Search Results (168)

Fat embolism is a critical medical emergency often resulting from long bone fractures or amputations, leading to acute respiratory distress syndrome (ARDS). The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is activated by reactive oxygen species and tissue damage, contributing to inflammatory responses. This study examines the role of NLRP3 in fat embolism-induced ARDS and evaluates the therapeutic potential of MCC950, a selective NLRP3 antagonist. Fat embolism was induced by fatty micelle injection into the tail vein of Sprague Dawley rats. Pulmonary injury was assessed through lung weight gain as an edema indicator, NLRP3 expression via Western blot, and IL-1β levels using ELISA. Histological damage and macrophage infiltration were evaluated with hematoxylin and eosin staining. Fat embolism significantly increased pulmonary NLRP3 expression, lipid peroxidation, IL-1β release, and macrophage infiltration within four hours, accompanied by severe pulmonary edema. NLRP3 was localized in type I alveolar cells, co-localizing with aquaporin 5. Administration of MCC950 significantly reduced inflammatory responses, lipid peroxidation, pulmonary edema, and histological damage, while attenuating MAPK cascade phosphorylation of ERK and Raf. These findings suggest that NLRP3 plays a critical role in fat embolism-induced acute respiratory distress syndrome, and its inhibition by MCC950 may offer a promising therapeutic approach. Full article

Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation below 75%, necessitating orotracheal intubation. During the procedure, he developed pulseless electrical activity cardiac arrest, achieving return of spontaneous circulation after advanced resuscitation. Diagnosis was confirmed by thick blood smear, demonstrating P. falciparum infection. The patient progressed to multiorgan failure, including acute respiratory distress syndrome with capillary leak pulmonary edema, refractory distributive shock, acute kidney injury with severe hyperkalemia, and consumptive thrombocytopenia. Management included invasive mechanical ventilation, vasopressor support, sedation-analgesia, neuromuscular blockade, methylene blue, unsuccessful hemodialysis due to hemorrhagic complications, and platelet transfusions. Despite these interventions, the patient experienced a second cardiac arrest and died. This case highlights the severity and rapid progression of severe malaria with multisystem involvement, underscoring the critical importance of early diagnosis and intensive multidisciplinary management. It also emphasizes the need for preventive strategies for travelers to endemic areas and the development of clinical protocols to improve outcomes in complicated malaria. Full article

High-altitude pulmonary edema (HAPE) is a severe condition associated with high-altitude environments, and its molecular mechanism has not been fully elucidated. This study systematically analyzed the DNA methylation status of HAPE patients and healthy controls using reduced-representation bisulfite sequencing (RRBS) and 850K DNA methylation chips, identifying key differentially methylated regions (DMRs). Targeted bisulfite sequencing (TBS) revealed significant abnormalities in DMRs of five genes, azurocidin 1 (AZU1), growth factor receptor bound protein 7 (GRB7), mannose receptor C-type 2 (MRC2), RUNX family transcription factor 3 (RUNX3), and septin 9 (SEPT9). The abnormal expression of AZU1 was validated using peripheral blood leukocytes from HAPE patients and normal controls, as well as rat lung tissue, indicating its potential importance in the pathogenesis of HAPE. To further validate the function of AZU1, we conducted experimental studies using a hypobaric hypoxia injury model in Human Umbilical Vein Endothelial Cells (HUVEC). The results showed that AZU1 was significantly upregulated under hypobaric hypoxia. Knocking down AZU1 mitigates the reduction in HUVEC proliferation, angiogenesis, and oxidative stress damage induced by acute hypobaric hypoxia. AZU1 induces cellular oxidative stress via the p38/mitogen-activated protein kinase (p38/MAPK) signaling pathway. This study is the first to elucidate the mechanism of AZU1 in HAPE via the p38/MAPK pathway, offering novel insights into the molecular pathology of HAPE and laying a foundation for future diagnostic and therapeutic strategies. Full article

Background/Objectives: Acute lung injury (ALI) is an inflammatory condition characterized by tissue barrier damage, which leads to vascular leakage, pulmonary edema, and compromised gas exchange. Lipopolysaccharides (LPS) are a component of Gram-negative bacteria, which trigger inflammation by Toll-like receptor 4 (TLR4) activation. Herein, we investigated the possibility that Pasireotide (PAS) exerts protective effects in an experimental model of ALI. Methods: C57BL/6 male mice received an intratracheal injection of saline or LPS, followed by PAS or vehicle treatment. Bronchoalveolar lavage fluid (BALF) was collected via tracheal catheterization, and Western blot analysis was used to detect protein expression variations. Results: Our results suggest that PAS treatment alleviates LPS-induced mouse lung injury and inflammation. JAK/STAT and MAPK activation levels in the inflamed lungs were suppressed due to PAS treatment, as well as BALF protein concentration. Additionally, PAS counteracted LPS-induced Grp94 protein reduction, suggesting the involvement of ATF6 in PAS-triggered barrier-protective effects. Grp94 is a downstream ATF6 target. Conclusions: Our data demonstrate that PAS protects mouse lungs against LPS in an experimental model of ALI. Full article

Background/Objectives: In preclinical research of airway inflammation, the endotoxin (lipopolysaccharide: LPS)–induced acute interstitial pneumonitis is the most commonly used mechanism model. However, studies apply different LPS serotypes, doses, administration routes, and reference compounds, making result interpretation challenging and drawing conclusions difficult. Therefore, here we aimed to optimize, characterize, and validate this model with dexamethasone in mice. Methods: Pneumonitis was induced by intratracheal LPS (0.25, 1, 2.5, 5 mg/kg; E. coli O111:B4) in C57BL/6J and NMRI mice; controls received phosphate-buffered saline (PBS). Dexamethasone (5 mg/kg i.p.) was used as a positive control. Respiratory functions were measured by restrained plethysmography 24 h after induction, and core body temperature was monitored. Lungs were excised and weighed, and then myeloperoxidase (MPO) activity and histopathological analysis were performed to assess pulmonary inflammation. Results: LPS-induced significant body weight loss, perivascular pulmonary edema, MPO activity increase, neutrophil infiltration, and respiratory function impairment in a dose-independent manner. However, LPS-induced hypothermia dynamics and duration were dose-dependent. The inhibitory effects of the reference compound dexamethasone were only detectable in the case of the 0.25 mg/kg LPS dose on most inflammatory parameters. These results did not differ substantially between C57BL/6J and NMRI mouse strains. Conclusions: Very low doses of LPS induce characteristic functional and morphological inflammatory alterations in the lung, which do not worsen in response to even 20 times higher doses. Since the effect of pharmacological interventions is likely to be detectable in the case of the 0.25 mg/kg LPS dose, we suggest this protocol for testing novel anti-inflammatory agents. Full article

Background: Sepsis-induced acute lung injury (ALI) is a serious disease constituting a heavy burden on society due to high mortality and morbidity. Inflammation and oxidative stress constitute key pathological mechanisms in ALI caused by sepsis. LL-37 can improve the survival of septic mice. Nevertheless, its function and underlying mechanism in sepsis-evoked ALI is elusive. Methods: The human A549 alveolar epithelial cell line was treated with LL-37 or ZBP1 recombinant vector under LPS exposure. Then, the effects on cell oxidative stress injury, inflammatory response, and autophagy were analyzed. RNA-seq analysis was performed to detect the differentially expressed genes (DEGs) between the LPS and LPS/LL-37 groups. Furthermore, the effects of LL-37 on cecal ligation and the puncture (CLP)-constructed ALI model were explored. Results: LL-37 attenuated LPS-evoked oxidative injury in human alveolar epithelial cells by increasing cell viability and suppressing ROS, malondialdehyde, and lactate dehydrogenase levels and apoptosis. Moreover, LPS-induced releases of pro-inflammatory IL-18, TNF-α, and IL-1β were suppressed by LL-37. Furthermore, LPS’s impairment of autophagy was reversed by LL-37. RNA-seq analysis substantiated 1350 differentially expressed genes between the LPS and LPS/LL-37 groups. Among them was ZBP1, a significantly down-regulated gene with the largest fold change. Moreover, LL-37 suppressed LPS-increased ZBP1 expression. Importantly, ZBP1 elevation restrained LL-37-induced autophagy in LPS-treated cells and abrogated LL-37-mediated protection against LPS-evoked oxidative injury and inflammation. LL-37 ameliorated abnormal histopathological changes, tissue edema, the lung injury score, oxygenation index (PaO2/FiO2), and glycemia contents in the CLP-constructed ALI model, which were offset through ZBP1 elevation via its activator CBL0137. Additionally, LL-37 suppressed inflammation and oxidative stress in lung tissues, concomitant with autophagy elevation and ZBP1 down-regulation. Conclusions: LL-37 may alleviate the progression of sepsis-evoked ALI by attenuating pulmonary epithelial cell oxidative injury and inflammatory response via ZBP1-mediated autophagy activation, indicating a promising approach for the therapy of ALI patients. Full article

An experimental model of acute pulmonary damage was developed based on the intravenous injection of the phospholipase A₂ (PLA₂)-rich venom of Pseudechis papuanus (Papuan black snake) in mice. Venom caused pulmonary edema, with the accumulation of a protein-rich exudate, as observed histologically and by analysis of bronchoalveolar lavage fluid (BALF). In parallel, venom induced an increase in all of the pulmonary mechanical parameters evaluated, without causing major effects in terms of tracheal and bronchial reactivity. These effects were abrogated by incubating the venom with the PLA₂ inhibitor varespladib, indicating that this hydrolytic enzyme is responsible for these alterations. The venom was cytotoxic to endothelial cells in culture, hydrolyzed phospholipids of a pulmonary surfactant, and reduced the activity of angiotensin-converting enzyme in the lungs. The pretreatment of mice with the nitric oxide synthase inhibitor L-NAME reduced the protein concentration in the BALF, whereas no effect was observed when mice were pretreated with inhibitors of cyclooxygenase (COX), tumor necrosis factor-α (TNF-α), bradykinin, or neutrophils. Based on these findings, it is proposed that the rapid pathological effect of this venom in the lungs is mediated by (a) the direct cytotoxicity of venom PLA₂ on cells of the capillary–alveolar barrier, (b) the degradation of surfactant factor by PLA₂, (c) the deleterious action of nitric oxide in pulmonary tissue, and (d) the cytotoxic action of free hemoglobin that accumulates in the lungs as a consequence of venom-induced intravascular hemolysis. Our findings offer clues on the mechanisms of pathophysiological alterations induced by PLA₂s in a variety of pulmonary diseases, including acute respiratory distress syndrome (ARDS). Full article

Background and Objectives: The introduction of portable ultrasound devices has transformed clinical practice in emergency medicine. Diagnostic accuracy and patient safety have been enhanced by point-of-care ultrasonography (POCUS), which has become a fundamental diagnostic and procedural tool. In addition to the standard clinical evaluation, POCUS provides quick patient assessments, allowing for the exclusion of life-threatening conditions and prognostication in different critical situations. Tissue Doppler imaging (TDI), as an advanced echocardiographic technique, offers additional quantitative data by measuring myocardial velocities, thereby improving the evaluation of systolic and diastolic ventricular function. The purpose of this review is to highlight the potential use of TDI in multiple acute and critical conditions. Materials and Methods: We conducted a narrative review of the main application topics for TDI. Results: TDI is an essential diagnostic and prognostic tool for acute coronary syndromes, assessing systolic or diastolic dysfunction, and etiological diagnosis of acute heart failure. It helps differentiate cardiogenic pulmonary edema from acute respiratory distress syndrome and identifies right ventricular systolic dysfunction in acute pulmonary embolism. TDI also facilitates distinctions between hypertension emergencies and urgencies and contributes to the stratification of atrial fibrillation reoccurrence risk. Furthermore, it aids in the differentiation of constrictive pericarditis from other restrictive cardiomyopathy patterns. In intensive care settings, TDI is particularly valuable during mechanical ventilation weaning, where elevated E/E’ values serve as a predictor of weaning failure. Due to its accessibility, rapid execution, and high reproducibility, it is suitable for longitudinal monitoring. Conclusions: TDI enhances the diagnostic precision, guides therapeutic strategies, and provides critical prognostic insights across a wide range of time-sensitive clinical scenarios, solidifying its role as an indispensable tool in modern emergency and critical care practice. Full article

Background and Clinical Significance: Ventricular septal defect (VSD) is a rare but serious complication following myocardial infarction (MI) that can lead to cardiogenic shock and carries a high mortality rate. Acute mitral regurgitation (MR) is another severe complication of MI with additional risks of mortality. The optimal timing of surgical intervention for VSD with MR is still being debated, and delaying surgery in medically manageable patients has been associated with improved survival. However, managing these patients in the intensive care unit (ICU) presents unique challenges. Case Presentation: In this paper, we present the case of a 52-year-old male with comorbidities who developed post-MI VSD with severe MR and underwent successful delayed surgical repair and mitral valve replacement. Our aim is to highlight the clinical characteristics, diagnostic approach, and management strategies of this rare complication in the critical care setting. The patient presented in cardiogenic shock and acute pulmonary edema. After stabilization using an intra-aortic balloon pump, pre- and afterload reducing pharmacotherapy and non-invasive mechanical ventilation, a watchful waiting strategy was employed, and surgery was performed on day 21 after hospital admission. Surgery was performed under general anesthesia, and the patient did not develop any complications related to the intra-aortic balloon pump or novel organ dysfunction. Conclusions: This case highlights the importance of a multidisciplinary approach to managing post-MI VSD with MR and emphasizes the need for careful patient selection and timing of surgical intervention in the critical care setting. Clinicians should be aware of the potential benefits of delaying surgical intervention in medically manageable patients, while also considering the unique challenges of managing these patients in the ICU. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic that devastated the world. While this is a respiratory virus, one feature of the SARS-CoV-2 infection was recognized to cause pathogenesis of other organs. Because the membrane fusion protein of SARS-CoV-2, the spike protein, binds to its major host cell receptor angiotensin-converting enzyme 2 (ACE2), which regulates a critical mediator of cardiovascular diseases, angiotensin II, COVID-19 is largely associated with vascular pathologies. The present study examined the pulmonary vasculature of COVID-19 patients using large sample sizes and provides mechanistic information through histological observations. We studied 56 postmortal lung samples from COVID-19 patients. The comparative group consisted of 17 postmortal lung samples from patients who died of influenza A virus subtype H1N1. The examination of 56 autopsy lung samples showed thickened vascular walls of small pulmonary arteries after 14 days of disease compared to H1N1 influenza patients who died before the COVID-19 pandemic started. Pulmonary vascular remodeling in COVID-19 patients was associated with hypertrophy of the smooth muscle layer, perivascular fibrosis, edema and lymphostasis, inflammatory infiltration, perivascular hemosiderosis, and neoangiogenesis. We found a correlation between the duration of hospital stay and the thickness of the muscular layer of the pulmonary arterial walls. These results demonstrate that COVID-19 significantly affected the pulmonary vasculature in fatal-course patients, also suggesting the need for careful follow-up in non-fatal cases, at risk of pulmonary hypertension. Full article

Background/Objectives: Cadmium (Cd) is a harmful metal commonly used in industry. Numerous clinical diseases, including osteomalacia, testicular damage, renal and hepatic failure, and pulmonary edema, are associated with Cd exposure. The current study evaluated the protective effect of Sinapic acid (SA) against Cd-induced hepatotoxicity by investigating different mechanistic pathways interfering with Cd-related liver injury. Methods: Forty rats were randomly assigned to four groups as follows; group 1 served as negative control and received saline, group 2 received saline for 14 days and CdCl₂ (3.5 mg/kg IP) as a single dose on day 14, groups 3 and 4 were treated with SA (20, 40 mg/kg PO), respectively, for 14 days and injected with CdCl₂ (3.5 mg/kg IP) on day 14. Serum was collected to evaluate liver function. Liver samples were collected for histopathological examination and the assessment of markers related to oxidative stress, inflammation, and apoptosis. Results: Acute Cd administration elevated liver enzymes and induced pathological changes in liver specimens, with the concurrent release of inflammatory markers and reduced antioxidant capabilities. Pretreatment with SA improved liver function and Cd-induced histopathological changes and elevated the activities of antioxidant enzymes. SA ameliorated inflammation, as evidenced by decreased expression of NF-κB, TNF-α, TLR-4, and COX-2, iNOS, and IL-1β levels along with suppression of mTOR, JNK, ERK, BAX, and Bcl-2. Conclusions: The present data suggest that SA represents a promising protective agent against Cd-induced hepatic injury by attenuating oxidative stress, inflammation, and apoptosis. Full article

All parts of Alocasia × amazonica (A. amazonica, Araceae) pose a toxicological risk due to oxalate production. Ingestion of the plant extract may cause multi-organ damage and fatal outcomes. Given the rarity of poisoning cases, its toxicological profile and systemic effects remain insufficiently characterized. This study aimed to investigate and report an appropriate approach to managing a patient intoxicated with A. amazonica (Araceae). A case of intentional self-poisoning with A. amazonica is presented. The patient, a 63-year-old woman, ingested approximately 200–300 mL of liquid prepared from the grated root of the plant. The initial clinical presentation involved localized injuries to the oral cavity and gastrointestinal tract, including severe pain, hoarseness, aphonia, dysphagia, mucosal erosions, and necrosis. Additional symptoms included hematinic vomiting, hemorrhagic diarrhea, and abdominal discomfort. These superficial and mucosal lesions resolved without the development of adhesions. Systemic effects comprised impaired consciousness indicative of encephalopathy, early metabolic acidosis, pulmonary edema with acute respiratory insufficiency, mild liver dysfunction, and hematuria. The therapeutic protocol for oral poisoning management was appropriate, leading to the patient’s discharge after 20 days of hospitalization. Full article

Positive airway pressure (PAP) therapy is widely used to manage both acute and chronic respiratory failure and plays an increasingly important role in cardiology, particularly in treating patients with respiratory comorbidities. PAP, including continuous positive airway pressure and noninvasive ventilation, significantly impacts hemodynamics by altering intrathoracic pressure, affecting preload, afterload, and stroke volume. These changes are crucial in conditions such as acute cardiogenic pulmonary edema, where PAP can enhance gas exchange, reduce the work of breathing, and improve cardiac output. PAP reduces the left ventricular afterload, which in turn increases stroke volume and myocardial contractility in patients with left-sided heart failure. However, the role of PAP in right ventricular function and its effects on venous return and cardiac output are critical in the cardiac intensive care setting. While PAP provides respiratory benefits, it must be used cautiously in patients with right heart failure or preload-dependent conditions to avoid adverse outcomes. Additionally, in recent years, the use of PAP has expanded in the treatment of severe obstructive sleep apnea and obesity hypoventilation syndrome, both of which significantly influence cardiovascular events and heart failure. This review provides an in-depth analysis of the hemodynamic effects of PAP in cardiovascular disease, focusing on its impact on ventricular function in both acute and chronic conditions. Evaluating clinical studies, guidelines, and recent advancements offers practical insights into the physiological mechanisms and key clinical considerations. Furthermore, this review aims to serve as a helpful guide for clinicians, assisting in decision-making processes where PAP therapy is applied. Full article

Wilderness medicine is a rapidly evolving field and has benefited from expanded research efforts. Moreover, with an escalating occurrence of severe and cataclysmic global climatologic events, human illness arising from interaction with wilderness and recreational environments warrants increasing consideration. Within the last decade, the Wilderness Medical Society (WMS) has aggregated research findings and created guidelines on prevention measures and therapeutic options for acute altitude illness, frostbite injuries, and avalanche and non-avalanche snow burials. As new research emerges, some guidelines have been updated to reflect the most current and sound scientific conclusions. In this review, we have synthesized the evidence-based guidelines and have reviewed the quality of the guidelines according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework. Further research efforts can expand the scope of evidence-based practice in travel medicine and ideally standardize the implementation of recommendations within both pre-travel and post-travel medical practices. Full article

Background: The recently updated definition of sepsis considers pathophysiologic mechanisms to guide initial therapy. Clearly, generalized recommendations for sepsis therapy may be limited by pre-existing multimorbidity in addition to sepsis-related multi-organ failure. In particular, a recommendation regarding fluid rescue therapy may require adequate cardiac function and/or the absence of sepsis-induced cardiomyopathy. In all sepsis patients with compromised cardiac function or sepsis-induced cardiomyopathy, a patient-specific therapy regimen is required to prevent pulmonary edema and early death. Similarly, in sepsis, acute kidney injury with or without pre-existing chronic kidney disease requires attention to be paid to excretory renal function to avoid hypervolemia-mediated acute heart failure. In addition, hyponatremia related to intravascular hypovolemia may be explained by vasopressin stimulation. However, hypothetically, vasopressin hyporesponsiveness may contribute to sepsis-related acute kidney injury. In this review, relevant cardiorenal pathomechanisms will be assessed in the context of sepsis therapy. Conclusions: In conclusion, therapy for sepsis with acute kidney injury has to take cardiac comorbidity, if present, into account. The extent to which vasopressin hyporesponsiveness aggravates sepsis-mediated hypovolemia and renal insufficiency should remain a subject of further study. Full article