The goal of this study was to assess the effect of enteral feeding on aspiration risk and progression of respiratory failure in adults on high-flow nasal cannula (HFNC) oxygen therapy. Single-center retrospective cohort study. Keck Hospital of the University of Southern California, a tertiary care academic hospital. Hospitalized adults treated with HFNC between January 1, 2020, and December 31, 2022, were included. Exclusion criteria were chronic total parenteral nutrition, chronic tracheostomy, history of total laryngectomy, and "Do Not Intubate" code status. None. The primary outcome was the progression of respiratory failure from HFNC to noninvasive positive pressure ventilation, mechanical ventilation, or extracorporeal membrane oxygenation. We included 220 patients in the primary analysis. The median age was 62.6 years, 54.1% of patients were male, and 43.6% of patients were White. The primary outcome of progression of respiratory failure occurred in 57 patients, of whom 19 (33.3%) were feeding enterally and 38 (66.7%) were NPO at the time of progression. Patients feeding enterally were less likely than those who were NPO to have progression of respiratory failure in a multivariate mixed effects linear regression model (odds ratio [OR], 0.33; 95% CI, 0.18-0.58; p < 0.001). Patients feeding enterally remained less likely to have progression of respiratory failure in a propensity score-matched analysis (OR, 0.30; 95% CI, 0.15-0.58; p < 0.001). In this single-center, retrospective cohort, enteral nutrition in patients on HFNC was associated with lower risk of progression of respiratory failure and was not associated with increased risk of poor clinical outcomes. Prospective multicenter studies are needed to confirm these findings.

Pulmonary fibrosis is an intractable lung disease characterized by scar tissue formation in pulmonary tissues and progressive respiratory failure. Recent research has increasingly highlighted the pivotal role of vascular endothelial cells in the initiation and progression of pulmonary fibrosis. Consequently, this review synthesizes current advances in elucidating vascular dysfunction, endothelial cell heterogeneity, and the associated molecular mechanisms underlying pulmonary fibrosis. Furthermore, it introduces the latest clinical research progress in targeting endothelial cells for therapeutic intervention against pulmonary fibrosis.

Myasthenia gravis is a chronic autoimmune disease characterised by fluctuating skeletal muscle weakness. The perioperative period is a time of increased risk for patients with myasthenia gravis. Surgical stress, drug interactions and other perioperative factors can exacerbate myasthenic symptoms, amplify postoperative complications and precipitate myasthenic crisis, a life-threatening condition characterised by progressive neuromuscular weakness and respiratory failure. This narrative review explores the perioperative management of long-term pharmacological therapy in myasthenia gravis, focusing on the perioperative resumption of acetylcholinesterase inhibitors, corticosteroids and non-steroidal immunosuppressants. Optimal management of these therapies is crucial for maintaining disease stability and reducing postoperative morbidity.

Duchenne muscular dystrophy (DMD) is a severe life-limiting X-linked neuromuscular disorder characterised by progressive skeletal muscle degeneration and respiratory failure. The mdx mouse, lacking dystrophin, is the most widely used preclinical model of DMD, yet the trajectory of respiratory dysfunction in this model remains incompletely defined. We evaluated neural respiratory drive (NRD), neuromechanical efficiency (NME), tension-time index (TTI), inspiratory drive rate and electromyographic (EMG) frequency spectrum parameters in the diaphragm, external intercostal and parasternal muscles across the natural history of disease (aged 1-16months). Despite early and persistent reductions in EMG activity and frequency spectrum parameters in mdx mice, NRD and TTI in respiratory muscles were largely equivalent to controls. NME was paradoxically increased in mdx mice, likely reflecting compensatory recruitment of accessory muscles rather than improved contractile efficiency of the major inspiratory muscles of breathing. The area under the pressure-time curve during sustained tracheal occlusion was reduced in mdx mice at 1month of age but was equivalent to wild-type values at all other ages, demonstrating robust compensation even in advanced disease. No significant differences in inspiratory duty cycle, respiratory muscle effort or TTI were observed across groups. We conclude that assessments of integrative respiratory morbidity in mdx mice should focus on animals aged ≥16months or alternative models with accelerated disease progression. Our results underscore the need for refined translational models and highlight the importance of integrating EMG-based indices for early detection and monitoring of respiratory compromise in DMD.

Smart nebulized ROS-responsive hydrogel microspheres loaded with UC-MSCs-derived exosomes for the treatment of acute lung injury

Patient: Female, 73-year-oldFinal Diagnosis: Respiratory failure (type II respiratory failure) • coronary atherosclerotic heart disease, moderate pulmonary hypertension, and cardiac insufficiency • electrolyte metabolism disorders (hypokalemia, hyponatremia) • hepatic insufficiency • pleural effusion • pulmonary interstitial fibrosis with infectionSymptoms: Dyspnea and chest distress after the activity for more than 10 days, and aggravation for 5 daysClinical Procedure: —Specialty: Critical Care MedicineObjective: Unusual clinical courseBackgroundThe anion gap is a critical parameter in the clinical assessment of acid-base disorders. While metabolic acidosis with an elevated anion gap is commonly encountered, cases involving a negative anion gap are rare and have been reported in the context of hypoalbuminemia, severe hyperkalemia, bromide intoxication, and laboratory error. Notably, metabolic alkalosis as a cause of negative anion gap has been rarely described in the literature.Case ReportA 73-year-old woman with a 4-year history of interstitial pulmonary fibrosis and a 1-year history of coronary artery disease had been taking oral spironolactone for the past year. Six months before admission, torasemide was added to her regimen in combination with spironolactone. Five days prior to admission, she developed progressive dyspnea and respiratory failure. Initial investigations revealed hypokalemia, hyponatremia, metabolic alkalosis (HCO3−=61.6 mmol/L), and a negative anion gap (−9.00 mmol/L), which remained negative after albumin correction (−6.35 mmol/L). Further evaluation identified loop diuretic overuse as the primary cause of severe metabolic alkalosis and negative anion gap. The application of targeted next-generation sequencing (t-NGS) successfully identified the infectious pathogen responsible for the patient’s clinical deterioration, thereby guiding appropriate antimicrobial therapy.ConclusionsThis case illustrates the diagnostic and educational value of recognizing a negative anion gap as a rare but physiologically predictable artifact of severe chloride–depletion alkalosis, underscoring the importance of mechanism-based interpretation in complex acid-base disorders.

A lupus-like condition induced by intraperitoneal administration of pristane (2,6,10,14-tetramethylpentadecane) in mice is widely used as a model of systemic lupus erythematosus (SLE). Due to their phylogenetic distance from humans, murine models are not always suitable tool for studying the specific activity of therapeutic agents and the pathogenesis of SLE. In order to overcome species-specific limitations of murine models, this approach was tested in non-human primates-cynomolgus monkeys (Macaca fascicularis). Two intraperitoneal injections at a dose of 3.5 mL/kg, administered at weeks 1 and 23, recapitulated SLE features, including: production of antinuclear autoantibodies (ANA), membranoproliferative glomerulonephritis with immune complex (IC) deposition in the glomeruli. However, from week 27 five of eight pristane-treated monkeys developed progressive respiratory failure. Two of these died at week 28 and the remaining were euthanized at week 32. The histology of the monkey lungs suggested exogenous lipoid pneumonia. Thus, while pristane induced serological autoimmunity and characteristic renal manifestations in Macaca fascicularis, the consequent lipoid pneumonia limited the observation period and prevented comprehensive evaluation of SLE manifestations beyond 32 weeks.

Acute severe nickel carbonyl poisoning is an uncommon yet potentially fatal occupational hazard that produces marked pulmonary injury and rapidly progressive respiratory failure. We describe three middle-aged men who developed severe nickel carbonyl intoxication after workplace exposure at a metal-processing facility. All patients presented with progressive dyspnea, cyanosis, hypoxemia, and pronounced neutrophilia. Chest computed tomography revealed bilateral pulmonary infiltrates with variable early distribution across patients. Prompt recognition permitted immediate initiation of high-dose methylprednisolone, moxifloxacin, and individualized supportive care according to oxygen (O2) requirements. All three patients exhibited striking clinical improvement within 72h. Serial imaging suggested substantial resolution of pulmonary inflammation, and every patient recovered without residual impairment. Nickel carbonyl exposure demanded a high index of suspicion and prompt initiation of high-dose corticosteroid therapy was required to prevent irreversible lung injury and improve survival. This case series provides valuable clinical evidence to inform diagnostic and therapeutic approaches for this rare occupational poisoning.

Silicosis is an incurable occupational lung disease characterized by progressive fibrosis and respiratory failure, imposing a significant global health burden. Surfactant protein A (SP-A) plays a critical role in maintaining pulmonary homeostasis, yet its mechanistic role in silicosis remains unclear. SP-A expression was assessed in lung tissues from patients with silicosis and in silica-exposed mice. Sftpa1 gene knockout (Sftpa1-/-) mice were generated to evaluate the functional role of SP-A in vivo, including lung pathology, collagen deposition, and pulmonary function. RNA sequencing was performed to uncover underlying molecular mechanisms. A549 cells with SP-A silenced by siRNA were employed for in vitro experiments. SP-A levels were notably reduced in the lung tissue of silicosis patients and in experimental silicosis mice, correlating inversely with disease severity. Sftpa1⁻/⁻ mice showed markedly exacerbated silica-induced pulmonary fibrosis, extracellular matrix deposition, and functional decline. RNA-seq analysis highlighted activation of intrinsic apoptosis pathways related to pulmonary fibrosis. Mechanistically, SP-A deficiency disrupted the balance of Bcl-2 and Bax, activated Caspase-3, and promoted epithelial apoptosis. Inhibition of the intrinsic apoptosis pathway mitigated the pro-apoptotic effects of SP-A silencing. These findings demonstrate that SP-A deficiency exacerbates silica-induced pulmonary fibrosis by promoting epithelial apoptosis involving the Bcl-2/Bax/Caspase pathway, highlighting the role of SP-A in fibrogenesis progression and providing a basis for its potential therapeutic target for silicosis.

BackgroundAcute respiratory distress syndrome (ARDS) is a complex syndrome characterized by acute diffuse lung injury and progressive respiratory failure, caused by various intra- and extra-pulmonary factors. The coronavirus disease 2019 (COVID-19) pandemic has significantly increased the incidence of ARDS, posing a tremendous threat to human health due to its high mortality rate and lack of effective therapeutic drugs. In recent years, mesenchymal stem cell-derived exosomes (MSC-exo) have been considered a new hope for the treatment of ARDS due to their potent immunomodulatory characteristics. Although multiple studies have demonstrated their efficacy and safety, the differential therapeutic effects of various administration routes and doses remain unclear. This study aimed to investigate the administration route of MSC-exo for ARDS treatment, with the goal of maximizing therapeutic benefits and providing valuable clinical insights.MethodsThis study aims to establish an ARDS disease model by intratracheal instillation of lipopolysaccharide (LPS) in male C57/BL6 mice. Subsequently, umbilical cord mesenchymal stem cell exosomes will be administered via three methods: inhalation, tail vein injection, and combination therapy (inhalation combined with tail vein injection). Following the establishment of the mouse ARDS model via intratracheal instillation of LPS, the animals were randomly divided into seven groups based on the timing and dosage of the treatment administration. Samples were harvested at 24 hours, 72 hours, and 7 days after modeling. The assessments included RNA transcriptome sequencing, cytokine levels in blood and bronchoalveolar lavage fluid, blood oxygen saturation, histopathological staining, and survival analysis.ResultsCompared to nebulized exosomes alone, dual-route administration significantly improved respiratory function, as evidenced by prolonged expiratory and inspiratory times and increased minute ventilation (P≤0.05). Furthermore, it decreased the levels of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the blood (P=0.01, P=0.041). Compared to intravenous exosomes alone, dual-route administration produced broader improvements. It significantly enhanced lung function by prolonging expiratory time (P=0.01), inspiratory time (P=0.004), and increasing minute ventilation (P=0.02). Additionally, it suppressed inflammation by lowering IL-6 levels in bronchoalveolar lavage fluid (P=0.01) and reduced the death of type II alveolar epithelial cells (P=0.03).ConclusionsThe dual-route administration of umbilical cord MSC-exo is more effective in controlling the inflammatory response and alleviating lung injury in LPS-induced ARDS animal models. Inhalation rapidly alleviates pulmonary inflammation with a smaller dose, while intravenous injection better manages the systemic inflammation. This dual-route approach holds promise as a novel ARDS treatment strategy.

Background: Neuroleptic Malignant Syndrome (NMS) is a rare but life-threatening potentially fatal adverse condition most commonly associated with dopamine receptor antagonists. It is characterized by hyperthermia, generalized muscular rigidity, autonomic dysregulation, and elevated serum creatine kinase levels. Prompt recognition and intervention are critical for reducing morbidity and mortality. Case Report: A 61-year-old female with multiple comorbidities developed atypical NMS following abrupt discontinuation of long-acting depot antipsychotic therapy. The patient presented with fever, altered mental status, autonomic dysfunction, and progressive respiratory failure without marked rigidity or significant elevation in creatine kinase levels. Her condition was further complicated by sepsis and hemodynamic instability, necessitating admission to the intensive care unit (ICU) and mechanical ventilation. The diagnosis was established based on the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders and clinical judgment. The patient responded favorably to bromocriptine and other supportive interventions.Conclusion: This case highlights the diagnostic complexity of atypical NMS, particularly in elderly patients undergoing depot antipsychotic therapy. A high index of clinical suspicion and prompt multidisciplinary intervention are essential to improve outcomes in such challenging presentations.

In a patient with a severe exacerbation of chronic obstructive pulmonary disease, there was a concomitant manifestation of cough-syncope syndrome with episodes of loss of consciousness at the height of cough attacks. The patient’s severe condition, progressive respiratory failure against the background of massive obstruction of the lower respiratory tract by bronchial secretions, forced to use bronchological aid. Instead of standard local anesthesia, deep sedation under the cover of glucocorticosteroids was used to suppress the cough reflex. Bronchological intervention was carried out in full and resolved pronounced bronchial obstruction. The performed bronchological interventions against the background of intensive systemic therapy allowed to stop the severe exacerbation of the disease and to level out the manifestations of cough-fainting syndrome.

PurposeA proportion of COVID-19 pneumonia patients develop respiratory failure despite tocilizumab administration. This retrospective cohort study aimed to identify prognostic factors associated with progressive respiratory failure within 14 days among patients with severe COVID-19 pneumonia treated with Tocilizumab and to describe treatment outcomes.Patients and MethodsPatients with severe COVID-19 pneumonia were assessed, and their demographic, clinical, laboratory data, and prior treatment were collected on the day of tocilizumab administration. A multivariable Cox proportional hazard model was employed to identify prognostic factors.ResultsOf the 109 patients, 32 (29.4%) progressed to respiratory failure. We identified the following independent prognostic factors for progressive respiratory failure: pulse oximetry saturation to fraction of inspired oxygen ratio (SpO2/FiO2) ≤ 160 (HR 2.97, 95% CI 1.41–6.23, P = 0.004), estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 (HR 3.21, 95% CI 1.23–8.39, P = 0.017), and serum potassium ≤ 4 mmol/L (HR 2.82, 95% CI 1.38–5.80, P = 0.005). A predictive model based on these factors effectively stratified the risk of progressive respiratory failure (area under the curve = 0.72, 95% CI 0.63–0.80). Patients experiencing progressive respiratory failure had poor clinical outcomes, with a mortality rate of 62.5%, compared to 0.0% in the non-respiratory failure group (p < 0.001).ConclusionIn severe COVID-19 pneumonia patients treated with Tocilizumab, low SpO2/FiO2 ratio, low eGFR, and relatively low serum potassium were independent predictors for progressive respiratory failure. This simple clinical score may help identify high-risk patients early, though external validation is required before routine implementation.

Interstitial lung diseases (ILDs) include various lung parenchymal disorders characterized by inflammation and fibrosis of the lung tissue, leading to progressive dyspnea and respiratory failure. Clinical evidence has suggested an association between human parvovirus B19 (B19V) infection and the progression of ILD and pulmonary fibrosis, but the mechanisms involved remain unclear. The present study screened 86 patients with connective tissue disease (CTD) and reported that B19V infection was significantly more prevalent among those with ILD than among those without (P<0.001). To investigate the potential underlying mechanisms, a bleomycin (BLM)-treated mouse model was employed to assess the effect of B19V nonstructural protein 1 (NS1) on pulmonary fibrosis. Mice treated with BLM or BLM + NS1 exhibited markedly higher fibrosis scores, hydroxyproline content, and higher levels of transforming growth factor-β and collagen I. Treatment with nintedanib attenuated fibrosis in both groups; however, lung fibrosis remained more pronounced in the BLM + NS1 group than in the BLM group. Furthermore, the levels of neutrophil-associated markers, including citrullinated histone H3 and myeloperoxidase, as well as inflammasome-related factors, such as IL-18 and IL-17A, were markedly elevated in lung tissues from both groups, with the highest levels observed in the BLM + NS1 group. These findings suggested that B19-NS1 may exacerbate fibrosis in patients with ILD by increasing neutrophil-driven responses and inflammasome activation, highlighting a need for nintedanib therapies to more effectively address B19V-associated pulmonary fibrosis.

BackgroundNeonatal respiratory distress syndrome (NRDS) is a life-threatening condition marked by progressive respiratory failure due to pulmonary surfactant (PS) deficiency, typically presenting within hours of birth. Exogenous pulmonary surfactant replacement therapy has significantly reduced mortality associated with NRDS and improved clinical outcomes. The current standard of care involves the intubation-surfactant-extubation (INSURE) technique. However, emerging evidence suggests that the laryngeal mask airway (LMA) may serve as a viable noninvasive alternative for neonatal resuscitation and therapeutic administration. This randomized controlled equivalence trial aims to compare the clinical efficacy and safety profiles of LMA and INSURE in delivering PS for NRDS management.MethodsSome of the preterm infants diagnosed with NRDS and requiring the first treatment with PS were included in this study. The included subjects were randomly assigned to the LMA group (experimental group) and the INSURE group (control group) by means of envelopes, and were given PS treatment by LMA or INSURE, respectively, and the SF index (SpO2/FiO2) before and after the use of PS; the placement time of artificial airway, the episodes of hypoxemia, bradycardia and tachycardia during artificial airway placement; the amount of PS residue in the stomach after the use of PS; the incidence of the second use of PS, and the incidence of pneumothorax were also monitored in order to compare the effect and prognosis of the two methods of treating NRDS.DiscussionThe use of PS with INSURE is currently the most prominent and classic method. Although some recent studies suggest that non-invasive use of PS through a laryngeal mask is also effective, relevant research remains limited. Through this trial, we aim to gather more data regarding the use of PS with a laryngeal mask and further validate its effectiveness.Trial registrationName of the registry: A randomized controlled trial of pulmonary surfactant administration via laryngeal mask airway versus endotracheal intubation.Trial identifying number: ChiCTR2500096315.Date of registration in primary registry: 2025-01-21 00:00:00.PID: 254631.Country of recruitment: China.URL of trial registry record: https://www.chictr.org.cn/showproj.html?proj=254631.

Hermansky-Pudlak Syndrome.

Background. In ANCA-associated vasculitis (AAV), despite the findings of the PEXIVAS trial, the usefulness of plasma exchange (PLEX) remains debated in selected clinical settings, such as diffuse alveolar hemorrhage (DAH). Methods. We report a case of life-threatening AAV successfully treated with an intensive, high-volume, and individualized PLEX protocol. Results. We describe a 40-year-old man with newly diagnosed AAV (c-ANCA/anti-PR3, high titer) who presented with rapidly progressive glomerulonephritis and severe respiratory failure (PaO2/FiO2 ratio &lt; 200) secondary to DAH, requiring mechanical ventilation. In addition to induction therapy with methylprednisolone pulses (total 3000 mg) and weekly rituximab (375 mg/m²), we initiated an intensive PLEX regimen consisting of 20 sessions over 52 days (three consecutive at onset), with a mean plasma exchange volume of 1.0–1.5 times the plasma volume (mean exchanged volume per session: 4450 ± 705 mL; total exchanged volume: 89 L). From the third PLEX session, we observed a marked reduction in ANCA titer and inflammatory markers, followed by significant respiratory improvement after the sixth session (Figure 1). The last four sessions were performed after extubation. At 48 months of follow-up, under maintenance therapy with mycophenolate mofetil, no vasculitis flares were observed, although renal recovery was not achieved. This case highlights the potential benefit of an intensive, high-volume PLEX protocol in life-threatening AAV with DAH, supporting several considerations: the PEXIVAS trial, cornerstone of current guidelines, adopted a limited PLEX schedule (7 sessions) without escalation in refractory cases—possibly underestimating efficacy in severe disease phenotypes (our patient achieved pulmonary recovery after the 6th session). Moreover, only 61 patients (8.7%) in PEXIVAS had DAH, and subgroup analysis showed lower one-year mortality in PLEX-treated patients (19.4% vs. 33.3%). A post-hoc analysis of PLEXIVAS demonstrated improved eGFR recovery at 4–8 weeks and greater renal recovery at one year in patients receiving PLEX. Although these findings are not generalizable, they retain potential clinical significance in selected severe cases. The KDIGO 2024 guidelines currently support PLEX in patients with serum creatinine ≥ 300 µmol/L (3.4 mg/dL), suggesting a tailored, individualized approach. Conclusions. Intensive and personalized PLEX regimens deserve renewed consideration in life-threatening AAV—especially in patients with DAH, rapidly progressive renal involvement, or refractoriness to conventional therapy. The efficacy of PLEX in these settings cannot be fairly dismissed based on the PEXIVAS trial alone.

Neutrophil degranulation in the lung microenvironment linked to idiopathic pulmonary fibrosis severity and survival

OMT-28, a synthetic analog of 17,18-epoxyeicosatetraenoic acid, mitigates lipopolysaccharide-induced lung injury in mice.

Rationale:Pneumonic-type lung carcinoma is a rare radiological lung cancer subtype. Its clinical and imaging manifestations are easily confused with pneumonia, leading to frequent misdiagnosis and mistreatment in clinical practice.Patient concerns:A 77-year-old female was admitted with “left-sided body pain for 1 week and head/facial pain for 2 days.” Initially lacking typical respiratory symptoms, she developed progressive respiratory failure requiring high-flow oxygen therapy after the initiation of anti-infective treatment.Diagnoses:Chest computed tomography revealed bilateral diffuse consolidation with air bronchograms. Ultrasound-guided percutaneous lung biopsy confirmed the diagnosis of invasive lung adenocarcinoma (non-mucinous). Genetic testing identified an epidermal growth factor receptor exon 19 deletion mutation (p.E746_A750del, variant allele frequency = 41.34%).Interventions:Supportive care, including anti-infectives, expectorants, and high-flow oxygen therapy, was administered upon admission. Following diagnosis, oral targeted therapy with osimertinib was initiated.Outcomes:The patient’s dyspnea gradually improved. Chest computed tomography performed 1 week later showed significant absorption of bilateral pulmonary shadows, and the oxygenation indices progressively normalized. Disease remission was sustained during the 2-month follow-up.Lessons:This critically ill patient presented with respiratory failure as the initial symptom, creating a high risk for misdiagnosis and mistreatment. Early recognition and definitive diagnosis are crucial for effective treatment. Bedside ultrasound-guided percutaneous biopsy is a viable diagnostic approach for critically ill patients.