The sacroiliac joint (SIJ) is a critical anatomic structure that connects the axial skeleton with the lower limbs. Compared with its adult counterpart, the pediatric SIJ exhibits unique anatomic features, and imaging evaluation may then present significant challenges due to overlapping features between normal developmental manifestations, anatomic variants, and true pathologic conditions. Two frequently observed developmental findings can resemble pathologic conditions: subchondral irregularities and subchondral flaring. These are commonly seen on MR images of the developing pelvis. A diverse range of anatomic variations has been documented in both the cartilaginous and ligamentous components of the SIJ. Though overall innocuous, some variations are linked to mechanical overload and pain. True sacroiliitis can arise from inflammatory, infectious, or traumatic causes. Inflammatory conditions may exhibit similar imaging characteristics and are best differentiated through MRI. The presence of unilateral sacroiliitis should prompt consideration of an infectious cause, with imaging indicators such as capsular edema and abscess formation suggesting infection. Traumatic injuries to the SIJ are uncommon in children and usually occur in the context of high-energy trauma. Mechanical overload or repetitive stress in the pediatric population can result in bone marrow edema in the weight-bearing regions of the SIJ and, less commonly, in sacral stress fractures, most often involving the sacral ala. It is crucial to accurately differentiate these imaging features to avoid functional impairments, morbidity, and unnecessary interventions. The authors aim to enhance radiologists' understanding of the pediatric SIJ by examining its unique anatomic characteristics, key imaging features, and pertinent differential diagnosis. © RSNA, 2026 Supplemental material is available for this article.

The pathophysiology of idiopathic steroid-sensitive nephrotic syndrome (ISSNS) remains unclear. This study aimed to explore the pathophysiology by examining E-cadherin injury, observed in atopic dermatitis, and VE-cadherin injury, associated with systemic edema formation. Twenty-one paediatric patients with ISSNS were enrolled. Serum E- and VE-cadherin levels were measured using ELISA and compared between the nephrotic and remission phases. Correlations between each serum E- and VE-cadherin level and urinary protein/creatinine (UP/UCr) ratios and serum albumin (Alb) levels were analysed. Additionally, a correlation between changes in serum VE-cadherin levels and in body weight between phases was analysed. Both serum E- and VE-cadherin levels were elevated in the nephrotic phase compared to the remission phase (p < 0.01 for both). Remission-phase E-cadherin levels remained higher than those in healthy children, while remission-phase VE-cadherin levels were similar to those in healthy children. Serum E-cadherin levels showed a significant correlation with UP/UCr ratios (p = 0.04), but not with serum Alb levels. Serum VE-cadherin levels did not correlate with either UP/UCr ratios or serum Alb levels. However, changes in VE-cadherin levels between the phases were significantly correlated with changes in body weight (p = 0.04). Elevated E- and VE-cadherin levels during the nephrotic phase suggest that injury to these adhesion molecules may be correlated with the disease status and could serve as biomarkers for paediatric ISSNS. Injury to E-cadherin may contribute to proteinuria while injury to VE-cadherin may lead to systemic edema. These findings provide new insights into paediatric ISSNS pathophysiology.

The skull bone marrow-meninges-brain axis: A new sentinel for neuroinflammation regulation in ischemic stroke.

Harrisia adscendens (Gürke) Britton & Rose is traditionally used to manage kidney problems, fever, and pain. Despite its traditional use, its pharmacological properties remain underexplored. The hydroethanolic extract (HE) of its cladodes is of particular interest given its demonstrated safety and presence of acetophenones, phenolic acids, and flavonoids. The present study evaluated the antinociceptive, anti-inflammatory, antipyretic, and wound-healing activities of HE. HE was administered orally at 100, 200, or 400mg/kg to male mice. Nociceptive inhibition was measured through the acetic acid-triggered writhing, tail immersion, and formalin tests. The capacity to reduce inflammation was evaluated via carrageenan-induced paw edema and peritonitis. Antipyretic effects were measured after yeast-induced hyperthermia following HE administration. Wound-healing activity was assessed using topical gels containing 5% or 10% HE on dorsal wounds. HE at 200 and/or 400mg/kg markedly reduced abdominal writhing, paw-licking time in the formalin test, and increased latency in the tail immersion test. HE (200 and 400mg/kg) inhibited paw edema formation up to 47.5%, and reduced leukocyte migration in the peritonitis model. Levels of interleukins 2, 6 and 17 and TNF-α were decreased in the peritoneal fluid. HE induced a reduction in body temperature in the antipyretic assay. It also accelerated wound closure in the 10% formulation. HE exhibited antinociceptive, anti-inflammatory, antipyretic, and wound-healing activities, likely due to flavonoids, acetophenones, and phenolic acids. These effects may involve modulation of inflammatory mediators and immune cell activity.

Intraoperative persistent severe hypotension (PSH) is a common complication following pancreaticoduodenectomy (PD) and may affect the prognosis of patients. The aim of this trial was to explore the ultrastructural alterations of capillary endothelia cells and relevant factors that is associated with PSH and postoperative outcomes in patients undergoing PD. Total 103 patients were divided into PSH or non-PSH group during PD. The basic clinical features, hemodynamic monitoring, electrolyte biochemical indexes, postoperative inflammatory biomarkers and adverse outcomes were analyzed. Particularly, the great omentum samples were collected and the morphological changes of capillary endothelial cells were revealed by electronic microscopy. PSH occurred in forty-four patients (42.7%) during PD. The PSH patients experienced greater extensive surgery scope, more bleeding, longer surgery time, increased fluid infusion and blood glucose. Hemodynamic monitoring revealed that the PSH patients primarily showed reduced vascular resistance with enhanced cardiac index. The postoperative inflammation biomarkers and incidence of postoperative complications in PSH group were significantly higher than those in non-PSH group (P < 0.05). Notably, the arterial plasma Ca2+ decreased significantly in PSH patients as that in non-PSH group (P < 0.001). Electron microscopy revealed in PSH patients ultrastructural evidence of capillary endothelial injury, including cellular swelling and increased pinocytotic activity. Endothelial cell permeability alteration and endothelial dysfunction might potentially reflect intensive surgical stress-inflammation-endocrine responses during PD. Endothelial edema formation and decreased plasma Ca2+ are probably associated with PSH and postoperative adverse outcomes of PD patients.Our study highlights the key point to keep the functionality and integrity of endothelia cells and timely supplement calcium to prevent PSH during pancreaticoduodenectomy and postoperative outcomes.

Edema formation and ascites are common features in liver disease. The excessive accumulation of body water is caused by increased kidney water retention; yet the mechanisms linking liver and kidney function remain incompletely understood. This review explores the emerging concept of a liver-kidney axis, with bile acids (BAs) as potential mediators for kidney water handling. In cholestatic liver disease, as seen in liver cirrhosis, impaired hepatic BA flow to the duodenum elevates systemic BA concentrations, which can modulate signaling pathways through the BA receptors Farnesoid X Receptor (FXR, NR1H4) and G-protein-coupled bile acid receptor 1 (TGR5, GPBAR1), thereby increasing kidney Na+ and water retention in experimental models. Moreover, BAs can directly activate the sodium channel ENaC in isolated mouse collecting ducts and in mouse distal colon epithelial cells. Thus, BAs can promote sodium and water retention in parallel with the classical sodium- and water-retaining systems, such as the renin-angiotensin-aldosterone system. This effect may potentially contribute to water retention in pregnancy-associated conditions and in proteinuric kidney diseases, where liver function is affected, e.g., by loss of plasma proteins, altering hepatic BA metabolism. In this review, we will describe the synthesis of BAs, their modifications, and kidney BA metabolism in health and disease, and highlight a potential dynamic interplay between liver and kidney function, mediated in part by BAs, with implications for understanding and treating water retention disorders.

Background: Atelectrauma is generally attributed to repetitive opening and closing of unstable lung units during mechanical ventilation. However, physiological airway closure and reopening occur normally during spontaneous breathing without apparent injury, suggesting that cyclicity alone may not fully explain ventilator-induced lung injury. We therefore reconsider atelectrauma from the perspective of the surrounding intrathoracic pressure environment in which recruitment occurs. Discussion: During spontaneous breathing, inspiration is generated by increasingly negative pleural pressure, resulting in lung inflation within a decompressive pressure environment. In contrast, during positive pressure ventilation, both airway pressure and pleural pressure increase, such that reopening of peripheral lung units occurs under elevated surrounding intrathoracic pressure. We propose that transpulmonary pressure and driving pressure describe lung distension, but do not fully characterize the absolute pressure environment surrounding lung tissue and peripheral airways. As a conceptual approximation, this surrounding pressure environment may be represented by the mean of airway pressure and pleural pressure. Numerical examples demonstrate that comparable transpulmonary pressures may occur under profoundly different surrounding pressure conditions. In acute respiratory distress syndrome, elevated intrathoracic pressure may contribute to airway closure, altered peripheral airway patency, edema formation and loss of alveolar-airway coupling. Experimental observations comparing positive and negative pressure ventilation, as well as a clinical case of occult pneumothorax during positive pressure ventilation becoming apparent during spontaneous breathing, support the physiological relevance of this concept. We suggest that the injurious component traditionally attributed to atelectrauma may arise less from cyclic opening and closing per se than from repeated recruitment occurring within a mechanically constrained and compressed lung environment. Conclusion: Atelectrauma may be better understood as a context-dependent phenomenon in which elevated surrounding intrathoracic pressure contributes importantly to injury generation. While transpulmonary pressure remains fundamental for describing lung distension, the surrounding pressure environment may represent an additional mechanical dimension relevant to airway closure, recruitment, edema formation and ventilator-induced lung injury. This perspective may have implications for ventilatory strategies aimed at reducing excessive intrathoracic pressure loading.

BackgroundPostoperative care following endoscopic sinus surgery (ESS) aims to optimize mucosal healing, reduce inflammation, and minimize infectious complications. Although saline irrigation is considered standard of care, the potential benefit of adding topical antibiotics, such as mupirocin, during the early postoperative period remains uncertain.ObjectiveTo evaluate whether short-term postoperative mupirocin nasal irrigation improves clinical, endoscopic, and microbiological outcomes compared with saline irrigation alone following ESS.MethodsThis prospective, randomized, double-blinded, placebo-controlled trial included adults with chronic rhinosinusitis undergoing ESS. Patients were randomized to receive either mupirocin (0.05%) nasal irrigation or placebo saline irrigation twice daily for 21 days postoperatively. Outcomes assessed within the first 3 months included patient-reported symptoms using the sinonasal outcomes test (SNOT-22) and visual analog scale (VAS), endoscopic findings (mucosal edema, polyp formation, crusting, granulation tissue, and purulence), postoperative sinus culture results, and need for systemic antibiotics.ResultsSixty-eight patients were enrolled, and 56 completed follow-up. Both groups demonstrated significant postoperative improvement in SNOT-22 and VAS scores compared with preoperative baseline, without significant between-group differences. However, the mupirocin group showed significantly lower rates of endoscopic mucosal edema and polyp formation at 1 month postoperatively. Negative postoperative cultures were also more frequent in the mupirocin group, with reduced need for systemic oral antibiotics. No significant differences were observed in crusting, granulation tissue, purulence, steroid use, or pain medication requirements.ConclusionShort-term prophylactic postoperative mupirocin nasal irrigation after ESS does not confer additional improvement in patient-reported quality-of-life outcomes compared with saline alone but appears to reduce early inflammatory endoscopic changes, bacterial culture positivity, and need for systemic antibiotics. Larger studies with longer follow-up are needed to confirm these findings.

Anti-inflammatory and antinociceptive properties of Handroanthus heptaphyllus (Vell.) Mattos hydroethanolic extract bark in mice.

PurposeSeveral recent trials have shown improved functional outcomes with endovascular thrombectomy (EVT) in patients presenting with large ischaemic lesions, yet the impact of reperfusion on lesion pathophysiology in this population remains incompletely understood. We hypothesised that EVT reduces ischaemic oedema formation and that attenuation of oedema mediates functional outcome improvement beyond changes in lesion extent.MethodsWe performed a secondary analysis of the randomised TENSION trial, which enrolled patients with anterior circulation ischaemic stroke and baseline ASPECTS 3–5. Oedema progression was quantified as the change in CT-based net water uptake between baseline and follow-up non-contrast CT (ΔNWU), derived from relative hypoattenuation within the infarct. Lesion extent change was assessed by the difference in ASPECTS between baseline and follow-up imaging (ΔASPECTS). Associations of ΔNWU and ΔASPECTS with 90-day modified Rankin Scale (mRS) were tested using ordinal logistic regression. Mediation analyses estimated the proportion of EVT’s treatment effect on functional outcome explained by ΔNWU and ΔASPECTS.ResultsAmong 177 patients, median follow-up NWU was 28.5% (IQR: 19.2–36.6) and follow-up ASPECTS was 2 (IQR: 1–3). EVT was associated with substantially lower oedema progression (ΔNWU 4.7% vs 15.9% without EVT; P < .001). Mediation analysis suggested that a model-estimated 34% of EVT-related improvement in mRS was associated with reduced oedema formation (ΔNWU), whereas 14% was associated with lesion extent change (ΔASPECTS). In a sensitivity analysis using nonparametric bootstrap with 5000 resamples, the mediation signal remained robust for ΔNWU but was substantially weaker for ΔASPECTS.ConclusionIn large-core stroke, EVT was associated with significantly attenuated oedema progression between baseline and follow-up imaging. Reduced ischaemic water uptake was strongly associated with EVT benefit on 90-day functional outcome in mediation models, supporting oedema attenuation as a plausible mechanistic pathway of EVT benefit.

Neurogenic pulmonary edema (NPE) is a complication that often affects patients following central nervous system (CNS) injury. Nevertheless, the complex relationship between CNS injury and NPE initiation and progression remains unclear. Here, we show that the leakage of brain proteins (BPs) following traumatic brain injury results in the formation of immune complexes and lung edema. Quantitative proteomic analysis revealed that BP preferentially affected the Kng1/SPHK2/S1P pathway. We treated rats with the S1P receptor antagonist fingolimod or conventional steroid drugs and showed that this was sufficient to attenuate the severity of pulmonary and related pathological changes. These results provide novel evidence that the immune complexes induced by BPs are deposited in the lung tissue, activating a series of inflammatory reactions that culminate in pulmonary edema. Considering these results, we propose the innovative concept of "neuroimmunogenic pulmonary edema" as a relevant pathological entity.

INTRODUCTION:White Matter Hyperintensities (WMH) are key radiographic biomarkers of cerebral small vessel disease (CSVD) and have been associated with worse outcomes after stroke. Since CSVD may involve blood-brain barrier disruption, we hypothesized that worse outcomes in those with WMH may be mediated through more severe cerebral edema and hemorrhagic transformation.METHODS:In this retrospective multicenter cohort study, we studied patients from four multinational stroke cohorts who presented within 12 hours of anterior circulation large vessel occlusion (LVO) stroke and received at least one follow-up CT between 12–48 hours. WMH were rated on baseline CTs using a Fazekas-derived system, with a subset also assessed with Fazekas-grading on MRI. Automated image analysis measured cerebrospinal fluid displacement (ΔCSF) and lesional-to-contralateral hemispheric CSF volumes (CSF-ratio) as quantitative edema biomarkers. We analyzed the association between WMH presence and edema severity, hemorrhagic transformation and poor functional outcome (mRS 3–6), adjusting for key covariates, overall and in the subgroup undergoing thrombectomy and those with successful reperfusion.RESULTS:Of 1,290 LVO patients, 782 were eligible for imaging analysis. Of these, 19% had WMH on CT. Patients with WMH were older, more often female and had a history of hypertension, and higher presenting systolic blood pressure and glucose levels. WMH presence was associated with worse functional outcome, adjusting for age and additional covariates [OR 1.84 (1.06–3.22), p = 0.04] but lower risk of any HT [OR 0.48 (0.25–0.88), p = 0.03]. However, WMH presence by CT or MRI was not associated with edema (ΔCSF, CSF-ratio, or midline shift) in the whole population or thrombectomy/reperfusion subgroups. Reperfusion was associated with less edema and improved recovery.CONCLUSIONS:Presence of CT-graded WMH was associated with worse outcome after LVO stroke, independent of age and other factors. However, this risk appears not to be mediated through greater risk of HT or cerebral edema formation.

Copeptin, an inert peptide derived from provasopressin and co-released with arginine vasopressin (AVP), has emerged as a stable circulating indicator of AVP system activation and has attracted growing interest in acute ischemic stroke (AIS). Over the past decade, both experimental and clinical investigations have explored its potential clinical relevance. A central challenge, however, is to distinguish the biological role of AVP signaling from the interpretive significance of copeptin as a biomarker. Current evidence indicates that AVP signaling may contribute to key pathological processes, including cerebral edema formation and post-ischemic inflammatory responses. In contrast, copeptin appears to reflect activation of the neuroendocrine stress axis rather than acting as a direct effector within these pathways. Clinically, copeptin levels rise rapidly during the early phase of AIS and are consistently associated with stroke severity and adverse outcomes, supporting its potential utility in early risk stratification and prognostic assessment. The use of copeptin in combination with neuroimaging parameters and other biomarkers has been explored, with some studies suggesting improved performance in early clinical evaluation. However, whether copeptin confers meaningful incremental value beyond established tools remains uncertain. Interpretation of the available evidence is further limited by heterogeneity in study design, variability in sampling strategies, the lack of standardized cutoff values, and the scarcity of large-scale prospective validation. Taken together, copeptin may serve as a useful component within multimarker frameworks for AIS. Its clinical interpretation, however, should remain anchored to its role as a surrogate indicator of AVP pathway activation, rather than being extended to a direct mediator of ischemic injury.

The formation of brain edema is one of the key factors that determine patient outcomes following traumatic brain injury (TBI). Despite decades of research, no causal treatment is available to date. Among the many factors discussed, inflammation is believed to facilitate brain edema formation. Following brain trauma, leukocytes become activated, interact with the vascular endothelium, and transmigrate into pericontusional tissue. It was hypothesized that this process may affect the permeability of the blood-brain barrier and facilitate vasogenic brain edema formation. Thus, our study aimed to investigate the role of leukocyte adherence and migration in brain edema formation after experimental TBI by inhibiting the integrin CD18. Male C57BL/6 mice (n = 7/group) underwent controlled cortical impact (CCI) and were randomly assigned to one of three groups: (1) sham operation, (2) CCI + control IgG, or (3) CCI + anti-CD18 antibody. Treatment was administered 30 min before and 24 h after CCI. The anti-inflammatory effect of the anti-CD18 treatment was verified using invivo two-photon microscopy and immunohistochemistry 48 h after CCI (n = 5/group). Lesion volume and brain edema formation were assessed by T2 and free-water diffusion magnetic resonance imaging longitudinally at 1, 2, 3, 5, and 7 days after the trauma or sham operation. Neurological function was determined daily using the Modified Neurological Severity Score. Vasogenic brain edema formation was detectable up to 7 days after trauma; no edema formation occurred in animals that underwent a sham operation. Anti-CD18 treatment reduced leukocyte-endothelium interaction and leukocyte migration into the brain after trauma to nearly control levels; however, it did not reduce lesion volume or brain edema formation. Preventing the adhesion of circulating leukocytes to cerebral vessels and their migration into the brain parenchyma does not reduce the formation of vasogenic brain edema and lesion volume after TBI in mice.

Retraction Note to: TiO2-Nanowired Delivery of DL-3-n-butylphthalide (DL-NBP) Attenuates Blood-Brain Barrier Disruption, Brain Edema Formation, and Neuronal Damages Following Concussive Head Injury.

Preservation of pediatric donor hearts via subnormothermic machine perfusion: Comparison to cold storage.

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood-brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries-including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury-as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases-including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis-Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial-neuronal communication and cognitive-emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood-brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx-particularly Cx43-occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation.

The objective of this study was to investigate the anti-inflammatory properties of n-hexane, ethyl acetate (EtOAc), dichloromethane (CH2Cl2), and aqueous extracts of Phellodendron amurense. The activity was evaluated in vitro by nitric oxide (NO) and prostaglandin E2 (PGE2) inhibition assays, and in vivo using carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced endotoxemia models in rats. In vitro anti-inflammatory activity was assessed by measuring the inhibition of NO and PGE2 production using RAW 264.7 macrophage cells. Among the tested extracts, the CH2Cl2 extract exhibited the most potent activity, with IC50 values of 10.88 ± 2.88 µg/mL for NO inhibition and 10.82 ± 1.22 µg/mL for PGE2 inhibition, followed by the aqueous extract, which also inhibited NO and PGE2 production without causing cytotoxicity. The CH2Cl2 extract of P. amurense (CPA) was orally administered to rats in both LPS-induced endotoxemia and carrageenan-induced hind paw edema models. In the endotoxemia model, CPA significantly improved survival and markedly reduced serum IL-6 and IL-1β levels, as well as white blood cell counts. Consistently, in the carrageenan-induced paw edema model, CPA significantly suppressed edema formation, reducing paw-volume increase by 36%, 48%, and 55% at 2, 3, and 4 h, respectively, compared with the carrageenan control group (p &lt; 0.05).

Acute respiratory distress syndrome (ARDS) is a life-threatening disease that is characterized by noncardiogenic pulmonary edema, respiratory distress, and hypoxemia, and has high mortality. Uncontrolled activation of neutrophils and formation of platelet-neutrophil complexes (PNCs) contribute significantly to its pathogenesis. In this study, we investigated whether suppression of systemic inflammation through simultaneous adsorption of inflammatory mediators, including PNCs, reduces lung invasion and offers an effective treatment strategy for ARDS. We investigated the efficacy of a novel hemoadsorption column, NOA-001, which simultaneously removes cytokines and PNCs, in an ovine model of smoke inhalation-induced ARDS. Animals were assigned to two groups: treatment with NOA-001 (n = 6) or a control group with a blood circuit without the column (n = 5). The impact on neutrophil dynamics, lung injury, edema formation, and inflammatory markers was assessed. Neutrophil capture rates by NOA-001 were significantly higher at 4 and 6h compared to controls, with a trend toward lower circulating neutrophil counts. Flow cytometry confirmed that NOA-001 predominantly removed PNCs (CD62+/CD11blow or CD11bhigh). At 27h, the NOA-001 group had significantly improved oxygenation (oxygenation index: 10.3 ± 3.0 vs. 18.8 ± 3.2, p < 0.05) and significantly lower lung injury scores (1.9 ± 0.3 vs. 2.8 ± 0.2, p < 0.05) compared to controls. Lung edema was significantly attenuated, as evidenced by reduced lung lymph flow (27.3 ± 6.4 vs. 57.8 ± 6.4mL/h), lower wet-to-dry weight ratios in lung (7.4 ± 0.3 vs. 9.2 ± 0.6) and trachea (2.7 ± 0.1 vs. 3.0 ± 0.1), and decreased thoracic exudate volume (90 ± 69 vs. 620 ± 183mL, p < 0.05). Pulmonary protein leakage and neutrophil migration indices were also significantly lower in the NOA-001 group. Interleukin-6 levels in bronchoalveolar lavage fluid tended to be lower in the NOA-001 group (p = 0.08). No adverse events were observed. Simultaneous removal of cytokines and PNCs using NOA-001 significantly reduced ARDS severity by attenuating pulmonary edema and improving pulmonary gas exchange. These results suggest that NOA-001 may be a novel and promising therapeutic strategy for ARDS.

This review outlines the physiological organization of heart-lung coupling that ensures efficient gas exchange. Subsequently, factors that compromise this efficiency are examined. The development of perturbation in lung fluid balance, originating from both capillary and alveolar sources, is discussed in detail, as it represents a frequently overlooked contributor to impaired gas exchange. Intrinsic mechanisms by which the lung resists edema formation are then presented. We provide a quantitative functional model based on physical principles to describe the diffusion-perfusion interaction in the air-blood barrier aiming to interpret several pathological conditions, including pulmonary fibrosis, lung resection, heart failure syndromes, and mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF).