Faculty Profiles - Obara Takafumi

Papers - Obara Takafumi

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当科における小児急性脳症と体温管理療法の現状

小原隆史, 塚原紘平, 平岡知浩, 本郷貴識, 湯本哲也, 内藤宏道, 中尾篤典

日本脳低温療法・体温管理学会誌 26 ( 1 ) 47 - 47 2023.6

Hydrogen inhalation attenuates lung contusion after blunt chest trauma in mice. Reviewed International journal

Kohei Ageta, Takahiro Hirayama, Toshiyuki Aokage, Mizuki Seya, Ying Meng, Tsuyoshi Nojima, Hirotsugu Yamamoto, Takafumi Obara, Atsunori Nakao, Tetsuya Yumoto, Kohei Tsukahara, Hiromichi Naito

Surgery 2023.5

Language：English Publishing type：Research paper (scientific journal)

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

DOI： 10.1016/j.surg.2023.04.029

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Hydrogen gas treatment improves survival in a rat model of crush syndrome by ameliorating rhabdomyolysis Reviewed

Tetsuya Yumoto, Toshiyuki Aokage, Takahiro Hirayama, Hirotsugu Yamamoto, Takafumi Obara, Tsuyoshi Nojima, Hiromichi Naito, Atsunori Nakao

European Journal of Inflammation 21 1721727X2311685 - 1721727X2311685 2023.3

Publishing type：Research paper (scientific journal) Publisher：SAGE Publications

Objectives

Crush syndrome (CS) is characterized by a systemic manifestation of traumatic rhabdomyolysis, leading to multiple organ dysfunction and death. Ischemia-reperfusion (IR) injury is commonly responsible for systemic response. Extending studies have shown that hydrogen gas treatment ameliorated IR injury in numerous experimental models; however, its effect on CS has not been well examined. This study aimed to investigate the effects of hydrogen gas inhalation following crush injury in an experimental model of CS.

Methods

Male Sprague-Dawley rats were subjected to experimental CS by applying a total of 3.0 kg weight to both hindlimb under general anesthesia for 6 h. Immediately after decompression, the animals were randomly placed in a gas chamber filled with either air or 1.3% hydrogen gas. Animals were sacrificed 18 h or 24 h following gas exposure for non-survival studies or for survival study, respectively.

Results

The rats with hydrogen treatment ( n = 6) had a higher 24-h survival than the rats with air treatment ( n = 9) (100% vs. 44%, p = 0.035). Lactate concentrations (2.9 ± 0.2 vs. 2.2 ± 0.2 mmol/L, p = 0.040) and creatine kinase (34,178 ± 13,580 vs. 5005 ± 842 IU/L, p = 0.016) were lower in the hydrogen group compared with the air group 18 h after decompression ( n = 4 in the air group, and n = 5 in the H₂ group). Histological analysis revealed that the damage to the rectus femoris muscle and kidney appeared to be ameliorated by hydrogen treatment.

Conclusion

Hydrogen gas inhalation may be a promising therapeutic approach in the treatment of CS.

DOI： 10.1177/1721727x231168547

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/1721727X231168547

Association of Prehospital Physician Presence During Pediatric Out-of-Hospital Cardiac Arrest With Neurologic Outcomes. Reviewed International journal

Takafumi Obara, Tetsuya Yumoto, Tsuyoshi Nojima, Takashi Hongo, Kohei Tsukahara, Naomi Matsumoto, Takashi Yorifuji, Atsunori Nakao, Jonathan Elmer, Hiromichi Naito

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 2023.2

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To examine the association of prehospital physician presence with neurologic outcomes of pediatric patients with out-of-hospital cardiac arrest (OHCA). DESIGN: Retrospective cohort study. SETTING: Data from the Japanese Association for Acute Medicine-OHCA Registry. INTERVENTIONS: None. PATIENTS: Pediatric patients (age 17 yr old or younger) registered in the database between June 2014 and December 2019. MEASUREMENT AND MAIN RESULTS: We used logistic regression models with stabilized inverse probability of treatment weighting (IPTW) to estimate the associated treatment effect of a prehospital physician with 1-month neurologically intact survival. Secondary outcomes included in-hospital return of spontaneous circulation (ROSC) and 1-month survival after OHCA. A total of 1,187 patients (276 in the physician presence group and 911 in the physician absence group) were included (median age 3 yr [interquartile range 0-14 yr]; 723 [61%] male). Comparison of the physician presence group, versus the physician absence, showed 1-month favorable neurologic outcomes of 8.3% (23/276) versus 3.6% (33/911). Physician presence was associated with greater odds of 1-month neurologically intact survival after stabilized IPTW adjustment (adjusted odds ratio [aOR] 1.98, 95% CI 1.08-3.66). We also found an association in the secondary outcome between physician presence, opposed to absence, and in-hospital ROSC (aOR 1.48, 95% CI 1.08-2.04). However, we failed to identify an association with 1-month survival (aOR 1.49, 95% CI 0.97-2.88). CONCLUSIONS: Among pediatric patients with OHCA, prehospital physician presence, compared with absence, was associated almost two-fold greater odds of 1-month favorable neurologic outcomes.

DOI： 10.1097/PCC.0000000000003206

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Organ Donation after Extracorporeal Cardiopulmonary Resuscitation and Brain Death. Reviewed

Takafumi Obara, Tetsuya Yumoto, Kenji Aoshima, Kohei Tsukahara, Hiromichi Naito, Atsunori Nakao

Acta medica Okayama 77 ( 1 ) 117 - 120 2023.2

Authorship：Lead author Language：English

A 38-year-old primipara Japanese woman suffered cardiac arrest due to a pulmonary thromboembolism 1 day after undergoing a cesarean section. Extracorporeal cardiopulmonary resuscitation was initiated and extracorporeal membrane oxygenation support was needed for 24 h. Despite intensive care, the patient was diagnosed with brain death on day 6. With the family's consent, comprehensive end-of-life care including organ donation was discussed based on our hospital's policy. The family decided to donate her organs. Specific training and education are required for emergency physicians to optimize the process of incorporating organ donation into end-of-life care while respecting the patient's and family's wishes.

DOI： 10.18926/AMO/64372

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Successfully treated case of severe hypothermia secondary to myxedema coma. Reviewed International journal

Hirotsugu Yamamoto, Takashi Hongo, Tsuyoshi Nojima, Takafumi Obara, Yoshinori Kosaki, Kohei Ageta, Kohei Tsukahara, Tetsuya Yumoto, Atsunori Nakao, Hiromichi Naito

Acute medicine & surgery 10 ( 1 ) e828 2023

Language：English

BACKGROUND: Myxedema coma is an extremely rare but fatal endocrine emergency that requires urgent recognition and treatment. We describe a case of severe hypothermia that rapidly deteriorated to cardiac arrest that was attributed to myxedema coma. CASE PRESENTATION: A 52-year-old man without a history of hypothyroidism was transferred to our emergency department due to coma and profound hypothermia. The patient developed cardiac arrest immediately after hospital arrival but return of spontaneous circulation was achieved shortly after resuscitation. The patient was noted to have generalized, nonpitting edema, dry skin, severe respiratory acidosis, hyponatremia, and elevated creatinine kinase, which was indicative of hypothyroidism. Myxedema coma was confirmed by a thyroid profile. The patient was successfully treated with intravenous levothyroxine and glucocorticoid. CONCLUSION: Although myxedema coma is a rare cause of severe hypothermia, emergency physicians should be familiar with its clinical features and management.

DOI： 10.1002/ams2.828

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Transcranial doppler ultrasound in a 3-month-old infant with brain death. Reviewed International journal

Tomohiro Hiraoka, Takafumi Obara, Takashi Hongo, Tsuyoshi Nojima, Kohei Tsukahara, Tetsuya Yumoto, Atsunori Nakao

Pediatrics international : official journal of the Japan Pediatric Society 65 ( 1 ) e15587 2023

Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing Reviewed

Hideharu Hagiya, Yasuhiro Nakano, Masanori Furukawa, Naruhiko Sunada, Toru Hasegawa, Yasue Sakurada, Kou Hasegawa, Koichiro Yamamoto, Hiroko Ogawa, Takafumi Obara, Kouhei Ageta, Naomi Matsumoto, Rumi Matsuo, Tomoka Kadowaki, Akihito Higashikage, Takao Hikita, Takashi Yorifuji, Shinichi Toyooka, Yoshinobu Maeda, Yoshinori Yokokura, Fumio Otsuka, Masanori Nakayama

Scientific Reports 12 ( 1 ) 2022.11

Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (> 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p < 0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated.

DOI： 10.1038/s41598-022-24464-3

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Other Link： https://www.nature.com/articles/s41598-022-24464-3

臓器移植におけるドナー管理(臓器保護の観点から) 6歳未満おける臓器移植ドナー管理の特徴

小原隆史, 内藤宏道, 塚原紘平, 青景聡之, 野島剛, 上田浩平, 小崎吉訓, 山田太平, 藤崎宣友, 中尾篤典

日本集中治療医学会雑誌 29 ( Suppl.1 ) 297 - 297 2022.11

臓器移植におけるドナー管理(臓器保護の観点から) 6歳未満おける臓器移植ドナー管理の特徴

小原隆史, 内藤宏道, 塚原紘平, 青景聡之, 野島剛, 上田浩平, 小崎吉訓, 山田太平, 藤崎宣友, 中尾篤典

日本集中治療医学会雑誌 29 ( Suppl.1 ) 297 - 297 2022.11

治療的医学ガス(Medical gas)を救急集中治療領域へ応用する救急医による挑戦

小原隆史, 青景聡之, 山本浩継, 野島剛, 上田浩平, 湯本哲也, 内藤宏道, 中尾篤典

日本救急医学会雑誌 33 ( 10 ) 823 - 823 2022.10

デジタル田園健康特区における救急救命士の権限・役割の拡大による救急体制の充実への取り組み

上田浩平, 本郷貴識, 小原隆史, 野島剛, 湯本哲也, 塚原紘平, 内藤宏道, 中尾篤典

日本救急医学会雑誌 33 ( 10 ) 872 - 872 2022.10

産科情報共有システム「iPicss」により迅速な対応ができた出産中の脳出血の搬送例

佐々並三紗, 小崎吉訓, 塚原紘平, 牧尉太, 中尾篤典, 内藤宏道, 湯本哲也, 上田浩平, 小原隆史, 本郷貴識, 平岡知浩

日本救急医学会雑誌 33 ( 10 ) 806 - 806 2022.10

Luminal administration of biliverdin ameliorates ischemia-reperfusion injury following intestinal transplant in rats. Reviewed International journal

Tsuyoshi Nojima, Takafumi Obara, Hirotsugu Yamamoto, Tetsuya Yumoto, Takuro Igawa, Toshiyuki Aokage, Mizuki Seya, Atsunori Nakao, Hiromichi Naito

Surgery 172 ( 5 ) 1522 - 1528 2022.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Intestinal grafts are susceptible to ischemia-reperfusion injury, resulting in the loss of mucosal barrier function and graft failure. Biliverdin is known to exert a variety of cytoprotective functions against oxidative tissue injury. Because the mucosal layer is the primary site of ischemia-reperfusion injury, mucosa-targeting strategies by luminal delivery of reagents might be beneficial. We tested whether intraluminal administration of biliverdin as an adjuvant to standard preservation solutions protected against ischemia-reperfusion injury. METHODS: Orthotopic syngeneic intestinal transplants were performed on Lewis rats after 6 hours of cold preservation. Saline containing biliverdin (10 μM) or without biliverdin was introduced into the lumen of the intestinal grafts immediately before cold preservation. RESULTS: Damage to the intestinal mucosa caused by ischemia-reperfusion injury resulted in severe morphological changes, including blunting of the villi and erosion, and led to significant loss of gut barrier function 3 hours after reperfusion. These changes to the mucosa were notably ameliorated by intraluminal administration of biliverdin. Biliverdin also effectively inhibited upregulation of messenger RNAs for interleukin-6, inducible nitric oxide synthase, and C-C motif chemokine 2. Additionally, biliverdin treatment prevented the loss of expression of claudin-1, a transmembrane, tight-junction barrier protein. The 14-day survival of recipients of biliverdin-treated grafts was significantly improved as compared with the recipients of saline-treated control grafts (83.3% vs 38.9%, P = .030). CONCLUSION: This study demonstrated that luminally delivered biliverdin provides beneficial effects during the transplant of rat small intestinal grafts and could be an attractive therapeutic option in organ transplantation.

DOI： 10.1016/j.surg.2022.07.021

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Luminal Administration of a Water-soluble Carbon Monoxide-releasing Molecule (CORM-3) Mitigates Ischemia/Reperfusion Injury in Rats Following Intestinal Transplantation. Reviewed International journal

Takafumi Obara, Hirotsugu Yamamoto, Toshiyuki Aokage, Takuro Igawa, Tsuyoshi Nojima, Takahiro Hirayama, Mizuki Seya, Michiko Ishikawa-Aoyama, Atsunori Nakao, Roberto Motterlini, Hiromichi Naito

Transplantation 106 ( 7 ) 1365 - 1375 2022.7

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

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

DOI： 10.1097/TP.0000000000004007

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キノコ中毒におけるプロカルシトニンによる診断は有用か

野島剛, 湯本哲也, 小崎吉訓, 小原隆史, 上田浩平, 塚原紘平, 山田太平, 内藤宏道, 中尾篤典

中毒研究 35 ( 2 ) 153 - 153 2022.7

Adult Scurvy Presenting with Painful Purpura on the Legs.

Nayu Tamura, Takafumi Obara, Taihei Yamada, Tsuyoshi Nojima, Shunsuke Nakamura, Yasuhiro Koide, Makoto Takaoka, Hiromichi Naito, Atsunori Nakao

Internal medicine (Tokyo, Japan) 61 ( 12 ) 1913 - 1916 2022.6

Language：English Publishing type：Research paper (scientific journal)

Prolonged vitamin C deficiency can result in numerous metabolic abnormalities like impaired tissue repair and defective collagen synthesis. This case report describes a middle-age Japanese man presenting painful purpura on his lower limbs, severe anemia, and altered consciousness. The patient had been eating a selective diet lacking in vegetables and fruits since childhood. A serum analysis demonstrated a low level of vitamin C. The patient was treated with vitamin supplementation and psychological intervention. Scurvy is an under-considered illness with a favorable prognosis if diagnosed early while it is still sporadically encountered in some patients with malabsorption or malnutrition even in modern times.

DOI： 10.2169/internalmedicine.8409-21

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Can Blood Ammonia Level, Prehospital Time, and Return of Spontaneous Circulation Predict Neurological Outcomes of Out-of-Hospital Cardiac Arrest Patients? A Nationwide, Retrospective Cohort Study. Reviewed International journal

Tsuyoshi Nojima, Hiromichi Naito, Takafumi Obara, Kohei Ageta, Hiromasa Yakushiji, Tetsuya Yumoto, Noritomo Fujisaki, Atsunori Nakao

Journal of clinical medicine 11 ( 9 ) 2022.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: This study aimed to test if blood ammonia levels at hospital arrival, considering prehospital time and the patient's condition (whether return of spontaneous circulation [ROSC] was achieved at hospital arrival), can predict neurological outcomes after out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective cohort study on data from a nationwide OHCA registry in Japan. Patients over 17 years old and whose blood ammonia levels had been recorded were included. The primary outcome was favorable neurological outcome at 30 days after OHCA. Blood ammonia levels, prehospital time, and the combination of the two were evaluated using the receiver operating characteristic curve to predict favorable outcomes. Then, cut-off blood ammonia values were determined based on whether ROSC was achieved at hospital arrival. RESULTS: Blood ammonia levels alone were sufficient to predict favorable outcomes. The overall cut-off ammonia value for favorable outcomes was 138 μg/dL; values were different for patients with ROSC (96.5 μg/dL) and those without ROSC (156 μg/dL) at hospital arrival. CONCLUSIONS: Our results using patient data from a large OHCA registry showed that blood ammonia levels at hospital arrival can predict neurological outcomes, with different cut-off values for patients with or without ROSC at hospital arrival.

DOI： 10.3390/jcm11092566

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脳卒中様症状を呈した急性大動脈解離の1例

加藤篤之, 野島剛, 小原隆史, 塚原紘平, 内藤宏道, 中尾篤典

日本臨床救急医学会雑誌 25 ( 2 ) 329 - 329 2022.5

日本外傷学会データバンクを用いた熱傷症例の検討

野島剛, 内藤宏道, 小原隆史, 小崎吉訓, 上田浩平, 塚原紘平, 中尾篤典

熱傷 48 ( 1 ) 38 - 39 2022.3

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Papers - Obara Takafumi