Pancreatic-pleural fistula (PPF) and re-expansion pulmonary edema (RPE) are rare but potentially fatal complications of pancreatitis. This report describes a 31-year-old man with a history of recurrent alcohol-associated pancreatitis who presented with acute hypoxic respiratory failure due to a large pleural effusion. Chest tube drainage revealed amylase-rich fluid, highly suggestive of a PPF. Rapid drainage of a large volume of pleural fluid precipitated RPE, followed by rapid clinical deterioration and cardiac arrest. This case highlights the importance of recognizing suspected PPF as a cause of large pleural effusions and the need for cautious drainage to prevent life-threatening complications such as RPE. To date, the coexistence of PPF complicated by fatal RPE has rarely been reported.

Disruption in alveolar type 2 epithelial cells (AT2s) homeostasis by oxidative stress plays an essential role in the pathogenesis of acute lung injury (ALI). However, significant discrepancies remain in understanding the mechanisms for AT2 as a main target for reactive oxygen species (ROS). Herein, we show that STUB1, an E3 ligase involved in protein homeostasis, was dominantly expressed in AT2s. Mild levels of ROS potentiated Nrf2-mediated transactivation of the STUB1 gene via activation of the ERK signaling, whereas high levels of ROS compromised STUB1 expression by dampening STUB1 protein half-life. Ablation of Stub1 in AT2s caused failure in conferring K63-mediated nonproteolytic polyubiquitination of SIK3 (salt-inducible kinase 3), which in turn abrogated CRTC2 (CREB-regulated transcription co-activator 2) substrate binding for SIK3 and thereby triggered CREB signaling-mediated proinflammatory phenotypes. Consequently, disruption in STUB1/SIK3 signaling aggravated lung edema, augmented inflammatory infiltrate, and increased AT2 apoptosis in vivo. Mice lacking STUB1 also demonstrated increased susceptibility to ischemia-reperfusion and overventilation-induced lung injury. These findings unambiguously uncover STUB1 as a critical post-translational regulator of ALI severity and outcomes.

Altered mental status (AMS) in advanced chronic kidney disease (CKD) frequently reflects overlapping metabolic, cardiopulmonary, and neurologic contributors rather than a single unifying diagnosis. We present a 59-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) progressing to end-stage renal disease (ESRD), congestive heart failure (CHF) with preserved ejection fraction (HFpEF), and stiff person syndrome (SPS) who developed recurrent encephalopathy accompanied by equivocal pulmonary findings and elevated cardiac troponin without electrocardiographic evidence of acute ischemia. Her hospital course was marked by severe renal dysfunction, metabolic acidosis, anemia, and intermittent electrolyte abnormalities. Management required iterative reassessment rather than reliance on a single explanatory diagnosis, included time-variable use of antibiotics and diuretics, continued chronic cardiometabolic therapies, and preparation for renal replacement therapy. This case highlights three practical teaching points: encephalopathy in ESRD is often multifactorial; troponin elevation in advanced kidney disease requires careful clinical correlation to avoid misclassification as acute coronary syndrome; and distinguishing pneumonia from pulmonary edema in volume-sensitive patients may necessitate repeated reassessment over time.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has revealed a complex interplay between respiratory and neurological manifestations. This study utilized K18-hACE2 transgenic mice to investigate the morphological, ultrastructural, and transcriptomic changes induced by SARS-CoV-2 infection in both lungs and brain tissues. Histopathological analysis at seven days post-infection revealed significant pulmonary damage characterized by interstitial pneumonia, alveolar septal thickening, with a marked inflammatory infiltrate predominantly consisting of neutrophils and lymphocytes, and an abnormal profile of type II pneumocytes. Concurrently, in the brain, we observed vasculitis, gliosis, and edema, indicating an inflammatory response and vascular compromise that can disturb the blood-brain barrier. In addition, gene expression in lung tissue presented increased CCL2, IL10, and GDDA45D in infected mice and the downregulation of proinflammatory genes. However, in brain tissue, the increased expression of CCL2, CASP1, IL6, IFNB1, and GDDA45G inflammatory genes was observed in infected K18-hACE2 mice.

Acute lung injury (ALI) is a life-threatening respiratory condition with limited therapeutic options, requiring safer and more effective therapeutic strategies. This study aims to investigate the potential of Houttuynia cordata-derived exosome-like nanovesicles (HcNVs) as a novel therapeutic approach for lipopolysaccharide (LPS)-induced ALI. HcNVs were isolated using tangential flow filtration and were characterized. Oral administration of HcNVs significantly alleviated ALI, as evidenced by reduced histopathological damage, pulmonary edema, vascular permeability, and pro-inflammatory cytokine production. Flow cytometry and immunofluorescence analyses demonstrated decreased infiltration of immune cells in lung tissue. From a correlational perspective, HcNVs treatment is associated with reduced activity of the p38 MAPK/ATF2 signaling pathway, accompanied by downregulation of CXCL10 expression and decreased inflammatory cell recruitment. In vitro, HcNVs suppressed LPS-induced inflammatory responses and apoptosis in RAW264.7 and MH-S macrophages. In addition, 16S rRNA sequencing results showed that HcNVs treatment was associated with an increase in gut microbial diversity and a decrease in the abundance of inflammation-related microbiota, which may be related to the regulation of the gut-lung axis. Importantly, biosafety assessments confirmed the excellent biocompatibility of HcNVs in both cell and animal models. These findings highlight the therapeutic potential of HcNVs as a natural, safe, and effective nanoplatform for treating inflammatory lung diseases and support their further development for clinical translation.

Pulmonary complications following stroke are a leading cause of death, with no targeted therapies available. Inflammation drives both post-stroke neurological damage and secondary acute lung injury (CIS-ALI). High mobility group box 1 (HMGB1), a key mediator in cerebral ischemia stroke (CIS), translocates from the nucleus to cytoplasm and is released extracellularly, triggering inflammatory cascades. The combination of two bioactive metabolites, baicalin and geniposide (BG), exhibits anti-inflammatory and neuroprotective properties, but its efficacy against CIS-ALI remains unexplored. This study investigated BG's mechanisms using in vitro and in vivo models.

Alveolar epithelial barrier damage is a key pathological feature of acute respiratory distress syndrome (ARDS). The glycocalyx and tight junctions are essential for maintaining epithelial barrier function, and their disruption exacerbates pulmonary edema. Although FK506-binding protein 51 (FKBP5) regulates inflammatory responses, its mechanistic role in ARDS remains unclear. Here, we show that FKBP5 levels in bronchoalveolar lavage fluid from patients with sepsis-associated ARDS are significantly elevated and positively correlated with disease severity. In a lipopolysaccharide (LPS)-induced ARDS mouse model, Fkbp5[-/-] markedly attenuated lung inflammatory injury and reduced damage to the epithelial glycocalyx and tight junctions. Transcriptomic analysis revealed that FKBP5 regulates inflammatory responses through the necroptosis pathway. Both in vivo and in vitro experiments further confirmed that genetic deletion or knockdown of FKBP5 suppresses necroptosis activation, reduces NF-κB signaling, and restores glycocalyx and tight junction integrity. Mechanistically, necroptosis-driven NF-κB activation promotes excessive cytokine production, which in turn damages the epithelial glycocalyx and tight junctions. These findings identify FKBP5 as a potential therapeutic target in ARDS and redefine the alveolar epithelium as an active contributor to the inflammatory microenvironment.

The acetazolamide challenge test is frequently performed to evaluate cerebral blood flow and reserve capacity in cerebrovascular disease. Most of its side effects are mild and transient. Acute pulmonary edema (PE) has never been reported to occur after acetazolamide challenge tests. Here, we present a case of acute noncardiogenic PE triggered by an acetazolamide challenge test. A 62-year-old man with carotid artery stenosis underwent an acetazolamide challenge test during an arterial spin labeling (ASL) magnetic resonance (MR) imaging study. The patient showed stable vital signs and no neurologic abnormalities. The patient had no pulmonary or cardiac problems that could induce acute PE. Routine laboratory findings, electrocardiography, and chest X-ray also produced normal findings. An acetazolamide challenge ASL MR study was performed with intravenous administration of 1 g of acetazolamide. Two hours after acetazolamide administration, sudden dyspnea and hypoxemia developed, and chest X-ray and computed tomography revealed diffuse PE. Immediately, the oxygen supply and furosemide treatment were initiated. The following day, the dyspnea and PE improved and the patient recovered completely. To the best of our knowledge, this is the first case report of acute noncardiogenic PE triggered by intravenous acetazolamide administration in an acetazolamide challenge test.

Broken heart syndrome (Takotsubo or stress cardiomyopathy) is a transient form of acute left ventricular dysfunction commonly triggered by emotional or physical stress. Despite its reversible nature, it may lead to severe complications such as pulmonary edema, arrhythmias, or cardiac arrest. Current management remains largely supportive, with no established pharmacological therapy. Metformin, a well-known anti-diabetic drug, has emerged as a potential cardioprotective agent due to its multifaceted actions on cellular metabolism, vascular function, and neuro-hormonal balance. By activating the AMP-activated protein kinase (AMPK) pathway, Metformin improves microvascular perfusion, enhances endothelial nitric oxide bioavailability, and inhibits oxidative stress and NLRP3 inflammasome activation, thereby reducing myocardial inflammation and injury. It also restores the adiponectin/leptin ratio, attenuates macrophage polarization, and modulates the PI3K/AKT/mTOR signaling cascade, thereby preserving mitochondrial function and cardiomyocyte viability. Furthermore, metformin contributes to stabilization of the autonomic and brain-heart axes by mitigating catecholamine-driven sympathetic surges and monoamine oxidase-mediated oxidative damage. Collectively, these mechanisms suggest that Metformin may have significant cardioprotective potential in broken heart syndrome by targeting endothelial dysfunction, neurogenic stress, and inflammatory responses, warranting further preclinical and clinical investigation to validate its therapeutic role.

Acute respiratory distress syndrome (ARDS) is a high-mortality lung disorder driven by excessive neutrophil activation. While neutrophils are central to ARDS, the metabolic pathways fueling their inflammatory response remain unclear. This study identifies CD177 as a critical regulator of neutrophil glycolysis and NLRP3 inflammasome activation. Bioinformatics and animal models show that elevated CD177 correlates strongly with increased lactate and IL-1β levels. In vitro experiments demonstrate that CD177 knockdown reduces glycolytic flux and suppresses IL-1β release, a process reversed by lactate supplementation. Furthermore, treating ARDS mice with anti-CD177 antibodies significantly reduces pulmonary edema and tissue injury. These results establish the CD177-glycolysis-NLRP3 axis as a major driver of lung inflammation. Targeting this metabolic checkpoint provides a promising strategy for treating ARDS.