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Mammalian type 2 carnitine parmitoyltransferase (EC 2.3.1.21), abbreviated as CPT2, is an enzyme involved in the translocation of fatty acid into the mitochondrial matrix space, and catalyzes the reaction acylcarnitine + CoA = acyl-CoA + carnitine. When rat CPT2 was expressed in Escherichia coli, its behavior was dependent on the presence or absence of i) its mitochondrial localization sequence and ii) a short amino acid sequence thought to anchor it to the mitochondrial inner membrane: CPT2 containing both sequences behaved as a hydrophobic protein, while recombinant CPT2 lacking both regions behaved as a water soluble protein; if only one region was present, the resultant proteins were observed in both fractions. Because relatively few protein species could be obtained from bacterial lysates as insoluble pellets under the experimental conditions used, selective enrichment of recombinant CPT2 protein containing both hydrophobic sequences was easily achieved. Furthermore, when CPT2 enriched in insoluble fraction was resuspended in an appropriate medium, it showed catalytic activity typical of CPT2: it was completely suppressed by the CPT2 inhibitor, ST1326, but not by the CPT1 inhibitor, malonyl-CoA. Therefore, we conclude that the bacterial expression system is an effective tool for characterization studies of mammalian CPT2.

Background: Acrylamide poisoning is often reported as chronic poisoning presenting with peripheral neuropathy or carcinogenic action due to long-term exposure to low concentrations. However, there have been few reports of acute poisoning due to oral ingestion of acrylamide, where the symptoms appear a few hours after ingestion. Here, we report a case of acute acrylamide poisoning where a high concentration was ingested in a short time, resulting in a fatal outcome due to the rapid course of events., Case Presentation: The patient was an adolescent female who ingested 150 ml (148 g) of acrylamide with suicidal intent. A disorder of consciousness was observed when the emergency medical team arrived 36 min later. An hour later, tracheal intubation and intravenous access were performed at a hospital, and 2 h after that, she was transported to our hospital. After she arrived at the hospital, circulatory dynamics could not be maintained despite vasopressor and colloid osmotic infusion, and hemodialysis could not be introduced. Subsequently, cardiopulmonary arrest occurred, and the patient passed away 7 h after ingestion. In the present case, severe symptoms appeared shortly after acrylamide ingestion, unlike other reported cases. In previous report summarizing animal studies, there was a relationship among the symptoms of acute poisoning, the dose, and onset time. The data from this case were compared to those from previous reports, and we were able to predict the early appearance of severe symptoms based on this comparison., Conclusion: The severity of acute acrylamide poisoning by oral ingestion was primarily dependent on the amount and rate of ingestion., (© 2023. The Author(s).)

Background: The primary purpose of this study was to investigate risk factors associated with the need for mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) in COVID-19 patients admitted to the intensive care unit (ICU)., Methods: We retrospectively enrolled 66 consecutive COVID-19 patients admitted to the ICUs of three Japanese institutions from February 2020 to January 2021. We performed logistic regression analyses to identify risk factors associated with subsequent MV and ECMO requirements. Further, multivariate analyses were performed following adjustment for Acute Physiology and Chronic Health Evaluation (APACHE) II scores., Results: At ICU admission, the risk factors for subsequent MV identified were: higher age (Odds Ratio (OR) 1.04, 95% Confidence Interval (CI) 1.00-1.08, P = 0.03), higher values of APACHE II score (OR 1.20, 95% CI 1.08-1.33, P < 0.001), Sequential Organ Failure Assessment score (OR 1.53, 95% CI 1.18-1.97, P < 0.001), lactate dehydrogenase (LDH) (OR 1.01, 95% CI 1.00-1.02, p<0.001) and C-reactive protein (OR 1.09, 95% CI 1.00-1.19, P = 0.04), and lower values of lymphocytes (OR 1.00, 95% CI 1.00-1.00, P = 0.02) and antithrombin (OR 0.95, 95% CI 0.91-0.95, P < 0.01). Patients who subsequently required ECMO showed lower values of estimated glomerular filtration rate (OR 0.98, 95% CI 0.96-1.00, P = 0.04) and antithrombin (OR 0.94, 95% CI 0.88-1.00, P = 0.03) at ICU admission. Multivariate analysis showed that higher body mass index (OR 1.19, 95% CI 1.00-1.40, P = 0.04) and higher levels of LDH (OR 1.01, 95% CI 1.01-1.02, P < 0.01) were independent risk factors for the need for MV. Lower level of antithrombin (OR 0.94, 95% CI 0.88-1.00, P = 0.03) was a risk factor for the need for ECMO., Conclusion: We showed that low antithrombin level at ICU admission might be a risk factor for subsequent ECMO requirements, in addition to other previously reported factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Takada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Sepsis is not only the leading cause of death in the intensive care unit (ICU) but also a major risk factor for physical and cognitive impairment and mental disorders, known as postintensive care syndrome (PICS), reduced health-related quality of life (HRQoL) and even mental health disorders in patient families (PICS-family; PICS-F). The ABCDEF bundle is strongly recommended to overcome them, while the association between implementing the bundle and the long-term outcomes is also unknown., Methods and Analysis: This is a multicentre prospective observational study at 26 ICUs. All consecutive patients between 1 November 2020 and 30 April 2022, who are 18 years old or older and expected to stay in an ICU for more than 48 hours due to sepsis or septic shock, are enrolled. Follow-up to evaluate survival and PICS/ PICS-F will be performed at 3, 6 and 12 months and additionally every 6 months up to 5 years after hospital discharge. Primary outcomes include survival at 12 months, which is the primary outcome, and the incidence of PICS defined as the presence of any physical impairment, cognitive impairment or mental disorders. PICS assessment scores, HRQoL and employment status are evaluated. The association between the implementation rate for the ABCDEF bundle and for each of the individual elements and long-term outcomes will be evaluated. The PICS-F, defined as the presence of mental disorders, and HRQoL of the family is also assessed. Additional analyses with data up to 5 years follow-up are planned., Ethics and Dissemination: This study received ethics approvals from Saiseikai Utsunomiya Hospital (2020-42) and all other participating institutions and was registered in the University Hospital Medical Information Network Clinical Trials Registry. Informed consent will be obtained from all patients. The findings will be published in peer-reviewed journals and presented at scientific conferences., Trial Registration Number: UMIN000041433., Competing Interests: Competing interests: The authors declare that they have no competing interests for the submitted work. Some authors report potential conflicts of interest outside of this submitted study. KL reports personal fees from MERA and is the core research member of TXP Medical completely outside the submitted work. KN reports personal fees from Abbott Laboratory, Nestle, TERUMO, GETINGE, Asahi Kasei Pharma, Ono Pharmaceutical, Japan Blood Products Organisation, Nihon Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Toray and Baxter, and grants from Asahi Kasei Pharma outside the submitted work. HK receives a salary from the Japanese Society for Early Mobilisation (non-profit society) as a chair (full time) outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine whether antithrombotic therapy with warfarin is effective and safe in patients who developed venous thromboembolism in the acute stage of polytrauma, which is associated with bleeding risk., Method: A retrospective study of 11 patients (8 males, 3 females; mean age, 39.8 years; injury severity score, 30.1; no fatalities) with deep venous thromboembolism and/or pulmonary embolism who were medicated with heparin and warfarin during their iCU stay., Results: Thrombosis was diagnosed at an average of 11.8 days after admission. Thrombus formation was confirmed in pulmonary arteries in 5 cases and in deep veins in 9 cases. Diagnosis was based on Doppler ultrasound findings in 6 cases and on computed tomography findings in 5 cases. anticoagulant therapy was used in 10 cases, but not in 1 case with cerebral contusion. approximately 33 days after starting anticoagulant therapy, thrombi had disappeared or were reduced in size in 9 of 10 patients with no complications observed., Conclusions: Heparin and warfarin therapy cleared deep vein and pulmonary artery thrombosis after polytrauma without any bleeding complications. Further studies are necessary to determine the safe anticoagulant dosage and duration for rapid thrombus removal.

In Japan, there has recently been a severe shortage of physicians in regional core hospitals, limiting the acceptance of emergency patients. Searching for available medical institutions over an extended area beyond the regular regional medical area should increase the possibility of finding medical institutions capable of accepting patients. Physician staffed helicopter ambulance system, so called the Doctor-Helicopter service is highly effective in saving patients life, since emergency doctors start to treat patients at the scene. It may be also useful to transport the critically ill patients for a long distance. A 29 year old female diagnosed twin fetus with twin-twin transfusion syndrome needs urgent delivery at about 29 weeks of gestation. The patients had to be transported to the perinatal care center which is 160 km from the hospital to where the patient was admitted because of a lack of NICU. During transportation, the maternal vital signs were stable without cervical dilatation. After arrived at the perinatal center, the patient underwent Caesarian section. Both babies had respiratory distress syndrome and admitted to NICU. With increasing cases in which medical institutions cannot accept peripartum emergency patients, it needs to search for medical institutions over an extended area and transport patients by Doctor-Helicopter.

Background: The lifesavers responsible for lifesaving at the waterside routinely undergo cardiopulmonary resuscitation (CPR) training, but in Japan, they are considered as lay persons. Lifesavers are likely to have better basic life support skills than lay persons. The objective of this study is to demonstrate that the accuracy of carotid pulse checks by lifesavers is not inferior to that of paramedics and is superior to that of lay persons by using CPR training mannequins., Methods and Results: This was an observational study in which the subjects included 48 lifesavers certified by the Japan Lifesaving Association, as well as 16 paramedics and 15 lay persons. The accuracy of the examinees' answers and the time taken to answer in the 3 groups were compared. The accuracy rate was 93% in lifesavers, 94% in paramedics, and the difference was not significant (P=1). The accuracy rate of the lay persons' answers was 63%, with significant differences between this group and the lifesavers (P<0.001) and the paramedics (P<0.001). The average time taken to answer the questions was 6.6 s for the lifesavers and 7.0 s for the paramedics, and the difference was not significant (P=0.44). The average time taken to answer the questions from the lay persons group was 20.5 s, with significant differences between this group and the lifesavers (P<0.001) and the paramedics (P<0.001)., Conclusions: The results of this evaluation, using CPR-training mannequins, to test the accuracy of carotid pulse checks by lifesavers were equivalent to those of paramedics and superior to those of lay persons.

Inhibition of NOS is not beneficial in septic shock; selective inhibition of the inducible form (iNOS) may represent a better option. We compared the effects of the selective iNOS inhibitor BYK191023 with those of norepinephrine (NE) in a sheep model of septic shock. Twenty-four anesthetized, mechanically ventilated ewes received 1.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. Animals were randomized into three groups (each n = 8): NE-only, BYK-only, and NE + BYK. The sublingual microcirculation was evaluated with sidestream dark-field videomicroscopy. MAP was higher in the NE + BYK group than in the other groups, but there were no significant differences in cardiac index or systemic vascular resistance. Mean pulmonary arterial pressure was lower in BYK-treated animals than in the NE-only group. PaO2/FiO2 was higher and lactate concentration lower in the BYK groups than in the NE-only group. Mesenteric blood flow was higher in BYK groups than in the NE-only group. Renal blood flow was higher in the NE + BYK group than in the other groups. Functional capillary density and proportion of perfused vessels were higher in the BYK groups than in the NE-only group 18 h after induction of peritonitis. Survival times were similar in the three groups. In this model of peritonitis, selective iNOS inhibition had more beneficial effects than NE on pulmonary artery pressures, gas exchange, mesenteric blood flow, microcirculation, and lactate concentration. Combination of this selective iNOS inhibitor with NE allowed a higher arterial pressure and renal blood flow to be maintained.

Background: In Japan, intravenous nifekalant (NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for resuscitation., Methods and Results: Between August 2007 and April 2009, 403 consecutive out-of-hospital patients with cardiopulmonary arrest were transferred to the Emergency Medical Service of Tokai University. Of these, 30 patients with first defibrillation failure or VF recurrence were enrolled for this NIF/AMD study. The final defibrillation success (and hospital survival rate) was 67% (10/15) in the AMD and 47% (7/15) in the NIF group. The discharge survival rate was 53% (8/15) in the AMD and 21% (4/15) in the NIF group (P = 0.06). Notably, all 4 survivors in the NIF group could take up normal daily life again, whereas this was restricted to only 2 patients from the 11 survivors in the AMD group. The difference is probably partly attributable to longer time from AMD administration to defibrillation success compared with NIF. In the cases of defibrillation failure, VF continued in 4/8 by NIF, however, asystole or pulseless electrical activity occurred in 4/5 patients by AMD., Conclusions: AMD may be borderline superior over NIF to facilitate defibrillation in out-of-hospital patients with cardiopulmonary arrest. However, from the view point of preservation of brain function, NIF is not inferior to AMD for CPR.

Objective: Accidental deep hypothermia (ADH)--a condition in which the core body temperature is less than 28 degrees C--is a medical emergency; the mortality rates for ADH remain high. The efficacy of cardiopulmonary bypass (CPB) rewarming has been proved in ADH patients with cardiopulmonary arrest; however, its efficacy in the ADH patients without cardiopulmonary arrest remains controversial. In our study, we evaluated the efficacy of portable percutaneous cardiopulmonary bypass (PPCPB) for rewarming and providing cardiovascular support in the hemodynamically unstable ADH patients without cardiopulmonary arrest., Methods: Between April 2001 and March 2006, we performed a retrospective study at Tokai University, Kanagawa, Japan. We studied 24 ADH patients without cardiopulmonary arrest (male:female ratio, 15:9; mean age, 68.5 +/- 12.9 years) with hemodynamic instability who had not developed intracranial hemorrhage. We evaluated the efficacy of PPCPB rewarming by estimating the mean time of initiation of PPCPB after admission, rewarming speed, the success rate of rewarming, the rate of weaning from PPCPB, the incidence of ventricular fibrillation (Vf) during rewarming, complications associated with PPCPB, mortality rate, and the Glasgow Outcome Scale (GOS) scores of the patients who survived., Results: The mean time of initiation of PPCPB after admission was 41.9 +/- 7.9 minutes. The rewarming speed was 4.0 +/- 1.5 degrees C/h. A 100% success rate was achieved after the rewarming procedure, whereas the rate of weaning from PPCPB was 91.7%. Vf during rewarming developed in one case; however, electrical defibrillation was possible. No direct complications of PPCPB were observed. The mortality rate was 12.5% (3/24). The GOS scores of the patients who survived were as follows: 5 points, 17 cases; 4 points, 3 cases; and 3 points, 1 case., Conclusion: PPCPB rewarming is a clinically efficacious procedure for rewarming and providing cardiovascular support in hemodynamically unstable ADH patients without cardiopulmonary arrest who have not developed intracranial hemorrhage.

Inflammatory pseudotumor (IPT) is a benign tumorous lesion of unknown cause, which is composed of fibrous tissue with infiltration of plasma cells and lymphocytes. A 57-year-old male with gastritis was indicated to have hepatic dysfunction during observation of the course of gastritis at a nearby hospital. He was referred to our facility to undergo detailed examinations. When he visited our hospital for the initial examination, he had no subjective symptoms. His past medical history was unremarkable. There were no distinct abnormalities on the medical examination. Blood tests revealed a white blood cell count of 10400 / L, CRP of 0.29 mg/dl, AST of 31 IU/L, ALT of 46 IU/L, ALP of 583 IU/L and -GTP of 408 IU/L, showing a mild inflammatory reaction and elevated hepatobiliary enzymes. Abdominal ultrasonographic examination revealed a tumor mass approximately 4 cm in diameter in a lateral hepatic segment. The margin and center of the mass were hypoechoic and iso- to hyperechoic, respectively, and the inside of the mass was non-homogeneous. Needle biopsy revealed only inflammatory findings with no indications of malignancy. Since computed tomography (CT) of the abdomen, done 4 months after detection of the tumor mass, revealed the mass to have increased to approximately 6 cm in diameter, excision biopsy was considered. The CT taken 2 months later revealed the mass to have regressed to approximately 2 cm in diameter, but excision of the lateral hepatic segment was undertaken at the patient's request. As a result, the diagnosis of IPT of the liver was confirmed. Imaging findings of hepatic IPT are variable and specific findings are lacking. Since the rate of correct diagnosis with needle biopsy is also low, IPT of the liver is often very difficult to differentiate from malignant tumors. On the other hand, since it may show spontaneous regression, indications for surgery must be assessed very carefully.

Heat stroke is often complicated by hepatic dysfunction as a manifestation of multiple organ dysfunctions, but acute hepatic failure rarely progresses to become the major morbid condition of heat stroke. We encountered a case who survived life-threatening classic heat stroke; the patient developed this condition, subsequently associated with acute hepatic failure, while bathing at home. A 73-year-old man was found in the bath in his home with unconsciousness, and was transferred to a nearby hospital. At the time he was in a coma, but no remarkable abnormalities were detected on blood examination. Rubor of his entire body beneath the cervical region was recognized. Under the diagnosis of a burn with consciousness disturbance, he was referred and transferred to our hospital. He was comatose and his axillary body temperature was 39.7°C. His consciousness improved after admission, but blood examination revealed rhabdomyolysis, DIC and hepato-renal dysfunction. Subsequent blood examination findings showed rapid exacerbation. On the 2nd hospital day, PT% was 12, INR was 4.8. On the 3rd hospital day, serum ALT was elevated to 3,873 U/L, and the patient had hyperammonemia. On the 13th hospital day, serum total bilirubin was elevated to 33 mg/dl. Thereafter, additional conservative treatment produced gradual recovery of hepatic function.

Objective: We aimed to evaluate prognostic factors and toxicokinetics in acute fenitrothion self-poisoning., Methods: We reviewed 12 patients with fenitrothion self-poisoning admitted to the intensive care unit between 2003 and 2006. We compared the characteristics, initial vital signs, physiological scores, corrected QT interval on electrocardiogram and laboratory data (serum fenitrothion concentration and cholinesterase activity) of non-survivors and survivors. Furthermore, we evaluated the correlation between the prognostic factors and severity of poisoning (lengths of intensive care unit and hospital stays), and the toxicokinetics of the patients., Results: In the 2 non-survivors, the estimated fenitrothion ingestion dose and the serum fenitrothion concentration at the emergency department and at 24 h after ingestion were significantly higher than those in the 10 survivors. (P = 0.008, 0.003, and 0.04, respectively). In the 10 survivors, the serum fenitrothion concentration at 24 h after ingestion was significantly correlated with the lengths of intensive care unit and hospital stays (P = 0.004 and 0.04, respectively); however, the initial vital signs, physiological scores, corrected QT interval on electrocardiogram at the emergency department, and serum cholinesterase activity did not show any correlation. In five patients successfully fitted to a two-compartment model, the distribution and elimination half-lives were 2.5 and 49.8 h, respectively, which is compatible with the slow and prolonged clinical course of fenitrothion poisoning. CONCLUSION. Estimated fenitrothion ingestion dose and serum fenitrothion concentration at the emergency department and at 24 h after ingestion may be useful prognostic factors in acute fenitrothion self-poisoning. Furthermore, we should take care for the patients whose serum fenitrothion concentration is high.

A 41-year-old female attempted suicide by taking 7.8g acetaminophen and was transferred to our hospital four hours after ingestion. The patient was diagnosed as non-hepatic toxicity (below the line set by the Rumack Matthew nomogram). Laboratory data showed an elevation in serum liver enzymes and coagulation defects at 3 days after ingestion, therefore, the patient was treated with plasma exchange and an oral administration of N-acetylcysteine (NAC). The elevation of liver enzymes was maximal at 4 days after ingestion, and the laboratory data became normalized at approximately 9 days after ingestion. In this case, habitual alcohol intake may have exacerbated the severe liver injury. We should consider an exacerbation of hepatotoxicity and administer NAC in any case having a history of habitual alcohol intake, even if the case was diagnosed as non-hepatic toxicity by the nomogram.

In Japan, the physician staffed helicopter ambulance system, "Doctor-Heli" System, was first founded in our University Hospital in 1999. In this system, a helicopter is based at an Emergency Medical Center at all times and dispatch with both emergency physicians and a nurse upon a request by paramedics. This system has made possible a critically earlier development of the initial management at the point of care and rapid transport to the hospital. We presented the case suffering from acute cerebral infarction was transported by the "Doctor-Heli" and received the intervention for thrombolysis successfully. It was less than three hours from the onset to the completion of the intervention. The "DoctorHeli" system has a potential benefit for patients with acute cerebral infarction because of it enables quite early clinical diagnosis and rapid transport.

We report a case of isolated brain stem injury caused by the tentorium cerebelli. A 17-year-old male was admitted to our hospital. Thirty minutes before admission, he was struck by another motorcycle while driving his own motorcycle. The Glasgow Coma Scale (GCS) was 10. He had no extremity weakness and his pupils were normal. CT scan showed no evidence of intracranial lesions except for facial bone fractures. His consciousness level improved to GCS 13 at 6 hours after admission. Follow-up CT scan was normal, however MRI 3 days after admission showed a contusion at the left lateral midbrain. He was discharged without any neurological deficits on 6 days after admission. Analysis of the distance between the brain stem and the tentorial margin using MR cisternography showed that the left side was shorter than the right side. We presumed that an isolated lateral brain stem injury was caused by the direct impact of the tentorium cerebelli. Typically the location of this type of lesion is present in the same side as that of impact. However in this case the orientation was opposite to that. We considered that the distance between the brain stem and the tentorial margin affected the mechanism of this lesion.

A 48-year-old woman presented after taking 2000 mg of selenium dioxide, corresponding to 10 times the experimental lethal dose in animals. She presented with mildly altered consciousness and hematemesis. Endoscopy revealed mucosal damage throughout the oral cavity, esophagus, and stomach. There was no evidence of perforation. After intubation and gastric lavage, hemodialysis was performed. The patient was discharged uneventfully on the 16(th) day. This case highlights a very rare acute selenium intoxication. Serum and urinary selenium levels and serum glutathione peroxidase activities during the patient's course were followed, as well as the mucosal corrosive damage caused by the selenium.