Bile pigments in emergency and critical care medicine

Bile pigments, such as bilirubin and biliverdin, are end products of the heme degradation pathway in mammals and are widely known for their cytotoxic effects. However, recent studies have revealed that they exert cytoprotective effects through antioxidative, anti-inflammatory, and immunosuppressive properties. All these mechanisms are indispensable in the treatment of diseases in the field of emergency and critical care medicine, such as coronary ischemia, stroke, encephalomyelitis, acute lung injury/acute respiratory distress syndrome, mesenteric ischemia, and sepsis. While further research is required before the safe application of bile pigments in the clinical setting, their underlying mechanisms shed light on their utilization as therapeutic agents in the field of emergency and critical care medicine. This article aims to summarize the current understanding of bile pigments and re-evaluate their therapeutic potential in the diseases listed above

Association of Japan Coma Scale score on hospital arrival with in-hospital mortality among trauma patients

BACKGROUND: The Japan Coma Scale (JCS) score has been widely used to assess patients' consciousness level in Japan. JCS scores are divided into four main categories: alert (0) and one-, two-, and three-digit codes based on an eye response test, each of which has three subcategories. The purpose of this study was to investigate the utility of the JCS score on hospital arrival in predicting outcomes among adult trauma patients. METHODS: Using the Japan Trauma Data Bank, we conducted a nationwide registry-based retrospective cohort study. Patients 16 years old or older directly transported from the trauma scene between January 2004 and December 2017 were included. Our primary outcome was in-hospital mortality. We examined outcome prediction accuracy based on area under the receiver operating characteristic curve (AUROC) and multiple logistic regression analysis with multiple imputation. RESULTS: A total of 222,540 subjects were included; their in-hospital mortality rate was 7.1% (n = 15,860). The 10-point scale JCS and the total sum of Glasgow Coma Scale (GCS) scores demonstrated similar performance, in which the AUROC (95% CIs) showed 0.874 (0.871-0.878) and 0.878 (0.874-0.881), respectively. Multiple logistic regression analysis revealed that the higher the JCS score, the higher the predictability of in-hospital death. When we focused on the simple four-point scale JCS score, the adjusted odds ratio (95% confidence intervals [CIs]) were 2.31 (2.12-2.45), 4.81 (4.42-5.24), and 27.88 (25.74-30.20) in the groups with one-digit, two-digit, and three-digit scores, respectively, with JCS of 0 as a reference category. CONCLUSIONS: JCS score on hospital arrival after trauma would be useful for predicting in-hospital mortality, similar to the GCS score

Heat-not-burn cigarettes induce fulminant acute eosinophilic pneumonia requiring extracorporeal membrane oxygenation

Background Although the cause of acute eosinophilic pneumonia (AEP) has not yet been fully clarified, cigarette smoking is reported to be a risk factor for developing AEP. The heat-not-burn cigarette (HNBC) was developed to reduce the adverse effects of smoke on the user's surroundings. However, the health risks associated with HNBCs have not yet been clarified. We report a successfully treated case of fatal AEP presumably induced by HNBC use. Presentation of case A 16-year-old man commenced HNBC smoking two weeks before admission and subsequently suffered from shortness of breath that gradually worsened. The patient was transferred to emergency department and immediately intubated because of respiratory failure. Computed tomography showed mosaic ground-glass shadows on the distal side of both lungs with a PaO2/FIO2 ratio of 76. The patient required veno-venous extracorporeal membrane oxygenation (ECMO) for severe respiratory failure. He was diagnosed with AEP by clinical course and detection of eosinophils in sputum; thus, methylprednisolone was administrated. The patient was weaned off ECMO four days after initiation and extubated the day after. He fully recovered without sequelae. Conclusion As far as we know, our patient is the first case of AEP induced by HNBC use successfully treated with ECMO. Emergency physicians must be aware that HNBCs can induce fatal AEP

Extracorporeal membrane oxygenation in Stenotrophomonas maltophilia pneumonia during acute myeloid leukemia: A case report

Stenotrophomonas maltophilia (S. maltophilia) is a Gram-negative, multidrug-resistant organism that both opportunistically infects the bloodstream and leads to pneumonia in immunosuppressed patients, including those with hematologic malignancies. In patients with severe respiratory failure, venovenous extracorporeal membrane oxygenation (VV ECMO) can stabilize the respiratory status. However, whether ECMO in patients with hematologic malignancies improves the clinical outcomes is still controversial because ECMO increases the risk of the exacerbation of sepsis and bleeding. We report a case of a 46-year-old man with Stenotrophomonas maltophilia hemorrhagic pneumonia acquired during consolidation chemotherapy for acute myeloid leukemia in whom VV ECMO lead to a good clinical outcome. The stabilization of his respiratory status achieved with VV ECMO allowed time for trimethoprim-sulfamethoxazole antibiotic therapy to improve the pneumonia. We suggest the background of patients, including comorbidities and general conditions, should be taken into account when considering the clinical indications of ECMO

Luminal administration of biliverdin ameliorates ischemia-reperfusion injury following intestinal transplant in rats

Background: Intestinal grafts are susceptible to ischemia-reperfusion injury, resulting in the loss of mucosal barrier function and graft failure. Biliverdin is known to exert a variety of cytoprotective functions against oxidative tissue injury. Because the mucosal layer is the primary site of ischemiareperfusion injury, mucosa-targeting strategies by luminal delivery of reagents might be beneficial. We tested whether intraluminal administration of biliverdin as an adjuvant to standard preservation solutions protected against ischemia-reperfusion injury. Methods: Orthotopic syngeneic intestinal transplants were performed on Lewis rats after 6 hours of cold preservation. Saline containing biliverdin (10 mM) or without biliverdin was introduced into the lumen of the intestinal grafts immediately before cold preservation. Results: Damage to the intestinal mucosa caused by ischemia-reperfusion injury resulted in severe morphological changes, including blunting of the villi and erosion, and led to significant loss of gut barrier function 3 hours after reperfusion. These changes to the mucosa were notably ameliorated by intraluminal administration of biliverdin. Biliverdin also effectively inhibited upregulation of messenger RNAs for interleukin-6, inducible nitric oxide synthase, and C-C motif chemokine 2. Additionally, biliverdin treatment prevented the loss of expression of claudin-1, a transmembrane, tight-junction barrier protein. The 14-day survival of recipients of biliverdin-treated grafts was significantly improved as compared with the recipients of saline-treated control grafts (83.3% vs 38.9%, P 1/4 .030). Conclusion: This study demonstrated that luminally delivered biliverdin provides beneficial effects during the transplant of rat small intestinal grafts and could be an attractive therapeutic option in organ transplantation

Therapeutic strategies for ischemia reperfusion injury in emergency medicine

Ischemia reperfusion (IR) injury occurs when blood supply, perfusion, and concomitant reoxygenation is restored to an organ or area following an initial poor blood supply after a critical time period. Ischemia reperfusion injury contributes to mortality and morbidity in many pathological conditions in emergency medicine clinical practice, including trauma, ischemic stroke, myocardial infarction, and post-cardiac arrest syndrome. The process of IR is multifactorial, and its pathogenesis involves several mechanisms. Reactive oxygen species are considered key molecules in reperfusion injury due to their potent oxidizing and reducing effects that directly damage cellular membranes by lipid peroxidation. In general, IR injury to an individual organ causes various pro-inflammatory mediators to be released, which could then induce inflammation in remote organs, thereby possibly advancing the dysfunction of multiple organs. In this review, we summarize IR injury in emergency medicine. Potential therapies include pharmacological treatment, ischemic preconditioning, and the use of medical gases or vitamin therapy, which could significantly help experts develop strategies to inhibit IR injury

The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury

Background : Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury. Methods : To test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined. Results : Mice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH(2)O, 95% CI 0.047-0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH(2)O, 95% CI 0.031-0.053, p = 0.02) and lower static elastance (BH 18.8 cmH(2)O/mL, [95% CI 15.4-22.2] vs. BA 26.7 cmH(2)O/mL [95% CI 19.6-33.8], p = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6-4.5%] vs. 1.1% [95% CI 0.3-1.8%], p = 0.008). Conclusions The results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury

Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations

Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients

Hydrogen in Transplantation: Potential Applications and Therapeutic Implications

Hydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and signaling pathways. Furthermore, hydrogen's capacity to activate cytoprotective pathways bolsters cellular resilience against stressors. In recent decades, significant advancements have been made in the critical medical procedure of transplantation. However, persistent challenges such as ischemia-reperfusion injury (IRI) and graft rejection continue to hinder transplant success rates. This comprehensive review explores the potential applications and therapeutic implications of hydrogen in transplantation, shedding light on its role in mitigating IRI, improving graft survival, and modulating immune responses. Through a meticulous analysis encompassing both preclinical and clinical studies, we aim to provide valuable insights into the promising utility of hydrogen as a complementary therapy in transplantation