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Introduction: Although largely used, the place of oxygen therapy and its devices in patients with acute hypoxemic respiratory failure (ARF) deserves to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Emergency Medicine Society (Société Française de Médecine d'Urgence, SFMU) organized a consensus conference on oxygen therapy in ARF (excluding acute cardiogenic pulmonary oedema and hypercapnic exacerbation of chronic obstructive diseases) in December 2023. Methods: A committee without any conflict of interest (CoI) with the subject defined 7 generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model. An independent work group reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Fifteen experts in the field from both societies proposed their own answers in a public session and answered questions from the jury (a panel of 16 critical-care and emergency medicine physicians, nurses and physiotherapists without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. Results: The jury provided 22 statements answering 11 questions: in patients with ARF (1) What are the criteria for initiating oxygen therapy? (2) What are the targets of oxygen saturation? (3) What is the role of blood gas analysis? (4) When should an arterial catheter be inserted? (5) Should standard oxygen therapy, high-flow nasal cannula oxygen therapy (HFNC) or continuous positive airway pressure (CPAP) be preferred? (6) What are the indications for non-invasive ventilation (NIV)? (7) What are the indications for invasive mechanical ventilation? (8) Should awake prone position be used? (9) What is the role of physiotherapy? (10) Which criteria necessarily lead to ICU admission? (11) Which oxygenation device should be preferred for patients for whom a do-not-intubate decision has been made? Conclusion: These recommendations should optimize the use of oxygen during ARF. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsDiscussionConclusionNaloxone is an effective antidote, but its short half-life means repeated doses, and infusions are often required. We investigated the effectiveness of adding intramuscular naloxone to titrated intravenous naloxone in opioid overdose in preventing recurrence of respiratory depression.This double-blinded randomised placebo-controlled trial was conducted in patients with suspected opioid poisoning and respiratory depression (respiratory rate <10 breaths/min or oxygen saturation <93%). Patients were randomised to receive either intramuscular naloxone 1,600 µg or saline placebo. All patients received titrated intravenous naloxone 100 µg and were managed on an opioid poisoning care pathway. The primary outcome was recurrence of respiratory depression within 4 h. Secondary outcomes were the proportion receiving naloxone infusions, number of naloxone boluses administered, reversal of respiratory depression at 10 min, and precipitation of opioid withdrawal (any symptom).Recurrence of respiratory depression within 4 h was less common in 28/69 (41%) patients receiving intramuscular naloxone versus 48/67 (72%) patients receiving placebo (difference 31%, 95% CI: 13–46%; P < 0.001). Fewer naloxone infusions (5/69; 7% versus 25/67; 37%, difference 30%, 95% CI: 15 to 55%; P < 0.001) and fewer naloxone doses were administered (median 2, IQR: 1 to 5, versus median 5, IQR: 2 to 8; P = 0.001) in the intramuscular group. Reversal of respiratory depression at 10 min was similar between groups (51/69; 74% intramuscular naloxone versus 47/67; 70% placebo; P = 0.703). Opioid withdrawal occurred in 35/69 (51%) given intramuscular naloxone compared to 28/67 (42%) in the placebo group (difference 9%; 95% CI: −8 to 27%; P = 0.308).The favourable pharmacokinetics of intramuscular naloxone, particularly its longer duration of activity, likely explains the improved effectiveness with lower recurrence of respiratory depression.The addition of intramuscular naloxone 1,600 µg to titrated intravenous naloxone prolonged effective reversal of respiratory depression, with fewer naloxone doses and infusions given, and no significant difference in patients developing withdrawal. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T-cell (CAR-T) therapy, a rapidly emerging treatment for cancer that has gained momentum since its approval by the FDA in 2017, involves the genetic engineering of patients' T cells to target tumors. Although significant therapeutic benefits have been observed, lifethreatening adverse pulmonary events have been reported. Methods: Using SAS 9.4 with MedDRA 26.1, we retrospectively analyzed data from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database, covering the period from 2017 to 2023. The analysis included the Reporting Odds Ratio Proportional Reporting Ratio Information Component and Empirical Bayes Geometric Mean to assess the association between CAR-T cell therapy and adverse pulmonary events (PAEs). Results: The FAERS database recorded 9,400 adverse events (AEs) pertaining to CAR-T therapies, of which 940 (10%) were PAEs. Among these CAR-T cell-related AEs, hypoxia was the most frequently reported (344 cases), followed by respiratory failure (127 cases). Notably, different CAR-T cell treatments demonstrated varying degrees of association with PAEs. Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs. Notably, the majority of these PAEs occurred within the first 30 days post-treatment. The fatality rates varied among the different CAR-T therapies, with Tisa-cel exhibiting the highest fatality rate (43.6%), followed by Ide-cel (18.8%). Conclusion: This study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers. [ABSTRACT FROM AUTHOR]

Blastomycosis can result in lung injury with high mortality rates. The literature on veno-venous extracorporeal membrane oxygenation (VV-ECMO) used as a rescue therapy is limited to case reports and small case series collected over extended time periods. This report describes the clinical course and post-hospitalization outcomes among patients with blastomycosis-induced respiratory failure requiring VV-ECMO in the most recent time frame. The data were collected retrospectively from the health records of eight patients with blastomycosis-induced respiratory failure admitted to a tertiary care center between 2019 and 2023. The mean time from the start of mechanical ventilation to ECMO initiation was 57 h. All patients survived to ECMO decannulation, and seven of them survived to hospital discharge. All six patients whose post-discharge follow-up information was available were weaned from mechanical ventilation and lived at home while two required supplemental oxygen. This includes a case where the provision of adequate ECMO support was challenging due to the patient's morbid obesity. The most common residual imaging abnormalities included pulmonary infiltrates and pneumatoceles. The study demonstrates the feasibility of VV-ECMO as a rescue therapy in patients with blastomycosis-related refractory respiratory failure. Rapid initiation of ECMO support in eligible patients may have contributed to the good outcomes. [ABSTRACT FROM AUTHOR]

Background: On March 16th 2024, the first case of Human infection with avian influenza H10N3 since the end of the global COVID-19 Pandemic was reported in Kunming, China. To enhance comprehension of the source of infection and risk factors of the H10N3 virus infection, this case report summarizes the clinical features, epidemiological investigation, and laboratory test results. Provides recommendations for the prevention and control of Human infection with avian influenza H10N3. Case presentation: A 51-year-old male with a history of COVID-19 infection and a smoking habit of 30 years, worked in livestock breeding and was exposed to sick and dead poultry before falling ill with fever and chills on 28th February 2024. A week later, he was diagnosed with severe pneumonia, influenza, and respiratory failure by the Third People's Hospital of Kunming(KM-TPH). He was discharged on 17th April and none of his 6 close contacts showed any symptoms of illness. Environmental samples taken from the epidemic spot revealed that peacock feces tested positive for avian influenza sub-type H9 and waterfowl specimens showed positive results for avian influenza sub-type H5. Gene sequencing conducted on positive specimens from the patient's respiratory tract by the Chinese Centre for Disease Control and Prevention (CCDC) showed a high degree of similarity (98.6–99.5%) with the strain responsible for the second global case of human infected with H10N3 (reported from Zhejiang, China 2022). Conclusions: According to the available epidemiological information, there is limited evidence to suggest that H10N3 viruses are excessively lethal. However, adaptive site mutations have been observed in the H10N3 isoform of mammals. While it is unlikely that the H10N3 virus will spread among humans, the possibility of additional cases cannot be entirely ruled out. Symptoms of human infection with H10N3 avian influenza are similar to those of common respiratory infections, which may result in them being overlooked during initial clinical consultations. Therefore, it is essential to improve surveillance of the H10 sub-type of avian influenza and to increase the awareness of hospital-related workers of cases of pneumonia of unknown origin. [ABSTRACT FROM AUTHOR]

Introduction Despite the significant need for mechanical ventilation in- and out-of-hospital, mechanical ventilators remain inaccessible in many instances because of cost or size constraints. Mechanical ventilation is especially critical in trauma scenarios, but the impractical size and weight of standard mechanical ventilators restrict first responders from carrying them in medical aid bags, leading to reliance on imprecise manual bag-mask ventilation. This is particularly important in combat-related injury, where airway compromise and respiratory failure are leading causes of preventable death, but medics are left without necessary mechanical ventilation. To address the serious gaps in mechanical ventilation accessibility, we are developing an Autonomous, Modular, and Portable Ventilation platform (AMP-Vent) suitable for austere environments, prolonged critical care, surgical applications, mass casualty incidents, and stockpiling. The core system is remarkably compact, weighing <2.3 kg, and can fit inside a shoebox (23.4 cm × 17.8 cm × 10.7 cm). Notably, this device is 65% lighter than standard transport ventilators and astoundingly 96% lighter than typical intensive care unit ventilators. Beyond its exceptional portability, AMP-Vent can be manufactured at less than one-tenth the cost of conventional ventilators. Despite its reduced size and cost, the system's functionality is uncompromised. The core system is equipped with closed-loop sensors and advanced modes of ventilation (pressure-control, volume-control, and synchronized intermittent mandatory ventilation), enabling quality care in a portable form factor. The current prototype has undergone preliminary preclinical testing and optimization through trials using a breathing simulator (ASL 5000) and in a large animal model (swine). This report aims to introduce a novel ventilation system and substantiate its promising performance through evidence gathered from preclinical studies. Materials and Methods Lung simulator testing was performed using the ASL 5000, in accordance with table 201.105 "pressure-control inflation-type testing" from ISO 80601-2-12:2020. Following simulations, AMP-Vent was tested in healthy 10-kg female domestic piglets. The Children's Hospital of Philadelphia Institutional Animal Care and Use Committee approved all animal procedures. Swine received 4-min blocks of alternating ventilation, where AMP-Vent and a conventional anesthesia ventilator (GE AISYS CS2) were used to titrate to varied end-tidal carbon dioxide (EtCO2) goals with the initial ventilator switching for each ascending target (35, 40, 45, 50, 55 mmHg). Results During ASL 5000 simulations, AMP-Vent exhibited consistent performance under varied conditions, maintaining a coefficient of variation of 2% or less within each test. In a large animal study, AMP-Vent maintained EtCO2 and SpO2 targets with comparable performance to a conventional anesthesia ventilator (GE AISYS CS2). Furthermore, the comparison of minute ventilation (V e) distributions between the conventional anesthesia ventilator and AMP-Vent at several EtCO2 goals (35, 40, 45, 50, and 55 mmHg) revealed no statistically significant differences (p  = 0.46 using the Kruskal–Wallis rank sum test). Conclusions Preclinical results from this study highlight AMP-Vent's core functionality and consistent performance across varied scenarios. AMP-Vent sets a benchmark for portability with its remarkably compact design, positioning it to revolutionize trauma care in previously inaccessible medical scenarios. [ABSTRACT FROM AUTHOR]

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]

Moderate-to-severe acute postsurgical pain (APSP) can prolong the recovery and worsen the prognosis of patients who undergo spinal surgery. Esketamine and pregabalin may resolve APSP without causing hyperpathia or respiratory depression after surgery. However, there are other risks, such as dissociative symptoms. We designed a randomized controlled trial to investigate the effect of the combination of these 2 drugs on the incidence of APSP in patients who underwent resection of spinal neoplasms. Patients aged 18 to 65 years were randomized to receive esketamine (a bolus dose of 0.5 mg⋅kg-1 and an infusion dose of 0.12 mg⋅kg-1⋅h-1 for 48 hours after surgery) combined with oral pregabalin (75-150 mg/day, starting 2 hours before surgery and ending at 2 weeks after surgery) or an identical volume of normal saline and placebo capsules. The primary outcome was the proportion of patients with moderate-to-severe APSP (visual analog scale score ≥ 40) during the first 48 hours after surgery. Secondary outcomes included the incidence of drug-related adverse events. A total of 90 patients were randomized. The incidence of moderate-to-severe APSP in the combined group (27.3%) was lower than that in the control group (60.5%) during the first 48 hours after surgery (odds ratio = 0.25, 95% CI 5 0.10-0.61; P = 0.002). The occurrence of mild dissociative symptoms was higher in the combined group than in the control group (18.2% vs 0%). In conclusion, esketamine combined with pregabalin could effectively alleviate APSP after spinal surgery, but an analgesic strategy might increase the risk of mild dissociative symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Allergic bronchopulmonary mycosis (ABPM) is a chronic airway disease characterized by the presence of fungi that trigger allergic reactions and airway obstruction. Here, we present a unique case of ABPM in which a patient experienced sudden respiratory failure due to mucus plug-induced airway obstruction. The patient's life was saved by venovenous extracorporeal membrane oxygenation (VV-ECMO) and bronchoscopic removal of the plug. This case emphasizes the clinical significance of mucus plug-induced airway obstruction in the differential diagnosis of respiratory failure in patients with ABPM. Case study: A 52-year-old female clerical worker with no smoking history, presented with dyspnea. CT scan revealed mucus plugs in both lungs. Despite treatment, the dyspnea progressed rapidly to respiratory failure, leading to VV-ECMO placement. Results: CT revealed bronchial wall thickening, obstruction, and extensive atelectasis. Bronchoscopy revealed extensive mucus plugs that were successfully removed within two days. The patient's respiratory status significantly improved. Follow-up CT revealed no recurrence. Fungal cultures identified Schizophyllum commune, confirming ABPM. Histological examination of the mucus plugs revealed aggregated eosinophils, eosinophil granules, and Charcot-Leyden crystals. Galectin-10 and major basic protein (MBP) staining supported these findings. Eosinophil extracellular traps (EETs) and eosinophil cell death (ETosis), which contribute to mucus plug formation, were identified by citrullinated histone H3 staining. Conclusion: Differentiating between asthma exacerbation and mucus plug-induced airway obstruction in patients with ABPM and those with acute respiratory failure is challenging. Prompt evaluation of mucous plugs and atelectasis using CT and timely decision to introduce ECMO and bronchoscopic mucous plug removal are required. [ABSTRACT FROM AUTHOR]

Background: Despite widespread use of combination antiretroviral therapy, people with HIV (PWH) continue to have an increased risk of admission to and mortality in the intensive care unit (ICU). Mortality risk after hospital discharge is not well described. Using retrospective data on adult PWH (≥18 years) admitted to ICU from 2000-2019 in an HIV-referral centre, we describe trends in 1-year mortality after ICU admission. Methods: One-year mortality was calculated from index ICU admission to date of death; with follow-up right-censored at day 365 for people remaining alive at 1 year, or day 7 after ICU discharge if lost-to-follow-up after hospital discharge. Cox regression was used to describe the association with calendar year before and after adjustment for patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation II [APACHE II] score, CD4+ T-cell count, and recent HIV diagnosis) at ICU admission. Analyses were additionally restricted to those discharged alive from ICU using a left-truncated design, with further adjustment for respiratory failure at ICU admission in these analyses. Results: Two hundred and twenty-one PWH were admitted to ICU (72% male, median [interquartile range] age 45 [38–53] years) of whom 108 died within 1-year (cumulative 1-year survival: 50%). Overall, the hazard of 1-year mortality was decreased by 10% per year (crude hazard ratio (HR): 0.90 (95% confidence interval: 0.87-0.93)); the association was reduced to 7% per year (adjusted HR: 0.93 (0.89-0.98)) after adjustment. Conclusions were similar among the subset of 136 patients discharged alive (unadjusted: 0.91 (0.84-0.98); adjusted 0.92 (0.84, 1.02)). Conclusions: Between 2000 and 2019, 1-year mortality after ICU admission declined at this ICU. Our findings highlight the need for multi-centre studies and the importance of continued engagement in care after hospital discharge among PWH. [ABSTRACT FROM AUTHOR]

Medical management is the standard treatment of chronic type B aortic dissection (CTBAD). However, the roles of open surgical repair (OSR) and thoracic endovascular repair (TEVAR) in patients with CTBAD remain controversial. Thus, this study aimed to assess and compare the mid- and long-term clinical outcomes of OSR via left thoracotomy with that of TEVAR for CTBAD. The data of 85 consecutive patients who underwent surgery for CTBAD from April 2007 to May 2021 were retrospectively reviewed. The patients were divided into two groups: Group G, which included patients who underwent OSR, and Group E, which included patients who underwent TEVAR. Groups G and E comprised 33 and 52 patients, respectively. Preoperative and postoperative computed tomography (CT) studies were retrospectively analyzed for the maximum diameter. The mean duration of the follow-up period was 5.8 years. Operative mortality did not occur. There was no difference in complications, such as stroke (G: 2 vs. E: 0, p = 0.30), paraplegia (G: 1 vs. E: 1, p = 0.66), and respiratory failure (G: 2, vs. E: 0, p = 0.30). The difference in preoperative factors was observed, including the intervals between onset and operation (G; 4.9 years vs. E; 1.9 years, p < 0.01), maximum diameter in preoperative CT (G; 59.0 mm vs. E; 50.5 mm, p < 0.001), and maximum false lumen diameter (G; 35.5 mm vs. E; 29.0 mm, p < 0.01). There was no significant difference in the mid- and long-term survival rates (p = 0.49), aorta-related deaths (p = 0.33), and thoracic re-intervention rates (p = 0.34). Postoperative adverse events occurred in Group E: four cases of retrospective type A aortic dissection, two cases of aorto-bronchial fistula, and one case of aorto-esophagus fistula. Aorta-related death and re-intervention rates crossed over in both groups after seven years postoperatively. Although endovascular repair of CTBAD is less invasive, the rate of freedom from re-intervention was unsatisfactory. Some fatal complications were observed in the endovascular group, and the mid- and long-term outcomes were reversed compared with those in the OSR group. Although OSR is an invasive procedure, it could be performed safely without perioperative complications. OSR has more feasible mid- and long-term outcomes. [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]

OBJECTIVES: To develop an electronic descriptor of clinical deterioration for hospitalized patients that predicts short-term mortality and identifies patient deterioration earlier than current standard definitions. DESIGN: A retrospective study using exploratory record review, quantitative analysis, and regression analyses. SETTING: Twelve-hospital community-academic health system. PATIENTS: All adult patients with an acute hospital encounter between January 1, 2018, and December 31, 2022. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Clinical trigger events were selected and used to create a revised electronic definition of deterioration, encompassing signals of respiratory failure, bleeding, and hypotension occurring in proximity to ICU transfer. Patients meeting the revised definition were 12.5 times more likely to die within 7 days (adjusted odds ratio 12.5; 95% CI, 8.9-17.4) and had a 95.3% longer length of stay (95% CI, 88.6-102.3%) compared with those who were transferred to the ICU or died regardless of meeting the revised definition. Among the 1812 patients who met the revised definition of deterioration before ICU transfer (52.4%), the median detection time was 157.0 min earlier (interquartile range 64.0-363.5 min). CONCLUSIONS: The revised definition of deterioration establishes an electronic descriptor of clinical deterioration that is strongly associated with short-term mortality and length of stay and identifies deterioration over 2.5 hours earlier than ICU transfer. Incorporating the revised definition of deterioration into the training and validation of early warning system algorithms may enhance their timeliness and clinical accuracy. [ABSTRACT FROM AUTHOR]

Noninvasive respiratory support delivered through a face mask has become a cornerstone treatment for adults and children with acute or chronic respiratory failure. However, an imperfect mask fit by using commercially available interfaces is frequently encountered, which may result in patient discomfort and treatment inefficiency or failure. To overcome this challenge, over the past decade, increasing attention has been given to the development of personalized face masks, which are custom-made to address the specific facial dimensions of an individual patient. With this scoping review, we aim to provide a comprehensive overview of the current advances and gaps in knowledge with regard to the personalization masks for CPAP and NIV. We performed a systematic search of the literature and identified and summarized a total of 23 studies. Most studies included were involved in the development of nasal masks. Studies that targeted adult respiratory care mainly focused on chronic (home) ventilation and included some clinical testing in a relevant subject population. In contrast, pediatric studies focused mostly on respiratory support in the acute setting, whereas testing was limited to bench or case studies only. Most studies were positive with regard to the performance (ie, comfort, level of air leak, and mask pressure applied to the skin) of personalized masks in bench testing or in human, healthy or patient, subjects. Advances in the field of 3-dimensional scanning and soft material printing were identified, but important gaps in knowledge remain. In particular, more insight into cushion materials, headgear design, clinical feasibility, and cost-effectiveness is needed before definite recommendations can be made with regard to implementation of large-scale clinical programs that personalize noninvasive respiratory support masks for adults and children. [ABSTRACT FROM AUTHOR]

BACKGROUND: The ratio of oxygen saturation index (ROX index; or .../.../breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. METHODS: We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. RESULTS: A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). CONCLUSIONS: The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death. [ABSTRACT FROM AUTHOR]

BACKGROUND: When treating acute respiratory failure, both hypoxemia and hyperoxemia should be avoided. ... should be monitored closely and O2 flows adjusted accordingly. Achieving this goal might be easier with automated O2 titration compared with manual titration of fixed-flow O2. We evaluated the feasibility of using an automated O2 titration device in subjects treated for acute hypoxemic respiratory failure in a tertiary care hospital. METHODS: Health-care workers received education and training about oxygen therapy, and were familiarized with an automated O2 titration device (FreeO2,). A coordinator was available from 8:00 AM to 5:00 PM during weekdays to provide technical assistance. The ability of the device to maintain ... within the prescribed therapeutic window was recorded. Basic clinical information was recorded. RESULTS: Subjects were enrolled from November 2020 to August 2022. We trained 508 health-care workers on the use of automated O2 titration, which was finally used on 872 occasions in 763 subjects, distributed on the respiratory, COVID-19, and thoracic surgery wards, and in the emergency department. Clinical information could be retrieved for 609 subjects (80%) who were on the system for a median (interquartile range) of 3 (2-6) d, which represented 2,567 subject-days of clinical experience with the device. In the 82 subjects (14%) for whom this information was available, the system maintained ... within the prescribed targets 89% of the time. Ninety-six subjects experienced clinical deterioration as defined by the need to be transferred to the ICU and/or requirement of high flow nasal oxygen but none of these events were judged to be related to the O2 device. CONCLUSIONS: Automated O2 titration could be successfully implemented in hospitalized subjects with hypoxemic respiratory failure from various causes. This experience should foster further improvement of the device and recommendations for an optimized utilization. [ABSTRACT FROM AUTHOR]

Background: Diffuse alveolar hemorrhage (DAH) is a catastrophic clinical syndrome and one of the manifestations of pulmonary involvement in systemic lupus erythematosus (SLE), which is characterized by hemoptysis, diffuse pulmonary infiltrates, and respiratory failure. However, the treatment options for DAH remain limited, and DAH-related studies are needed to explore more effective therapeutic directions for better disease management and improved prognosis. Methods: This study utilized the pristane-induced DAH murine model to mimic the pathological process of DAH in patients with SLE. Proteomic analysis was conducted to detect differentially expressed proteins (DEPs) in the plasma of surviving and non-surviving mice, followed by an analysis of biological functions and pathways. The most significant DEP was then confirmed in the plasma of SLE patients with or without DAH and DAH murine model with or without fatal outcomes. Finally, the therapeutic value of haptoglobin (Hp) replacement was validated in a DAH murine model through lung histopathology, RT-qPCR, and survival analysis. Results: This study identified 178 DEPs, with 118 upregulated and 60 downregulated DEPs in the non-survival group. Within a set of notable Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, complement and coagulation cascades emerged as the most prominent pathway associated with the process of DAH. Later, the most significant DEP, haptoglobin (Hp), was confirmed to exhibit a significant decrease in the plasma of individuals with SLEDAH and DAH murine model with poor outcomes by the ELISA test. Finally, compared with the control group, the severity of DAH in the Hp treatment group was alleviated significantly, as manifested by the decreased levels of proinflammatory cytokines (IL-6 and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-β), and decreased mortality. Conclusion: A reduction in plasma Hp levels was observed in SLE-DAH, and the replacement therapy with Hp could alleviate pulmonary hemorrhage and reduce mortality in DAH mice. This study identified Hp as a potential biomarker for its clinical diagnosis and a direction for treatment. [ABSTRACT FROM AUTHOR]

Purpose: Investigate the clinical characteristics of splenomegaly secondary to acute pancreatitis (SSAP) and construct a nomogram prediction model based on Lasso-Logistic regression. Methods: A retrospective case-control study was conducted to analyze the laboratory parameters and computed tomography (CT) imaging of acute pancreatitis (AP) patients recruited at Xuanwu Hospital from December 2014 to December 2021. Lasso regression was used to identify risk factors, and a novel nomogram was developed. The performance of the nomogram in discrimination, calibration, and clinical usefulness was evaluated through internal validation. Results: The prevalence of SSAP was 9.2% (88/950), with the first detection occurring 65(30, 125) days after AP onset. Compared with the control group, the SSAP group exhibited a higher frequency of persistent respiratory failure, persistent renal failure, infected pancreatic necrosis, and severe AP, along with an increased need for surgery and longer hospital stay (P < 0.05 for all). There were 185 and 79 patients in the training and internal validation cohorts, respectively. Variables screened by Lasso regression, including platelet count, white blood cell (WBC) count, local complications, and modified CT severity index (mCTSI), were incorporated into the Logistic model. Multivariate analysis showed that WBC count ≦9.71 × 109/L, platelet count ≦140 × 109/L, mCTSI ≧8, and the presence of local complications were independently associated with the occurrence of SSAP. The area under the receiver operating characteristic curve was 0.790. The Hosmer-Lemeshow test showed that the model had good fitness (P = 0.954). Additionally, the nomogram performed well in the internal validation cohorts. Conclusions: SSAP is relatively common, and patients with this condition often have a worse clinical prognosis. Patients with low WBC and platelet counts, high mCTSI, and local complications in the early stages of the illness are at a higher risk for SSAP. A simple nomogram tool can be helpful for early prediction of SSAP. [ABSTRACT FROM AUTHOR]

Background: Progressive pulmonary fibrosis is the symptomatic, physiological, and radiological progression of interstitial lung diseases. The aim of this study was to examine the relationship between progressive pulmonary fibrosis and demographic characteristics and to evaluate the effect on clinical outcomes and mortality. Methods: This cross-sectional study included 221 patients diagnosed with non-idiopathic pulmonary fibrosis interstitial lung diseases who were followed in the last 5 years. Patient symptoms, clinical, radiological, and demographic data were examined. Risk factors for the development of progressive pulmonary fibrosis and the relationship with clinical outcomes and mortality were examined. Results: Of the patients, 33.0% (n = 73) had fibrotic idiopathic nonspecific interstitial pneumonia (iNSIP), 35.7% (n = 79) had fibrotic hypersensitivity pneumonia (HP), 18.1% (n = 40) had fibrotic connective tissue disease (CTD) interstitial lung diseases (ILD), and 13.1% (n = 29) had postinfectious fibrotic ILD. The progressive pulmonary fibrosis development rates of the subtypes were 46.5% iNSIP (n = 34), 86.0% fibrotic HP (n = 68), 42.5% fibrotic CTD-ILD (n = 17), and 20.7% postinfectious ILD (n = 6). The presence of progressive pulmonary fibrosis was associated with the development of respiratory failure and mortality (odds ratio [OR]: 2.70, 95% CI: 1.04–7.05 and OR: 2.13, 95% CI: 1.23–3.69). Progressive pulmonary fibrosis development was higher in hypersensitivity pneumonia patients with farmer's lung (OR: 5.06, 95% CI: 1.02–25.18). Conclusion: Progressive pulmonary fibrosis was more prevalent in older patients. Farming was an important risk factor in the development of hypersensitivity pneumonia-progressive pulmonary fibrosis. Respiratory failure and mortality were higher in those who developed progressive pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression. Methods: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission. Results: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C-reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71). Discussion: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF. [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]

Background: The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed to predict extubation outcomes. However, few studies focused on the predicting value of E/Ea and DE at different positions during a spontaneous breathing trial (SBT), as well as the effects of △E/Ea and △DE (changes in E/Ea and DE during a SBT). Methods: This study was a reanalysis of the data of 60 difficult-to-wean patients in a previous study published in 2017. All eligible participants were organized into respiratory failure (RF) group and extubation success (ES) group within 48 h after extubation, or re-intubation (RI) group and non-intubation (NI) group within 1 week after extubation. The risk factors for respiratory failure and re-intubation including E/Ea and △E/Ea, DE and △DE at different positions were analyzed by multivariate logistic regression, respectively. The receiver operating characteristic (ROC) curves of E/Ea (septal, lateral, average) and DE (right, left, average) were compared with each other, respectively. Results: Of the 60 patients, 29 cases developed respiratory failure within 48 h, and 14 of those cases required re-intubation within 1 week. Multivariate logistic regression showed that E/Ea were all associated with respiratory failure, while only DE (right) and DE (average) after SBT were related to re-intubation. There were no statistic differences among the ROC curves of E/Ea at different positions, nor between the ROC curves of DE. No statistical differences were shown in △E/Ea between RF and ES groups, while △DE (average) was remarkably higher in NI group than that in RI group. However, multivariate logistic regression analysis showed that △DE (average) was not associated with re-intubation. Conclusions: E/Ea at different positions during a SBT could predict postextubation respiratory failure with no statistical differences among them. Likewise, only DE (right) and DE (average) after SBT might predict re-intubation with no statistical differences between each other. [ABSTRACT FROM AUTHOR]

AbstractIntroduction: Chlorine gas can be toxic when inhaled or absorbed at high concentrations through the skin. It can cause pulmonary edema, pulmonary inflammation, respiratory failure, and potentially death. Monitoring chlorine exposure helps in determining treatment regimens and may inform safeguards, such as personal protective equipment and ventilation systems. Therefore, verification of chlorine exposure is crucial to protecting human health. This has led to identification of multiple biomarkers of Cl2 exposure with associated innovations in methods of analysis to monitor these markers. Materials and methods: In this review of the last 30 years of literature, biomarkers and associated methods of detection for the determination of chlorine exposure from biological samples are detailed and critically evaluated. Results and discussion: From the 36 included studies, the most useful biomarkers for Cl2 exposure include tyrosine adducts, chlorohydrin, chloro-fatty-acids, chloro-fatty-aldehydes, and chloro-fatty-alcohols. The most common sample preparation methods for these markers are hydrolysis and extraction and the most common analysis techniques are chromatographic separation with mass spectrometric detection. Conclusion: The findings of this review emphasize the need for continued research into biomarkers and stronger evaluation of proposed analytical methods, including validation, to allow more appropriate comparison, which will ultimately improve patient outcomes.  [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a lung disease that worsens over time, causing fibrosis in the lungs and ultimately resulting in respiratory failure and a high risk of death. Macrophages play a crucial role in the immune system, showing flexibility by transforming into either pro-inflammatory (M1) or antiinflammatory (M2) macrophages when exposed to different stimuli, ultimately impacting the development of IPF. Recent research has indicated that the polarization of macrophages is crucial in the onset and progression of IPF. M1 macrophages secrete inflammatory cytokines and agents causing early lung damage and fibrosis, while M2 macrophages support tissue healing and fibrosis by releasing anti-inflammatory cytokines. Developing novel treatments for IPF relies on a thorough comprehension of the processes involved in macrophage polarization in IPF. The review outlines the regulation of macrophage polarization and its impact on the development of IPF, with the goal of investigating the possible therapeutic benefits of macrophage polarization in the advancement of IPF. [ABSTRACT FROM AUTHOR]

Introduction: Morbidly obese patients occasionally have respiratory problems owing to hypoventilation. Airway pressure release ventilation is one of the ventilation settings often used for respiratory management of acute respiratory distress syndrome. However, previous reports indicating that airway pressure release ventilation may become a therapeutic measure as ventilator management in morbid obesity with respiratory failure is limited. We report a case of markedly improved oxygenation in a morbidly obese patient after airway pressure release ventilation application. Case report: A 50s-year-old Asian man (body mass index 41 kg/m2) presented with breathing difficulties. The patient had respiratory failure with a PaO2/FIO2 ratio of approximately 100 and severe atelectasis in the left lung, and ventilator management was initiated. Although the patient was managed on a conventional ventilate mode, oxygenation did not improve. On day 11, we changed the ventilation setting to airway pressure release ventilation, which showed marked improvement in oxygenation with a PaO2/FIO2 ratio of approximately 300. We could reduce sedative medication and apply respiratory rehabilitation. The patient was weaned from the ventilator on day 29 and transferred to another hospital for further rehabilitation on day 31. Conclusion: Airway pressure release ventilation ventilator management in morbidly obese patients may contribute to improving oxygenation and become one of the direct therapeutic measures in the early stage of critical care. [ABSTRACT FROM AUTHOR]

Opioid use disorders (OUD) and overdoses are ever-evolving public health threats that continue to grow in incidence and prevalence in the United States and abroad. Current treatments consist of opioid receptor agonists and antagonists, which are safe and effective but still suffer from some limitations. Murine and humanized monoclonal antibodies (mAb) have emerged as an alternative and complementary strategy to reverse and prevent opioid-induced respiratory depression. To explore antibody applications beyond traditional heavy-light chain mAbs, we identified and biophysically characterized a novel singledomain antibody specific for fentanyl from a camelid variableheavy-heavy (VHH) domain phage display library. Structural data suggested that VHH binding to fentanyl was facilitated by a unique domain-swapped dimerization mechanism, which accompanied a rearrangement of complementarity-determining region loops leading to the formation of a fentanyl-binding pocket. Structure-guided mutagenesis further identified an amino acid substitution that improved the affinity and relaxed the requirement for dimerization of the VHH in fentanyl binding. Our studies demonstrate VHH engagement of an opioid and inform on how to further engineer a VHH for enhanced stability and efficacy, laying the groundwork for exploring the in vivo applications of VHH-based biologics against OUD and overdose. [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.

Background: While high-flow nasal cannulas (HFNCs) represent the standard of care in the intensive care unit for patients with severe hypoxemia, its use in homecare settings is uncommon despite its potential. The potential benefits and challenges of the high-flow nasal cannula (HFNC) in homecare settings compared to standard long-term oxygen via nasal low-flow therapy are unclear. Methods: We conducted a prospective monocentric feasibility study at the Department of Respiratory Medicine, University Hospital, Goethe University Frankfurt, Germany. Patients with interstitial lung disease or severe bronchiectasis (including cystic fibrosis) were enrolled into the study. The HFNC was introduced during hospitalization. The patients' compliance with home use advice and arterial blood gas results were evaluated at a 4–6-week follow-up. Results: A total of 12 patients were analyzed. HFNC initiation did not result in a significant improvement of the pO2/fiO2 (p/f) ratio. Only 8 out of 12 (66.6%) patients used the HFNC at home after the initial in-hospital initiation. Only 7 of the total 12 patients were using the therapy at a follow-up 3–6 weeks after HFNC onset. Two patients died during the observation, resulting in a surveillance mortality rate of 16.7%. Conclusions: The feasibility data showed low adherence to the HFNC at home. The lack of any positive effect on the p/f ratio may be due to low airflow rates and overall mild hypoxemia compared to patients with severe respiratory failure in the ICU. [ABSTRACT FROM AUTHOR]

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]

Objective: To evaluate the clinical efficacy, safety and compliance of quality nursing intervention in the treatment of chronic heart failure combined with respiratory tract infections. Methods: This was a retrospective study. One hundred and twenty patients with chronic heart failure combined with respiratory tract infections were recruited at Baoding No.1 Central Hospital from June 2021 to March 2023 and randomly divided into the control group (n=60) and the experimental group (n=60). Patients in the control group were given regular specialist care on the basis of basic treatment, while those in the experimental group were given a quality care intervention model. The differences in clinical efficacy, improvement time of symptoms after treatment, etc. between the two groups were compared and analyzed. Results: The response rate of the experimental group was 88%, which was significantly higher than that of the control group (73%), with a statistically significant difference (P=0.04). The time of fever reduction, cough subsidence and lung rales disappearance in the experimental group were significantly shorter than those of the control group, with statistically significant differences (P<0.05). The incidence of nursing related adverse events in the experimental group was 8%, which was lower than that of 23% in the control group, with a statistically significant difference(P=0.03). Conclusion: Quality nursing intervention is an effective treatment for patients with chronic heart failure combined with respiratory infections, boasting a variety of benefits such as reduced nursing risk, improved quality of nursing, and increased patient compliance and satisfaction. It contributes to rapid symptom improvement and significant clinical efficacy. [ABSTRACT FROM AUTHOR]

A 13-day-old, late preterm male, born appropriate for gestational age, presented to the pediatric clinic for his routine 2-week well visit with less than 1-day history of decreased oral intake and lethargy. During the baby's well exam, he acutely decompensated and required resuscitation and transfer to the emergency department, where he was intubated for frequent apneic events. He was admitted to the NICU for management and further workup. Physical examination and initial laboratory tests were unremarkable. An EEG demonstrated electrographic and clinical seizures. His initial MRI was unremarkable, and infection studies revealed the diagnosis. We review the patient's initial presentation, evaluation, hospital course, and the long-term implications of his diagnosis. [ABSTRACT FROM AUTHOR]

Protoporphyria is a subtype of porphyria characterized primarily by painful phototoxic skin reactions after light exposure at specific wavelengths. Historically, phototherapy is not contraindicated in patients with protoporphyria since there have not been any reports of phototoxic reactions. However, patients with protoporphyria are advised to avoid direct sunlight. In this case report, we describe a neonate not known to have X-linked protoporphyria who received phototherapy for 1 to 2 hours. Within hours after initiation of phototherapy, this neonate developed a life-threatening reaction consisting of rash over the distribution of phototherapy, acute liver failure with coagulopathy, diffuse hypotonia with diaphragmatic failure, and subsequent acute respiratory failure that required mechanical ventilation. As in this case, patients with protoporphyria-related acute liver failure can have signs and symptoms similar to that of an acute hepatic porphyria attack. Neither neonatal reactions to phototherapy nor liver failure temporally associated with phototherapy have been reported in patients with X-linked protoporphyria. Early recognition of this entity is crucial in light of potential life-threatening complications. Therefore, providers must react quickly when neonates have abnormal reactions to phototherapy and consider protoporphyria in the differential diagnosis. [ABSTRACT FROM AUTHOR]

The prone position is an immediately available and easily implemented procedure that was introduced more than 50 years ago as a method for improvement of gas exchange in patients with acute respiratory distress syndrome (ARDS). In the meantime, a survival advantage could also be shown in patients with severe ARDS, which led to the recommendation of the prone position for treatment of severe ARDS by expert consensus and specialist society guidelines. The continuing coronavirus disease 2019 (COVID-19) pandemic moved the prone position to the forefront of medicine, including the widespread implementation of the prone position for awake, spontaneously breathing nonintubated patients with acute hypoxemic respiratory insufficiency. The survival advantage is possible due to a reduction of the ventilator-associated lung damage. In this article, the physiological effects, data on clinical results, practical considerations and open questions with respect to the prone position are discussed. [ABSTRACT FROM AUTHOR]

Inhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients. In this single-center interventional non-inferiority randomized trial (ClinicalTrials.gov , NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO 200/20) or the high-dose iNO group (iNO 200). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO 200 treatments were evaluated. MetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value<0.01). Both groups presented similar SpO 2 /FiO 2 ratio at 48 h (iNO 200 vs. iNO 200/20 341[334–356] vs. 359 [331–380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04–6.33). During the 228 treatments, iNO 200 and iNO 200/20 groups were comparable for safety, hemodynamic stability, and respiratory function improvement. iNO 200/20 and iNO 200 are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO 2. Larger studies should investigate whether iNO 200/20 leads to better outcomes compared to non-iNO treated patients. • 20 patients were randomized to receive high-dose inhaled nitric oxide (iNO) or a combination of high-dose + low-dose iNO. • A total of 228 high-dose iNO treatments were administered to the 20 patients over a range of days. • Safety findings: No adverse events or safety concerns were observed in any of the 20 patients. Methemoglobin levels were comparable between the groups. • Patients treated with iNO demonstrated faster clearance of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients' progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine, an alpha 2 agonist, has emerged as a desirable sedative agent in the pediatric intensive care unit due to its minimal effect on respiratory status and reduction in delirium. Bradycardia and hypotension are common side effects, however there are emerging reports of more serious cardiovascular events, including sinus arrest and asystole. These case reports have been attributed to high vagal tone or underlying cardiac conduction dysfunction. Objectives: To describe the development of sinus arrest during sedation with dexmedetomidine in a patient without clinical features of high vagal tone, underlying cardiac conduction dysfunction, or intervening episodes of bradycardia. Case Presentation: An 11 month-old patient requiring sedation during mechanical ventilation for acute respiratory failure secondary to Adenovirus. To facilitate sedation, a dexmedetomidine infusion was initiated at.5 mcg/kg/hr and increased to maximum 1 mcg/kg/hr. Within 8 hours of initiating therapy, the patient had three episodes of sinus arrest. There was no intervening bradycardia between episodes and no further episodes occurred following discontinuation of dexmedetomidine. The patient did not have any clinical features associated with high vagal tone or underlying cardiac conduction dysfunction. Conclusions: As result of these findings, understanding risk factors for bradycardia, or more serious hemodynamic instability with dexmedetomidine infusions, is important to help identify high risk patients and weigh the associated risks and benefits of its administration. [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]

Introduction: The use of high-flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure has been increasing in the emergency department (ED). However, studies are lacking on the prediction of HFNC failure before therapy initiation in the ED. We investigated whether the existing indices, such as the ratio of pulse oximetry oxygen saturation/fraction of inspired oxygen to respiratory rate (ROX) and ratio of ROX index to heart rate (ROX-HR), can accurately predict HFNC failure at the conventional oxygen therapy phase in the ED. Methods: This retrospective single-center study included patients treated with HFNC in the ED. The ROX and ROX-HR indices were calculated before initiating HFNC. An estimated fraction of inspired oxygen was used for conventional oxygen therapy. We plotted each index's receiver operating characteristics curve and calculated the area under the curve (AUC) for diagnostic capacity. The optimal cutoff values were assessed using the Youden index. The primary outcome was HFNC failure, defined as intubation in the ED. Results: Among the 97 included patients, 25 (25.8%) failed HFNC therapy in the ED. The ROX and ROX-HR indices measured before initiating HFNC showed AUCs of 0.709 and 0.754, respectively. A ROX index of <5.614 and a ROX-HR index of <6.152 were associated with a high risk of intubation, even after correcting for confounding variables. Conclusion: The ROX and ROX-HR indices measured before initiating HFNC provide a relatively fair predictive value of HFNC failure in the ED. [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]

Pulmonary fibrosis (PF) is the end stage of lung injury and chronic lung diseases that results in diminished lung function, respiratory failure, and ultimately mortality. Despite extensive research, the pathogenesis of this disease remains elusive, and effective therapeutic options are currently limited, posing a significant clinical challenge. In addition, research on traditional Chinese medicine and naturopathic medicine is hampered by several complications due to complex composition and lack of reference compounds. Natural product monomers, possessing diverse biological activities and excellent safety profiles, have emerged as potential candidates for preventing and treating PF. The effective anti-PF ingredients identified can be generally divided into flavonoids, saponins, polysaccharides, and alkaloids. Specifically, these monomeric compounds can attenuate inflammatory response, oxidative stress, and other physiopathological processes of the lung through many signaling pathways. They also improve pulmonary factors. Additionally, they ameliorate epithelial–mesenchymal transition (EMT) and fibroblast–myofibroblast transdifferentiation (FMT) by regulating multiple signal amplifiers in the lungs, thereby mitigating PF. This review highlights the significant role of monomer compounds derived from natural products in reducing inflammation, oxidative stress, and inhibiting EMT process. The article provides comprehensive information and serves as a solid foundation for further exploration of new strategies to harness the potential of botanicals in the treatment of PF. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer mortality worldwide. Fortunately, the advent of precision medicine, which includes targeted therapy and immunotherapy, offers hope. However, identifying specific mutations is imperative before initiating precise medications. Traditional methods, such as real-time PCR examination of individual mutations, are time-consuming. Contemporary techniques, such as tissue- and plasma-based next-generation sequencing (NGS), allow comprehensive genome analysis concurrently. Notably, plasma-based NGS has a shorter turnaround time (TAT) and thus a shorter time-to-treatment (TTT). In this case report, we demonstrate the benefits of plasma-based NGS before pathological diagnosis in a patient with image-suspected non-small cell lung cancer (NSCLC). An 82-year-old Taiwanese woman presented with lower back pain persisting for one month and left-sided weakness for two weeks. Whole-body computed tomography (CT) revealed lesions suspicious for brain and bone metastases, along with a mass consistent with a primary tumor in the left upper lobe, indicative of advanced NSCLC with T4N3M1c staging. The patient underwent a bronchoscopic biopsy on Day 0, and the preliminary report that came out on Day 1 was suggestive of metastatic NSCLC. Blood was also collected for plasma-based NGS on Day 0. The patient was Coronavirus disease 2019-positive and was treated with molnupiravir on Day 6. On Day 7, pathology confirmed pulmonary adenocarcinoma, and the results of plasma-based NGS included EGFR L858R mutation. The patient was started on targeted therapy (afatinib) on Day 9. Unfortunately, the patient died of hypoxic respiratory failure on Day 26, a complication of underlying viral infection. Plasma-based NGS offers a rapid and efficient means of mutation detection in NSCLC, streamlining treatment initiation and potentially improving the negative emotions of patients. Its utility, particularly in regions with a high prevalence of specific mutations, such as EGFR alterations in East Asian populations, highlights its relevance in guiding personalized therapy decisions. [ABSTRACT FROM AUTHOR]

Background: Chronic respiratory insufficiency from progressive muscle weakness causes morbidity and mortality in late-onset Pompe disease (LOPD). Previous Pompe Registry (NCT00231400) analyses for ≤ 5 years' alglucosidase alfa treatment showed a single linear time trend of stable forced vital capacity (FVC) % predicted. Methods: To assess longer term Pompe Registry data, piecewise linear mixed model regression analyses estimated FVC% predicted trajectories in invasive-ventilator-free patients with LOPD aged ≥ 5 years. We estimated annual FVC change 0–6 months, > 6 months–5 years, and > 5–13 years from treatment initiation, adjusting for baseline age, sex, and non-invasive ventilation. Findings: Among 485 patients (4612 FVC measurements; 8.3 years median follow-up), median ages at symptom onset, diagnosis, and alglucosidase alfa initiation were 34.3, 41.1, and 44.9 years, respectively. FVC% increased during the first 6 months' treatment (slope 1.83%/year; 95% confidence interval: 0.66, 3.01; P = 0.0023), then modestly declined −0.54%/year (−0.79, −0.30; P < 0.0001) during > 6 months–5 years, and −1.00%/year (−1.36, −0.63; P < 0.0001) during > 5–13 years. The latter two periods' slopes were not significantly different from each other (Pdifference = 0.0654) and were less steep than published natural history slopes (−1% to −4.6%/year). Estimated individual slopes were ≥ 0%/year in 96.1%, 30.3%, and 13.2% of patients during the 0–6 month, > 6 month–5 year, and > 5–13 year periods, respectively. Conclusion: These real-world data indicate an alglucosidase alfa benefit on FVC trajectory that persists at least 13 years compared with published natural history data. Nevertheless, unmet need remains since most individuals demonstrate lung function decline 5 years after initiating treatment. Whether altered FVC trajectory impacts respiratory failure incidence remains undetermined. Trial registration: This study was registered (NCT00231400) on ClinicalTrials.gov on September 30, 2005, retrospectively registered. [ABSTRACT FROM AUTHOR]

Patients with EGFR -mutated non-small-cell lung cancer (NSCLC) and MET amplification as a mechanism of resistance to first-line osimertinib have few treatment options. Here, we report the primary analysis of the phase 2 INSIGHT 2 study evaluating tepotinib, a highly selective MET inhibitor, combined with osimertinib in this population. This open-label, phase 2 study was conducted at 179 academic centres and community clinics in 17 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 and advanced or metastatic EGFR -mutated NSCLC of any histology, with MET amplification by tissue biopsy fluorescence in-situ hybridisation (FISH; MET gene copy number of ≥5 or MET -to- CEP7 ratio of ≥2) or liquid biopsy next-generation sequencing (MET plasma gene copy number of ≥2·3), following progression on first-line osimertinib. Patients received oral tepotinib 500 mg plus oral osimertinib 80 mg once daily. The primary endpoint was independently assessed objective response in patients with MET amplification by central FISH treated with tepotinib plus osimertinib with at least 9 months of follow-up. Safety was analysed in patients who received at least one study drug dose. This study is registered with ClinicalTrials.gov , NCT03940703 (enrolment complete). Between Feb 13, 2020, and Nov 4, 2022, 128 patients (74 [58%] female, 54 [42%] male) were enrolled and initiated tepotinib plus osimertinib. The primary activity analysis population included 98 patients with MET amplification confirmed by central FISH, previous first-line osimertinib and at least 9 months of follow-up (median 12·7 months [IQR 9·9–20·3]). The confirmed objective response rate was 50·0% (95% CI 39·7–60·3; 49 of 98 patients). The most common treatment-related grade 3 or worse adverse events were peripheral oedema (six [5%] of 128 patients), decreased appetite (five [4%]), prolonged electrocardiogram QT interval (five [4%]), and pneumonitis (four [3%]). Serious treatment-related adverse events were reported in 16 (13%) patients. Deaths of four (3%) patients were assessed as potentially related to either trial drug by the investigator due to pneumonitis (two [2%] patients), decreased platelet count (one [1%]), respiratory failure (one [1%]), and dyspnoea (one [1%]); one death was attributed to both pneumonitis and dyspnoea. Tepotinib plus osimertinib showed promising activity and acceptable safety in patients with EGFR -mutated NSCLC and MET amplification as a mechanism of resistance to first-line osimertinib, suggesting a potential chemotherapy-sparing oral targeted therapy option that should be further investigated. Merck (CrossRef Funder ID: 10.13039/100009945). [ABSTRACT FROM AUTHOR]

The number of cesarean sections performed is increasing every year, and obstetric anesthesia is of great interest to physicians and research scholars because of its specificity, high risk, and high complication rate. To investigate the effects of combined spinal epidural anesthesia (CSEA) with different intervertebral spaces during cesarean section on anesthesia effect, anesthesia onset time, anesthesia recovery time, maternal adverse reactions, and neonates. Ninety-two women who underwent cesarean section in our hospital from September 2022 to February 2023 were selected as the study subjects and randomly divided them into two groups (group A and group B), 46 women in each group. Group A underwent CSEA via an L2-3 gap and group B underwent CSEA via an L3-4 gap puncture. The anesthesia effect, anesthesia onset time, sensory recovery time, adverse effects, and neonatal Apgar score were compared between the two groups. When CSEA was performed from L2-3, the anesthesia efficiency was higher, but the difference was not statistically significant. When anesthesia was performed by puncture from L2-3, the onset of anesthesia and recovery time was shorter, and the incidence of intraoperative maternal nausea and vomiting, hypotension, respiratory depression, and other adverse reactions was low with a statistically significant difference. However, the Apgar scores of the neonates in the two groups have no difference. When CSEA is induced via L2-3 interspace, anesthesia has a rapid onset of action, shorter recovery time, and few maternal adverse effects, without affecting the final anesthetic outcome. [ABSTRACT FROM AUTHOR]

Tubulinopathies are associated with malformations of cortical development but not Walker–Warburg Syndrome. Intensive monitoring of a Croatian infant presenting as Walker–Warburg Syndrome in utero began at 21 weeks due to increased growth of cerebral ventricles and foetal biparietal diameter. Monitoring continued until Caesarean delivery at 34 weeks where the infant was eutrophic. Clinical assessment of a progressive neurological disorder of unknown aetiology found a macrocephalic head and markedly hypoplastic genitalia with a micropenis. Neurological examination showed generalized hypotonia with very rare spontaneous movements, hypotonia-induced respiratory insufficiency and ventilator dependence, and generalized myoclonus intensifying during manipulation. With clinical features of hypotonia, lissencephaly, and brain malformations, Walker–Warburg Syndrome was suspected; however, eye anomalies were absent. Genetic trio analysis via whole-exome sequencing only identified a novel de novo mutation in the TUBA1A gene (NM_006009.4:c.848A>G; NP_006000.2:p.His283Arg) in the infant, who died at 2 months of age, as the likely cause. We report a previously unpublished, very rare heterozygous TUBA1A mutation with clinical features of macrocephaly and hypoplastic genitalia which have not previously been associated with the gene. The absence of eye phenotypes or mutations in Walker–Warburg-associated genes confirm this as not a new presentation of Walker–Warburg Syndrome but a novel TUBA1A tubulinopathy for neonatologists to be aware of. [ABSTRACT FROM AUTHOR]

Purpose: Although noninvasive ventilation (NIV) may reduce reintubation in patients with acute hypoxemic respiratory failure following abdominal surgery, this strategy has not been specifically assessed in patients with obesity. Methods: We conducted a post hoc analysis of a multicenter randomized controlled trial comparing NIV delivered via facial mask to standard oxygen therapy among patients with obesity and acute hypoxemic respiratory failure within 7 days after abdominal surgery. The primary outcome was reintubation within 7 days. Secondary outcomes were invasive ventilation-free days at day 30, intensive care unit (ICU)-acquired pneumonia and 30-day survival. Results: Among 293 patients with hypoxemic respiratory failure following abdominal surgery, 76 (26%) patients had obesity and were included in the intention-to-treat analysis. Reintubation rate was significantly lower with NIV (13/42, 31%) than with standard oxygen therapy (19/34, 56%) within 7 days (absolute difference: − 25%, 95% confidence interval (CI) − 49 to − 1%, p = 0.03). NIV was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (27.1 ± 8.6 vs 22.7 ± 11.1 days; p = 0.02), while fewer patients developed ICU-acquired pneumonia (1/42, 2% vs 6/34, 18%; p = 0.04). The 30-day survival was 98% in the NIV group (41/42) versus 85% in the standard oxygen therapy (p = 0.08). In patients with body mass index (BMI) < 30 kg/m2, no significant difference was observed between NIV (36/105, 34%) and standard oxygen therapy (47/109, 43%, p = 0.03). An interaction test showed no statistically significant difference between the two subsets (BMI ≥ 30 kg/m2 and BMI < 30 kg/m2). Conclusions: Among patients with obesity and hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of reintubation within 7 days, contrary to patients without obesity. However, no interaction was found according to the presence of obesity or not, suggesting either a lack of power to conclude in the non-obese subgroup despite existing differences, or that the statistical difference found in the overall sample was driven by a large effect in the obese subsets. [ABSTRACT FROM AUTHOR]

Purpose: Optimal oxygenation targets for patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are not clearly defined due to substantial variability in design of previous trials. This study aimed to perform a pre-specified individual patient data meta-analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) and the Handling Oxygenation Targets in coronavirus disease 2019 (COVID-19) (HOT-COVID) trials to compare targeting a partial pressure of arterial oxygen (PaO2) of 8–12 kPa in adult ICU patients, assessing both benefits and harms. Methods: We assessed 90-day all-cause mortality and days alive without life support in 90 days using a generalised mixed model. Heterogeneity of treatment effects (HTE) was evaluated in 14 subgroups, and results graded using the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN). Results: At 90 days, mortality was 40.4% (724/1792) in the 8 kPa group and 40.9% (733/1793) in the 12 kPa group (risk ratio, 0.99; 95% confidence interval [CI] 0.92–1.07; P = 0.80). No difference was observed in number of days alive without life support. Subgroup analyses indicated more days alive without life support in COVID-19 patients targeting 8 kPa (P = 0.04) (moderate credibility), and lower mortality (P = 0.03) and more days alive without life support (P = 0.02) in cancer-patients targeting 12 kPa (low credibility). Conclusion: This study reported no overall differences comparing a PaO2 target of 8–12 kPa on mortality or days alive without life support in 90 days. Subgroup analyses suggested HTE in patients with COVID-19 (moderate credibility) and cancer (low credibility). [ABSTRACT FROM AUTHOR]