of this closed‐loop ventilation in clinical practice. Relevance to clinical practice: INTELLiVENT‐ASV is attractive to use in clinical practice. It is safe and effective in providing lung‐protective ventilation. A closely observing user always remains needed. INTELLiVENT‐ASV has a strong potential to reduce the workload associated with ventilation because of the automated adjustments. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We used independent lung ventilation (ILV) during veno‐venous extracorporeal membrane oxygenation (V‐V ECMO) after lung abscess surgery in a patient with severe hypoxia and air leak. ILV can be effective in V‐V ECMO as unilateral lung air leak. [ABSTRACT FROM AUTHOR]

Summary: Operating theatre fires are rare but can result in significant morbidity. A 76‐year‐old male with complex airway disease sustained superficial facial burns during an elective airway debulking procedure. His airway was being managed with high‐flow nasal oxygen at 70 l.min−1 and FiO2 1.0 delivered by Optiflow™ (Fisher and Paykel Healthcare Limited, Auckland, New Zealand). When suction monopolar diathermy was used to excise hyperkeratotic tissue beside his epiglottis, an arc was created to the tip of the suspension laryngoscope, followed by a jet of flame as the Optiflow circuit ignited. This resulted in burns to the patient's face and shoulder. He required admission to the intensive care unit and had a complicated postoperative course that included the need for surgical tracheostomy to facilitate weaning from mechanical ventilation. This case highlights the dangers of using high‐flow nasal oxygen alongside an ignition source. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between heart failure (HF) and respiratory tract infections, specifically lower respiratory tract infections (LRTI). The burden of comorbidities in patients with HF exposes them to a higher risk of non-cardiovascular events, including infections. LRTIs, such as pneumonia, are common in patients with HF and can lead to HF decompensation or be a consequence of it, increasing the risk of hospitalizations and mortality. The article also explores the potential protective role of HF drugs, specifically empagliflozin, in preventing LRTIs. The study found that empagliflozin was associated with a lower risk of incident LRTI compared to a placebo. However, there was no impact on the incidence of COVID-19. Further research is needed to confirm these findings and explore the impact of SGLT2 inhibitors on LRTI risk in patients with HF. [Extracted from the article]

Background and Purpose: Opioid-induced respiratory depression limits the use of μ- opioid receptor agonists in clinical settings and is the main cause of opioid overdose fatalities. The relative potential of different opioid agonists to induce respiratory depression at doses exceeding those producing analgesia is understudied despite its relevance to assessments of opioid safety. Here we evaluated the respiratory depressant and anti-nociceptive effects of three novel opioids and relate these measurements to their in vitro efficacy. Experimental Approach: Respiration was measured in awake, freely moving male CD-1 mice using whole body plethysmography. Anti-nociception was measured using the hot plate test. Morphine, oliceridine and tianeptine were administered intraperitoneally, whereas methadone, oxycodone and SR-17018 were administered orally. Receptor activation and arrestin-3 recruitment were measured in HEK293 cells using BRET assays. Key Results: Across the dose ranges examined, all opioids studied depressed respiration in a dose-dependent manner, with similar effects at the highest doses, and with tianeptine and oliceridine showing reduced duration of effect, when compared with morphine, oxycodone, methadone and SR-17018. When administered at doses that induced similar respiratory depression, all opioids induced similar anti-nociception, with tianeptine and oliceridine again showing reduced duration of effect. These data were consistent with the in vitro agonist activity of the tested compounds. Conclusion and Implications: In addition to providing effective anti-nociception, the novel opioids, oliceridine, tianeptine and SR-17018 depress respiration in male mice. However, the different potencies and kinetics of effect between these novel opioids may be relevant to their therapeutic application in different clinical settings. [ABSTRACT FROM AUTHOR]

Guillain–Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence‐based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence‐to‐Decision (EtD) frameworks. For the six intervention PICOs, evidence‐based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti‐ganglioside antibodies is of limited clinical value in most patients with typical motor‐sensory GBS, but anti‐GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal–paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute‐onset chronic inflammatory demyelinating polyradiculoneuropathy (A‐CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2–4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12–15 L in four to five exchanges over 1–2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission. [ABSTRACT FROM AUTHOR]

Introduction: Female lung transplant recipients (LTRs) of reproductive age are increasingly considering pregnancy due to advances in post‐transplant management and improved survival. We report our experience with pregnancy in LTRs, with an emphasis on two or more successful full‐term pregnancies in individual transplant recipients. Methods: We conducted a retrospective analysis of pregnancies in LTRs at our transplant center and collected maternal and fetal outcomes. Results: In our patient cohort, eight female LTRs conceived a total of 17 pregnancies, resulting in 13 newborns, 12 at full term, and 11 with a birth weight > 2.5 kg. Three of the LTRs had two or more successful full‐term pregnancies. LTRs required a significant tacrolimus dose increase to maintain target trough levels during pregnancy. Six recipients are currently clinically stable and active, three with lung function comparable to pre‐pregnancy values, and three with evidence of chronic lung allograft dysfunction (CLAD), but stable lung function. Two of the eight LTRs died subsequent to childbirth secondary to chronic respiratory failure due to CLAD, at a mean of 11 years post‐transplantation and a mean of 4.5 years after childbirth. Conclusion: Pregnancy following lung transplantation is feasible and can be achieved with acceptable maternal and newborn outcomes. Importantly, LTRs can successfully have two or more full‐term pregnancies. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine if extended‐release, bioabsorbable, subcutaneous naltrexone (NTX) implants inhibit respiratory depression after an IV injection of fentanyl. Bioabsorbable implants fabricated from two different release‐controlling polymers, poly‐D‐L‐lactide (PDLLA) and polycaprolactone (PCL), alone (placebo) or containing NTX, were subcutaneously implanted in Sprague Dawley rats. After 3.5 months of implantation, the rodents were administered an IV bolus of fentanyl through the tail vein. The placebo implant rats received a dose of 4 micrograms (mcg) ‐ (10 mcg/kg/dose), while the NTX implanted animals received a dose of 8 mcg (20 mcg/kg/dose). The minimum active dose of fentanyl that caused a > 50 ± 2% depression in the respiration rate in the placebo implanted rodents was 4 mcg. The respiration rate of the placebo implanted rats dropped from 208 ± 14 breaths/minute at predose, to 84 ± 12 breaths/minute (p = 0.0003) at 2 min. In contrast, all NTX implanted animals easily tolerated twice the dose of 8 mcg of fentanyl without any significant reduction in respiration rate. The mean respiration rate = increased from 164 ± 22 breaths/minute at predose to 178 ± 17 breaths/minute (p = 0.24) at 2 min. The mean plasma concentrations of NTX, 3.5 months after implantation, ranged from 7.4 (±1.1) ng/mL to 80.3 (±37.5) ng/mL. Bioabsorbable implants containing NTX effectively blocked fentanyl‐induced respiratory depression in rodents as compared with placebo implants, 3.5 months after implantation. [ABSTRACT FROM AUTHOR]

Asynchrony is a frequent problem in critical care units, being underdiagnosed by the treating team and often requiring advanced monitoring equipment for its detection. Ultrasonography of the diaphragm allows direct observation, in real time, of muscle displacement and its synchronization with the ventilator waveforms, which results in a promising tool for interpreting difficult to diagnose asynchronies. [ABSTRACT FROM AUTHOR]

Background and Aims: The timing of transition from non‐invasive ventilation (NIV) to invasive ventilation in the intensive care unit (ICU) is uncertain due to a lack of clinical evidence. This study aimed to identify the optimal timing of intubation in patients with respiratory failure managed with NIVs. Methods: A single‐center observational study was conducted in Tokyo, Japan. Patients in the ICU managed with NIV between 2013 and 2022 were screened. The primary outcome was 28‐day invasive ventilator‐free days. Statistical analyses used locally estimated scatter plot smoothing (LOESS) and generalized linear mixed models to estimate the association between the timing of transition and prolonged intubation duration. Results: During the study period, 139 of 589 adult ICU patients receiving NIV transitioned to invasive ventilation. The LOESS curve indicated the longest 28‐day ventilator‐free days around 24 h after NIV initiation, after which the primary outcome decreased linearly. Late intubation after 24 h of NIV initiation was associated with fewer 28‐day ventilator‐free days (adjusted mean difference: −0.22 days [95% confidence interval: −0.31, −0.13]). Conclusion: We identified a non‐linear association between the timing of intubation and 28‐day invasive ventilator‐free days. The critical 24‐h time window for patients on NIV was associated with longer 28‐day invasive ventilator‐free days. Key points: The timing of transition from non‐invasive ventilation (NIV) to invasive ventilation in the ICU is uncertain.This study showed that the 28‐day invasive ventilator‐free days peaked around 24 h after the start of NIV for patients with respiratory failure who required tracheal intubation after using NIV.Patients using NIV should be closely monitored and evaluated within 24‐h window to determine if tracheal intubation is necessary. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease can lead to acute hypercapnic respiratory failure (AHRF), often treated using noninvasive ventilation (NIV). Emerging research suggests the potential utility of high flow nasal cannula (HFNC) for AHRF. This systematic review and meta‐analysis aimed to determine the effect of HFNC versus NIV on AHRF management. A search of electronic databases (CINAHL, MEDLINE, and Academic Search Complete), web sources, and trial registries was last conducted on 9 February 2023. Quality and risk of bias assessments were conducted. Meta‐analyses were used to synthesise data. Seven randomised controlled trials were included. No statistically significant differences between HFNC and NIV were found within the following outcomes of interest: (i) correction of pCO2: standardised mean difference (SMD) = −0.16, 95% confidence interval (CI) (−0.34 to 0.02), p = 0.08; (ii) correction of pH: SMD = −0.05, 95% CI (−0.25 to 0.14), p = 0.59; (iii) correction of pO2: SMD = −0.15, 95% CI (−0.40 to 0.09), p = 0.22; (iv) intubation rates: risk ratio (RR) = 0.87, 95% CI (0.41 to 1.82), p = 0.71; (v) mortality rates: RR = 0.85, 95% CI (0.47 to 1.56), p = 0.61; and (vi) treatment switch: RR = 1.30, 95% CI (0.43 to 3.94), p = 0.64. More controlled trials with large sample sizes are required to investigate the management of AHRF of various aetiologies. HFNC may be used as a final exhaustive measure for COPD‐related AHRF where NIV is not tolerated, and when it is not clinically indicated to extend to endotracheal intubation. [ABSTRACT FROM AUTHOR]

Background: Differentiating cardiogenic vs noncardiogenic causes of respiratory signs can be challenging when echocardiography is unavailable. Radiographic vertebral left atrial size (VLAS) and vertebral heart size (VHS) have been shown to predict echocardiographic left heart size, with VLAS specifically estimating left atrial size. Hypothesis/Objectives: Compare the diagnostic accuracy of VLAS and VHS to predict left‐sided congestive heart failure (CHF) in dogs presenting with respiratory signs. Animals: One‐hundred fourteen dogs with respiratory signs and radiographic pulmonary abnormalities. Methods: Retrospective cross‐sectional study. Dogs had to have an echocardiogram and thoracic radiographs obtained within 24 hours. Diagnosis of CHF was confirmed based on the presence of respiratory signs, cardiac disease, LA enlargement, and cardiogenic pulmonary edema. Results: Fifty‐seven dogs had CHF and 57 did not have CHF. Compared to VHS (area under the curve [AUC] 0.85; 95% confidence interval [CI], 0.77‐0.91), VLAS was a significantly (P =.03) more accurate predictor of CHF (AUC, 0.92; 95% CI, 0.85‐0.96). Optimal cutoff for VLAS was >2.3 vertebrae (sensitivity, 93.0%; specificity, 82.5%). Murmur grade (P =.02) and VLAS (P <.0001) were independently associated with CHF and VHS was not. Increased VHS (54%) was significantly (P =.01) more common than increased VLAS (24%) in dogs without CHF. Results were similar in a subsample of older and smaller dogs. Conclusions and Clinical Importance: When echocardiography is unavailable, VLAS and murmur grade have clinically utility to aid in differentiating cardiogenic from noncardiogenic respiratory signs. These findings might be especially useful to help rule out CHF in dogs with increased VHS that present with respiratory signs. [ABSTRACT FROM AUTHOR]

Given the high prevalence of pain in older adults and current trends in opioid prescribing, inclusion of genetic information in risk prediction tools may improve opioid risk assessment. Our objectives were to (1) determine the feasibility of recruiting socioeconomically disadvantaged and racially diverse middle aged and older adult populations for a study seeking to identify risk factors for opioid‐related falls and other serious adverse effects and (2) explore potential associations between the Risk Index for Overdose or Serious Opioid‐induced Respiratory Depression (CIP‐RIOSORD) risk class and other patient factors with falls and serious opioid adverse effects. This was an observational study of 44 participants discharged home from the emergency department with an opioid prescription for acute pain and followed for 30 days. We found pain interference may predict opioid‐related falls or serious adverse effects within older, opioid‐treated patients. If validated, pain interference may prove to be a beneficial marker for risk stratification of older adults initiated on opioids for acute pain. [ABSTRACT FROM AUTHOR]

Background: Procedural sedation aims to facilitate a successful diagnostic or therapeutic procedure. The pharmacokinetic properties and pharmacodynamic effects need to be taken into consideration when choosing the ideal sedative. Midazolam and propofol are frequently employed. However, they are associated with respiratory depression with increasing dosage. Also, midazolam has a potentially unpredictable pharmacodynamic response and propofol may cause hypotension and injection site pain. Remimazolam may provide a superior alternative due to its rapid pharmacodynamic profile and insignificant circulatory effects. Methods: This protocol employs the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines. The review aims to assess the beneficial and harmful clinical effects of remimazolam versus placebo or other sedatives in adult patients requiring sedation in relation to a diagnostic or therapeutic procedure, or due to other circumstances. Three primary outcomes are identified: Sedation success rate, respiratory complications, and hemodynamic complications. Six secondary outcomes are identified: among these are quality of recovery and serious adverse events. All randomized trials are included. The search strategy includes six major biomedical databases. Literature screening and data extraction will be performed independently by two authors. Risk of systemic error will be assessed with Risk of Bias 2 Tool. Risk of random error will be assessed with trial sequential analysis. Heterogeneity will be evaluated by appropriate statistical tests. The certainty of the evidence will be judged using Grading of Recommendations Assessment, Development, and Evaluation. Meta‐analysis will be carried out with Rstudio. A "Summary of Findings" table will be presented with our primary and secondary outcome results. Discussion: The systematic review with up‐to‐date methodology outlined in this protocol investigates the clinical effects of remimazolam in relation to procedural sedation. The results may guide clinicians in the clinical use of remimazolam. [ABSTRACT FROM AUTHOR]

Background and Aims: The approach to the burden of disease is a demographic, economic, and a health problem, which requires the design and application of specific measures of cost of the disease, such as disability‐adjusted life years (DALYs), to establish better public health policies in the pediatric population. The aim of this study is to approach the burden of disease in children with acute respiratory failure (ARF) through the calculation of DALYs. Methods: This study was conducted in the framework of a prospective, multicenter cohort in Bogotá, Colombia. Inclusion criteria were all pediatric patients admitted to the emergency department, hospitalization, and intensive care unit with respiratory distress; eligible patients were all those who developed ARF between April 2020 and December 2021. They were followed‐up during hospitalization, at 30 and 60 days after admission. The Infant/Toddler Quality of Life Questionnaire and KIDSCREEN quality of life scales were applied for follow‐up according to the age group. The results were used to calculate DALYs Results: Six hundred and eighty‐five eligible patients, 296 (43.08%) developed ARF, of these 22 (6.08%) patients died (mortality rate = 7.43%). The total DALYs was 277.164 years. For younger than 9 years, the DALYs were 302.64 years, while for older than 10 years were 40.49 years. Conclusion: ARF is one of the main causes of preventable mortality in pediatrics, its progression to respiratory failure is a highly prevalent condition in pediatric age, a condition that has a great impact on mortality, morbidity, and disability in our patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Acute‐on‐chronic liver failure (ACLF) is a clinically and pathophysiologically distinct condition from acutely decompensated cirrhosis and is characterised by systemic inflammation, extrahepatic organ failure, and high short‐term mortality. Aims: To provide a narrative review of the diagnostic criteria, prognosis, epidemiology, and general management principles of ACLF. Four specific interventions that are explored in detail are intravenous albumin, extracorporeal liver assist devices, granulocyte‐colony stimulating factor, and liver transplantation. Methods: We searched PubMed and Cochrane databases for articles published up to July 2023. Results: Approximately 35% of hospital inpatients with decompensated cirrhosis have ACLF. There is significant heterogeneity in the criteria used to diagnose ACLF; different definitions identify different phenotypes with varying mortality. Criteria established by the European Association for the Study of the Liver were developed in prospective patient cohorts and are, to‐date, the most well validated internationally. Systemic haemodynamic instability, renal dysfunction, coagulopathy, neurological dysfunction, and respiratory failure are key considerations when managing ACLF in the intensive care unit. Apart from liver transplantation, there are no accepted evidence‐based treatments for ACLF, but several different approaches are under investigation. Conclusion: The recognition of ACLF as a distinct entity from acutely decompensated cirrhosis has allowed for better patient stratification in clinical settings, facilitating earlier engagement with the intensive care unit and liver transplantation teams. Research priorities over the next decade should focus on exploring novel treatment strategies with a particular focus on which, when, and how patients with ACLF should be treated. [ABSTRACT FROM AUTHOR]