Ryosuke Takegawa

Background: Acute nicotine intoxication can cause cardiac arrest. We report a case of cardiac arrest managed with veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) alongside serial serum nicotine monitoring. Case Presentation: A 36‐year‐old woman collapsed after ingesting an unknown amount of liquid nicotine, up to 20 g. Emergency medical services found her in cardiac arrest with pulseless electrical activity (PEA). On arrival, she remained in cardiac arrest with PEA/asystole and severe acidosis, and VA‐ECMO was established 82 min after ingestion. Cardiac function gradually improved, and VA‐ECMO was discontinued on Day 3. However, she died on Day 28 from post‐cardiac arrest brain injury. Liquid chromatography–mass spectrometry (LC/MS) revealed an admission serum nicotine concentration of 6.44 μg/mL, declining to 0.057 μg/mL within 18 h. This decline paralleled hemodynamic recovery. Conclusion: Although neurological outcome was unfavorable, VA‐ECMO may provide temporary circulatory support during the toxic phase of massive nicotine intoxication.

Mitochondrial transplantation (MTx) has emerged as a potential therapeutic approach for diseases associated with mitochondrial dysfunction, yet its scalability and cross-species feasibility remain underexplored. This study aimed to evaluate the dose-dependent uptake and molecular effects of xenogeneic mitochondrial transplantation (xeno-MTx) using rat-derived mitochondria in mouse neuronal systems. HT-22 hippocampal neuronal cells and a murine model of cardiac arrest-induced global cerebral ischemia were used to assess mitochondrial uptake, gene expression, and mitochondrial DNA presence. Donor mitochondria were isolated from rat pectoralis muscle and labeled with MitoTracker dyes. Flow cytometry and confocal microscopy revealed a dose-dependent increase in donor mitochondrial uptake in vitro. Quantitative PCR demonstrated a corresponding increase in rat-specific mitochondrial DNA and upregulation of Mfn2 and Bak1, with no changes in other fusion, fission, or apoptotic genes. Inhibitor studies indicated that mitochondrial internalization may involve actin-dependent macropinocytosis and cholesterol-sensitive endocytic pathways. In vivo, rat mitochondrial DNA was detected in mouse brains post–xeno-MTx, confirming donor mitochondrial delivery to ischemic tissue. These findings support the feasibility of xeno-MTx and its dose-responsive biological effects in neuronal systems while underscoring the need for further research to determine long-term functional outcomes and clinical applicability.

Background: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia–reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. Results: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. Conclusions: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest.

S: Upper-extremity deep venous thrombosis (UEDVT) after whole blood donation is rarely reported. Blood donation has a low rate of complications and is typically safe. A small percentage of blood donors experience donation-related events such as UEDVT, which are extremely rare. We are reporting a rare case of a UEDVT following blood donation. This is an extremely rare event; only five cases were reported to our knowledge. A 22-year-old Caucasian woman with a past medical history of provoked pulmonary embolism completed 6 months of apixaban and negative thrombophilia workup presented to the hospital with complaints of progressive pain and swelling in her right arm. The patient reports donating blood using her right arm in January 2021. Phlebotomy duration for blood donation was approximately 10minutes. She reported pain and swelling several days after blood donation. Subsequently, a duplex ultrasound showed a thrombus in the right brachial vein. The patient was started on apixaban for 6 months. Although most whole blood donors do not experience complications, DVT is a rare complication from whole blood donation with severe consequences. It should be considered in a donor with worsening pain and swelling.

Deep vein thrombosis (DVT) is a major complication in critical care. There are various methods of prophylaxis, but none of them fully prevent DVT, and each method has adverse effects. Electrical muscle stimulation (EMS) could be a new effective approach to prevent DVT in intensive care unit (ICU) patients. We hypothesized that EMS increases the venous flow of the lower limbs and has a prophylactic effect against the formation of DVT. This study included 26 patients admitted to a single ICU. We enrolled patients who could not move themselves due to spinal cord injury, head injury, central nervous system abnormalities, and sedation for mechanical ventilation. The patients were randomly allocated to either the EMS group or the control group. Patients in the EMS group received 30-min sessions of EMS applied to the bilateral lower extremities on arbitrary days within 14 days after admission. The control patients received no EMS. The peak flow velocity and diameter of the popliteal vein (Pop.V) and common femoral vein (CFV) were measured by ultrasound and then the volumes of venous flow were calculated using a formula. There were no statistically significant differences in patient characteristics between the two groups except for the mortality rate. In the EMS group, the median and interquartile range (IQR, 25th–75th percentile) of velocities of the Pop.V and CFV were higher during EMS compared with at rest: 10.6 (8.0–14.8) vs 24.5 (15.1–37.8) cm/s and 17.0 (12.3–23.8) vs 24.3 (17.0–33.0) cm/s, respectively (p < 0.05). The median (IQR) of volumes of venous flow of the Pop.V and CFV at rest and during EMS were 4.2 (2.7–7.2) vs 8.6 (5.4–16.1) cm3/s and 12.9 (9.7–21.4) vs 20.8 (12.3–34.1) cm3/s, respectively (p < 0.05). There were no major complications related to EMS. EMS increased the venous flow of the lower limbs. EMS could be one potential method for venous thromboprophylaxis. UMIN000013642