Population Pharmacokinetic Model and Dosing Simulation of Meropenem Using Measured Creatinine Clearance for Patients with Sepsis.

PURPOSE: Creatinine clearance (CCr) and pharmacokinetic parameters are markedly affected by pathophysiological changes in patients with sepsis. However, only a few reports have assessed renal function in patients with sepsis using the measured CCr. Furthermore, the administration regimen has not been sufficiently evaluated using a population PK (PPK) model across renal function broad ranges. Therefore, this study was performed to construct a meropenem PPK model for patients with sepsis using the measured CCr and evaluate the optimized meropenem dosing regimen based on the CCr. METHODS: Patients with sepsis who received intravenous meropenem at the Showa University Hospital were enrolled in this prospective observational study. The PPK model was constructed using blood samples and clinical information of patients. The probability of target attainment (PTA) indicates the likelihood of achieving 50% time above the minimum inhibitory concentration (% T > MIC) based on 10,000 virtual patients using Monte Carlo simulations. The PTA for each meropenem regimen was 50% T > MIC based on different renal functions using the Monte Carlo simulation. RESULTS: One hundred samples were collected from 31 patients. The final PPK model incorporating the measured CCr as a covariate in CL displayed the best fit. The recommended dosing regimen to achieve a PTA of 50% T > MIC of 4 mcg/mL was 1 g every 8 hours as a 3-hour prolonged infusion for patients with CCr 85-130 mL/min and 1 g every 8 hours as an 8-hour continuous infusion for patients with CCr ≥ 130 mL/min. CONCLUSIONS: This model precisely predicted meropenem concentrations in patients with sepsis by accurately evaluating renal function using the measured CCr. Extended dosing was demonstrated to be necessary to achieve a PTA of 50% T > MIC for patients with CCr ≥ 85 mL/min. Meropenem effectiveness can be maximized in patients with sepsis by selecting the appropriate dosing regimen based on renal function and the MIC.

Effect of PACAP on Heat Exposure.

Heat stroke is a life-threatening illness caused by exposure to high ambient temperatures and relative humidity. The incidence of heat stroke is expected to increase due to climate change. Although pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in thermoregulation, the role of PACAP on heat stress remains unclear. PACAP knockout (KO) and wild-type ICR mice were subjected to heat exposure at an ambient temperature of 36 °C and relative humidity of 99% for 30-150 min. After heat exposure, the PACAP KO mice had a greater survival rate and maintained a lower body temperature than the wild-type mice. Moreover, the gene expression and immunoreaction of c-Fos in the ventromedially preoptic area of the hypothalamus, which is known to harbor temperature-sensitive neurons, were significantly lower in PACAP KO mice than those in wild-type mice. In addition, differences were observed in the brown adipose tissue, the primary site of heat production, between PACAP KO and wild-type mice. These results suggest that PACAP KO mice are resistant to heat exposure. The heat production mechanism differs between PACAP KO and wild-type mice.

Guillain-Barré syndrome diagnosed as central cervical spinal cord injury after hyperextension injury.

The clinical features of Guillain-Barré syndrome (GBS) are progressive, fairly symmetric muscle weakness, and patients present a few days to a week after onset of symptoms. A 63-y-old man strongly hit his forehead, and next day felt paresthesia in both upper limbs, with difficulty in walking. Spinal cord injury (SCI) was suspected; the cervical cord was severely compressed at the C4 level. He was diagnosed with central cervical SCI and transferred to a community hospital. Three days after the injury, oxygenation worsened, and the patient was transferred to our hospital for laminoplasty. After admission, we noticed bilateral ptosis-an atypical finding for SCI. Under analgesic sedation, he could only move his fingertips. Severe respiratory muscle weakness and absence of reflexes were observed. Moreover, albuminocytologic dissociation and decreased motor nerve conduction were observed, and GBS was suspected. Intravenous immunoglobulin was administered; thereby, the muscle weakness gradually improved, and the patient returned to work. Muscle weakness usually starts in the legs in GBS; however, in 10% of patients, it starts in the arms. In our patient, the symptoms started with paresthesia, followed by severe respiratory muscle weakness in a short period. Furthermore, intubation made history-taking and neurological examination difficult. The degree of inflammation in the acute GBS phase correlates with the severity of nerve injury. Therefore, early diagnosis and treatment of GBS is important. We should perform detailed history-taking and consider GBS as a differential diagnosis, especially when neurological examination cannot be performed at the emergency department.

Obstructive shock due to right ventricular compression by a massively expanded reconstructed gastric tube.

Obstructive shock is often associated with poor right ventricular (RV) output and requires rapid obstruction release. A 54-year-old man was brought to our emergency department, presenting with shock. He had previously undergone esophagectomy with gastric interposition through the retrosternal route, after which he could not eat solid foods. After eating a ball of rice, he became critically ill, with a significantly increased lactate level, an indicator of shock. Though initial examinations showed no abnormalities, he was hospitalized for observation. The following day, he experienced similar discomfort while in the supine position, an hour after breakfast. Cardiac sonography revealed that the RV was remarkably compressed by a massively expanded gastric tube, causing diastolic dysfunction. After propping him into a sitting position, he recovered from shock. Upon a second examination of CT images, we recognized the massively dilated gastric tube compressing the RV. Anatomically, the retrosternal route is located directly in front of the RV. Thus, it is thought that the massively dilated gastric tube externally compressed the RV, preventing adequate RV filling and causing the obstructive shock. In such cases, the patient's position should be changed immediately to release the RV compression.

High early phase hemoglobin level is associated with favorable neurological outcome in patients with severe traumatic brain injury.

BACKGROUND: The appropriate hemoglobin (Hb) level threshold for the early phase (i.e. from Emergency Department to ICU admission) in patients with severe traumatic brain injury (TBI) is still unknown. Therefore, we aimed to examine the association between Hb levels during the early phase and neurological outcomes in patients with severe TBI using data from the Brain Hypothermia (B-HYPO) Study Group. METHODS: We performed a post-hoc analysis of the B-HYPO study (a prospective, multicenter, randomized controlled trial on patients with severe TBI who received either mild therapeutic hypothermia [MTH; 32.0 °C-34.0 °C] or fever control [35.5 °C-37.0 °C]). We calculated Hb levels during early phase by the formula: (admission Hb + Hb on day 1) / 2. The primary outcome was the association between during early phase Hb levels and 6-month neurological outcome after the TBI based on the Glasgow Outcome Scale scores (a measure of functional recovery defined as moderate disability or good recovery). RESULTS: We reviewed data from 130 patients and found favorable neurological outcomes in 48.5% of them. We found significant differences between the favorable and unfavorable neurological outcome groups in terms of their Hb levels on admission and on day 1. But, we found no Hb level differences after day 3 (including 1 day after rewarming). Our multivariable analysis showed that Hb levels during early phase were significantly associated with favorable neurological outcomes (odds ratio, 1.387; 95% confidence interval, 1.057-1.858; P = 0.018). CONCLUSIONS: High early phase Hb levels are associated with favorable neurological outcomes after severe TBI.

[Japanese Guideline for Traumatic Intracranial Hypotension:Interpretation and Current Situation].

Since the 2000s, "intracranial hypotension syndrome associated with trauma" has become a social problem in relation to litigation and compensation issues in Japan. To address this problem, guidelines for correct diagnosis have been developed. The basic pathogenesis of this disease is cerebrospinal fluid leakage caused by fragile tissue injury due to trauma. In order to improve the treatment outcome of this disease, it is important to prove the CSF leakage directly, using diagnostic imaging based on the guidelines, rather than diagnosing it based on clinical manifestations alone. For management, an epidural blood patch(EBP)should be used only after careful consideration. As such, rest and adequate fluid replacement should generally be given first. However, in cases with concomitant subdural hematoma, the order of hematoma irrigation and EBP should be determined according to the condition and urgency of each patient. In addition, it is necessary to standardize the formal name of this condition in papers to ensure rigorous academic discussion.

Diagnosis of neurofibromatosis type 1 after rupture of aneurysm and consequent fatal hemothorax.

Patients with neurofibromatosis type 1 (NF1) can develop both benign and malignant tumors throughout their lives. A 49-year-old man was transferred to the emergency department with complaints of sudden right dorsal pain and respiratory discomfort. He was in shock on arrival. On finding significantly decreased permeability of the left lung field in chest X-ray, drainage was immediately performed. Subsequent computed tomography (CT; Lammert et al., 2005) angiography revealed the extravasation of contrast media from the deep carotid artery, a branch of subclavian artery. It suggested rupture of an aneurysm located at a rare site; the ruptured aneurysm penetrated the pleura, causing shock. The patient was resuscitated. Transcatheter arterial embolization (TAE; Evans et al., 2010) was successfully performed. Immediate drainage, resuscitation, and TAE 2 improved his condition. Most NF1 patients have café-au-lait macules; café-au-lait macules tend to fade with age. Importantly, café-au-lait macules, neurofibromas, and Lisch nodules were noticed at admission. NF1 patients are likely to have a malignant neoplasm when they are young. The patient had been diagnosed with thyroid cancer when he was young. As his deceased mother was an NF1 patient, we diagnosed him with NF1. Detailed patient history and early-stage examination led to the early diagnosis. NF1 should be considered as an early differential diagnosis to improve the outcome of patients in such cases.

Mild decrease in heart rate during early phase of targeted temperature management following tachycardia on admission is associated with unfavorable neurological outcomes after severe traumatic brain injury: a post hoc analysis of a multicenter randomized controlled trial.

BACKGROUND: The association between isolated admission heart rate (HR) and prognosis has been discussed, but not that between gross HR change and neurological outcome in patients with severe traumatic brain injury (TBI). In the acute phase of severe TBI, HR is influenced by several factors (e.g., pain, sympathetic activation, hypovolemia, fever, body temperature). Therefore, admission HR and gross HR change should be examined in patients with TBI treated with a well-designed protocol, such as was done in the Brain Hypothermia (B-HYPO) Study. METHODS: This was a post hoc analysis of the B-HYPO Study, which was conducted as a prospective, multicenter, randomized controlled trial in patients with severe TBI receiving mild therapeutic hypothermia (MTH; 32.0 °C-34.0 °C) or fever control (35.5 °C-37.0 °C) in Japan. Patients with MTH were examined, and HR change (%HR) in the early MTH phase was calculated as follows: [admission HR - HR at day 1]/admission HR × 100. Patients were divided into six groups, using admission HR (< 80, 80-99, ≤ 100) and median of %HR; i.e., group (Admission HR < 80 and %HR ≥ 18.6); group (Admission HR < 80 and %HR < 18.6); group (Admission HR 80-99 and %HR ≥ 18.6); group (Admission HR 80-99 and %HR < 18.6); group (Admission HR ≥100 and %HR ≥ 18.6); and group (Admission HR ≥100 and %HR < 18.6). The primary outcome was an adjusted predicted probability of unfavorable neurological outcome at 6 months after TBI according to Glasgow Outcome Scale score, which is a measure of functional recovery and defined as severe disability, persistent vegetative state, and death. RESULTS: Overall, 79 patients with MTH (52.7% of the original trial) were examined; among these, unfavorable neurological outcomes were observed in 53.2%. Among all the groups, group (Admission HR ≥100 and %HR < 18.6) exhibited the highest proportion of unfavorable outcomes, and 82.3% of patients had an adjusted predicted probability of unfavorable outcomes, whereas those in group (Admission HR < 80 and %HR ≥ 18.6) developed only 22.8% (p = 0.04). CONCLUSIONS: Mild HR decrease during the early phase of targeted temperature management following tachycardia at admission can be associated with unfavorable neurological outcomes after severe TBI.

The exploration of population pharmacokinetic model for meropenem in augmented renal clearance and investigation of optimum setting of dose.

In recent years, augmented renal clearance (ARC), in which renal function is excessively enhanced, has been reported, and its influence on ß-lactam antibiotics has been investigated. In this study, we aimed to determine the optimum population pharmacokinetic model of meropenem in patients with sepsis with ARC, and evaluated dosing regimens based on renal function. Seventeen subjects (6 with ARC and 11 without) were enrolled in this study. Predicted meropenem concentrations were evaluated for bias and precision using the Bland-Altman method. To examine the dosing regimen, Monte Carlo simulation was performed to calculate the cumulative fraction of response (CFR). In patients with ARC, the bias (average of the predicted value and measured value residuals) of models constructed by Crandon et al. (2011), Roberts et al. (2009), and Jaruratanasirikul et al. (2015) were 5.96 µg/mL, 10.91 µg/mL, and 4.41 µg/mL, respectively. Following 2 g meropenem every 8 h (180 min infusion), CFR ≥ 90%, a criterion of success for empirical therapy, was achieved, even with creatinine clearance of 130-250 mL/min. For patients with sepsis and ARC, the model of Jaruratanasirikul et al. showed the highest degree of accuracy and precision and confirmed the efficacy of the meropenem dosing regimen in this patient population.

Elevated Serum High-Mobility Group Box-1 Protein Level Is Associated with Poor Functional Outcome in Ischemic Stroke.

BACKGROUND: In experimental models, inhibition of high-mobility group box-1 (HMGB1) signaling has been reported to protect against the sequelae of ischemic stroke. Here, we determined the clinical significance of serum HMGB1 levels in patients with acute ischemic stroke. METHODS: We enrolled 183 patients (114 men, 69 women; mean age: 72.7 years) over 6 consecutive months. On admission and day 7, we recorded the National Institutes of Health Stroke Scale scores and measured serum high-sensitivity C-reactive protein (hs-CRP) and HMGB1 levels. Stroke volumes were estimated using diffusion-weighted magnetic resonance imaging performed on admission. One year later, clinical outcome was assessed using the modified Rankin Scale (mRS). RESULTS: Serum hs-CRP and HMGB1 levels in patients with ischemic stroke were increased relative to healthy controls (both P < .01). On day 7, hs-CRP, but not HMBG1, levels had increased significantly relative to levels at admission (P < .01 and .54, respectively). Higher HMGB1, but not hs-CRP, levels at day 7 correlated with larger stroke volumes (P < .01 and .28, respectively). HMGB1 levels did not significantly differ between stroke subtypes. Multiple logistic regression analysis indicated that a serum HMGB1 level higher than 7.5 ng/mL was an independent risk factor for poor prognosis, defined as a 1-year mRS score of 3-6 (odds ratio, 2.34; 95% confidence interval, 1.02-5.38). CONCLUSIONS: Acute ischemic stroke is associated with elevated serum HMGB1 levels, and HMGB1 levels at admission independently predict poor outcome at 1 year. These results suggest that HMGB1 quantification provides more accurate prognostic information after ischemic stroke.

Molecular hydrogen in the treatment of acute and chronic neurological conditions: mechanisms of protection and routes of administration.

Oxidative stress caused by reactive oxygen species is considered a major mediator of tissue and cell injuries in various neuronal conditions, including neurological emergencies and neurodegenerative diseases. Molecular hydrogen is well characterized as a scavenger of hydroxyl radicals and peroxynitrite. Recently, the neuroprotective effects of treatment with molecular hydrogen have been reported in both basic and clinical settings. Here, we review the effects of hydrogen therapy in acute neuronal conditions and neurodegenerative diseases. Hydrogen therapy administered in drinking water may be useful for the prevention of neurodegenerative diseases and for reducing the symptoms of acute neuronal conditions.

Assessing blood granulocyte colony-stimulating factor as a potential biomarker of acute traumatic brain injury in mice and humans.

Previous work has found that serum G-CSF was acutely elevated in mice 24h but not one week after controlled cortical impact (CCI). The purpose of this study was to investigate whether blood G-CSF correlates with the elevated brain cytokines in mice after CCI and also if it correlates with traumatic brain injury (TBI) in humans. Here, we found in mice undergoing CCI, a procedure that induces direct injury to the brain, that serum G-CSF correlated directly or indirectly with several brain cytokines, indicating it is a useful marker for the neuroinflammation of TBI. A pilot study in humans (phase I, n=19) confirmed that plasma G-CSF is acutely elevated on day 1 (p<0.001) of TBI and has returned to baseline by one week. In a second human sample (phase II) (n=80), we found plasma G-CSF peaks about 12h after arriving in the emergency department (41.6+/-5.4 pg/ml). Aging was weakly associated (p<0.05) with a less robust elevation in serum G-CSF, but there was no difference with gender. ISS, a measure of total severity of injury, correlated with the degree of elevation in serum G-CSF (r=.419; p<0.05), but severity of head injury (via AIS) did not. The latter may have been because of the statistically narrow range of head injuries among our cases and the high number of cases diagnosed with closed head injury (a non-codable diagnosis). In conclusion, plasma G-CSF may be a useful biomarker of TBI, correlating with neuroinflammation in the animal model and in the human studies with time since injury and total severity of injury. As such, it may be useful in determining whether TBI has occurred within the last 24h.

Human mesenchymal stem/stromal cells suppress spinal inflammation in mice with contribution of pituitary adenylate cyclase-activating polypeptide (PACAP).

BACKGROUND: Adult human mesenchymal stem/stromal cells (hMSCs) from bone marrow have been reported to exhibit beneficial effects on spinal cord injury (SCI). A neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP) is known to decrease neuronal cell death and inflammatory response after ischemia, SCI, and other neuronal disorders. Recently, we found that expression of the gene for mouse PACAP (Adcyap1) was greater in animals receiving hMSCs with neural injury such as ischemia. However, the association of PACAP with hMSCs to protect nerve cells against neural injuries is still unclear. METHODS: Wild-type and PACAP-gene-deficient (Adcyap1 (+/-) ) mice were subjected to spinal cord transection, and hMSCs (5 × 10(5) cells) were injected into the intervertebral spinal cord on day 1 post-operation (p.o.). Locomotor activity, injury volume, retention of hMSCs, mouse and human cytokine genes (which contribute to macrophage (MΦ) and microglial activation), and Adcyap1 were evaluated. RESULTS: hMSCs injected into wild-type mice improved locomotor activity and injury volume compared with vehicle-treated mice. In contrast, non-viable hMSCs injected into wild-type mice, and viable hMSCs injected into Adcyap1 (+/-) mice, did not. Wild-type mice injected with hMSCs exhibited increased Adcyap1 expression, and observed PACAP immunoreaction in neuron-like cells. Gene expression levels for IL-1, tumor necrosis factor α (TNFα), interleukin-10 (IL-10), and transforming growth factor ß (TGFß) decreased, while that for interleukin-4 (IL-4) increased, in hMSC-injected wild-type mice. In contrast, IL-1, TGFß, and IL-4 gene expression levels were all abolished in hMSC-injected Adcyap1 (+/-) mice on day 7 post-operation. Moreover, the mice-implanted hMSCs increased an alternative activating macrophage/microglial marker, arginase activity. The human gene profile indicated that hMSCs upregulated the gene of IL-4 and growth factors which were reported to enhance Adcyap1 expression. Finally, we demonstrated that hMSCs express human ADCYAP1 and its receptor gene after the inflammation-related interferon-γ (IFNγ) in vitro. CONCLUSIONS: These results suggest that hMSCs attenuate the deleterious effects of SCI by reducing associated inflammatory responses and enhancing IL-4 production. This effect could be mediated in part by cell-cell cross-talk involving the neuropeptide PACAP.

Reply to Maxwell, A. Comment on "Miyamoto et al. Laryngopharyngeal Mucosal Injury Due to Nasogastric Tube Insertion during Cardiopulmonary Resuscitation: A Retrospective Cohort Study. J. Clin. Med. 2024, 13, 261".

We are grateful for the insightful comments provided by the author [...].

Laryngopharyngeal Mucosal Injury Due to Nasogastric Tube Insertion during Cardiopulmonary Resuscitation: A Retrospective Cohort Study.

BACKGROUND: Patients under cardiopulmonary resuscitation (CPR) are at high risk of aspirating gastric contents. Nasogastric tube insertion (NGTI) after tracheal intubation is usually performed blindly. This sometimes causes laryngopharyngeal mucosal injury (LPMI), leading to severe bleeding. This study clarified the incidence of LPMI due to blind NGTI during CPR. METHODS: We retrospectively analyzed 84 patients presenting with cardiopulmonary arrest on arrival, categorized them into a Smooth group (Smooth; blind NGTI was possible within 2 min), and Difficult group (blind NGTI was not possible), and consequently performed video laryngoscope-assisted NGTI. The laryngopharyngeal mucosal condition was recorded using video laryngoscope. Success rates and insertion time for the Smooth group were calculated. Insertion number and LPMI scores were compared between the groups. Each regression line of outcome measurements was obtained using simple regression analysis. We also analyzed the causes of the Difficult group, using recorded video laryngoscope-assisted videos. RESULTS: The success rate was 78.6% (66/84). NGTI time was 48.8 ± 4.0 s in the Smooth group. Insertion number and injury scores in the Smooth group were significantly lower than those in the Difficult group. The severity of LPMI increased with NGT insertion time and insertion number. CONCLUSIONS: Whenever blind NGTI is difficult, switching to other methods is essential to prevent unnecessary persistence.

Therapeutic challenges in transcatheter arterial embolization for an enlarging subcutaneous hematoma in a patient with neurofibromatosis type 1: A case report.

A 60-year-old woman with a history of neurofibromatosis type 1, who was admitted with pulmonary hypertension, developed buttock pain and anemia, and contrast-enhanced computed tomography showed a large subcutaneous hematoma with minimal active extravasation. Angiography of the bilateral internal iliac arteries revealed diffuse, irregular blood vessels without extravasation. As the exact bleeding site could not be identified, the patient was managed conservatively. However, the patient's symptoms and anemia worsened the following day. Repeat angiography revealed two pseudoaneurysms in the right inferior gluteal artery, which were embolized using n-butyl-2-cyanoacrylate. Nonetheless, the patient's anemia further worsened the following day. Repeat contrast-enhanced CT revealed another site of extravasation in the enlarging hematoma, but no extravasation was observed on the subsequent angiography. Owing to the worsening anemia and enlarging hematoma, proximal embolization of the irregular bilateral inferior gluteal arteries was performed using gelatin sponge particles. The patient's anemia and symptoms improved. Vasculopathy associated with neurofibromatosis type 1 is rare, with an incidence of approximately 3%. In patients with neurofibromatosis type 1, the blood vessels become fragile because of tunica media thinning and elastic-lamina rupture. Histopathologically, neurofibromatosis type 1-associated vasculopathy is characterized by a mixture of normal and abnormal vessels. Abnormally fragile blood vessels may repeatedly rupture followed by physiological hemostasis, which may explain the diagnostic and therapeutic challenges during angiography in this case. In patients with neurofibromatosis type 1 with acute bleeding, irregular vessels without active extravasation on angiography may be indicated for embolization.

Establishment and characterization of primary adult microglial culture in mice.

Microglial cells account for approximately 12-15 % of the cells in the central nervous system (CNS). Microglial cells are polarized by pathological stimuli such as cytokines, chemokines, and growth factors, and play important roles in the deterioration and repair of the CNS. Here, we established cultures of primary microglial cells isolated from the brains of adult C57/BL6 mice using Percoll density gradients. The cells were cultured and stained with antibodies against CD11b, glial fibrillary acidic protein, myelin basic protein and NeuN to determine microglial, astroglial, oligodendroglial, and neuronal cells respectively. Moreover, the cells were exposed to interferon-γ (IFNγ) plus interleukin-1ß (IL-1ß) or IL-4 for 24 h to demonstrate the activating phenotypes with inducible nitric oxide synthase (iNOS), Ym1, and Iba-1 immunoblotting. At least 95 % of the cultured cells were CD11b-positive and -negative for astroglial, neuronal, and oligodendrocyte markers. IFNγ plus IL-1ß treatment resulted in classical activation, which was represented by an increase in iNOS. The cells also displayed alternative activation, which increased Ym1 when treated with IL-4. The present study indicates that the microglial cells isolated as described here are a useful tool for elucidating adult microglial function.

Edaravone increases regional cerebral blood flow after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a major cause of preventable death and serious morbidity, with subsequent low cerebral blood flow (CBF) considered to be associated with poor prognosis. In the present study, we demonstrated the effect of the free radical scavenger edaravone on regional CBF (rCBF) after TBI. Male mice (C57/BL6) were subjected to TBI using a controlled cortical impactor device. Immediately after TBI, the animals were intravenously administered 3.0 mg/kg of edaravone or a vehicle saline solution. Two-dimensional rCBF images were acquired before and 24 h post-TBI, and were quantified in the ipsilateral and contralateral hemispheres (n = 5 animals per group). CBF in the vehicle-treated animals decreased broadly over the ipsilateral hemisphere, with the region of low rCBF spreading from the frontal cortex to the occipital lobe. The zone of lowest rCBF matched that of the contusion area. The mean rCBF at 24 h for a defined elliptical region between the bregma and lambda was 73.7 ± 5.8 %. In comparison, the reduction of rCBF in edaravone-treated animals was significantly attenuated (93.4 ± 5.7 %, p < 0.05). The edaravone-treated animals also exhibited higher rCBF in the contralateral hemisphere compared with that seen in -vehicle-treated animals. It is suggested that edaravone reduces neuronal damage by scavenging reactive oxygen species (ROS) and by maintaining intact the autoregulation of the cerebral vasculature.

Medical Care Management Based on Disaster Medicine for the Triathlon Events at the XXXII Olympiad and Tokyo 2020 Paralympic Games.

Planning the medical services for the triathlon competition at the 2020 Tokyo Olympic and Paralympic Games was predicted to be challenging because of possible last-minute changes related to the COVID-19 pandemic and abnormally high temperatures. Therefore, event planners organized and executed a disaster medical care plan, a plan for providing care during emergencies. Based on the basic medical plan for all venues provided by the Tokyo 2020 Organizing Committee, planners for the triathlon venue prepared a medical care plan according to the CSCATTT principles: Command and control, Safety, Communication, Assessment, Treatment, Triage, and Transport. After the event, planners evaluated the number of COVID-19, heatstroke, and injury cases at the venue. The events were conducted without spectators in July and August 2022 because at the last minute, planners held the event without spectators. The triathlon competition involved 638 individuals, including athletes and staff. In total, 7 cases of injuries, 3 cases of mild heatstroke, and 13 other cases were reported, with only 2 requiring emergency transportation. No cases of COVID-19 were reported from the triathlon venue, including during the observation period after the event. This medical plan was effective in preventing heatstroke and COVID-19 cases during the big event. Efficiently and effectively responding to various situations is possible in a shorter period by planning large-scale medical services for such special circumstances according to CSCATTT, a principle of disaster medical care.

Benign noninfectious subcutaneous emphysema with minor injury: A case report.

Posttraumatic subcutaneous emphysema, which can be benign and noninfectious, is associated with necrotizing fasciitis. Rarely, extensive emphysema occurs after a minor traumatic injury. A 23-year-old man came to our hospital with extensive emphysema, ranging from the left hand to the axilla, after a minor injury. Necrotizing fasciitis was suspected. Based on the blood and imaging tests, necrotizing fasciitis was not actively suspected. He was admitted and observed for one day, and he was discharged the following day. The mechanism by which air can enter through a small injury is unclear, but the one-way ball-valve mechanism is the most commonly proposed explanation. The nontraumatic causes of non-infectious subcutaneous emphysema include insect bites, skin biopsies, and the use of shock absorbers. Since it developed from a minor wound, other mechanisms, aside from the one-way ball-valve, were possibly involved. Based on the imaging results of this case, the air was predominantly distributed in the subcutaneous tissue along the neurovascular bundle. The relatively sparse tissue likely caused the extensive subcutaneous emphysema. While evaluating post-traumatic subcutaneous emphysema, benign and noninfectious cases should be differentiated to prevent unnecessary therapeutic intervention.