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1.
BMC Pulm Med ; 21(1): 339, 2021 Oct 31.
Article in English | MEDLINE | ID: mdl-34719405

ABSTRACT

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/cmH2O, 95% CI 0.047-0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH2O, 95% CI 0.031-0.053, p = 0.02) and lower static elastance (BH 18.8 cmH2O/mL, [95% CI 15.4-22.2] vs. BA 26.7 cmH2O/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.


Subject(s)
Hydrogen/pharmacology , Lung Injury/drug therapy , Lung Injury/physiopathology , Administration, Inhalation , Animals , Antibiotics, Antineoplastic , Bleomycin , Interleukins/metabolism , Lung Injury/chemically induced , Macrophages/drug effects , Male , Mice , Mice, Inbred C57BL , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology , Respiratory Distress Syndrome/complications
2.
Pediatr Transplant ; 24(7): e13848, 2020 11.
Article in English | MEDLINE | ID: mdl-32997862

ABSTRACT

Prolonged intestinal cold storage causes considerable mucosal breakdown, which could bolster bacterial translocation and cause life-threatening infection for the transplant recipient. The intestine has an intraluminal compartment, which could be a target for intervention, but has not yet been fully investigated. Hydrogen gas exerts organ protection and has used been recently in several clinical and basic research studies on topics including intestinal transplantation. In this study, we aimed to investigate the cytoprotective efficacy of intraluminally administered hydrogen-rich saline on cold IR injury in intestinal transplantation. Isogeneic intestinal transplantation with 6 hours of cold ischemia was performed on Lewis rats. Hydrogen-rich saline (H2 concentration at 5 ppm) or normal saline was intraluminally introduced immediately before preservation. Graft intestine was excised 3 hours after reperfusion and analyzed. Histopathological analysis of control grafts revealed blunting of the villi and erosion. These mucosal changes were notably attenuated by intraluminal hydrogen. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h post-reperfusion. However, this decline in permeability was critically prevented by hydrogen treatment. IR-induced upregulation of proinflammatory cytokine mRNAs such as IL-6 was mitigated by hydrogen treatment. Western blot revealed that hydrogen treatment regulated loss of the transmembrane protein ZO-1. Hydrogen-rich saline intraluminally administered in the graft intestine modulated IR injury to transplanted intestine in rats. Successful abrogation of intestinal IR injury with a novel strategy using intraluminal hydrogen may be easily clinically applicable and will compellingly improve patient care after transplantation.


Subject(s)
Intestine, Small/transplantation , Organ Transplantation/adverse effects , Postoperative Complications/prevention & control , Reperfusion Injury/prevention & control , Saline Solution/pharmacology , Animals , Disease Models, Animal , Graft Survival , Intestinal Mucosa/metabolism , Male , Organ Preservation/methods , Postoperative Complications/metabolism , Rats , Rats, Inbred Lew , Reperfusion Injury/metabolism , Zonula Occludens-1 Protein/metabolism
3.
BMC Emerg Med ; 19(1): 65, 2019 11 06.
Article in English | MEDLINE | ID: mdl-31694575

ABSTRACT

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.


Subject(s)
Coma/mortality , Hospital Mortality/trends , Trauma Severity Indices , Adolescent , Adult , Age Factors , Aged , Eye Movements , Female , Humans , Japan/epidemiology , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Sex Factors , Vital Signs , Young Adult
4.
Biomedicines ; 12(1)2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38255223

ABSTRACT

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.

5.
Circ J ; 77(4): 944-51, 2013.
Article in English | MEDLINE | ID: mdl-23502987

ABSTRACT

BACKGROUND: Hospitalized heart failure (HHF) is a critical issue in Japan. To improve its management and outcomes, the clinical features, in-hospital management, and outcomes should be analyzed to improve the guidelines for HHF. METHODS AND RESULTS: The acute decompensated heart failure syndromes (ATTEND) registry is the largest study of HHF in Japan. The present report covers the clinical features and in-hospital management of HHF patients. The data from 4,842 enrolled patients have demonstrated that most Japanese HHF patients are elderly, with new onset, and a history of hypertension and orthopnea on admission. During hospitalization, furosemide and carperitide were commonly used and the length of stay was extremely long (mean 30 days), with 6.4% in-hospital mortality. CONCLUSIONS: The findings of the present study suggest the following: (1) the focus for hypertensive elderly and diabetic patients should be on primary prevention of HHF,(2) more intensive management with noninvasive positive pressure ventilation should be performed at the urgent stage, (3) it is necessary to clarify the clinical benefit of carperitide and angiotensin-receptor blockers, because they are commonly used in Japan, and (4) it is necessary to clarify the relationship between in-hospital mortality and length of stay from the viewpoint of both outcome and cost of patient care.


Subject(s)
Angiotensin Receptor Antagonists/administration & dosage , Atrial Natriuretic Factor/administration & dosage , Furosemide/administration & dosage , Heart Failure/drug therapy , Heart Failure/mortality , Hospital Mortality , Length of Stay , Registries , Sodium Potassium Chloride Symporter Inhibitors/administration & dosage , Aged , Aged, 80 and over , Diabetes Complications/drug therapy , Diabetes Complications/mortality , Female , Humans , Hypertension/drug therapy , Hypertension/mortality , Japan/epidemiology , Male , Prospective Studies
6.
Exp Gerontol ; 180: 112270, 2023 09.
Article in English | MEDLINE | ID: mdl-37572992

ABSTRACT

INTRODUCTION: With the global population aging, there is an increased prevalence of sepsis among the elderly, a demographic particularly susceptible to inflammation. This study aimed to evaluate the therapeutic potential of hydrogen gas, known for its anti-inflammatory and antioxidant properties, in attenuating inflammation specifically in the lungs and liver, and age-associated molecular markers in aged mice. METHODS: Male mice aged 21 to 23 months, representative of the human elderly population, were subjected to inflammation via intraperitoneal injection of lipopolysaccharide (LPS). The mice were allocated into eight groups to examine the effects of varying durations and concentrations of hydrogen gas inhalation: control, saline without hydrogen, saline with 24-hour 2 % hydrogen, LPS without hydrogen, LPS with 24-hour 2 % hydrogen, LPS with 6-hour 2 % hydrogen, LPS with 1-hour 2 % hydrogen, and LPS with 24-hour 1 % hydrogen. Parameters assessed included survival rate, activity level, inflammatory biomarkers, and organ injury. RESULTS: Extended administration of hydrogen gas specifically at a 2 % concentration for 24 h led to a favorable prognosis in the aged mice by reducing mRNA expression of inflammatory biomarkers in lung and liver tissue, mitigating lung injury, and diminishing the expression of the senescence-associated protein p21. Moreover, hydrogen gas inhalation selectively ameliorated senescence-related markers in lung tissue, including C-X-C motif chemokine 2, metalloproteinase-3, and arginase-1. Notably, hydrogen gas did not alleviate LPS-induced liver injury under the conditions tested. CONCLUSION: The study highlights that continuous inhalation of hydrogen gas at a 2 % concentration for 24 h can be a potent intervention in the geriatric population for improving survival and physical activity by mitigating pulmonary inflammation and modulating senescence-related markers in aged mice with LPS-induced inflammation. This finding paves the way for future research into hydrogen gas as a therapeutic strategy to alleviate severe inflammation that can lead to organ damage in the elderly.


Subject(s)
Hydrogen , Lipopolysaccharides , Aged , Humans , Male , Mice , Animals , Hydrogen/pharmacology , Hydrogen/therapeutic use , Lung/metabolism , Inflammation/metabolism , Biomarkers
7.
Surgery ; 174(2): 343-349, 2023 08.
Article in English | MEDLINE | ID: mdl-37210236

ABSTRACT

BACKGROUND: Lung contusion caused by blunt chest trauma evokes a severe inflammatory reaction in the pulmonary parenchyma that may be associated with acute respiratory distress syndrome. Although hydrogen gas has antioxidant and anti-inflammatory effects and is protective against multiple types of lung injury at safe concentrations, the effects of inhaled hydrogen gas on blunt lung injury have not been previously investigated. Therefore, using a mouse model, we tested the hypothesis that hydrogen inhalation after chest trauma would reduce pulmonary inflammation and acute lung injury associated with lung contusion. METHODS: Inbred male C57BL/6 mice were randomly divided into 3 groups: sham with air inhalation, lung contusion with air inhalation, and lung contusion with 1.3% hydrogen inhalation. Experimental lung contusion was induced using a highly reproducible and standardized apparatus. Immediately after induction of lung contusion, mice were placed in a chamber exposed to 1.3% hydrogen gas in the air. Histopathological analysis and real-time polymerase chain reaction in lung tissue and blood gas analysis were performed 6 hours after contusion. RESULTS: Histopathological examination of the lung tissue after contusion revealed perivascular/intra-alveolar hemorrhage, perivascular/interstitial leukocyte infiltration, and interstitial/intra-alveolar edema. These histological changes and the extent of lung contusion, as determined by computed tomography, were significantly mitigated by hydrogen inhalation. Hydrogen inhalation also significantly reduced inflammatory cytokine and chemokine mRNA levels and improved oxygenation. CONCLUSION: Hydrogen inhalation therapy significantly mitigated inflammatory responses associated with lung contusion in mice. Hydrogen inhalation therapy may be a supplemental therapeutic strategy for treating lung contusion.


Subject(s)
Acute Lung Injury , Contusions , Lung Injury , Thoracic Injuries , Wounds, Nonpenetrating , Animals , Mice , Male , Lung Injury/etiology , Wounds, Nonpenetrating/complications , Thoracic Injuries/complications , Thoracic Injuries/therapy , Hydrogen/therapeutic use , Mice, Inbred C57BL , Contusions/complications , Contusions/pathology , Lung/diagnostic imaging , Lung/pathology , Acute Lung Injury/etiology , Acute Lung Injury/prevention & control
8.
PLoS One ; 18(10): e0287501, 2023.
Article in English | MEDLINE | ID: mdl-37883347

ABSTRACT

BACKGROUND: Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections. METHODS: This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or no-teprenone groups in a 1:1 ratio. We stratified patients by sex, age < and ≥ 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate. RESULTS: One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325). CONCLUSION: Teprenone afforded no clinical benefit. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs061200002 (registered on 20/May/2020).


Subject(s)
COVID-19 , Diterpenes , Humans , Aged , SARS-CoV-2 , Intensive Care Units , Treatment Outcome
9.
BMJ Open ; 13(10): e072680, 2023 10 18.
Article in English | MEDLINE | ID: mdl-37852764

ABSTRACT

INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.


Subject(s)
Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Humans , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/therapy , Tidal Volume , Ventilators, Mechanical , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
10.
J Anesth ; 26(5): 650-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22618953

ABSTRACT

PURPOSE: To evaluate procedures and outcomes of extracorporeal membrane oxygenation (ECMO) therapy applied to 2009 influenza A(H1N1) severe respiratory failure patients in Japan. METHODS: This observational study used database information about adults who received ECMO therapy for H1N1-related severe respiratory failure from April 1, 2010 to March 31, 2011. RESULTS: Fourteen patients from 12 facilities were enrolled. Anti-influenza drugs were used in all cases. Before the start of ECMO, the lowest PaO(2)/FiO(2) was median (interquartile) of 50 (40-55) mmHg, the highest peak inspiratory pressure was 30 (29-35) cmH(2)O, and mechanical ventilation had been applied for at least 7 days in 5 patients. None of the facilities had extensive experience with ECMO for respiratory failure (6 facilities, no previous experience; 5 facilities, one or two cases annually). The blood drainage cannula was smaller than 20 Fr. in 10 patients (71.4 %). The duration of ECMO was 8.5 (4.0-10.8) days. The duration of each circuit was only 4.0 (3.2-5.3) days, and the ECMO circuit had to be renewed 19 times (10 cases). Thirteen patients (92.9 %) developed adverse events associated with ECMO, such as oxygenator failure, massive bleeding, and disseminated intravascular coagulation. The survival rate was 35.7 % (5 patients). CONCLUSION: ECMO therapy for H1N1-related severe respiratory failure in Japan has very poor outcomes, and most patients developed adverse events. However, this result does not refute the effectiveness of ECMO. One possible cause of these poor outcomes is the lack of satisfactory equipment, therapeutic guidelines, and systems for patient transfer to central facilities.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/therapy , Influenza, Human/virology , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Adult , Databases, Factual , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/standards , Female , Humans , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Japan/epidemiology , Male , Middle Aged , Pandemics , Respiration, Artificial/methods , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/epidemiology , Survival Rate , Treatment Outcome
11.
Eur J Med Res ; 27(1): 224, 2022 Oct 29.
Article in English | MEDLINE | ID: mdl-36309733

ABSTRACT

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.


Subject(s)
Bile Pigments , Respiratory Distress Syndrome , Animals , Humans , Bile Pigments/metabolism , Biliverdine/metabolism , Antioxidants/therapeutic use , Critical Care , Mammals/metabolism
12.
Intern Med ; 61(22): 3409-3414, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35370234

ABSTRACT

Anti-asparaginyl transfer RNA (tRNA) synthetase (KS) antibodies, detected in <5% patients with anti-aminoacyl-tRNA synthetase antibody syndrome, are strongly associated with interstitial pneumonia but not myositis and skin symptoms. A recent report suggested that most patients with interstitial pneumonia and anti-KS antibody (KS-ILD) may present with chronic disease. We herein report a rare case of severe acute respiratory failure in a KS-ILD patient requiring extracorporeal membrane oxygenation (ECMO). ECMO is useful for facilitating not only lung rest until recovery but also the definitive diagnosis and treatment of ILD. KS-ILD can develop acutely with fulminant respiratory failure, as observed in this case.


Subject(s)
Amino Acyl-tRNA Synthetases , Lung Diseases, Interstitial , Myositis , Respiratory Insufficiency , Humans , Autoantibodies , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/diagnosis , Myositis/diagnosis , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy
13.
Transplantation ; 106(7): 1365-1375, 2022 07 01.
Article in English | MEDLINE | ID: mdl-34966108

ABSTRACT

BACKGROUND: The protective effects of carbon monoxide (CO) against ischemia/reperfusion (IR) injury during organ transplantation have been extensively investigated. Likewise, CO-releasing molecules (CORMs) are known to exert a variety of pharmacological activities via liberation of controlled amounts of CO in organs. Therefore, we hypothesized that intraluminal administration of water-soluble CORM-3 during cold storage of intestinal grafts would provide protective effects against IR injury. METHODS: Orthotopic syngeneic intestinal transplantation was performed in Lewis rats following 6 h of cold preservation in Ringer solution or University of Wisconsin solution. Saline containing CORM-3 (100 µmol/L) or its inactive counterpart (iCORM-3) was intraluminally introduced in the intestinal graft before cold preservation. RESULTS: Histopathological analysis of untreated and iCORM-3-treated grafts revealed a similar erosion and blunting of the intestinal villi. These changes in the mucosa structure were significantly attenuated by intraluminal administration of CORM-3. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h postreperfusion. CORM-3 significantly inhibited upregulation of proinflammatory mRNA levels, ameliorated intestinal morphological changes, and improved graft blood flow and mucosal barrier function. Additionally, CORM-3-treated grafts increased recipient survival rates. Pharmacological blockade of soluble guanylyl cyclase activity significantly reversed the protective effects conferred by CORM-3, indicating that CO partially mediates its therapeutic actions via soluble guanylyl cyclase activation. CONCLUSIONS: Our study demonstrates that luminally delivered CORM-3 provides beneficial effects in cold-stored rat small intestinal grafts and could be an attractive therapeutic application of CO in the clinical setting of organ preservation and transplantation.


Subject(s)
Organometallic Compounds , Reperfusion Injury , Adenosine , Allopurinol , Animals , Carbon Monoxide/pharmacology , Glutathione , Humans , Insulin , Ischemia , Organ Preservation Solutions , Organometallic Compounds/pharmacology , Raffinose , Rats , Rats, Inbred Lew , Reperfusion Injury/etiology , Soluble Guanylyl Cyclase/therapeutic use , Water
14.
Surgery ; 172(5): 1522-1528, 2022 11.
Article in English | MEDLINE | ID: mdl-36088170

ABSTRACT

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 ischemia-reperfusion 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 µM) 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 = .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.


Subject(s)
Biliverdine , Reperfusion Injury , Animals , Biliverdine/metabolism , Chemokines/metabolism , Claudin-1/metabolism , Interleukin-6/metabolism , Nitric Oxide Synthase Type II/metabolism , Rats , Rats, Inbred Lew , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Reperfusion Injury/prevention & control
15.
Respir Med Case Rep ; 31: 101224, 2020.
Article in English | MEDLINE | ID: mdl-32995263

ABSTRACT

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.

16.
Acute Med Surg ; 7(1): e501, 2020.
Article in English | MEDLINE | ID: mdl-32431842

ABSTRACT

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.

17.
ASAIO J ; 66(2): 214-225, 2020 02.
Article in English | MEDLINE | ID: mdl-30946060

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy for severe respiratory and circulatory failure. It is best performed in high-volume centers to optimize resource utilization and outcomes. Regionalization of ECMO might require the implementation of therapy before and during transfer to the high-volume center. The aim of this international survey was to describe the manner in which interhospital ECMO transport care is organized at experienced centers. Fifteen mobile ECMO centers from nine countries participated in this survey. Seven (47%) of them operated under the "Hub-and-Spoke" model. Transport team composition varies from three to nine members, with at least one ECMO specialist (i.e., nurse or perfusionist) participating in all centers, although intensivists and surgeons were present in 69% and 50% of the teams, respectively. All centers responded that the final decision to initiate ECMO is multidisciplinary and made bedside at the referring hospital. Most centers (75%) have a quality control system; all teams practice simulation and water drills. Considering the variability in ECMO transport teams among experienced centers, continuous education, training and quality control within each organization itself are necessary to avoid adverse events and maintain a low mortality rate. A specific international ECMO Transport platform to share data, benchmark outcomes, promote standardization, and provide quality control is required.


Subject(s)
Cardiology/methods , Cardiology/organization & administration , Extracorporeal Membrane Oxygenation , Patient Transfer/methods , Patient Transfer/organization & administration , Surveys and Questionnaires , Humans
18.
Respir Med Case Rep ; 26: 87-90, 2019.
Article in English | MEDLINE | ID: mdl-30560050

ABSTRACT

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.

19.
Medicine (Baltimore) ; 98(16): e15187, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31008940

ABSTRACT

RATIONALE: Eclampsia, an obstetric emergency frequently seen in pregnant or puerperal women, is a risk factor for posterior reversible encephalopathy syndrome (PRES). Most cases of eclampsia occur postpartum. We report a woman with PRES associated with eclampsia 10 weeks post-delivery, the latest onset ever reported. PATIENT CONCERNS: A 23-year-old healthy woman presented headache and nausea 10 weeks after delivery. Two days later, she generalized tonic-clonic seizure. Her brain MRI presented the foci which is typical of PRES. DIAGNOSIS: The patient was diagnosed as PRES associated with eclampsia. INTERVENTIONS: The patient received levetiracetam and edaravone. OUTCOMES: Her clinical course was uneventful and she fully recovered without neurological complications LESSONS:: The possible diagnosis of late onset postpartum eclampsia, even weeks post-delivery, should be considered, since initiation of early treatment averts severe complications and decreases mortality. Sharing our experience may increase awareness of PRES induced by late-onset postpartum eclampsia.


Subject(s)
Eclampsia , Posterior Leukoencephalopathy Syndrome/etiology , Puerperal Disorders/etiology , Female , Humans , Pregnancy , Young Adult
20.
J Med Case Rep ; 13(1): 361, 2019 Dec 10.
Article in English | MEDLINE | ID: mdl-31818327

ABSTRACT

INTRODUCTION: Abdominal pseudocysts comprising cerebrospinal fluid are an uncommon but significant complication in patients with ventriculoperitoneal shunt. We present a successfully treated 12-year-old boy with a history of ventriculoperitoneal shunting and a huge abdominal cerebrospinal fluid pseudocyst. CASE PRESENTATION: A12-year-old Japanese boy presented with a deteriorated consciousness and a palpable and elastic large lower abdominal mass. Computed tomography of his abdomen demonstrated a collection of homogenous low-density fluid near the catheter tip of the ventriculoperitoneal shunt. Cerebral computed tomography revealed an increased ventricular size. Based on the clinical diagnosis of abdominal pseudocyst, the peritoneal shunt catheter was secured and divided into two parts by cutting it on the chest; then, the proximal side of the peritoneal shunt catheter was externalized for extraventricular drainage. The cyst was percutaneously aspirated with ultrasound guidance, and the distal side of the peritoneal shunt catheter was removed. The distal side of the peritoneal shunt catheter was reinserted in another position into his abdomen after 3-week extraventricular drainage management. CONCLUSION: Emergency physicians should know about this potential complication as an important differential diagnosis resulting from acute abdominal complaints in patients with ventriculoperitoneal shunts.


Subject(s)
Abdomen/diagnostic imaging , Abdomen/physiopathology , Cysts/cerebrospinal fluid , Cysts/surgery , Ventriculoperitoneal Shunt/adverse effects , Child , Drainage , Humans , Japan , Male , Treatment Outcome
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