Hemorrhage is the most common cause of traumatic cardiac arrest (TCA), and post-resuscitation renal injury remains a challenging clinical research focus. Sodium octanoate has been reported to exert protective effects in models of cerebral, cardiac, and intestinal injury. To investigate the effects of sodium octanoate on post-resuscitation renal injury, we established a porcine model of controlled hemorrhage-induced cardiac arrest, which simulates the ischemic injury of TCA. A total of 18 pigs were enrolled as experimental subjects and divided into three groups: SHAM group (n = 6), TCA group (n = 6), and Sodium octanoate (SO) group (n = 6). The SHAM group underwent anesthesia only, with endotracheal intubation and arterial/venous cannulation. In the TCA group, in addition to the procedures performed in the SHAM group, a TCA model was established by withdrawing blood via the femoral artery using a blood pump and reinfusing it through the femoral vein for resuscitation. In the SO group, after the TCA model was established, sodium octanoate was intravenously infused at a total dose of 30 mg/kg, starting 5 min after return of spontaneous circulation (ROSC), with the infusion completed within 1 h. Resuscitation parameters and survival outcomes were recorded for all groups. Serum creatinine and blood urea nitrogen levels were measured at baseline and at multiple time points after resuscitation. Euthanasia was performed 24 h post-resuscitation, and renal tissue samples from the same anatomical location were collected to evaluate histopathological changes, expression of proteins associated with pyroptosis, and levels of inflammatory cytokines. All animals were successfully resuscitated and remained alive at 24 h post-resuscitation. Following TCA model establishment, serum creatinine and blood urea nitrogen levels increased in both the TCA and SO groups. At 4 and 24 h post-resuscitation, SCr levels were significantly lower in the SO group than in the TCA group (both P < 0.05). BUN levels were significantly lower in the SO group than in the TCA group at all time points post-resuscitation (all P < 0.01). At 24 h post-resuscitation, renal tissue levels of NGAL, KIM-1, NLRP3, caspase-1, GSDMD-N, IL-1β, and IL-18 were significantly lower in the SO group than in the TCA group (all P < 0.05). Histopathological examination revealed prominent inflammatory cell infiltration and focal cellular necrosis in the TCA group, whereas the SO group treated with sodium octanoate exhibited only minimal inflammatory cell infiltration with no significant necrosis. Furthermore, at 2 and 4 h post-resuscitation, HR, MAP, and CO differed significantly between the TCA and SO groups (all P < 0.05). At 4 h post-resuscitation, Lac levels were significantly lower in the SO group than in the TCA group (P < 0.05). This study suggests that sodium octanoate may attenuate early renal injury at 24 h post-resuscitation in a porcine model of controlled hemorrhage-induced cardiac arrest. The potential mechanism may involve the modulation of inflammasome-associated inflammatory signaling, leading to reduced inflammatory response and cellular necrosis. Sodium octanoate shows potential therapeutic value for early renal injury following resuscitation from TCA.

BackgroundDl-3-n-butylphthalide (NBP) is a small-molecule compound derived from celery seeds with anti-inflammatory, antioxidant, and anti-apoptotic properties. Although NBP has shown protective effects in various kidney diseases, its role in traumatic cardiac arrest (TCA)-induced acute kidney injury (AKI) remains unclear. This study aimed to investigate the effects of NBP on AKI following TCA in pigs and to determine whether these effects were associated with modulation of ERS/UPR-associated apoptotic readouts.MethodsWe integrated ischemia–reperfusion injury (IRI)-related bulk transcriptomic/microarray datasets with single-cell RNA sequencing (scRNA-seq) data. Differential expression analysis, Hallmark GSEA, and GSVA/ssGSEA were performed to quantify unfolded protein response (UPR) and apoptosis, focusing on proximal tubule (PT) cells via PT-state stratification, pseudo-bulk differential analysis, and pseudotime inference. For in vivo validation, healthy male Bama minipigs were randomized to Sham, TCA, or TCA+NBP groups. NBP (2.5 mg/kg, i.v.) was administered within 120 min after return of spontaneous circulation (ROSC). Serum creatinine (Cr) and blood urea nitrogen (BUN) were measured at 1, 2, 4, and 24 h; kidneys harvested at 24 h underwent H&E and TUNEL staining, immunohistochemistry (KIM-1, NGAL), and Western blotting (PERK, CHOP, caspase-12, caspase-3).ResultsIntegrated bulk, single-cell, PT-state, pseudotime, and PT pseudo-bulk analyses prioritized a PT-enriched PERK–ATF4–CHOP-associated stress-apoptosis module, predominantly within injury-associated PT states. Along PT injury-state progression, HSPA5/GRP78, PERK/EIF2AK3, ATF4, CHOP/DDIT3, and apoptosis-related effectors showed coordinated transcript-level remodeling, suggesting engagement of an ERS/UPR-associated stress-apoptosis program rather than establishing pathway causality. Compared with TCA, NBP significantly reduced Cr and BUN, alleviated histopathologic injury, decreased KIM-1/NGAL expression, reduced TUNEL-positive cells and caspase-3 abundance, and was associated with lower PERK, CHOP, and caspase-12 protein expression.ConclusionA PT-enriched PERK-ATF4-CHOP-associated ERS/UPR stress-apoptosis module was prioritized in injury-associated proximal tubule states during IRI-related AKI. In a porcine TCA model, NBP was associated with reduced early AKI severity within a 24 h observation window, accompanied by lower PERK/CHOP/caspase-related ERS/UPR-associated and apoptosis-related readouts.

BackgroundSeptic cardiomyopathy (SCM) is a reversible acute cardiac dysfunction caused by sepsis. The use of QT-prolonging agents such as moxifloxacin and amiodarone may induce life-threatening arrhythmias, including torsades de pointes (TdP) and ventricular fibrillation (VF), both associated with high morbidity and mortality, posing significant challenges in clinical management.Case presentationWe report the case of an 89-year-old male who developed septic cardiomyopathy secondary to enterogenic septic shock, presenting with marked corrected QT (QTc) prolongation and impaired cardiac function. Following intravenous administration of moxifloxacin and amiodarone, QTc interval further prolonged, leading to frequent premature ventricular contractions that progressed to refractory TdP and VF. Despite conventional treatment, including electrolyte correction, defibrillation, and cardiopulmonary resuscitation, the arrhythmias remained uncontrollable. Intravenous maintenance therapy with lidocaine combined with anisodamine was initiated, resulting in gradual resolution of arrhythmias. No further TdP or VF episodes occurred. After 2 weeks, left ventricular function returned to baseline, and the patient was discharged in stable condition. A 9-month follow-up revealed near-complete recovery of cardiac function.ConclusionMoxifloxacin and amiodarone may trigger refractory TdP and VF in patients with septic cardiomyopathy. Intravenous lidocaine combined with anisodamine may be a potential therapeutic option for terminating these refractory arrhythmias.

Introduction: This study aimed to investigate the effects of nicotinamide adenine dinucleotide (NAD+) on lung injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in swine and to explore the potential underlying mechanisms.Methods: Twenty-two domestic male swine were randomly assigned to Sham (n = 6), CPR (n = 8), and CPR + NAD+ (n = 8) groups. The CA/CPR model was established by 10 minutes ventricular fibrillation followed by 6 minutes CPR. The Sham group underwent surgical preparation only. At 5 minutes after successful resuscitation, the CPR + NAD+ group received intravenous NAD+ (20 mg/kg over 1 hour), while the other groups received a vehicle solution. Before model induction and during the 4 hours post-resuscitation observation period, extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were measured using pulse index continuous cardiac output monitoring, oxygenation index (OI) was obtained from arterial blood gas analysis, and serum surfactant protein D (SP-D) concentrations were determined. At 24-hour post-resuscitation, lung tissue samples were harvested for histopathological analysis, apoptosis assessment, and evaluation of ferroptosis-related markers, including ferrous iron (Fe2+), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), glutathione (GSH), and reactive oxygen species. Expression of Yes-associated protein (YAP) and acyl-CoA synthetase long-chain family member 4 (ACSL4) was also evaluated.Results: Six animals in each intervention group achieved return of spontaneous circulation. Compared with the CPR group, NAD+ treatment significantly improved lung injury indices, including SP-D, ELWI, PVPI, and OI. Significant differences between the CPR and CPR + NAD+ groups were observed in serum SP-D at multiple time points, lung tissue SP-D at 24 hours, and ELWI and PVPI at 4 hours. Histopathological analysis revealed marked lung tissue injury and increased apoptosis in both intervention groups compared with the Sham group; however, these changes were significantly attenuated in the CPR + NAD+ group. Compared with the Sham group, lung tissue levels of Fe2+, MDA, 4-HNE, reactive oxygen species, and ACSL4 expression were significantly increased, whereas GSH levels and YAP expression were significantly decreased in both intervention groups. Notably, NAD+ administration significantly reversed these ferroptosis-related alterations compared with the CPR group.Conclusions: NAD+ effectively attenuates lung injury after CA/CPR in swine. The underlying mechanism may be associated with suppression of ferroptosis through modulation of the YAP/ACSL4 signaling pathway.

Tetanus is an infectious disease caused by the exotoxin produced by the anaerobic bacterium Clostridium tetani(C.tetani).[1]Tetanus is classified into four clinical types:generalized tetanus,neonatal tetanus,localized tetanus,and cerebral tetanus.Generalized tetanus is the most common type.[2,3]

Background:Leptospirosis is a globally prevalent zoonotic acute infectious disease that can rapidly progress to severe pulmonary form of leptospirosis (SPFL), leading to multiple organ failure with a high mortality rate. It is estimated that approximately 58,900 deaths occur annually due to leptospirosis, with critically ill patients admitted to intensive care units facing extremely high fatality rates. Therefore, timely and effective treatment strategies are crucial. Case presentation:Two patients developed fever after farm work exposure, followed by progressive dyspnea and hemoptysis, leading to hospitalization. They rapidly developed acute respiratory distress syndrome (ARDS) and diffuse alveolar hemorrhage (DAH) with severe thrombocytopenia, accompanied by a continuous decline in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO₂/FiO₂ [P/F]). Despite endotracheal intubation and mechanical ventilation, hypoxemia persisted. Venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated to provide oxygenation support, heparin anticoagulation was not used in the early stage. Meanwhile, prone ventilation and bronchoscopy alveolar lavage were performed to promote the clearance of pulmonary hemorrhage, along with anti-infection treatment. The diagnosis of leptospirosis was confirmed through Metagenomic Next-Generation Sequencing (mNGS). Both patients ultimately recovered, were successfully weaned from life support, discharged in stable condition, and returned to normal life. Conclusion:Early VV-ECMO support, combined with prone ventilation and bronchoalveolar lavage, can improve the prognosis of patients with SPFL. mNGS testing aids in the definitive diagnosis of leptospirosis and provides a reliable basis for antibiotic selection.

BackgroundTraumatic cardiac arrest (TCA) poses significant challenges in resuscitation, with extremely high mortality rates, making it a critical issue in emergency and critical care medicine. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a crucial rescue technology for patients with cardiac arrest, providing short-term support for cardiopulmonary failure. However, the successful application and related clinical experience of VA-ECMO in TCA remain limited and require further investigation.Case presentationA male patient sustained a stab wound to the left lower limb, resulting in femoral artery and vein injuries, massive hemorrhage, and subsequent hemorrhagic shock. The patient experienced cardiac arrest upon admission to a local hospital. Following cardiopulmonary resuscitation (CPR) and emergency femoral vascular reconstruction surgery, spontaneous circulation was temporarily restored, but the patient remained hemodynamically unstable postoperatively. Initial treatment at the local hospital was ineffective. On the second morning, the patient was transferred to our hospital via air medical transport, with a transport time of 35 min. Upon arrival, the patient was promptly evaluated, and VA-ECMO support was initiated within 17 min. After 3 days of VA-ECMO support and 5 days of mechanical ventilation, the patient was successfully weaned from life support and discharged in good condition.ConclusionVA-ECMO can significantly improve the survival outcomes of patients with cardiogenic shock following traumatic cardiac arrest. The use of interhospital air medical transport effectively reduces rescue time, providing critical opportunities for the timely management of severely ill patients.

BACKGROUND:Following successful cardiopulmonary resuscitation, those survivors of cardiac arrest (CA) often suffer from severe brain injury, and the latter can result in significant mortality and morbidity. Emerging evidence implicates that ferroptosis is involved in the pathogenesis of post-resuscitation brain injury, and its regulatory mechanisms remain to be investigated. Recently, some studies manifested that long noncoding RNAs could be critical regulators of cell ferroptosis in diverse ischemia-reperfusion injuries of vital organs. This study was designed to explore the role and mechanism of a newly screened long noncoding RNA ENSSSCG00000035331 in alleviating post-resuscitation hippocampal neuronal ferroptosis and further investigate its potential regulation by a novel antioxidant sulforaphane. METHODS AND RESULTS:Healthy male pigs and mice were used to establish the models of CA and resuscitation in vivo. A hypoxia/reoxygenation (H/R) model using primary porcine hippocampal neurons was constructed to replicate post-resuscitation brain injury in vitro. We found that the expression of ENSSSCG00000035331 was significantly decreased in the post-resuscitation impaired hippocampus using RNA sequencing analysis and verification. Subsequently, ENSSSCG00000035331 overexpression significantly reduced ferroptosis-related ferrous iron and reactive oxygen species production while markedly increased glutathione and further alleviated post-resuscitation brain injury. Mechanistically, ENSSSCG00000035331 interacted with miR-let7a, then inhibited its binding with glutathione peroxidase 4 (GPX4) mRNA and finally promoted the recovery of the latter's translation after H/R stimulation. In addition, sulforaphane treatment significantly increased ENSSSCG00000035331 and GPX4 expression while markedly decreased miR-let7a expression and hippocampal neuronal ferroptosis and finally alleviated post-resuscitation brain injury. CONCLUSIONS:Our findings highlighted that ENSSSCG00000035331 was a critical regulator of hippocampal neuronal ferroptosis after CA and resuscitation by targeting the miR-let7a/GPX4 axis, and additionally, sulforaphane might be a promising therapeutic agent for alleviating post-resuscitation brain injury by regulating the signaling axis mentioned above.

Abstract Background: Inflammation plays a critical role in the pathogenesis of limb injury caused by Deinagkistrodon acutus snakebite. Investigating its regulatory mechanisms and intervention strategies may help identify effective treatments. Recent studies have shown that pyroptosis exacerbates organ damage by amplifying inflammatory responses. Additionally, immune and matrix-regulatory cells (IMRC), a novel type of mesenchymal stem cell, and their exosomes (Exo) have demonstrated potential in mitigating inflammation-mediated injury by suppressing pyroptosis. This study aimed to evaluate whether IMRC-Exo could alleviate D. acutus venom-induced limb injury in rabbits by suppressing pyroptosis, thereby attenuating the associated inflammatory response. Methods: Eighteen healthy male New Zealand white rabbits were randomly assigned to Sham, Model, and IMRC-Exo groups. The Model group was established by intramuscular injection of D. acutus venom (1.5 mg/kg), followed by intravenous snake antivenom (80 U/kg) after 2 hours. The IMRC-Exo group received IMRC-Exo (7.5 × 1010 particles) post-modeling. Within 24 hours, left thigh circumference, serum creatine kinase (CK), and myoglobin (Mb) were assessed. Muscle tissues were collected for histopathology, apoptosis analysis, inflammatory cytokine quantification [high-mobility group box 1 (HMGB1), IL-1β, IL-18], and pyroptosis-related protein detection [caspase-3, cleaved caspase-3, gasdermin E (GSDME), N-terminal GSDME (N-GSDME)]. Results: Compared to Sham, venom injection significantly increased thigh circumference, CK, Mb, histopathological damage, apoptosis, inflammatory cytokines, and pyroptosis-related proteins. IMRC-Exo significantly reduced these indicators, mitigating muscle injury and inflammation. Additionally, inflammatory cytokines and pyroptosis markers were significantly lower in the IMRC-Exo group than in the Model group. Conclusion: IMRC-Exo effectively alleviates D. acutus venom-induced limb injury in rabbits, likely through inhibition of GSDME-dependent pyroptosis-mediated inflammation. These findings suggest that IMRC-Exo may serve as a promising therapeutic approach for snakebite-induced inflammatory injury.

BackgroundCoronavirus disease 2019 (COVID-19) is a global pandemic, while both fulminant myocarditis (FM) and thyroid storm (TS) are life-threatening critical conditions. When these three conditions coexist in a single patient, the survival outcome can be severely compromised.Case introductionWe report a case of cardiac arrest in a hyperthyroid patient triggered by COVID-19 infection. The patient developed symptoms such as fatigue, chest tightness, and chest pain following SARS-CoV-2 infection, and experienced respiratory and CA en route to the hospital. Ultimately, the patient was diagnosed with FM and TS. The patient was treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) combined with continuous renal replacement therapy (CRRT). After hemodynamic stabilization, the patient received pharmacological management for arrhythmia control and hyperthyroidism, along with other symptomatic treatments. The patient eventually recovered and was discharged.ConclusionIn hyperthyroid patients infected with SARS-CoV-2, clinicians should remain vigilant for the potential development of FM and TS. VA-ECMO combined with CRRT represents an effective therapeutic approach in such critical scenarios.

Deinagkistrodon acutus is one of the unique venomous snakes native to Southeast Asia. Limb injury caused by this species is the main cause of disability in snake bite patients, while the relevant pathogenesis mechanism and intervention strategies need to be further explored. In recent years, studies have established that mesenchymal stem cell-derived exosome (MSC-Exo) exerts a positive therapeutic effect on reducing limb injuries caused by a variety of factors, but this effect in limb injuries caused by snake bite is still unclear. Immunity-and-matrix regulatory cell (IMRC) is a type of mesenchymal stem cell derived from human embryonic stem cells, characterized by its unique capabilities in immune regulation and regulation of extracellular matrix production. In this study, IMRC was selected to investigate the effects and mechanisms of its Exo on limb injury induced by Deinagkistrodon acutus venom. Eighteen healthy male white rabbits were divided into Sham (S) group, Snake venom (SV) group and SV + IMRC-Exo group according to a random number table, with 6 rabbits in each group. Rabbit models of snakebite were established by limb injection of 1.5 mg/kg snake venom, followed by intravenous injection of 80 U/kg antivenom 2 h later. Additionally, subcutaneous injection of 7.5 × 1010 particles of Exo in the SV + IMRC-Exo group was given. After modeling, the limb circumference was measured regularly and the serum levels of muscle injury markers such as Creatine Kinase (CK) and Myoglobin (Mb) were detected. At the end of the experiment, muscle tissue samples of the injured limb were obtained to detect gross pathological damage and cell apoptosis. Ferroptosis-related products including iron deposition, reactive oxygen species(ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), glutathione (GSH), and superoxide dismutase (SOD)were quantified, and key proteins including acyl-CoA synthetase long chain family member 4 gene (ACSL4), nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), cyclooxygenase-2 (COX2), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) were measured. Compared with group S, the limb circumference and CK and Mb levels were significantly increased after modeling in the SV group and the SV + IMRC-Exo groups. However, the limb circumference and levels of muscle injury markers were significantly lower in the SV + IMRC-Exo group than in the SV group. Histopathological analysis showed that those animals in the SV and SV + IMRC-Exo groups had obvious muscle tissue damage and apoptosis compared with the S group. However, these pathological changes were significantly milder in the SV + IMRC-Exo group than in the SV group. In addition, compared with group S, the levels of iron deposition, ROS, MDA and 4-HNE, and the mRNA expression of ACSL4, NOX1 and COX2 in muscle tissues in the SV and SV + IMRC-Exo groups were significantly increased while the levels of GSH and SOD, and the mRNA expression of GPX4 and FTH1 were significantly decreased. However, compared with the SV group, the application of IMRC-Exo significantly reversed the changes in ferroptosis-related indices mentioned above. IMRC-Exo has a protective effect on limb injury induced by Deinagkistrodon acutus venom in rabbits, in which the mechanism is potentially related to the inhibition of ferroptosis.

Background Inflammation plays a critical role in the pathogenesis of limb injury caused by Deinagkistrodon acutus snakebite. Investigating its regulatory mechanisms and intervention strategies may uncover effective therapeutic approaches for this condition. Recent studies have identified pyroptosis as a key pathway exacerbating target organ damage by amplifying inflammatory responses. Immune and Matrix-Regulatory Cells (IMRC), a novel type of mesenchymal stem cell, and their derived exosomes (Exo) that have shown potential in mitigating inflammation-mediated tissue damage by suppressing pyroptosis. This study aimed to evaluate whether IMRC-Exo could alleviate Deinagkistrodon acutus venom-induced limb injury by inhibiting pyroptosis-mediated inflammation in rabbits. Methods Eighteen healthy male New Zealand white rabbits were randomly assigned to the Sham, Model, and IMRC-Exo groups. The Model group was established by intramuscular injection of Deinagkistrodon acutus venom (1.5 mg/kg), followed by intravenous infusion of anti-D. acutus venom serum (80 U/kg) after 2 hours. The IMRC-Exo group received IMRC-Exo treatment (7.5 × 10^10 particles) after model establishment. Within 24 hours post-modeling, the left thigh circumference, serum creatine kinase (CK), and myoglobin (Mb) levels were dynamically assessed. Animals were euthanized to collect muscle tissues for histopathological examination, apoptosis analysis, inflammatory cytokine quantification (HMGB1, IL-1β, IL-18), and pyroptosis-related protein detection, including caspase-3, cleaved caspase-3, gasdermin E (GSDME), and N-terminal GSDME (N-GSDME). Results Compared with the Sham group, both venom-injected groups exhibited a significant increase in left thigh circumference, elevated serum CK and Mb levels, and aggravated histopathological damage and apoptosis in muscle tissues. However, the IMRC-Exo group showed significantly reduced limb circumference, decreased muscle injury markers, and attenuated tissue damage compared with the Model group. Additionally, venom injection significantly increased HMGB1, IL-1β, IL-18 levels, and the expression of caspase-3, cleaved caspase-3, GSDME, and N-GSDME in muscle tissues of the Model and IMRC-Exo groups compared to the Sham group. Notably, these inflammatory cytokine levels and pyroptosis-related protein expressions were significantly lower in the IMRC-Exo group than in the Model group. Conclusion IMRC-Exo effectively alleviates limb wound damage induced by Deinagkistrodon acutus snakebite in rabbits. Its protective mechanism may involve the inhibition of GSDME-dependent pyroptosis-mediated inflammatory injury.

OBJECTIVE:Envenomation by Deinagkistrodon acutus (D. acutus) often results in severe limb damage, but therapeutic strategies to counteract the damage are limited. Botulinum neurotoxin A (BoNT/A) has shown protective effects in various models of tissue damage. The present study employed a rabbit model of D. acutus-induced limb damage to investigate the potential therapeutic use and underlying mechanisms of BoNT/A. METHODS:Twenty-two New Zealand white rabbits were randomly assigned to three groups: Sham (S, n = 6), Snake Venom (SV, n = 8), and Snake Venom plus BoNT/A (SV + BoNT/A, n = 8). D. acutus venom was injected intramuscularly into the left thigh to cause limb injury. Antivenom (80 U/kg) was given intravenously 2 h later. In the SV + BoNT/A group, BoNT/A was injected subcutaneously around the venom injection site immediately after modeling. The myoglobin, serum creatine kinase, and limb circumference were monitored. After 24 h, muscle tissue near the injection site was collected for histological evaluation, assessment of apoptosis (cleaved caspase-3), analysis of TNF-α, IL-6, and IL-10, and examination of macrophage polarization markers. RESULTS:Both SV and SV + BoNT/A groups displayed significant increases in limb swelling, inflammatory cytokines, apoptosis, histological damage, macrophage polarization in comparison to the Sham group. Treatment with BoNT/A reduced pro-inflammatory cytokines (TNF-α, IL-6) while increasing IL-10 (P < 0.05). Moreover, BoNT/A decreased the proportion of CD86+ and iNOS + cells (M1 phenotype) while increasing the proportion of CD206+ and Arg1+ cells (M2 phenotype). CONCLUSION:BoNT/A alleviates D. acutus -induced limb injury in rabbits potentially through promoting macrophage polarization.

Background Mediastinal and cervical subcutaneous emphysema caused by anaerobic infections is rare in clinical practice, particularly when accompanied by sepsis, septic shock, and severe acute respiratory distress syndrome (ARDS). These cases pose significant treatment challenges. Veno-venous extracorporeal membrane oxygenation (VV-ECMO), as a life-saving intervention, has been increasingly utilized in patients with severe infections and refractory hypoxemia. This report aims to evaluate the effectiveness of VV-ECMO in the treatment of mediastinal and subcutaneous emphysema, sepsis, and severe ARDS caused by anaerobic infections, and to summarize relevant therapeutic strategies.Case presentation A 49-year-old male was admitted with fever, sore throat, chest tightness, and hoarseness. On admission, he presented with severe hypoxemia, sepsis, and acute kidney injury. Chest computed tomography (CT) revealed bilateral mediastinal emphysema and cervical subcutaneous emphysema. Next-generation sequencing (NGS) confirmed an anaerobic bacterial infection. Despite high-flow oxygen therapy and antibiotic treatment, the patient's oxygenation continued to deteriorate, culminating in cardiopulmonary arrest. VV-ECMO was initiated to improve oxygenation, alongside prone positioning ventilation, sputum clearance, and alveolar lavage. After 7 days of ECMO support and anti-infective treatment, the patient's oxygenation improved significantly, inflammatory markers decreased, and ECMO was successfully weaned.Conclusion VV-ECMO is of critical value in managing septic shock and ARDS caused by severe anaerobic infections, effectively improving oxygenation and supporting organ function. This case highlights the pivotal role of airway management, VV-ECMO support, and comprehensive therapeutic strategies in the management of complex infectious ARDS, providing valuable insights for similar clinical scenarios.

Introduction Global ischemia reperfusion (I/R) stimulation induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) triggers multiple forms of programmed cell death including pyroptosis and necroptosis, and further results in post-resuscitation myocardial damage. Recently, a specific inhibitor of histone deacetylase 6 activity, tubastatin A (TubA) was preliminarily shown to protect the heart against global and regional I/R stimulation. The present study was designed to investigate the effect of TubA on post-resuscitation myocardial pyroptosis and necroptosis in a porcine model of CA and resuscitation. Methods A total of 18 pigs were randomly assigned to one of the following three groups (n=6 each): Sham group, CA/CPR group, and CA/CPR+TubA group. The setting of 9 min of CA and 6 min of CPR was used to establish the porcine model of CA and resuscitation. A dose of 4.5 mg/kg of TubA was intravenously infused within 1 h after successful resuscitation. Myocardial function including stroke volume and global ejection fraction, and cardiac injury biomarkers including cardiac troponin I and creatine kinase-MB were regularly evaluated for 24 h after resuscitation. Thereafter, the pigs were euthanized, and myocardial tissues were harvested to evaluate the ratio of cell apoptosis, the contents of high mobility group box 1, IL-1β, and IL-18, and the expression levels of caspase 3, gasdermin E (GSDME), GSDME N-terminal (GSDME-N), receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL), and phosphorylated MLKL (p-MLKL). Results After resuscitation, stroke volume and global ejection fraction were significantly decreased while serum cardiac troponin I and creatine kinase-MB were significantly increased in the two groups experiencing the CA/CPR procedure compared with the Sham group. However, myocardial dysfunction and cardiac injury were significantly milder in the CA/CPR+TubA group than in the CA/CPR group. At 24 h after resuscitation, apoptosis ratio, pyroptosis-related proteins (caspase 3, GSDME, GSDME-N), necroptosis-related proteins (RIP1, RIP3, MLKL, p-MLKL), and proinflammatory cytokines (high mobility group box 1, IL-1β, IL-18) in myocardium were significantly increased in the CA/CPR and CA/CPR+TubA groups compared with the Sham group. Nevertheless, all of them were significantly decreased in those pigs treated with the TubA compared to the CA/CPR group. Conclusions TubA could effectively alleviate post-resuscitation myocardial damage in a porcine model of CA and resuscitation, in which the protective role was possibly related to the inhibition of GSDME-mediated pyroptosis and MLKL-mediated necroptosis.

BackgroundAcute pulmonary embolism (APE) is a common and potentially fatal cardiovascular disease that can lead to sudden cardiac arrest in severe cases. When conventional cardiopulmonary resuscitation measures fail to achieve the return of spontaneous circulation (ROSC) in patients with APE, venoarterial extracorporeal membrane oxygenation (ECMO) becomes a viable therapeutic option. As an advanced life support treatment, ECMO ensures the perfusion of critical organs, providing sufficient time for interventions necessary for ROSC.Case introductionWe report the case of a patient who experienced cardiac arrest due to pulmonary embolism. During the treatment, the patient received two sessions of external cardiopulmonary resuscitation (ECPR) as supportive care and experienced cerebral hemorrhage. Ultimately, the patient improved and was discharged following support from extracorporeal membrane oxygenation (ECMO), careful anticoagulation strategies, and intervention with balloon pulmonary angioplasty.ConclusionECMO can serve as an important life support technology for patients with severe APE. Through a cautious anticoagulation therapy, not only was the ECMO support successfully maintained but also was further deterioration of cerebral hemorrhage effectively prevented. For patients with concurrent main pulmonary artery embolism and bleeding, balloon pulmonary angioplasty may be an option.

In 2009, the World Health Organization included snakebite on the list of neglected tropical diseases, acknowledging it as a common occupational hazard for farmers, plantation workers, and others, causing tens of thousands of deaths and chronic physical disabilities every year. This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims. These recommendations are based on clinical experience and clinical research evidence. This guideline focuses on the following topics: snake venom, clinical manifestations, auxiliary examination, diagnosis, treatments, and prevention.

Background: Chlamydia abortus is a pathogen capable of infecting both humans and animals. In most known cases, this pathogen primarily infects pregnant women, leading to miscarriage and preterm birth. However, it is exceedingly rare for this pathogen to cause pneumonia that progresses to severe Acute Respiratory Distress Syndrome (ARDS). case introduction: We present a case of a 76-year-old male patient who was clinically diagnosed with Acute Respiratory Distress Syndrome (ARDS) caused by Chlamydia abortus and successfully treated. The patient's condition rapidly deteriorated over six days, evolving from a lung infection to severe pneumonia, ultimately leading to ARDS and sepsis. Initially, he was admitted to a local hospital for a lung infection where routine etiological examinations failed to identify any significant pathogens, and he received only empirical antimicrobial therapy. However, the lung infection was not controlled, and the patient's condition rapidly worsened, resulting in severe respiratory distress. This necessitated tracheal intubation and assisted ventilation, after which he was transferred to our hospital for treatment. Due to the patient's family's inability to afford the cost of ECMO treatment, we adopted a prone positioning ventilation strategy to improve the patient's ventilation-perfusion matching. Additionally, we performed metagenomic next-generation sequencing on the patient's bronchoalveolar lavage fluid, which confirmed the infection with Chlamydia abortus. These measures ultimately led to the successful treatment of the patient. Conclusion：Chlamydia abortus infection can lead to severe ARDS, necessitating timely diagnosis and active intervention by clinicians. This case highlights the crucial role of metagenomic next-generation sequencing in diagnosing rare pathogens. Timely adoption of prone positioning ventilation can significantly improve ventilation-perfusion matching, effectively treating ARDS caused by Chlamydia abortus. Additionally, the combination of moxifloxacin and piperacillin-tazobactam can treat ARDS caused by Chlamydia abortus.

Objective: To establish a preclinical large -animal model of Deinagkistrodon acutus snakebite envenomation and evaluate its feasibility. Methods: The venom of D. acutus (0 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, or 10 mg/kg) was injected into the left biceps femoris of 11 male pigs. Then, the circumferences of the limbs were regularly measured, and changes in muscle injury biomarkers, blood parameters, coagulation function, vital organ function and injury biomarkers were regularly detected. At 24 h after venom injection, the animals were euthanized, and the pathological damage to the vital organs mentioned above was evaluated. Results: The two pigs receiving 10 mg/kg and 5 mg/kg snake venom died at 8 h and 12 h after injection, respectively. The remaining pigs were equally divided into 0 mg/kg, 1 mg/kg, and 2 mg/kg snake venom groups, and all of them survived to 24 h after injection. Compared with the pigs receiving 0 mg/kg snake venom, the pigs receiving 1 mg/kg or 2 mg/kg snake venom exhibited significant abnormities, including limb swelling; increased muscle injury biomarker creatine kinase (CK) and coagulation function indicators prothrombin time and Ddimer; and decreased blood routine indicator platelet and coagulation function indicator fibrinogen. Moreover, significant abnormalities in myocardial and cerebral function and injury biomarkers in the heart, brain, liver, kidney and intestine were also observed. In particular, the abnormalities mentioned above were significantly obvious in those pigs receiving 2 mg/kg snake venom. Pathological evaluation revealed that the morphology of muscle, heart, brain, liver, kidney, and intestine in those pigs receiving 0 mg/kg snake venom was normal; however, pathological damage was observed in those pigs receiving 1 mg/kg and 2 mg/kg snake venom. Similarly, the pathological damage was more severe in those pigs receiving 2 mg/kg snake venom. Conclusion: The intramuscular injection of 2 mg/kg D. acutus venom seems to be an optimal dose for examining the preclinical efficacy of existing and novel therapeutics for treating D. acutus envenomation in pigs.

BackgroundParaganglioma (PGL) is a neuroendocrine tumor located outside the adrenal gland that can secrete catecholamines. Clinical manifestations include headaches, hypertension, and, rarely, cardiomyopathy. Among these, reverse Takotsubo cardiomyopathy (rTTS) is a rare Takotsubo cardiomyopathy (TTS) associated with a surge in catecholamines.Case introductionThis article reports a case of a hypertensive patient admitted for recurrent dizziness and chest tightness. During treatment, the patient suddenly experienced chest tightness and shortness of breath, followed by refractory cardiogenic shock, and was eventually diagnosed with rTTS. The patient gradually recovered and was successfully discharged after receiving treatments, including tracheal intubation with mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and surgery.ConclusionThe diagnosis of rTTS is significantly aided by the presence of free plasma metanephrines and specific changes observed in cardiac ultrasound. In the treatment of severe rTTS, ECMO can serve as a crucial life support technology. Under VA-ECMO support, early resection of the PGL after accelerated preoperative preparation may be a feasible approach.