Organ-Specific Mitochondrial Alterations Following Ischemia-Reperfusion Injury in Post-Cardiac Arrest Syndrome: A Comprehensive Review.

BACKGROUND: Mitochondrial dysfunction, which is triggered by systemic ischemia-reperfusion (IR) injury and affects various organs, is a key factor in the development of post-cardiac arrest syndrome (PCAS). Current research on PCAS primarily addresses generalized mitochondrial responses, resulting in a knowledge gap regarding organ-specific mitochondrial dynamics. This review focuses on the organ-specific mitochondrial responses to IR injury, particularly examining the brain, heart, and kidneys, to highlight potential therapeutic strategies targeting mitochondrial dysfunction to enhance outcomes post-IR injury. METHODS AND RESULTS: We conducted a narrative review examining recent advancements in mitochondrial research related to IR injury. Mitochondrial responses to IR injury exhibit considerable variation across different organ systems, influenced by unique mitochondrial structures, bioenergetics, and antioxidative capacities. Each organ demonstrates distinct mitochondrial behaviors that have evolved to fulfill specific metabolic and functional needs. For example, cerebral mitochondria display dynamic responses that can be both protective and detrimental to neuronal activity and function during ischemic events. Cardiac mitochondria show vulnerability to IR-induced oxidative stress, while renal mitochondria exhibit a unique pattern of fission and fusion, closely linked to their susceptibility to acute kidney injury. This organ-specific heterogeneity in mitochondrial responses requires the development of tailored interventions. Progress in mitochondrial medicine, especially in the realms of genomics and metabolomics, is paving the way for innovative strategies to combat mitochondrial dysfunction. Emerging techniques such as mitochondrial transplantation hold the potential to revolutionize the management of IR injury in resuscitation science. CONCLUSIONS: The investigation into organ-specific mitochondrial responses to IR injury is pivotal in the realm of resuscitation research, particularly within the context of PCAS. This nuanced understanding holds the promise of revolutionizing PCAS management, addressing the unique mitochondrial dysfunctions observed in critical organs affected by IR injury.

Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914).

Delayed stomach necrosis in a patient with injured celiac artery branches after penetrating abdominal trauma.

Injuries of the celiac artery and its branches are rare, but potentially lethal. Ligation of these arteries is performed to control significant hemorrhage. However, few reports have described the adverse effects of ligating these arteries. A 69-year-old woman with a self-inflicted stab wound was brought to our hospital. Her blood pressure could not be measured, therefore aortic cross-clamping was performed, and epinephrine was administered for resuscitation, an emergency laparotomy was performed, and the roots of splenic artery and common hepatic artery were ligated. The left gastric artery which was anomalous and arose directly from the aorta, was also injured and had to be ligated. Norepinephrine was required after the surgery. Enhanced computed tomography performed on hospital day 4 revealed a disrupted celiac artery. The patient developed gastric necrosis on hospital day 23 and, hence, underwent total gastrectomy was performed. The possibility of delayed stomach necrosis should be considered during the postoperative management of patients who undergo ligation of all of the celiac artery branches and experience global hypoperfusion after the surgery.

Petal formation law in a cellophane diaphragm subjected to a pressure difference.

In this study, a layer of cellophane, subjected to an air-pressure difference, was ruptured using a piercing needle. Accordingly, petal-like fragmentation was observed in the layer via high-speed imaging. Two types of crack-propagation regimes were subsequently observed experimentally. If a tensile stress lower than 20.6 MPa acted on the cellophane diaphragm, a single crack was generated, whose propagation speed was lower than that under higher-stress conditions. For tensile stresses greater than 23.7 MPa, the crack-propagation speed remained constant at approximately 0.86 km/s, even after altering the device size, pressure, and humidity on the low-pressure side. The number of cracks equidistant from the piercing point was expressed as a linear function of the tensile stress acting on the diaphragm.

Intravenous Immunoglobulin Attenuates Cecum Ligation and Puncture-Induced Acute Lung Injury by Inhibiting Apoptosis of Alveolar Epithelial Cells.

PURPOSE: Intravenous immunoglobulin (IVIG) therapy has been used to treat sepsis, but its mechanisms of action remain unclear. Sepsis causes multiple organ failure, such as acute lung injury (ALI), which involves apoptosis of alveolar epithelial cells. In this study, we hypothesized that IVIG suppresses apoptosis in alveolar epithelial cells and evaluated mortality, cytokine levels, histological changes in the lung, and alveolar epithelial cell apoptosis after IVIG administration, in mice with experimentally induced sepsis. METHODS: Mice received an injection of vehicle (saline) or immunoglobulin (100 mg/kg or 400 mg/kg) into the tail vein, after which they underwent cecal ligation and puncture. A sham-operated group was used as the normal control. Survival was assessed in all groups after 72 hours. Plasma levels of TNF-α and IL-6, histopathological changes and wet-to-dry ratio in lung, and alveolar epithelial cell apoptosis were evaluated in all groups at 4 hours after surgery. RESULTS: In the vehicle group, histopathological injury of the lung was severe, and apoptosis of alveolar epithelial cells was significant. Survival and plasma cytokine levels were better in the IVIG treatment groups than in the vehicle group. IVIG 400 mg/kg suppressed apoptosis of alveolar epithelial cells and reduced ALI. CONCLUSION: IVIG suppressed inflammatory cytokine levels and improved survival. Lung histopathology and alveolar epithelial cell apoptosis were improved by IVIG treatment, in a dose-dependent manner. Suppressing apoptosis in alveolar epithelial cells appears to be a mechanism by which IVIG improves survival.

Fatal fulminant Clostridioides difficile colitis caused by Helicobacter pylori eradication therapy; a case report.

A 74-year-old male was referred to our critical care department for refractory severe watery diarrhea with advanced leukocytosis (over 70,000/µl) after multiple administrations of eradication therapy against Helicobacter pylori (HP). He was diagnosed as having fulminant colitis due to Clostridioides difficile after antimicrobial eradication therapy. He was given intravenous metronidazole and oral vancomycin. He also received supportive therapy including continuous hemodiafiltration for severe metabolic acidosis. However, despite emergency open sigmoidectomy, he died. The C. difficile isolate recovered was PCR-ribotype 002, which was positive for toxins A and B but negative for binary toxin. HP eradication therapy for prevention of chronic gastritis and stomach cancer is now in widespread use. Although such secondary severe complications are rare, we consider it to be necessary to pay sufficient attention when administering HP eradication therapy.

Delayed development of portal vein thrombosis in a patient initially detected with portal venous gas and pneumatosis intestinalis: a case report.

BACKGROUND: Portal venous gas (PVG) and pneumatosis intestinalis (PI) are rare pathologic findings, and a delayed appearance of portal vein thrombosis (PVT) in such patients is extremely rare. CASE PRESENTATION: A 51-year-old man complaining of epigastric pain was referred to our hospital. Computed tomography (CT) at admission revealed massive PVG and extensive PI, but no PVT. Emergency laparotomy was carried out, but bowel resection was unnecessary. On follow-up CT on postoperative day 5, thrombosis was noted in the portal venous system, and anticoagulant was started immediately. This patient was discharged and continued to take the anticoagulant. Seven months after discharge, PVT had disappeared on CT without any thromboembolic complications. CONCLUSION: If acute PVT is detected, anticoagulant is needed to prevent bowel ischemia and/or portal hypertension due to the growth of the thrombus. Clinicians should be aware of the potential for such a complication, and make their best efforts to exclude this entity using CT or sonography.

Overview of doctor-staffed ambulance use in Japan: a nationwide survey and 1-week study.

AIM: In Japan, standard prehospital care is provided by emergency medical services teams. Doctor-staffed ambulances play a role in facilitating the immediate treatment of critically ill patients to increase the survival rates. However, little is known about their activities. We revealed the present situation of doctor-staffed ambulances in Japan. METHODS: First, we surveyed all the fire departments in Japan and determined whether a doctor-staffed ambulance was present within their district boundary. Second, we surveyed hospitals that operate doctor-staffed ambulances in their system to list their activities during a 1-week period. RESULTS: Of 133 hospitals that operated a doctor-staffed ambulance, 73 (55%) replied to our questionnaire. Only 26 (36%) of them provided 24-h ambulance deployment. Additionally, 51 (70%) of hospitals bore the operational costs of ambulances. Within 1 week, 345 doctor-staffed ambulances were dispatched, but 97 (28%) were cancelled. In total, 62 patients (28%) were diagnosed with cardiac arrest, 48 (19%) with trauma or burns, 36 (15%) with stroke, and 22 (9%) with acute coronary syndrome; 159 (58%) were transferred to a tertiary emergency medical center. CONCLUSIONS: Doctor-staffed ambulances have the advantage of deployment at night and in urban areas compared to doctor-staffed helicopters. Among the 73 hospitals that responded to the questionnaire, doctor-staffed ambulances were dispatched almost as frequently as doctor-staffed helicopters. However, doctor-staffed ambulances did not receive adequate funding. Future data collection is necessary to determine the efficacy of doctor-staffed ambulances among hospitals that operate this service.

Quantitative pupillometry and neuron-specific enolase independently predict return of spontaneous circulation following cardiogenic out-of-hospital cardiac arrest: a prospective pilot study.

This study aimed to identify neurological and pathophysiological factors that predicted return of spontaneous circulation (ROSC) among patients with out-of-hospital cardiac arrest (OHCA). This prospective 1-year observational study evaluated patients with cardiogenic OHCA who were admitted to a tertiary medical center, Nippon Medical School Hospital. Physiological and neurological examinations were performed at admission for quantitative infrared pupillometry (measured with NPi-200, NeurOptics, CA, USA), arterial blood gas, and blood chemistry. Simultaneous blood samples were also collected to determine levels of neuron-specific enolase (NSE), S-100b, phosphorylated neurofilament heavy subunit, and interleukin-6. In-hospital standard advanced cardiac life support was performed for 30 minutes.The ROSC (n = 26) and non-ROSC (n = 26) groups were compared, which a revealed significantly higher pupillary light reflex ratio, which was defined as the percent change between maximum pupil diameter before light stimuli and minimum pupil diameter after light stimuli, in the ROSC group (median: 1.3% [interquartile range (IQR): 0.0-2.0%] vs. non-ROSC: (median: 0%), (Cut-off: 0.63%). Furthermore, NSE provided the great sensitivity and specificity for predicting ROSC, with an area under the receiver operating characteristic curve of 0.86, which was created by plotting sensitivity and 1-specificity. Multivariable logistic regression analyses revealed that the independent predictors of ROSC were maximum pupillary diameter (odds ratio: 0.25, 95% confidence interval: 0.07-0.94, P = 0.04) and NSE at admission (odds ratio: 0.96, 95% confidence interval: 0.93-0.99, P = 0.04). Pupillary diameter was also significantly correlated with NSE concentrations (r = 0.31, P = 0.027). Conclusively, the strongest predictors of ROSC among patients with OHCA were accurate pupillary diameter and a neuronal biomarker, NSE. Quantitative pupillometry may help guide the decision to terminate resuscitation in emergency departments using a neuropathological rationale. Further large-scale studies are needed.

The long-term outcomes of early abdominal wall reconstruction by bilateral anterior rectus abdominis sheath turnover flap method in critically ill patients requiring open abdomen.

Background: In a previous study, we reported the usefulness of early abdominal wall reconstruction using bilateral anterior rectus abdominis sheath turnover flap method (turnover flap method) in open abdomen (OA) patients in whom early primary fascial closure was difficult to achieve. However, the long-term outcomes have not been elucidated. In the present study, we aimed to evaluate the procedure, particularly in terms of ventral hernia, pain, and daily activities. Methods: Between 2001 and 2013, 15 consecutive patients requiring OA after emergency laparotomy and in whom turnover flap method was applied were retrospectively identified. The long-term outcomes were evaluated based on medical records, physical examinations, CT imaging, and a ventral hernia pain questionnaire (VHPQ). Results: The turnover flap method was applied in 2 trauma and 13 non-trauma patients.In most of cases, primary fascial closure could not be achieved due to massive visceral edema. The turnover flap method was performed for abdominal wall reconstruction at the end of OA. The median duration of OA was 6 (range 1-42) days. One of the 15 patients died of multiple organ failure during initial hospitalization after the performance of the turnover flap method. Fourteen patients survived, and although wound infection was observed in 3 patients, none showed enteric fistula, abdominal abscess, graft infection, or ventral hernia during hospitalization. However, it was found that 1 patient developed ventral hernia during follow-up at an outpatient visit. Nine of 14 patients were alive and able to be evaluated with a VHPQ (follow-up period: median 10 years; range 3-15 years). Seven out of nine patients were satisfied with this procedure, and none complained of pain or were limited in their daily activities. Conclusions: Based on the results of this study, early abdominal reconstruction using the turnover flap method can be considered to be safe and effective as an alternative technique for OA patients in whom primary fascial closure is considered difficult to achieve.

Kodamaea ohmeri fungemia in severe burn: Case study and literature review.

Kodamaea ohmeri is a relatively rare yeast isolated form clinical specimens, and it is known to be a causative fungus of severe invasive infectious diseases in immunocompromised hosts. Herein, we describe fungemia due to K. ohmeri in a patient with a severe extended burn. The isolate was obtained from not only blood specimens but also skin lesions. We should be aware of risk for fungemia including K. ohmeri in case of severe burn.

Successful abdominal wound closure for treatment of severe peritonitis using negative pressure wound therapy with continuous mesh fascial traction: a case report.

BACKGROUND: Surgery for severe peritonitis often entails difficult wound closure and may require open abdominal management due to gut edema and/or concern of abdominal compartment syndrome. Negative pressure wound therapy (NPWT) is known to have good outcomes for wound closure after surgery for severe peritonitis. NPWT with continuous mesh fascial traction may result in even better outcomes, especially for fascial closure. CASE PRESENTATION: An 81-year-old man was hospitalized for abdominal pain. At admission, computed tomography (CT) demonstrated multiple liver metastases and a tumor perforating the sigmoid colon. Acute peritonitis due to perforated sigmoid colon cancer was diagnosed, and emergency peritonitis surgery and Hartmann's operation were performed. However, at the end of the operation, the surgical abdominal wound could not be closed due to gut edema and concern of abdominal compartment syndrome. Thus, the abdominal wound was left open and NPWT was performed in the primary operation. In the second and subsequent operations, NPWT with mesh fascial traction was performed. The wound was ultimately closed in the fifth operation, which took place 9 days after the primary operation. CONCLUSIONS: Treatment of severe peritonitis requires that gastroenterological surgeons learn some form of open abdominal management. This case suggests that NPWT with fascial mesh traction is a suitable solution. Furthermore, it does not require any special materials, and surgeons will find it easy to perform. In sum, NPWT with fascial mesh traction may be the preferred method of open abdominal management over other techniques currently available.

Long-term outcomes of patients evacuated from hospitals near the Fukushima Daiichi nuclear power plant after the Great East Japan Earthquake.

INTRODUCTION: After the accident of the Fukushima Daiichi nuclear power plant due to the Great East Japan Earthquake in March 2011, the Japanese government issued a mandatory evacuation order for people living within a 20 km radius of the nuclear power plant. The aim of the current study was to investigate long-term outcomes of these patients and identify factors related to mortality. MATERIALS AND METHODS: Patients who were evacuated from hospitals near the Fukushima Daiichi nuclear power plant to the Aizu Chuo Hospital from 15 to 26 March, 2011 were included in this study. The following data were collected from medical records: age, sex, activities of daily life, hospital they were admitted in at the time of earthquake, distance between the facility and the nuclear power plant, reasons of evacuation and number of transfers. The patient outcomes were collected from medical records and/or investigated on the telephone in January 2012. RESULTS: A total of 97 patients (28 men and 69 women) were transferred from 10 hospitals via ambulances or buses. No patients died or experienced exacerbation during transfer. Median age of the patients was 86 years. Of the total, 36 patients were not able to obey commands, 44 were bed-ridden and 61 were unable to sustain themselves via oral intake of food. Among 86 patients who were followed-up, 41 (48%) died at the end of 2011. Multiple-regression analysis showed that non-oral intake [Hazard Ratio (HR): 6.07, 95% Confidence interval (CI): 1.94-19.0] and male sex [HR: 8.35, 95% CI: 2.14-32.5] had significant impact on mortality. CONCLUSION: This study found that 48% of the evacuated patients died 9 months after the earthquake and they had significantly higher mortality rate than the nursing home residents. Non-oral intake and male sex had significant impact on mortality. These patients should be considered as especially vulnerable in case of hospital evacuation.

A novel technique for managing open abdomen with the combined use of mesh-mediated traction and the bilateral anterior rectus abdominis sheath turnover flap method: how to do it.

Proper management of abdominal compartment syndrome and open abdomen is important for improving the survival of critically ill patients. However, in cases requiring a prolonged period of open abdomen, it is frequently difficult to perform definitive fascial closure due to lateralization of the abdominal musculature. We herein present a novel combined technique for managing open abdomen. A 74-year-old male with diffuse peritonitis was transferred to our department, after which a long period of open abdomen made it difficult to achieve fascial closure. Polypropylene mesh was sutured to the fascial edges to reduce the gap, which was then serially tightened under negative pressure wound therapy. However, since it was not possible to accomplish definitive fascial closure, abdominal closure was performed using the bilateral anterior rectus abdominis sheath turnover flap method after removing the mesh, without any complications. This combined technique may be an effective alternative in patients requiring open abdomen with subsequent difficulty in achieving definitive fascial closure.

New information technology tools for a medical command system for mass decontamination.

In a mass decontamination during a nuclear, biological, or chemical (NBC) response, the capability to command, control, and communicate is crucial for the proper flow of casualties at the scene and their subsequent evacuation to definitive medical facilities. Information Technology (IT) tools can be used to strengthen medical control, command, and communication during such a response. Novel IT tools comprise a vehicle-based, remote video camera and communication network systems. During an on-site verification event, an image from a remote video camera system attached to the personal protective garment of a medical responder working in the warm zone was transmitted to the on-site Medical Commander for aid in decision making. Similarly, a communication network system was used for personnel at the following points: (1) the on-site Medical Headquarters; (2) the decontamination hot zone; (3) an on-site coordination office; and (4) a remote medical headquarters of a local government office. A specially equipped, dedicated vehicle was used for the on-site medical headquarters, and facilitated the coordination with other agencies. The use of these IT tools proved effective in assisting with the medical command and control of medical resources and patient transport decisions during a mass-decontamination exercise, but improvements are required to overcome transmission delays and camera direction settings, as well as network limitations in certain areas.

Medical relief activities, medical resourcing, and inpatient evacuation conducted by Nippon Medical School due to the Fukushima Daiichi Nuclear Power Plant accident following the Great East Japan Earthquake 2011.

On March 11, 2011, after the Great East Japan Earthquake and tsunami, the government declared a nuclear emergency following damage to the Fukushima Daiichi Nuclear Power Plant. A second hydrogen explosion occurred on March 14 at the plant's No. 3 reactor and injured 11 people. At that time the prime minister urged people living 20 to 30 km from the Daiichi plant to stay indoors. Under these circumstances, many residents of Iwaki City, which was largely outside the 30-km zone, left the city, making it difficult to get supplies to the remaining residents. The only transportation route open for supplies and medical resources was roads, and many drivers feared the rumor that the city was contaminated by radioactive materials and, so, refused to go there. Nippon Medical School (NMS) heard that medical resources were running short at Iwaki Kyoritsu Hospital, which requested water, medications, food, fuel (gasoline), medical support, and the evacuation of 300 inpatients. As a first step, NMS decided to evaluate the situation at the hospital and, on March 16, the director of the NMS Advanced Emergency Center visited the hospital and helped provide triage for about 200 patients. Critically ill patients receiving ventilatory support were given priority for evacuation because they would be most at risk of not being able to evacuate should the Japanese government order an immediate evacuation of the city. We tried to evacuate the inpatients via an official framework, such as the Disaster Medical Assistance Team (DMAT), but DMAT could not support this mission because this hospital was not within the 30-km evacuation zone. Moreover, the Iwaki City government could not support the evacuation efforts because they were fearful of the rumor that Iwaki was contaminated by radioactive material. Ultimately, we realized that we had to conduct the mission ourselves and, so, contacted our colleagues in the Tokyo metropolitan area to prepare enough hospital beds. We evacuated 15 patients to 8 hospitals over a 5-day period. As a result, we could reduce the number of patients at Iwaki Kyoritsu Hospital, and, thereby, the collapse of medical services in the city was avoided. In retrospect, someone might say the government--either central or local--should ideally have carried out this mission and created a system by which to do it. At the same time, however, to overcome any future bureaucratic issues, we should also prepare private networks, such as those used by NMS, because they can respond flexibly to unexpected large-scale disasters.