2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:Tc1b, Objective This systematic review evaluates the safety, feasibility, tolerability, and efficacy outcomes of intranasally administered stem cells and their derivatives (MSCs, NSCs, secretome, and EVs) for the treatment of neurological and respiratory disorders. Methods A literature search was conducted across PubMed, Google Scholar, Web of Science, Scopus, and ClinicalTrials.gov for published research from January 2011 to December 2025. A total of 19 studies were included (7 published articles, 12 registry-only or grey literature records). Risk of bias was assessed using two complementary Cochrane tools, the RoB 2 tool for all 19 studies and the ROBINS-I tool for the 6 n-RCTs. Sources of heterogeneity were systematically characterized across 5 clinical dimensions, and structural publication bias was evaluated against a 30% registry-only threshold. A random-effects model was selected for pooled analyses, with a planned subgroup analysis of treatment dosage against adverse events. Effect sizes were extracted using SMD, mean differences, risk ratios, and odds ratios as appropriate per outcome type. Results This systematic review was conducted in accordance with PRISMA 2020 guidelines. A total of 104 participants were enrolled in 7 published studies, with one completed registry trial (NCT04602104) confirming actual enrolment of an additional 18 participants. No study achieved an overall low risk of bias under either assessment tool. Under RoB 2, 1 published study was rated as having some concerns, others were rated high risk or some concerns. Under ROBINS-I, 3 n-RCT studies were rated critical overall. The remaining 3 were rated serious. Across the 7 published studies, 98 participants contributed to the analyzed outcomes. Structural publication bias was confirmed. Substantial clinical heterogeneity was identified across 9 conditions, multiple cell product categories, and mixed intranasal and intravenous delivery routes. Conclusion Although current evidence suggests that intranasal administration of stem cells, particularly MSCs and NSCs, in humans is a safe and feasible approach, with possible therapeutic improvements in CNS disorders. However, there is a serious risk of bias, critically small sample sizes, and pervasive publication bias in the available literature. Adequately powered, quadruple-blinded, placebo-controlled randomized trials need to be conducted before clinical translation can be considered. 31:T422,Type III interferons are essential immune mediators playing pleiotropic roles during health and disease. In this review, we highlight the molecular and cellular pathways that lead to the production of type III interferons. We also describe their exquisite capacity to act at primary barrier tissues such as those in the intestine, airways, urogenital tract, and skin, as well as to act in other organs such as the liver and thymus. We characterize the activity of type III interferons on distinct cell types in different tissues and organs and detail their impact for the host in the context of viral, bacterial, helminth, and fungal infections. Additionally, we illustrate roles of type III interferons during the development of inflammatory diseases such as inflammatory bowel disease, acute respiratory distress syndrome, asthma, solid tumors, and lupus. Overall, we summarize the dichotomous roles played by this class of interferons and highlight the knowledge gaps that must be addressed to harness type III interferons against multiple human diseases.32:T433,Type III interferons are essential immune mediators playing pleiotropic roles during health and disease. In this review, we highlight the molecular and cellular pathways that lead to the production of type III interferons. We also describe their exquisite capacity to act at primary barrier tissues such as those in the intestine, airways, urogenital tract, and skin, as well as to act in other organs such as the liver and thymus. We characterize the activity of type III interferons on distinct cell types in different tissues and organs and detail their impact for the host in the context of viral, bacterial, helminth, and fungal infections. Additionally, we illustrate roles of type III interferons during the development of inflammatory diseases such as inflammatory bowel disease, acute respiratory distress syndrome, asthma, solid tumors, and lupus. Overall, we summarize the dichotomous roles played by this class of interferons and highlight the knowledge gaps that must be addressed to harness type III interferons against multiple human diseases.33:T795,Patients with sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) commonly suffer from severe pulmonary thrombosis, but clinical trials of anticoagulant therapies in patients with sepsis and ARDS have failed. Patients with ARDS plus thrombocytopenia also exhibit increased mortality, and widespread pulmonary thrombosis is often seen in patients with COVID-19 ARDS. Different amounts of microbeads were administered intravenously to adult mice to induce various levels of pulmonary thrombosis. ALI was induced by either intraperitoneal lipopolysaccharide or cecal ligation and puncture. Endothelial cell (EC)-targeted nanoparticles were used to deliver plasmid DNA expressing the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) system for EC-specific gene knockout of Alox15 (arachidonate 15-lipoxygenase) or plasmid DNA expressing Alox15 for EC-specific overexpression. Lipidomic profiling and in vivo rescue studies with the identified Alox15-regulated lipids were performed. In addition, thrombocytopenia was induced by genetic depletion of platelets using We show that although severe pulmonary thrombosis or thrombocytopenia augments sepsis-induced ALI, the induction of mild pulmonary thrombosis conversely reduces EC apoptosis, ALI, and mortality via sustained expression of endothelial Alox15. Endothelial We have demonstrated that moderate levels of lung thrombosis protect against sepsis-induced inflammatory lung injury via endothelial Alox15. Overexpression of endothelial Alox15 inhibits severe pulmonary thrombosis-induced increases in ALI. Thus, upregulation of ALOX15 expression or treatment with ALOX15-dependent protective lipid(s) represents a promising therapeutic strategy for treatment of ARDS, especially in subpopulations of patients with thrombocytopenia or widespread pulmonary thrombosis.34:T1040, BACKGROUND: Patients with sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) commonly suffer from severe pulmonary thrombosis, but clinical trials of anticoagulant therapies in patients with sepsis and ARDS have failed. Patients with ARDS plus thrombocytopenia also exhibit increased mortality, and widespread pulmonary thrombosis is often seen in patients with COVID-19 ARDS. METHODS: Different amounts of microbeads were administered intravenously to adult mice to induce various levels of pulmonary thrombosis. ALI was induced by either intraperitoneal lipopolysaccharide or cecal ligation and puncture. Endothelial cell (EC)–targeted nanoparticles were used to deliver plasmid DNA expressing the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat–associated 9) system for EC-specific gene knockout of Alox15 (arachidonate 15-lipoxygenase) or plasmid DNA expressing Alox15 for EC-specific overexpression. Lipidomic profiling and in vivo rescue studies with the identified Alox15-regulated lipids were performed. In addition, thrombocytopenia was induced by genetic depletion of platelets using DTR Pf4Cre mice, and the effects of restoration of pulmonary thrombosis were assessed. RESULTS: We show that although severe pulmonary thrombosis or thrombocytopenia augments sepsis-induced ALI, the induction of mild pulmonary thrombosis conversely reduces EC apoptosis, ALI, and mortality via sustained expression of endothelial Alox15. Endothelial Alox15 knockout in adult mice abolished the protective impact of mild lung thrombosis. Conversely, overexpression of endothelial Alox15 inhibited the increases in ALI caused by severe pulmonary thrombosis. Treatment of the endothelial Alox15 knockout mice with 1-palmitoyl-2-oleoyl-3-arachidonoyl-rac-glycerol (C 57 H 100 O 6 ), a top candidate of the 32 Alox15-regulated lipids identified by lipidomic profiling, markedly reversed the defective phenotype, suggesting that Alox15 protects from lung injury via protective lipids. The clinical relevance of the findings was supported by the observation of reduced ALOX15-expressing ECs in lung autopsy samples of patients with ARDS. In addition, restoration of pulmonary thrombosis in thrombocytopenic mice normalized endotoxemia-induced ALI. CONCLUSIONS: We have demonstrated that moderate levels of lung thrombosis protect against sepsis-induced inflammatory lung injury via endothelial Alox15. Overexpression of endothelial Alox15 inhibits severe pulmonary thrombosis-induced increases in ALI. Thus, upregulation of ALOX15 expression or treatment with ALOX15-dependent protective lipid(s) represents a promising therapeutic strategy for treatment of ARDS, especially in subpopulations of patients with thrombocytopenia or widespread pulmonary thrombosis. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Acute Respiratory Distress Syndrome: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Acute Respiratory Distress Syndrome (condition). Clinician-written summaries and actionable practice insights. 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Anti-inflammatory interventions (dexamethasone and IL-6 receptor blockade) showed benefit **only** in the more inflamed (hyperinflammatory) mouse subgroup.","limitations":"The human cohort is observational (n=548), limiting causal inference; mouse-to-human translational fidelity of pneumococcal pneumonia models is inherently uncertain; therapeutic findings are preclinical only and not yet validated in human RCTs stratified by phenotype.","practice_takeaway":"Clinicians should be aware that a 'one-size-fits-all' anti-inflammatory approach in severe pneumonia/ARDS may not work—hyperinflammatory patients may benefit from corticosteroids or IL-6 blockade while hypoinflammatory patients may not. Biomarker-based phenotyping at ICU admission could become a key step before initiating these therapies."}},{"doi":"10.1093/ajrccm/aamag391","pmid":"42496581","title":"Macrophage membrane-coated nanoparticles control pathological inflammation and enhance survival in models of severe bacterial pneumonia","journal_title":"American Journal of Respiratory and Critical Care Medicine","journal_issn":"1073-449X","published_at":"2026-07-24T00:00:00.000Z","url":"https://doi.org/10.1093/ajrccm/aamag391","source_score":8,"is_retracted":false,"is_open_access":null,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":false},"created_at":"2026-07-31T13:37:04.641Z","updated_at":"2026-07-31T13:37:04.641Z","tags":[{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"condition","value":"Acute Respiratory Distress Syndrome","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"condition","value":"Bacterial Pneumonia","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"condition","value":"MRSA Pneumonia","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"condition","value":"Pseudomonas aeruginosa Infection","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"generic","value":"macrophage membrane-coated nanoparticles","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"modality","value":"Biomimetic Nanoparticle","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"study_design","value":"Preclinical Animal Study","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"warning","value":"Sex of murine models is not reported in the abstract; sex tag omitted.","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"warning","value":"Specific survival percentages and quantitative bacterial burden data are not provided in the abstract — key result summary reflects qualitative descriptions only.","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag391","tag_type":"warning","value":"Study design tag reflects a hybrid in vitro/in vivo preclinical approach; no human clinical trial data are present.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated macrophage membrane-coated nanoparticles (MΦ-NPs) as a host-directed therapy for severe bacterial pneumonia, using in vitro models with human lung endothelial/epithelial cells and neutrophils, plus in vivo murine models of *Pseudomonas aeruginosa* (PA) and MRSA pneumonia.","key_result":"MΦ-NP treatment improved survival, reduced bacterial burden, lowered proinflammatory cytokines, and preserved lung architecture in both PA and MRSA murine models; proteomics showed suppression of inflammatory, coagulation, and fibrotic pathways linked to poor outcomes in pneumonia and ARDS.","limitations":"All in vivo data are from murine models only — no human clinical data. Specific survival rates and bacterial burden numbers are not reported in the abstract. The study does not assess pharmacokinetics, dosing optimization, or safety in higher organisms.","practice_takeaway":"MΦ-NPs are not yet clinically available, but this preclinical work positions them as a potential adjunct to antibiotics that targets host inflammation without blunting neutrophil antimicrobial function — a key concern with current anti-inflammatory strategies in pneumonia and ARDS."}},{"doi":"10.1007/s15010-026-02883-y","pmid":"42467174","title":"Severe pneumonia and acute respiratory distress syndrome caused by avian influenza A (H10N3) in a young female: a case report","journal_title":"Infection","journal_issn":"0300-8126","published_at":"2026-07-17T00:00:00.000Z","url":"https://doi.org/10.1007/s15010-026-02883-y","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-21T13:34:30.457Z","updated_at":"2026-07-21T13:34:30.457Z","tags":[{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"brand","value":"Tamiflu","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"brand","value":"Xofluza","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"category","value":"Infectious Diseases","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"condition","value":"Acute Respiratory Distress Syndrome","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"condition","value":"Avian Influenza A (H10N3)","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"condition","value":"Severe Pneumonia","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"generic","value":"baloxavir marboxil","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"generic","value":"oseltamivir","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"modality","value":"Extracorporeal Membrane Oxygenation","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"modality","value":"Neuraminidase Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"modality","value":"Polymerase Acidic Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"sample_size","value":"n=1","value_numeric":1},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"warning","value":"Dual antiviral (baloxavir + oseltamivir) efficacy inference is based on a single patient without a control; viral clearance timing may reflect natural disease course.","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"warning","value":"Neurological complication (lower limb numbness and motor dysfunction) noted in this case was not reported in prior H10N3 cases; causality vs. ECMO-related complication is unclear.","value_numeric":null},{"paper_doi":"10.1007/s15010-026-02883-y","tag_type":"warning","value":"Only 4 human H10N3 cases exist globally; cross-case comparisons are descriptive and limited by very small numbers.","value_numeric":null}],"summaries":{"what_studied":"This case report describes a 23-year-old previously healthy female in Nanning, China, who developed severe pneumonia and ARDS after occupational exposure to poultry, confirmed as the fourth documented human infection with avian influenza A (H10N3). Clinical course, treatment response, and genomic characteristics were compared across all four known human H10N3 cases.","key_result":"The patient required invasive mechanical ventilation and V-V ECMO (PaO2/FiO2 ratio of 44.1 at nadir) and recovered after ~3 months of intensive care. RT-PCR cleared negative within 48 h of starting combined baloxavir marboxil + oseltamivir. Across all 4 reported human H10N3 cases, 75% (3/4) required mechanical ventilation or ECMO; ARDS onset was typically 8–10 days after symptom onset. The strain carried the human-adapted P221 substitution but lacked G228S, suggesting G228S is not required for human infection. No NAI-resistance mutations were found.","limitations":"- Single case with no environmental sampling from exposure sites, leaving the spillover pathway uncharacterized.\n- No seroepidemiological studies in high-risk occupational contacts, so asymptomatic exposure burden is unknown.\n- Dual antiviral efficacy (baloxavir + oseltamivir) is based on one patient with no comparator arm.","practice_takeaway":"Clinicians should consider avian influenza (including H10N3) in patients with severe, rapidly progressive pneumonia and recent poultry or live-market exposure, especially when standard respiratory pathogen panels are negative. Early mNGS of BAL fluid enabled diagnosis here; baloxavir + oseltamivir achieved rapid viral clearance and the virus showed no NAI resistance."}},{"doi":"10.1183/16000617.0058-2026","pmid":"42386311","title":"Bench evidence, bedside uncertainty: hyperoxia, mechanical ventilation and lung injury","journal_title":"European Respiratory Review","journal_issn":"0905-9180","published_at":"2026-07-01T00:00:00.000Z","url":"https://doi.org/10.1183/16000617.0058-2026","source_score":5,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-08T13:26:37.586Z","updated_at":"2026-07-08T13:26:37.586Z","tags":[{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"condition","value":"Acute Hypoxaemic Respiratory Failure","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"condition","value":"Acute Respiratory Distress Syndrome","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"condition","value":"Hyperoxic Lung Injury","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"condition","value":"Ventilator-Induced Lung Injury","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"modality","value":"Mechanical Ventilation","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"modality","value":"Oxygen Therapy","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"warning","value":"Mechanistic data are predominantly from rodent and in vitro models; direct translation to adult human physiology is uncertain.","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"warning","value":"No sample_size tag applied — this is a review article with no single study population.","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"warning","value":"Several cited RCTs (LOCO2, Oxygen-ICU) were terminated early, limiting the strength of their conclusions.","value_numeric":null},{"paper_doi":"10.1183/16000617.0058-2026","tag_type":"warning","value":"This is a narrative review, not a systematic review or meta-analysis; study selection was guided by author judgment and may reflect publication bias.","value_numeric":null}],"summaries":{"what_studied":"This narrative review synthesizes pre-clinical and clinical evidence on how hyperoxia (supra-atmospheric oxygen) primes the adult lung for injury during mechanical ventilation, examining mechanisms (oxidative stress, cytoskeletal remodeling, inflammation, alveolar-capillary barrier dysfunction) and evaluating liberal vs. conservative oxygen strategies in critically ill adults.","key_result":"Animal models consistently show hyperoxia and mechanical ventilation synergistically worsen lung injury — e.g., combining 12 h of hyperoxia with 4 h of high tidal volume ventilation caused the most severe injury in mice. Clinically, major RCTs (ICU-ROX, UK-ROX, PILOT, HOT-ICU) found conservative oxygen therapy non-inferior but not superior to usual care for 90-day mortality; only Oxygen-ICU and HOT-COVID showed a mortality benefit with conservative targets. Mechanically ventilated ARDS patients receive a mean FiO₂ of 74% on ICU day 1; in one cohort, patients spent 59% of hospital time in a hyperoxaemic state.","limitations":"- Most mechanistic evidence comes from animal models; adult human lung data are sparse, and neonatal findings cannot be directly extrapolated.\n- Clinical trials face pre-randomisation oxygen exposure bias, narrow separation between study arms (e.g., 42.1% nonadherence in UK-ROX), and rely on mortality endpoints insensitive to subclinical oxidative or histological injury.\n- No consensus definition of hyperoxaemia (thresholds range from PaO₂ >100 to >125 mmHg) and no validated biomarkers to track lung-specific oxygen toxicity in humans.","practice_takeaway":"Target SpO₂ 92–96% (or 88–92% in hypercapnia risk) and avoid unnecessary high FiO₂ during mechanical ventilation — conservative oxygen is safe and animal data strongly support harm from excess oxygen, even if large RCTs have not yet shown a clear mortality benefit. Apply lung-protective ventilation (6 mL·kg⁻¹ IBW, plateau pressure <28 cmH₂O) rigorously, as each 1 mL·kg⁻¹ increase in mean tidal volume was linked to an 18% higher 2-year mortality risk."}},{"doi":"10.1016/j.rmed.2026.109013","pmid":"42379531","title":"Pathophysiology of silent hypoxia in COVID-19: Truth and mystery","journal_title":"Respiratory Medicine","journal_issn":"0954-6111","published_at":"2026-06-30T00:00:00.000Z","url":"https://doi.org/10.1016/j.rmed.2026.109013","source_score":5,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-15T13:26:12.897Z","updated_at":"2026-07-15T13:26:12.897Z","tags":[{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"condition","value":"Acute Lung Injury","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"condition","value":"Acute Respiratory Distress Syndrome","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"condition","value":"COVID-19","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"condition","value":"Silent Hypoxia","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"warning","value":"No sample size is applicable as this is a review article with no primary patient cohort.","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"warning","value":"Study design classification as 'Narrative Review' is inferred from abstract language; the paper does not explicitly label its methodology.","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"warning","value":"The paper is dated June 2026 but was processed in July 2026 — content is recent and some cited mechanisms may still be under active investigation.","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.109013","tag_type":"warning","value":"This is a narrative review without systematic methods or meta-analysis; conclusions reflect author interpretation rather than pooled evidence.","value_numeric":null}],"summaries":{"what_studied":"This narrative review examines the pathophysiology of silent hypoxia (hypoxemia without dyspnea) in COVID-19, focusing on proposed mechanisms including carotid chemoreceptor impairment, reduced respiratory center sensitivity, and acute vascular distress syndrome (AVDS).","key_result":"AVDS is the best-supported mechanism, backed by imaging and pathological evidence; carotid body dysfunction and other proposed mechanisms remain incompletely validated and require further study.","limitations":"Narrative review design limits causal inference; proposed mechanisms are not uniformly validated; no original patient data or quantitative outcomes are reported.","practice_takeaway":"Clinicians should monitor SpO₂ actively in COVID-19 patients who lack subjective dyspnea, as silent hypoxia can precede rapid deterioration. AVDS-related vascular pathology should be considered when evaluating unexplained hypoxemia in these patients."}},{"doi":"10.1080/10903127.2026.2691373","pmid":"42314024","title":"The Prone Position During Helicopter Transport of Critically Ill Patients: A Case Series from North Norway","journal_title":"Prehospital Emergency Care","journal_issn":"1090-3127","published_at":"2026-06-24T00:00:00.000Z","url":"https://doi.org/10.1080/10903127.2026.2691373","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-26T13:25:27.568Z","updated_at":"2026-06-26T13:25:27.568Z","tags":[{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"category","value":"Emergency Medicine","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"condition","value":"Acute Respiratory Distress Syndrome","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"condition","value":"Hypoxemic Respiratory Failure","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"modality","value":"Helicopter Air Medical Transport","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"modality","value":"Mechanical Ventilation","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"modality","value":"Prone Positioning","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"sample_size","value":"n=6","value_numeric":6},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"study_design","value":"Case Series","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"warning","value":"50% hospital mortality likely reflects disease severity, but the small sample makes it impossible to distinguish transport-attributable from disease-attributable outcomes.","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"warning","value":"AI-assisted writing (ChatGPT GPT-5.4 Thinking) was used during manuscript preparation; authors state all output was reviewed and revised.","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"warning","value":"Majority of transports (5/6) used large-cabin search-and-rescue helicopters, which is atypical for most HEMS systems — results may not apply to standard rotor-wing platforms.","value_numeric":null},{"paper_doi":"10.1080/10903127.2026.2691373","tag_type":"warning","value":"Only 6 patients included; findings are hypothesis-generating only and cannot support definitive safety conclusions.","value_numeric":null}],"summaries":{"what_studied":"A retrospective case series of 6 consecutive intubated adults with severe ARDS (P/F ratio <100 mmHg) transported in the prone position by helicopter between community hospitals and tertiary ICUs in North Norway from June 2020 to February 2025, with median transport time of 73 min (range 45–135 min).","key_result":"No catastrophic events (cardiac arrest, accidental extubation, or emergency supination) occurred. One patient had clinically significant hypotension and one had worsening oxygenation requiring ventilator adjustment. P/F ratio improved post-arrival in 5 of 6 patients. Three of 6 patients survived to hospital discharge.","limitations":"- Extremely small sample (n=6) with no comparison group, limiting any inference about safety or efficacy.\n- Retrospective design; minor or transient adverse events may be underreported.\n- 5 of 6 transports used large-cabin search-and-rescue helicopters with bigger crews than typical HEMS, limiting generalizability to standard air medical systems.","practice_takeaway":"For critically ill ARDS patients in remote regions who cannot safely wait for ground or fixed-wing transfer, prone helicopter transport appears feasible when performed by experienced teams with deliberate pre-departure preparation (~95 min on-scene) and minimal patient handling. Careful matching of patient severity to available aircraft size and crew capability is essential."}},{"doi":"10.1016/j.rmed.2026.108982","pmid":"42320602","title":"Unraveling the link: A systematic review and meta analysis of acute respiratory distress syndrome and delirium","journal_title":"Respiratory Medicine","journal_issn":"0954-6111","published_at":"2026-06-19T00:00:00.000Z","url":"https://doi.org/10.1016/j.rmed.2026.108982","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-25T13:25:23.206Z","updated_at":"2026-06-25T13:25:23.206Z","tags":[{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"condition","value":"Acute Respiratory Distress Syndrome","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"condition","value":"Delirium","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"sample_size","value":"n=10052","value_numeric":10052},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"study_design","value":"Systematic Review and Meta-Analysis","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"warning","value":"Age and sex breakdowns were not reported in the abstract or results; the adult/mixed tags are inferred from the ICU/ARDS context.","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"warning","value":"The comparison between ARDS patients and controls for delirium risk was not statistically significant; causal inference should be made with caution.","value_numeric":null},{"paper_doi":"10.1016/j.rmed.2026.108982","tag_type":"warning","value":"The pooled delirium prevalence estimate has wide confidence intervals (23–58%) due to substantial heterogeneity, limiting the reliability of the point estimate.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and meta-analysis examined the prevalence of delirium in ARDS patients, its impact on clinical outcomes, and the association between ARDS and delirium development — drawing from 13 studies (n=10,052) identified via PubMed, Scopus, and Web of Science up to September 2024.","key_result":"Pooled delirium prevalence in ARDS patients was 41% (95% CI: 23–58%); the risk of delirium was higher in ARDS vs. controls but did not reach statistical significance (RR 1.34, 95% CI: 0.63–2.83). Delirium was consistently linked to prolonged ICU stay, longer mechanical ventilation, and worse clinical outcomes.","limitations":"- Substantial heterogeneity across studies limits the precision of pooled estimates.\n- The primary association (ARDS vs. controls for delirium risk) was not statistically significant, so causality cannot be established.\n- Only 13 studies met inclusion criteria, which may limit generalizability.","practice_takeaway":"Given a ~41% delirium rate in ARDS patients, clinicians should proactively screen for delirium and apply bundle-based strategies: minimize sedation, start early mobilization, and provide psychological support. A multidisciplinary team approach is key to reducing delirium-related complications such as prolonged ventilation and ICU stay."}},{"doi":"10.1152/ajplung.00128.2026","pmid":"42313146","title":"Alternative splicing of toll-like receptor pathway mRNAs in lung immune cells from patients with ARDS","journal_title":"American Journal of Physiology-Lung Cellular and Molecular Physiology","journal_issn":"1040-0605","published_at":"2026-06-18T00:00:00.000Z","url":"https://doi.org/10.1152/ajplung.00128.2026","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-29T13:31:14.589Z","updated_at":"2026-07-29T13:31:14.589Z","tags":[{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"condition","value":"Acute Respiratory Distress Syndrome","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"generic","value":"IRAK1","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"generic","value":"MyD88","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"modality","value":"Molecular Biomarker","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"study_design","value":"Observational Cohort Study","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"warning","value":"Sample size (total N) is not reported in the abstract; the sample_size tag was omitted accordingly.","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"warning","value":"Sex distribution of the study population is not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"warning","value":"The study design is described as observational based on the abstract; the exact design (e.g., prospective vs. retrospective) is not explicitly stated.","value_numeric":null},{"paper_doi":"10.1152/ajplung.00128.2026","tag_type":"warning","value":"The survival correlation finding for MyD88 is framed cautiously ('may correlate'), suggesting preliminary or underpowered data — clinical interpretation should await replication.","value_numeric":null}],"summaries":{"what_studied":"This study examined alternative splicing of two key toll-like receptor (TLR) pathway genes — MyD88 and IRAK1 — in lung immune cells (bronchoalveolar lavage leukocytes) from patients with ARDS, to determine whether altered splicing contributes to pathological inflammation.","key_result":"MyD88 gene expression was **decreased** and IRAK1 gene expression was **increased** in BAL immune cells from ARDS patients; IRAK1 splicing was shifted toward the proinflammatory isoform (IRAK1 vs. anti-inflammatory IRAK1c). MyD88 expression levels may also correlate with survival.","limitations":"- Sample size and patient demographics are not reported in the abstract, limiting assessment of generalizability.\n- Correlation between MyD88 levels and survival is described as potential, suggesting it may not reach statistical significance or is based on a small cohort.\n- BAL leukocytes represent local lung immune cells only; systemic splicing changes were not assessed.","practice_takeaway":"While not yet practice-changing, clinicians should be aware that TLR pathway splicing — particularly IRAK1 and MyD88 isoform ratios in BAL — may emerge as prognostic biomarkers and potential therapeutic targets in ARDS. Splicing-modulating therapies for ARDS warrant further investigation."}},{"doi":"10.1016/j.chest.2025.11.004","pmid":"42108035","title":"Lung Ultrasound","journal_title":"CHEST","journal_issn":"0012-3692","published_at":"2026-05-08T00:00:00.000Z","url":"https://doi.org/10.1016/j.chest.2025.11.004","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-13T13:19:22.777Z","updated_at":"2026-05-19T13:22:48.177Z","tags":[{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"condition","value":"Acute Respiratory Distress Syndrome","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"condition","value":"COVID-19 Pneumonia","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"condition","value":"Heart Failure","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"condition","value":"Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"condition","value":"Respiratory Failure","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"modality","value":"Artificial Intelligence / Machine Learning","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"modality","value":"Point-of-Care Ultrasound","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"study_design","value":"Expert Commentary / Editorial","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"No sample size applicable; level of evidence set to 7 (expert opinion).","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"Only bibliographic details were provided; no abstract, methods, or results to summarize.","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"Study design is ambiguous between 'Commentary' and 'Review'; classified as Expert Commentary based on content and journal section label.","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"Study design, population, and outcomes are not discernible from the information given.","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"The paper metadata provided contains only the title ('Lung Ultrasound'), DOI, journal, and publication date — no abstract, methods, results, or conclusions were included. All summary fields and tags have been left null or empty, as no content can be extracted or inferred without speculating. Please provide the full text or abstract for a complete structured extraction.","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"The paper metadata provided contains only the title ('Lung Ultrasound'), DOI, journal, and publication date — no abstract, methods, results, or conclusions were supplied. All summary fields and tags have been left null or empty because no content from the paper is available to support structured extraction. Please provide the full text or abstract for complete analysis.","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"The paper metadata provides only a title ('Lung Ultrasound'), DOI, journal, and publication date — no abstract, methods, results, or any body text were supplied. It is not possible to extract meaningful summaries, tags, or evidence-based content without the full text. Please provide the abstract or full paper content for a complete extraction.","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"The paper provided contains only a title ('Lung Ultrasound'), DOI, URL, journal name, and publication date — no abstract, methods, results, or conclusions were included. Structured summaries and tags cannot be populated without source content. Please provide the full text or abstract for complete extraction.","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"The paper provided contains only metadata (title, DOI, journal, and publication date) with no abstract, methods, results, or discussion text. Structured summaries and tags cannot be extracted without source content. The suggested searches are based solely on the topic implied by the title 'Lung Ultrasound'.","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"The paper record provides only a title ('Lung Ultrasound'), journal, DOI, and publication date — no abstract, methods, results, population, or conclusions were supplied. Structured summaries and tags cannot be generated without source content. Please provide the full text or abstract for a complete extraction.","value_numeric":null},{"paper_doi":"10.1016/j.chest.2025.11.004","tag_type":"warning","value":"This is a single-expert opinion commentary with no original data — conclusions should be interpreted as expert perspective, not systematic evidence.","value_numeric":null}],"summaries":{"what_studied":"This expert commentary examines current controversies and pitfalls in lung ultrasound (LUS) practice, covering the B-lines debate, misuse of aeration and congestion scores, pleural line quantification, and the role of AI — arguing that overengineering LUS undermines its core clinical value.","key_result":"The author argues that LUS's strength lies in standardized pattern recognition within clinical context, and that efforts to over-quantify artifacts (e.g., pixel-level pleural analysis, exact B-line counts) or misapply scoring systems (e.g., using the aeration score diagnostically in COVID-19 or ARDS) risk reducing reproducibility and bedside practicality without meaningful clinical gain.","limitations":"This is a single-author opinion piece with no original data; conclusions are based on narrative synthesis and expert perspective rather than systematic review or meta-analysis.","practice_takeaway":"Avoid conflating the aeration score (validated for quantification against CT/pressure-volume curves) with the congestion score (validated against extravascular lung water) — they serve different purposes and mixing them can lead to wrong decisions. Use AI in LUS to support context-aware triage and decision-making for non-experts, not to replace clinical pattern recognition with artifact counting."}},{"doi":"10.3389/fnagi.2026.1834543","pmid":null,"title":"Intranasal administration of stem cells and their derivatives for neurological and respiratory disorders: a systematic review of human clinical trials","journal_title":"Frontiers in Aging Neuroscience","journal_issn":"1663-4365","published_at":"2026-05-07T00:00:00.000Z","url":"https://doi.org/10.3389/fnagi.2026.1834543","source_score":184,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-10","doi":"10.3389/fnagi.2026.1834543","days":"7","issn":"1663-4365","rank":"2","field":"Clinical Medicine","score":"184","category":"Neurosciences","categories":["Neurosciences"],"_categories":["Neurosciences"]},"pubmed":null,"crossref":{"DOI":"10.3389/fnagi.2026.1834543","URL":"https://doi.org/10.3389/fnagi.2026.1834543","ISSN":["1663-4365"],"link":[{"URL":"https://www.frontiersin.org/articles/10.3389/fnagi.2026.1834543/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Intranasal administration of stem cells and their derivatives for neurological and respiratory disorders: a systematic review of human clinical trials"],"author":[{"given":"Umm E.","family":"Habiba","sequence":"first","affiliation":[{"name":"Research and Development (R&D) Department, R3 Stem Cell LLC"},{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Roshini","family":"Sathyanarayanan","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Sabiha","family":"Shamim","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Aishwarya","family":"Manian","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Ammar","family":"Haider","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Iqra","family":"Sarwar","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"David Lawrence","family":"Greene","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Stem Cell LLC"},{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]}],"issued":{"date-parts":[[2026,5,7]]},"member":"1965","prefix":"10.3389","source":"Crossref","volume":"18","created":{"date-time":"2026-05-07T05:41:35Z","timestamp":1778132495000,"date-parts":[[2026,5,7]]},"indexed":{"date-time":"2026-05-07T06:14:44Z","timestamp":1778134484033,"date-parts":[[2026,5,7]]},"license":[{"URL":"https://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000,"date-parts":[[2026,5,7]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$30","relation":{},"resource":{"primary":{"URL":"https://www.frontiersin.org/articles/10.3389/fnagi.2026.1834543/full"}},"subtitle":[],"deposited":{"date-time":"2026-05-07T05:41:36Z","timestamp":1778132496000,"date-parts":[[2026,5,7]]},"issn-type":[{"type":"electronic","value":"1663-4365"}],"published":{"date-parts":[[2026,5,7]]},"publisher":"Frontiers Media SA","reference":[{"DOI":"10.1186/s13287-025-04254-0","key":"ref1","year":"2025","issue":null,"author":"Allouh","volume":"16","first-page":"127","unstructured":null,"article-title":"Mesenchymal stromal/stem cells from perinatal sources: biological facts, molecular biomarkers, and therapeutic promises","journal-title":"Stem Cell Res Ther","doi-asserted-by":"publisher"},{"DOI":"10.3390/pharmaceutics14020381","key":"ref2","year":"2022","issue":null,"author":"Alvites","volume":"14","first-page":"381","unstructured":null,"article-title":"Mesenchymal stem/stromal cells and their paracrine activity—immunomodulation mechanisms and how to influence the therapeutic potential","journal-title":"Pharmaceutics","doi-asserted-by":"publisher"},{"DOI":"10.25259/SNI_233_2020","key":"ref3","year":"2020","issue":null,"author":"Boika","volume":"11","first-page":"380","unstructured":null,"article-title":"Mesenchymal stem cells in Parkinson’s disease: motor and nonmotor symptoms in the early posttransplant period","journal-title":"Surg. 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Across 98 analyzed participants from 7 published studies, intranasal delivery was consistently reported as safe with no serious adverse events, and preliminary signals of benefit appeared in cerebral palsy, perinatal stroke, and Alzheimer's disease — but no efficacy conclusion is interpretable due to open-label design, absent sham controls, and unblinded outcome assessment in every published trial.","limitations":"- Every published study lacked randomization, sham/placebo intranasal control, and blinded outcome assessment, making efficacy estimates uninterpretable as biological activity.\n- Multiple studies combined intranasal and intravenous delivery, preventing route-specific attribution of any observed effect.\n- The review itself was not pre-registered in PROSPERO, and several authors have direct conflicts of interest (employment by the stem cell manufacturer whose products were evaluated).","practice_takeaway":"Do not adopt intranasal stem cell or exosome therapy for any neurological or respiratory condition based on current evidence — no adequately powered, blinded, sham-controlled trial has been completed or published. The safety signal across ~98 participants is reassuring enough to justify rigorously designed Phase 2 trials, but not clinical use."}},{"doi":"10.1146/annurev-immunol-083024-032807","pmid":"41481813","title":"Molecular, Cellular, Tissue, and Organismal Functions of Type III Interferons","journal_title":"Annual Review of Immunology","journal_issn":"0732-0582","published_at":"2026-01-02T00:00:00.000Z","url":"https://doi.org/10.1146/annurev-immunol-083024-032807","source_score":37,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-05-02","doi":"10.1146/annurev-immunol-083024-032807","days":"14","issn":"0732-0582","rank":"6","field":"Clinical Medicine","score":"37","category":"Immunology","categories":["Immunology"],"_categories":["Immunology"]},"pubmed":{"doi":"10.1146/annurev-immunol-083024-032807","title":"Molecular, Cellular, Tissue, and Organismal Functions of Type III Interferons.","journal":"Annual review of immunology","methods":"","results":"","abstract":"$31","keywords":["ARDS","IBD","SLE","acute respiratory distress syndrome","asthma","bacteria","fungi","inflammatory bowel disease","systemic lupus erythematosus","tumor","viruses"],"pubmed_id":"41481813","conclusions":"","publication_date":"2026-01-02T00:00:00"},"crossref":{"DOI":"10.1146/annurev-immunol-083024-032807","URL":"https://doi.org/10.1146/annurev-immunol-083024-032807","ISSN":["0732-0582","1545-3278"],"link":[{"URL":"https://www.annualreviews.org/content/journals/10.1146/annurev-immunol-083024-032807?crawler=true&mimetype=application/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"121-147","type":"journal-article","issue":"1","score":1,"title":["Molecular, Cellular, Tissue, and Organismal Functions of Type III Interferons"],"author":[{"given":"Daniel","family":"Boehmer","sequence":"first","affiliation":[{"name":"1Division of Immunology and Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; email: ivan.zanoni@childrens.harvard.edu"},{"name":"2Department of Medicine II, LMU University Hospital, LMU Munich, Munich, Germany"}]},{"given":"Sreya","family":"Ghosh","sequence":"additional","affiliation":[{"name":"1Division of Immunology and Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; email: ivan.zanoni@childrens.harvard.edu"}]},{"given":"Kautilya K.","family":"Jena","sequence":"additional","affiliation":[{"name":"1Division of Immunology and Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; email: ivan.zanoni@childrens.harvard.edu"}]},{"given":"Sara Svensson","family":"Akusjärvi","sequence":"additional","affiliation":[{"name":"1Division of Immunology and Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; email: ivan.zanoni@childrens.harvard.edu"},{"name":"3Division of Immunology and Respiratory Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden"},{"name":"4Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden"}]},{"given":"Ivan","family":"Zanoni","sequence":"additional","affiliation":[{"name":"1Division of Immunology and Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; email: ivan.zanoni@childrens.harvard.edu"}]}],"issued":{"date-parts":[[2026,4,27]]},"member":"22","prefix":"10.1146","source":"Crossref","volume":"44","created":{"date-time":"2026-01-02T19:40:58Z","timestamp":1767382858000,"date-parts":[[2026,1,2]]},"indexed":{"date-time":"2026-04-28T03:33:47Z","timestamp":1777347227876,"date-parts":[[2026,4,28]]},"license":[{"URL":"https://creativecommons.org/licenses/by-nc-nd/4.0","start":{"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000,"date-parts":[[2026,4,27]]},"delay-in-days":0,"content-version":"unspecified"}],"subject":[],"abstract":"$32","language":"en","relation":{},"resource":{"primary":{"URL":"https://www.annualreviews.org/content/journals/10.1146/annurev-immunol-083024-032807"}},"subtitle":[],"deposited":{"date-time":"2026-04-28T02:41:53Z","timestamp":1777344113000,"date-parts":[[2026,4,28]]},"issn-type":[{"type":"print","value":"0732-0582"},{"type":"electronic","value":"1545-3278"}],"published":{"date-parts":[[2026,4,27]]},"publisher":"Annual Reviews","reference":[{"DOI":"10.1016/j.cell.2025.06.044","key":"B1","year":"2025","issue":"17","author":null,"volume":"188","first-page":"4480","unstructured":null,"article-title":"Interferons in health and disease","journal-title":"Cell","doi-asserted-by":"crossref"},{"DOI":null,"key":"B2","year":"1957","issue":"927","author":null,"volume":"147","first-page":"258","unstructured":null,"article-title":"Virus interference. 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for patients transferred already on ECMO.","value_numeric":null}],"summaries":{"what_studied":"Retrospective review at an American Burn Association–verified center of 12 adult burn patients with severe ARDS placed on ECMO for refractory hypoxemia (Apr 1, 2017–Jun 30, 2022). Mean TBSA was 37.3%; 83.3% had inhalation injury; 75% were male; none were proned before ECMO.","key_result":"Survival to discharge was 8/12 (66.7%), including 7/9 (77.7%) on VV ECMO and 1/3 (33.3%) on VA/V‑VA. Mean ECMO run was 258 h (range 112.5–692.5); median transfusion while on ECMO was 17.9 L (IQR 47.7); predicted mortality was 40.0% (APACHE II) and 40.2% (revised Baux); deaths were due to comfort care (n=2), thrombotic circuit occlusion (n=1), and cardiac arrest (n=1).","limitations":"Retrospective, single-center series with heterogeneous patients and practice patterns and variable ECMO expertise. Some data were unavailable for patients cannulated at referring centers.","practice_takeaway":"In selected adult burn patients with severe ARDS who cannot be proned or fail standard measures, ECMO support was feasible, with 66.7% survival to discharge in this series and higher survival on VV ECMO than VA/V‑VA. 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