Updated on 2024/04/10

写真a

 
NISHIDA Kazuki
 
Organization
Nagoya University Hospital Assistant professor of hospital
Title
Assistant professor of hospital
External link

Degree 2

  1. Doctor of Philosophy (Medical Science) ( 2022.3   Nagoya University ) 

  2. M.D. ( 2014.3   Nagoya University ) 

Research Interests 5

  1. Observational Study

  2. Clinical Trial

  3. Epidemiology

  4. Biostatistics

  5. Machine Learning

Research Areas 1

  1. Life Science / Hygiene and public health (non-laboratory)  / Biostatistics

Research History 1

  1. Nagoya University   Nagoya University Hospital   Assistant professor of hospital

    2020.4

Professional Memberships 1

  1. The Biometric Society of Japan

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Papers 70

  1. MEFV variants are a predisposing factor for generalized pustular psoriasis. Reviewed International journal

    Takenori Yoshikawa, Takuya Takeichi, Kazuki Nishida, Yumiko Kobayashi, Hozumi Sano, Akitaka Shibata, Haruka Koizumi, Reiko Tsutsumi, Ryo Fukaura, Masahiro Hayashi, Akiko Imanishi, Kenta Nakamura, Yasutomo Mikoshiba, Eisaku Ogawa, Shinya Sano, Manao Kinoshita, Takashi Okamoto, Reiko Kageyama, Yuko Sano, Sakae Kaneko, Jun Aoi, Toshihide Hara, Yaei Togawa, Mari Kishibe, Yuichi Yoshida, Hiroaki Yagi, Tetsuya Honda, Kazumitsu Sugiura, Shigetoshi Sano, Tamio Suzuki, Tomoo Ogi, Yoshinao Muro, Masashi Akiyama

    Journal of the American Academy of Dermatology   Vol. 90 ( 4 ) page: 852 - 854   2024.4

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    DOI: 10.1016/j.jaad.2023.10.070

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  2. Evaluation of 4D Flow MRI-Derived Relative Residence Time as a Marker for Cirrhosis Associated Portal Vein Thrombosis. Reviewed International journal

    Ryota Hyodo, Yasuo Takehara, Yoji Ishizu, Kazuki Nishida, Takashi Mizuno, Kazushige Ichikawa, Ryota Horiguchi, Nobuhiko Kurata, Yasuhiro Ogura, Shinya Yokoyama, Shinji Naganawa, Ning Jin, Yoshito Ichiba

    Journal of magnetic resonance imaging : JMRI     2024.3

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    BACKGROUND: Portal vein thrombosis (PVT) is thought to arise from stagnant blood flow, yet conclusive evidence is lacking. Relative residence time (RRT) assessed using 4D Flow MRI may offer insight into portal flow stagnation. PURPOSE: To explore the relationship between RRT values and the presence of PVT in cirrhotic participants. STUDY TYPE: Prospective. POPULATION: Forty-eight participants with liver cirrhosis (27 males, median age 67 years [IQR: 57-73]) and 20 healthy control participants (12 males, median age 45 years [IQR: 40-54]). FIELD STRENGTH/SEQUENCE: 3 T/4D Flow MRI. ASSESSMENT: Laboratory (liver and kidney function test results and platelet count) and clinical data (presence of tumors and other imaging findings), and portal hemodynamics derived from 4D Flow MRI (spatiotemporally averaged RRT [RRT-mean], flow velocity, and flow rate) were analyzed. STATISTICAL TESTS: We used multivariable logistic regression, adjusted by selected covariates through the Lasso method, to explore whether RRT-mean is an independent risk factor for PVT. The area under the ROC curve (AUC) was also calculated to assess the model's discriminative ability. P < 0.05 indicated statistical significance. RESULTS: The liver cirrhosis group consisted of 16 participants with PVT and 32 without PVT. Higher RRT-mean values (odds ratio [OR] 11.4 [95% CI: 2.19, 118]) and lower platelet count (OR 0.98 per 1000 μL [95% CI: 0.96, 0.99]) were independent risk factors for PVT. The incorporation of RRT-mean (AUC, 0.77) alongside platelet count (AUC, 0.75) resulted in an AUC of 0.84. When including healthy control participants, RRT-mean had an adjusted OR of 12.4 and the AUC of the combined model (RRT-mean and platelet count) was 0.90. DATA CONCLUSION: Prolonged RRT values and low platelet count were significantly associated with the presence of PVT in cirrhotic participants. RRT values derived from 4D Flow MRI may have potential clinical relevance in the management of PVT. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

    DOI: 10.1002/jmri.29357

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  3. Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer. Reviewed International journal

    Yao Liang, Osamu Maeda, Kazushi Miyata, Mitsuro Kanda, Shizuki Sugita, Dai Shimizu, Kazuki Nishida, Yasuhiro Kodera, Yuichi Ando

    Cancer chemotherapy and pharmacology   Vol. 93 ( 2 ) page: 121 - 127   2024.2

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    PURPOSE: This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer. METHODS: Preoperative DCF (docetaxel, 70 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; fluorouracil, 750 mg/m2/day, days 1-5) was repeated every 3 weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients. RESULTS: According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3'-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027). CONCLUSIONS: ABCC2-24C > T (rs717620), TYMS 3'-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.

    DOI: 10.1007/s00280-023-04607-7

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  4. Risk factors for rebleeding in gastroduodenal ulcers. Reviewed International journal

    Nobuhito Ito, Kohei Funasaka, Toshihisa Fujiyoshi, Kazuki Nishida, Yusuke Satta, Kazuhiro Furukawa, Naomi Kakushima, Satoshi Furune, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Keiko Maeda, Takuya Ishikawa, Takeshi Yamamura, Eizaburo Ohno, Masanao Nakamura, Ryoji Miyahara, Yoji Sasaki, Jun-Ichi Haruta, Mitsuhiro Fujishiro, Hiroki Kawashima

    Irish journal of medical science   Vol. 193 ( 1 ) page: 173 - 179   2024.2

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    BACKGROUND: Rebleeding after hemostasis of the gastroduodenal ulcer (GDU) is one of the indicators associated with death among GDU patients. However, there are few studies on risk score that contribute to rebleeding after endoscopic hemostasis of bleeding peptic ulcers. AIMS: The aim of this study was to identify factors associated with rebleeding, including patient factors, after endoscopic hemostasis of bleeding gastroduodenal ulcers and to stratify the risk of rebleeding. METHODS: We retrospectively enrolled 587 consecutive patients who were treated for Forrest Ia to IIa bleeding gastroduodenal ulcers with endoscopic hemostasis at three institutions. Risk factors associated with rebleeding were assessed using univariate and multivariate logistic regression analyses. The Rebleeding Nagoya University (Rebleeding-N) scoring system was developed based on the extracted factors. The Rebleeding-N score was internally validated using bootstrap resampling methods. RESULTS: Sixty-four patients (11%) had rebleeding after hemostasis of gastroduodenal ulcers. Multivariate logistic regression analysis revealed four independent rebleeding risk factors: blood transfusion, albumin <2.5, duodenal ulcer, and diameter of the exposed vessel ≧2 mm. Patients with 4 risk factors in the Rebleeding-N score had a 54% rebleeding rate, and patients with 3 risk factors had 44% and 25% rebleeding rates. In the internal validation, the mean area under the curve of the Rebleeding-N score was 0.830 (95% CI = 0.786-0.870). CONCLUSIONS: Rebleeding after clip hemostasis of bleeding gastroduodenal ulcers was associated with blood transfusion, albumin <2.5, diameter of the exposed vessel ≧2 mm, and duodenal ulcer. The Rebleeding-N score was able to stratify the risk of rebleeding.

    DOI: 10.1007/s11845-023-03450-2

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  5. Anxiety evaluated by the Hospital Anxiety and Depression Scale as a predictor of postoperative nausea and vomiting: a pilot study. Reviewed

    Tatsuro Yokoyama, Takahiro Tamura, Kazuki Nishida, Ryohei Ito, Kimitoshi Nishiwaki

    Nagoya journal of medical science   Vol. 86 ( 1 ) page: 72 - 81   2024.2

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    The incidence of postoperative nausea and vomiting (PONV) remains high, and improving the accuracy of PONV prediction remains challenging. The primary aim of this study is to examine the impact of anxiety scores evaluated using the Hospital Anxiety and Depression Scale (HADS) on the PONV prediction model. We hypothesized that anxiety and depression, quantified using the HADS, could improve the accuracy of the PONV predictive model. This pilot study evaluated 100 patients. The HADS was conducted by a self-evaluation method before thoracoscopic surgery for lung tumors, and the anesthesia method was standardized. The criterion was whether the nurse in charge of the patient who complained of PONV assessed that drug administration was necessary. As the main analysis, the odds ratio of the HADS score for predicting PONV was evaluated using multivariable logistic regression models. Further, the receiver operating characteristic (ROC) curves of the model with the HADS score added to the variables of without-anxiety predictors and the model with the variables of without-anxiety predictors only were compared. The anxiety score was significantly higher in the PONV group than in the no PONV group (P = 0.021). For predictive accuracy, the model that included age, sex, smoking history, history of PONV, and anxiety score had a higher area under the ROC curve than did the model excluding the anxiety score (P = 0.021). In conclusion, the findings indicate that the HADS is worth investigating as a predictor of PONV.

    DOI: 10.18999/nagjms.86.1.72

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  6. Efficacy of intraoperative irrigation with artificial cerebrospinal fluid in chronic subdural hematoma surgery: study protocol for a multicenter randomized controlled trial. Reviewed International journal

    Yoshitaka Nagashima, Yoshio Araki, Kazuki Nishida, Shunichiro Kuramitsu, Kenichi Wakabayashi, Shinji Shimato, Takeshi Kinkori, Toshihisa Nishizawa, Takahisa Kano, Toshinori Hasegawa, Atsushi Noda, Kenko Maeda, Yu Yamamoto, Osamu Suzuki, Naoki Koketsu, Takeshi Okada, Masashige Iwasaki, Kiyo Nakabayashi, Shigeru Fujitani, Hideki Maki, Yachiyo Kuwatsuka, Masahiro Nishihori, Takafumi Tanei, Tomohide Nishikawa, Yusuke Nishimura, Ryuta Saito

    Trials   Vol. 25 ( 1 ) page: 6 - 6   2024.1

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    BACKGROUND: The surgical techniques for treatment of chronic subdural hematoma (CSDH), a common neurosurgical condition, have been discussed in a lot of clinical literature. However, the recurrence proportion after CSDH surgery remains high, ranging from 10 to 20%. The standard surgical procedure for CSDH involves a craniostomy to evacuate the hematoma, but irrigating the hematoma cavity during the procedure is debatable. The authors hypothesized that the choice of irrigation fluid might be a key factor affecting the outcomes of surgery. This multicenter randomized controlled trial aims to investigate whether intraoperative irrigation using artificial cerebrospinal fluid (ACF) followed by the placement of a subdural drain would yield superior results compared to the placement of a subdural drain alone for CSDH. METHODS: The study will be conducted across 19 neurosurgical departments in Japan. The 1186 eligible patients will be randomly allocated to two groups: irrigation using ACF or not. In either group, a subdural drain is to be placed for at least 12 h postoperatively. Similar to what was done in previous studies, we set the proportion of patients that meet the criteria for ipsilateral reoperation at 7% in the irrigation group and 12% in the non-irrigation group. The primary endpoint is the proportion of patients who meet the criteria for ipsilateral reoperation within 6 months of surgery (clinical worsening of symptoms and increased hematoma on imaging compared with the postoperative state). The secondary endpoints are the proportion of reoperations within 6 months, the proportion being stratified by preoperative hematoma architecture by computed tomography (CT) scan, neurological symptoms, patient condition, mortality at 6 months, complications associated with surgery, length of hospital stay from surgery to discharge, and time of the surgical procedure. DISCUSSION: We present the study protocol for a multicenter randomized controlled trial to investigate our hypothesis that intraoperative irrigation with ACF reduces the recurrence proportion after the removal of chronic subdural hematomas compared with no irrigation. TRIAL REGISTRATION: ClinicalTrials.gov jRCT1041220124. Registered on January 13, 2023.

    DOI: 10.1186/s13063-023-07889-7

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  7. Temporary Mechanical Circulatory Support in Sepsis-associated Cardiogenic Shock With and Without Acute Myocardial Infarction Reviewed International journal

    Ryota Sato, Daisuke Hasegawa, Stephanie C. Guo, Kazuki Nishida, Siddharth Dugar

    Journal of Cardiothoracic and Vascular Anesthesia   Vol. 38 ( 1 ) page: 207 - 213   2024.1

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    OBJECTIVES: To describe the current use and outcomes of temporary mechanical circulatory support (MCS) in patients with sepsis-associated cardiogenic shocks with and without acute myocardial infarction (AMI) in the United States. DESIGN: Retrospective cohort study. SETTING: The National Inpatient Sample database from 2017 to 2019. PARTICIPANTS: Adult patients with sepsis-associated cardiogenic shock with and without AMI. INTERVENTIONS: Temporary MCSs, including intra-aortic balloon pump (IABP), percutaneous left ventricular assist device (pLVAD), and extracorporeal membrane oxygenation (ECMO). MEASUREMENTS AND MAIN RESULTS: Multivariate logistic regression analyses adjusting for patient characteristics, organ failures, and socioeconomic status. Although the uses of IABP and pLVAD were associated with significantly lower odds of in-hospital mortality in patients with sepsis-associated cardiogenic shock (IABP: adjusted odds ratio [aOR] 0.57, 95% CI 0.44-0.73, p < .001; pLVAD: aOR 0.66, 95% CI 0.45-0.98, p = .037), ECMO was not (aOR 1.51, 95% CI 0.93-2.45, p = 0.096). In the subgroup with AMI, temporary MCSs were not associated with significantly lower or higher odds of in-hospital mortality. In the subgroup without AMI, IABP was associated with significantly lower odds of in-hospital mortality (aOR 0.43, 95% CI 0.28-0.65, p < 0.001). CONCLUSIONS: Although temporary MCS is deemed to be a feasible option in sepsis-associated cardiogenic shock, the selection of the right patients whose shock is driven mainly by cardiogenic shock rather than septic shock, as represented by low cardiac output and high systemic vascular resistance, plays a critical role in the feasibility of this approach in the absence of clinical trials.

    DOI: 10.1053/j.jvca.2023.09.026

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  8. Optimal D-dimer cut-off values for diagnosing deep vein thrombosis in patients with comorbid malignancies. Reviewed International journal

    Kiyoaki Niimi, Kazuki Nishida, Changi Lee, Shuta Ikeda, Yohei Kawai, Masayuki Sugimoto, Hiroshi Banno

    Annals of vascular surgery   Vol. 98   page: 293 - 300   2024.1

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    BACKGROUND: Patients with malignancy are at high risk of VTE, and early diagnosis is important. The Khorana score is known as a risk assessment for cancer-related thrombosis during chemotherapy, but there are still few reports on its diagnostic potential, the optimal D-dimer cut-off values for indications other than chemotherapy and the use of the Khorana score in combination with D-dimers. In this study, we examined the clinical appropriateness of increasing the D-dimer cut-off value. METHODS: We retrospectively studied 208 malignancies out of 556 patients who underwent lower extremity venous ultrasonography at our hospital over a two-year period from January 2018 to December 2019. The optimal D-dimer cut-off value for predicting DVT in patients with malignancy was calculated by the Youden index. The usefulness of the Khorana score alone and the model combining the Khorana score with D-dimer for predicting DVT diagnosis was compared using receiver operating characteristic analysis. RESULTS: Of 208 eligible patients, 59 (28.4%) had confirmed DVT. The optimal D- dimer cut-off value for predicting DVT comorbidity in patients with malignancy was 3.96 μg/mL. When the new D-dimer cut-off value was set at 4.0 μg/mL, the odds ratio for DVT diagnosis was 4.23 (95% CI 2.10-8.55, p<0.001), which was higher than the odds ratio of 1.33 (95% CI: 0.98-1.81, p=0.064) for the Khorana score. The AUC for the Khorana score and D-dimer was 0.714, which was significantly higher than the 0.611 for the Khorana score alone, with the difference being significantly higher at 0.103 (p=0.004, 95% CI: 0.033-0.173). CONCLUSIONS: The optimal D-dimer cut-off value for the diagnosis of DVT in patients with malignancy was 4.0 μg/mL. It was also suggested that the combination of the Khorana score with the D-dimer level was more accurate in diagnosing DVT than the Khorana score alone.

    DOI: 10.1016/j.avsg.2023.06.033

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  9. Docetaxel, cisplatin, and fluorouracil with pegfilgrastim on day 3 as neoadjuvant chemotherapy for esophageal cancer. Reviewed International journal

    Osamu Maeda, Satoshi Furune, Mitsuro Kanda, Kazushi Miyata, Dai Shimizu, Shizuki Sugita, Kazuki Nishida, Masahiko Ando, Yasuhiro Kodera, Yuichi Ando

    Cancer medicine   Vol. 13 ( 2 ) page: e6974   2024.1

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    PURPOSE: A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. METHODS: Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m2 per day) on days 1-5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. RESULTS: Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. CONCLUSION: Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

    DOI: 10.1002/cam4.6974

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  10. Total Hydrocortisone Dosage in the Neonatal Period May Be Related to Low Developmental Quotient in Extremely Low Birth Weight Infants: A Retrospective Cohort Study. Reviewed International journal

    Akinobu Taniguchi, Kazuki Nishida, Toshihiko Suzuki, Erina Kataoka, Naozumi Fujishiro, Eiko Kato, Hikaru Yamamoto, Koji Takemoto, Miharu Ito, Seiji Hayashi, Yuichiro Sugiyama, Takashi Maeda, Yoshiyuki Takahashi, Yoshiaki Sato

    Neonatology   Vol. 121 ( 2 ) page: 195 - 202   2024

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    INTRODUCTION: The effects of hydrocortisone (HDC) administration to extremely low birth weight (ELBW) infants on later development remain unclear. This study examined the association between HDC dosage during neonatal period and neurodevelopmental outcomes in ELBW infants. METHODS: This study was a retrospective cohort study conducted in eight centers in Japan. The subjects of this study were ELBW infants born between April 2015 and March 2017. The association between postnatal total HDC dosage up to 36 weeks postmenstrual age and the developmental quotient (DQ) at 3 years of age was examined. Multiple linear regression evaluated the association, adjusting for weeks of gestation, birth weight, and the presence of bronchopulmonary dysplasia, late-onset circulatory collapse, intracranial hemorrhage, necrotizing enterocolitis, and sepsis. RESULTS: This study included 218 ELBW infants, of whom 144 underwent a developmental test at 3 years of age. Simple linear regression analysis revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.65, 95% CI: -3.73, -1.57). Multiple linear regression analysis adjusted for the presence of bronchopulmonary dysplasia and late-onset circulatory collapse also revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.66, 95% CI: -3.89, -1.42). CONCLUSION: Higher total HDC dosage up to 36 weeks postmenstrual age in ELBW infants was associated with impaired neurodevelopmental outcomes. Although HDC is often needed in the treatment of ELBW infants, clinicians should be aware that an increased dose of HDC may be associated with impaired neurodevelopmental outcomes.

    DOI: 10.1159/000534934

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  11. Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19. Reviewed International journal

    Daisuke Kasugai, Taku Tanaka, Takako Suzuki, Yoshinori Ito, Kazuki Nishida, Masayuki Ozaki, Takeo Kutsuna, Toshiki Yokoyama, Hitoshi Kaneko, Ryo Ogata, Ryohei Matsui, Takahiro Goshima, Hiroshi Hamada, Azusa Ishii, Yusuke Kodama, Naruhiro Jingushi, Ken Ishikura, Ryo Kamidani, Masashi Tada, Hideshi Okada, Takanori Yamamoto, Yukari Goto

    Frontiers in immunology   Vol. 15   page: 1337070 - 1337070   2024

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    BACKGROUND: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. METHODS: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. RESULTS: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. CONCLUSIONS: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

    DOI: 10.3389/fimmu.2024.1337070

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  12. Assessing the Real-World, Long-Term Impact of Lemborexant on Sleep Quality in a Home-Based Clinical Study. Reviewed International journal

    Seiko Miyata, Kunihiro Iwamoto, Ippei Okada, Akihiro Fujimoto, Yuki Kogo, Daisuke Mori, Manabu Amano, Nao Matsuyama, Kazuki Nishida, Masahiko Ando, Toshiaki Taoka, Shinji Naganawa, Norio Ozaki

    Nature and science of sleep   Vol. 16   page: 291 - 303   2024

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    PURPOSE: Both subjective and objective evaluations are essential for the treatment of insomnia. Lemborexant has been shown to be effective in the long-term based solely on a subjective basis, and no long-term objective measures have been evaluated under natural sleep conditions. Small, lightweight sleep electroencephalogram (EEG) monitor was used, instead of polysomnography, to objectively evaluate sleep at home 4 and 12 weeks after lemborexant treatment. PATIENTS AND METHODS: Adults and elderly subjects with insomnia disorder, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were enrolled in this open-label, single-arm, single-center trial. Objective and subjective measures of sleep were prospectively assessed. Sleep disturbance, excessive sleepiness, and depressive symptoms were assessed using questionnaires. RESULTS: A total of 45 subjects were screened, of which 33 were enrolled. Paired t-tests were conducted to evaluate changes in sleep variables and compared with the baseline; subjects showed significant improvements in objective sleep efficiency (SE) and subjective sleep parameters at weeks 4 and 12 following treatment with lemborexant. When baseline values were taken into account, a repeated-multivariate analysis of variance (MANOVA) revealed statistically significant changes in the objective measures. Sleep disturbance, excessive sleepiness, and depressive symptoms improved after three months of lemborexant treatment. CONCLUSION: Furthermore, lemborexant therapy improved nocturnal sleep, when measured objectively using sleep EEG monitoring at home, and improved daytime sleepiness and depressive symptoms in older adults with insomnia disorder.

    DOI: 10.2147/NSS.S448871

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  13. Invasive Hemodynamic Monitoring with Pulmonary Artery Catheter in Sepsis-associated Cardiogenic Shock. Reviewed International journal

    Ryota Sato, Daisuke Hasegawa, Stephanie C Guo, Kazuki Nishida, Siddharth Dugar

    Shock (Augusta, Ga.)     2023.12

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    BACKGROUND: Both sepsis-induced cardiomyopathy and worsening of pre-existing cardiac disease can contribute to circulatory shock in septic patients, The early use of pulmonary artery catheter (PAC) could play a pivotal role in the management of sepsis-associated cardiogenic shock. In this study, we aimed to evaluate the impact of early invasive hemodynamic monitoring with PAC in patients with sepsis-associated cardiogenic shock. METHOD: We performed a retrospective study using the National Inpatient Sample data from 01/2017 to 12/2019. The early use of PAC was defined as the use of PAC within 2 days from the admission. We performed the multivariable logistic regression analysis to investigate the association between the early use of PAC and in-hospital mortality in patients with sepsis-associated cardiogenic shock and sepsis without cardiogenic shock, respectively. RESULTS: There was no difference in in-hospital mortality between PAC and No PAC groups in sepsis without cardiogenic shock (adjusted odds ratio [aOR]: 1.05, 95% confidence interval [CI]: 0.82 - 1.35, p = 691). On the other hand, the early use of PAC was independently associated with lower in-hospital mortality in patients with sepsis-associated cardiogenic shock (aOR: 0.58, 95% confidence interval [CI]: 0.46 - 0.72, p < 0.001). The use of PAC was also associated with increased use of MCS in those with sepsis-associated cardiogenic shock (aOR: 12.26, 95% CI: 9.37 - 16.03, p < 0.001). For patients with sepsis-associated cardiogenic shock, the use of PAC after 2 days of admission was associated with significantly higher in-hospital mortality and decreased use of mechanical circulatory support. CONCLUSION: The use of pulmonary artery catheters in sepsis-associated cardiogenic shock was associated with significantly lower in-hospital mortality and increased use of mechanical circulatory supports in patients with sepsis-associated cardiogenic shock.

    DOI: 10.1097/SHK.0000000000002290

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  14. Pelvic morphologies of developmental dysplasia and primary osteoarthritis on range of motion after total hip arthroplasty. Reviewed International journal

    Hiroto Funahashi, Yusuke Osawa, Taisuke Seki, Yasuhiko Takegami, Kazuki Nishida, Shiro Imagama

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society   Vol. 41 ( 9 ) page: 2007 - 2015   2023.9

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    Bony impingement, especially in the anterior inferior iliac spine (AIIS) after total hip arthroplasty (THA), may cause dislocation. However, the influence of AIIS characteristics on bony impingement after THA is not fully understood. Thus, we aimed to determine the morphological characteristics of AIIS with developmental dysplasia of the hip (DDH) and primary osteoarthritis (pOA) and to evaluate its effect on range of motion (ROM) after THA. Hips from 130 patients who underwent THA, including primary osteoarthritis (pOA) were analyzed. In total, we had 27 male and 27 female participants with pOA, and 38 male and 38 female participants with DDH. The horizontal distances of AIIS from tear drop (TD) were compared. In the computed tomography simulation, flexion ROM was measured, and its relationship to the distance between TD and AIIS was investigated. DDH had a more medial (male: DDH, 36.9 ± 5.8; pOA, 45.5 ± 6.1; p < 0.001) (female: DDH, 31.5 ± 10.0; pOA, 36.2 ± 4.7; p < 0.001) position of AIIS than pOA. In the male with pOA group, flexion ROM was significantly smaller than that in the other groups, and there was a correlation between flexion ROM and horizontal distances(r = -0.543; 95% confidence interval = -0.765 - -0.206; p = 0.003). AIIS position is a factor that limits ROM during flexion after THA, particularly in males. Further studies are required to develop surgical strategies for cases of impingement at the AIIS site after THA. This article is protected by copyright. All rights reserved.

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  15. Cardiogenic shock complicating sepsis and septic shock: A national inpatient sample analysis. Reviewed International journal

    Ryota Sato, Daisuke Hasegawa, Kazuki Nishida, Siddharth Dugar

    Medicina intensiva   Vol. 47 ( 9 ) page: 547 - 551   2023.9

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  16. Prevalence and Prognosis of Sepsis-Induced Cardiomyopathy: A Systematic Review and Meta-Analysis. Reviewed International journal

    Daisuke Hasegawa, Yoshiko Ishisaka, Tetsuro Maeda, Narut Prasitlumkum, Kazuki Nishida, Siddharth Dugar, Ryota Sato

    Journal of intensive care medicine   Vol. 38 ( 9 ) page: 797 - 808   2023.9

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    PURPOSE: The prevalence and its impact on mortality of sepsis-induced cardiomyopathy (SICM) remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and prognosis of SICM. MATERIALS AND METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Titles and abstracts were evaluated based on the following criteria: (1) published in English, (2) randomized controlled trials, cohort studies, or cross-sectional studies, (3) ≥ 18 years with sepsis, (4) reporting the prevalence and/or comparison of short-term mortality between those with and without SICM, defined as the new-onset reduction in left ventricular ejection fraction (LVEF) within 72 h on admission or from the diagnosis of sepsis. The random-effect model was used for all analyses. This meta-analysis was registered at PROSPERO (CDR42022332896). RESULTS: Sixteen studies reported the prevalence of SICM and the pooled prevalence of SICM was 20% (95% confidence interval [CI], 16-25%; I2  =  89.9%, P < 0.01). Eleven studies reported short-term mortality and SICM was associated with significantly higher short-term mortality (The pooled odds ratio: 2.30, 95% CI, 1.43-3.69; I2  =  0%, P  =  0.001). CONCLUSION: The prevalence of SICM was 20% in patients with sepsis, and the occurrence of SICM was associated with significantly higher short-term mortality.

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  17. Comparison of Bivalirudin Versus Heparin for Anticoagulation During Extracorporeal Membrane Oxygenation. Reviewed International journal

    Daisuke Hasegawa, Ryota Sato, Narut Prasitlumkum, Kazuki Nishida, Brian Keaton, Samuel O Acquah, Young Im Lee

    ASAIO journal (American Society for Artificial Internal Organs : 1992)   Vol. 69 ( 4 ) page: 396 - 401   2023.4

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    The effect and safety of bivalirudin compared with heparin in patients undergoing extracorporeal membrane oxygenation (ECMO) remains unclear. Therefore, we conducted a systematic review and meta-analysis to compare the effectiveness and safety of heparin and bivalirudin in patients who underwent ECMO. We searched Embase, the Cochrane Central Register of Controlled Trials, and MEDLINE. Inclusion criteria included patients (1) undergoing ECMO and (2) receiving bivalirudin or heparin. We excluded studies where the majority of patients switched heparin to bivalirudin or vice versa during the clinical course. The primary outcome was short-term mortality. We presented the results of all analyses with the use of random-effects models. Eleven studies reported short-term mortality. The use of bivalirudin was associated with significantly lower short-term mortality, compared with heparin (odds ratio: 0.71, 95% confidence interval, 0.55-0.92; p = 0.01, I2 = 7%). In this meta-analysis of observational studies, the use of bivalirudin was associated with significantly lower short-term mortality, compared with heparin. Further prospective studies are warranted to clarify this finding.

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  18. Fixation of intra-articular calcaneal fractures: A comparative study of the postoperative outcome between HA/PPLA screws and locking plates Reviewed International journal

    Takuya Usami, Naoya Takada, Kazuki Nishida, Hiroaki Sakai, Hidetoshi Iwata, Hiroki Yonezu, Isato Sekiya, Yuko Nagaya, Yoshino Ueki, Hideki Murakami, Gen Kuroyanagi

    Heliyon   Vol. 9 ( 3 ) page: e14046 - e14046   2023.3

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    BACKGROUND: Forged unsintered hydroxyapatite and poly l-lactic acid (F-u-HA/PLLA) screw is bioactivite, bioabsorbable, and radiopaque with high mechanical strength. Its efficacy has been previously demonstrated in the treatment of lateral humeral condylar, lateral tibial condylar, ankle, and patellar fractures. However, studies on its efficacy in treatment of calcaneal fractures is lacking. This study aimed to compare the postoperative results of F-u-HA/PLLA screw fixation and locking plate fixation for intra-articular calcaneal fractures. METHODS: From January 2013 to December 2019, 47 closed intra-articular fractures treated with either F-u-HA/PLLA screws (group S, 18 feet in 17 patients) or locking plates (group P, 29 feet in 28 patients) in a single trauma center were retrospectively reviewed. The sinus tarsi approach was used in both groups. The time to bone union, step-off, varus deformity, Bohler's angle, and width and height of the calcaneus were assessed after surgery. Ankle joint range of motion (ROM) and postoperative complications were also assessed. RESULTS: All fractures were successfully treated. The Kaplan-Meier curves of the two groups showed similar trends. The log-rank test showed no significant difference in the time to bone union between the two groups (p = 0.48). In the Cox proportional hazards model adjusted for preoperative width and Bohler's angle, the hazard ratio for bone union was not statistically significant (HR: 1.13, 95%CI: 0.50-2.56, p = 0.78). Other variables included step-off (group S: 2.0 vs group P: 2.2 mm, p = 0.84), varus deformity (2.0° vs. 3.0°, p = 0.7), Gissane's angle (103.5° vs 104.0°, p = 0.84), width (38.0 vs 34.8 mm, p = 0.12), height (42.1 vs 44.0 mm, p = 0.07), and ankle ROM degrees (dorsal flexion, 20.0° vs. 20.0°, p = 0.13; plantar flexion 40.0° vs 40.0°, p = 0.56), which were not significantly different between groups P and S. The Bohler's angle was smaller in group S than in group P (20.5° vs 27.0°, p < 0.01). No skin necrosis or infection was observed in either group. CONCLUSION: Postoperative results of F-u-HA/PLLA screw fixation using the sinus tarsi approach for intra-articular calcaneal fractures were as good as those of locking plate fixation.

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  19. Hyaluronan in articular cartilage: analysis of hip osteoarthritis and osteonecrosis of femoral head. Reviewed International journal

    Jiarui Zhang, Yoshihiro Nishida, Hiroshi Koike, Kan Ito, Lisheng Zhuo, Kazuki Nishida, Koji Kimata, Kunihiro Ikuta, Tomohisa Sakai, Hiroshi Urakawa, Taisuke Seki, Shiro Imagama

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society   Vol. 41 ( 2 ) page: 307 - 315   2023.2

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    Hyaluronan (HA) plays crucial roles in the maintenance of high-quality cartilage extracellular matrix. Several studies have reported the HA in synovial fluid in patients with osteoarthritis (OA), but few have described the changes of HA in articular cartilage of OA or idiopathic osteonecrosis of femoral head (ONFH). KIAA1199 was recently reported to have strong hyaluronidase activity. The aim of this study was to clarify the HA metabolism in OA and ONFH, particularly the involvement of KIAA1199. Immunohistochemical analysis of KIAA1199 and HA deposition was performed for human OA (n=10), ONFH (n=10), and control cartilage (n=7). The concentration and molecular weight of HA were determined by competitive HA ELISA and Chromatography, respectively. Regarding HA metabolism related molecules, HAS1, HAS2, HAS3, HYAL1, HYAL2, and KIAA1199 gene expression was assessed by RT-PCR. Histological analysis showed the overexpression of KIAA1199 in OA cartilage, which was accompanied by decreased HABP staining compared with ONFH and control. Little KIAA1199 expression was observed in cartilage at the collapsed area of ONFH, which was accompanied by a slight decrease in HABP staining. The mRNA expression of HAS2 and KIAA1199 was up-regulated in OA cartilage, while the mRNA expression of genes related to HA catabolism in ONFH cartilage showed mostly a downward trend. The MW of HA in OA cartilage increased while that in ONFH cartilage decreased. HA metabolism in ONFH is suggested to be generally indolent, and is activated in OA including high expression of KIAA1199. Interestingly, MW of HA in OA cartilage was not reduced. This article is protected by copyright. All rights reserved.

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  20. Impact of an improved driveline management for HeartMate II and HeartMate 3 left ventricular assist devices Reviewed International journal

    Masato Mutsuga, Takahiro Okumura, Ryota Morimoto, Toru Kondo, Hideki Ito, Sachie Terazawa, Yoshiyuki Tokuda, Yuji Narita, Kazuki Nishida, Toyoaki Murohara, Akihiko Usui

    Artificial Organs   Vol. 47 ( 2 ) page: 387 - 395   2023.2

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    BACKGROUND: We evaluated the impact of a standardized driveline care strategy, including a subfascial-tunneling method and dressing protocol, on the incidence of driveline infection (DLI). METHODS: DLI data from all HeartMate II (HMII) and HeartMate 3 (HM3) patients (including exchange devices) were retrospectively collected between 2013 and 2021. The driveline subfascial-tunneling method was altered in three steps (A: right direct; B: left triple, C: right triple), and the shower protocol was changed in two steps (A: with/without cover, B: with cover). Disinfection was individually tailored after changing the shower protocol. Complications associated with morbidity and mortality were evaluated for each modification. RESULTS: During the study period, 80 devices were implanted (HMII, n = 54; HM3, n = 26). The 8-year incidence of DLI was 15% (n = 8) in HMII patients and 0% in HM3 patients (p = 0.039). DLI was not associated with hospital mortality. The modified dressing protocol and tunneling method was associated with a significantly better DLI incidence rate in comparison to the previous one: Protocol-A (n = 17), Protocol-B (n = 63), 35% vs 3% (p = 0.0009), Method-A (n = 13), Method-B (n = 42), Method-C (n = 25), 46% vs 5% vs 0% (p = 0.0001). The rete of freedom form DLI at 1, 2, and 3 years had also significant difference between groups: Protocol-A and Protocol-B, 80%, 54%, 54% vs 96%, 96%, 96%, respectively (p < 0.0001), Method-A, Method-B and Method-C, 76%, 44%, 44%, vs 94%, 94%, 94% vs 100%, 100%, respectively (p < 0.0001). CONCLUSIONS: A standardized triple driveline tunneling strategy and waterproof dressing protocol reduced driveline infection in HM3 patients to 0%.

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  21. Impact of Early Ambulation on the Prognosis of Coronary Artery Bypass Grafting Patients.

    Yohei Tsuchikawa, Yoshiyuki Tokuda, Hideki Ito, Miho Shimizu, Shinya Tanaka, Kazuki Nishida, Daichi Takagi, Akimasa Fukuta, Natsuki Takeda, Hiromasa Yamamoto, Masaya Hori, Yoshihiro Nishida, Masato Mutsuga

    Circulation journal : official journal of the Japanese Circulation Society   Vol. 87 ( 2 ) page: 306 - 311   2023.1

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    BACKGROUND: The effect of delayed ambulation on the outcome of coronary artery bypass grafting (CABG) remains to be clarified.Methods and Results: The long-term and in-hospital outcomes of 887 patients who underwent isolated CABG (455 off-pump cases, 135 urgent cases) were evaluated, with a focus on the timing of first ambulation. In-hospital mortality cases were excluded. Early ambulation (first ambulation within 3 days after operation) was achieved in 339 (38%) patients. In the multivariable logistic regression analysis, longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. Delayed ambulation was associated with a high incidence of postoperative complications, such as pneumonia, and stroke (P<0.01). Following discharge, 22.2% of patients experienced major cardiac events and 13.8% died during the follow-up period (median follow-up 60 months). Cox hazards analysis revealed that delayed ambulation was associated with long-term adverse events (hazard ratio 1.04 per day, P<0.001). With adjustment for preoperative factors, the estimated future risk of adverse events was found to be increased day-by-day during the delay until initial ambulation. CONCLUSIONS: In isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation protocol after cardiac surgery.

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  22. Scoring system for predicting the prognosis of elderly gastric cancer patients after endoscopic submucosal dissection. Reviewed International journal

    Nobuhito Ito, Kohei Funasaka, Toshihisa Fujiyoshi, Kazuki Nishida, Kazuhiro Furukawa, Naomi Kakushima, Satoshi Furune, Eizaburo Ohno, Masanao Nakamura, Noriyuki Horiguchi, Tomoyuki Shibata, Ryoji Miyahara, Jun-Ichi Haruta, Yoshiki Hirooka, Mitsuhiro Fujishiro, Hiroki Kawashima

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   Vol. 35 ( 1 ) page: 67 - 76   2023.1

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    OBJECTIVES: Comprehensive assessments of the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the elderly are unavailable. We aimed to create a scoring system to predict the long-term prognosis after ESD for EGC among patients aged ≥75 years. METHODS: We conducted retrospective studies of two cohorts: a single-center cohort (2006-2011) for developing the scoring system, and a multicenter cohort for validating the developed system (2012-2016). In the development cohort, factors related to death after ESD were identified using multivariable Cox regression analysis, and a predictive scoring system was developed. In the validation cohort, the scoring system was validated in 295 patients. RESULTS: In the development cohort, Charlson comorbidity index (CCI) ≥3 (hazard ratio [HR] 3.017), high psoas muscle index (PMI) (HR 2.206), and age ≥80 years (HR 1.978) were significantly related to overall survival after ESD. Therefore, high CCI, low PMI, and age ≥80 years were assigned 1 point each. The patients were categorized into low (≤1 point) and high (≥2 points) score groups based on their total scores. In the validation cohort, 184 and 111 patients were assigned to the low- and high-score groups, respectively. In comparisons based on Kaplan-Meier curves, the 5-year survival rate was 91.5% in the low-score group and 57.8% in the high-score group (log-rank test; P < 0.001). CONCLUSION: Our scoring system including high CCI, low PMI, and age ≥80 years could stratify the long-term prognosis of elderly patients aged ≥75 years after ESD for EGC.

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  23. Diagnostic Performance of Endocytoscopy for Esophageal Eosinophilia. Reviewed International journal

    Emiko Hida, Koichi Muroi, Naomi Kakushima, Satoshi Furune, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Maeda Keiko, Takeshi Yamamura, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Masanao Nakamura, Kazuki Nishida, Mitsuhiro Fujishiro, Hiroki Kawashima

    Digestion   Vol. 104 ( 3 ) page: 202 - 211   2023

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    INTRODUCTION: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. METHODS: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. RESULTS: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94-5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). DISCUSSION/CONCLUSION: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients.

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  24. Phase 1b study on the repurposing of meclizine hydrochloride for children with achondroplasia. Reviewed International journal

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Yasunari Kamiya, Daisaku Kato, Genta Takemoto, Kenta Sawamura, Shinji Ueno, Nakai Yasuhiro, Kazuki Nishida, Shiro Imagama

    PloS one   Vol. 18 ( 7 ) page: e0283425   2023

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    Achondroplasia (ACH) is a common skeletal dysplasia characterized by a disproportionately short stature. We found that meclizine, which is an over-the-counter drug for motion sickness, inhibited the fibroblast growth factor receptor 3 (FGFR3) gene using a drug repositioning strategy, and meclizine 1 and 2 mg/kg/day promoted bone growth in a mouse model of ACH. A previous phase 1a clinical trial for children with ACH demonstrated that a single dose of meclizine 25 and 50 mg was safe and that the simulated plasma concentration achieved steady state approximately 10 days after the first dose. The current study aimed to evaluate the safety and pharmacokinetics (PK) of meclizine in children with ACH after a 14-day-repeated dose of meclizine. Twelve patients with ACH aged 5-10 years were enrolled. Meclizine 12.5 (cohort 1) and 25 mg/day (cohort 2) were administered after meals for 14 days, and adverse events (AEs) and PK were evaluated. No patient experienced serious AEs in either group. The average (95% confidential interval [CI]) maximum drug concentration (Cmax), peak drug concentration (Tmax), area under the curve (AUC) from 0 to 24 h, and terminal elimination half-life (t1/2) after a 14-day-repeated administration of meclizine (12.5 mg) were 167 (83-250) ng/mL, 3.7 (3.1-4.2) h, 1170 (765-1570) ng·h/mL, and 7.4 (6.7-8.0) h, respectively. The AUC0-6h after the final administration was 1.5 times that after the initial dose. Cmax and AUC were higher in cohort 2 than in cohort 1 in a dose-dependent manner. Regarding the regimen of meclizine 12.5 and 25 mg in patients < 20 kg and ≥ 20 kg, respectively, the average (95% CI) AUC0-24h was 1270 (1100-1440) ng·h/mL. Compartment models demonstrated that the plasma concentration of meclizine achieved at a steady state after the 14th administration. Long-term administration of meclizine 12.5 or 25 mg/day is recommended for phase 2 clinical trials in children with ACH.

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  25. Preoperative docetaxel, cisplatin, and fluorouracil treatment with pegfilgrastim on day 7 for patients with esophageal cancer: A phase II study. Reviewed International journal

    Osamu Maeda, Masahide Fukaya, Masahiko Koike, Kazushi Miyata, Mitsuro Kanda, Kazuki Nishida, Masahiko Ando, Yasuhiro Kodera, Yuichi Ando

    Asia-Pacific journal of clinical oncology   Vol. 18 ( 6 ) page: 578 - 585   2022.12

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    AIMS: The docetaxel and cisplatin plus 5-fluorouracil (5-FU) (DCF) regimen is expected to be superior to cisplatin plus 5-FU for the preoperative treatment of esophageal cancer. However, a high risk of adverse effects, including febrile neutropenia (FN), has been reported. To evaluate the effectiveness and safety of DCF with prophylactic pegfilgrastim, we conducted a phase II study. METHODS: The regimen consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and a continuous infusion of 5-FU (750 mg/m2 per day) on days 1-5. A single 3.6-mg dose of pegfilgrastim was given as a subcutaneous injection on day 7 of each cycle. This regimen was repeated every 3 weeks for a maximum of three cycles. The primary endpoint was the grade-2/3 histopathological response rate. RESULTS: Thirty-seven eligible patients were enrolled and received DCF. Thirty-four patients underwent esophagectomy. Two patients received chemoradiotherapy or radiotherapy without surgery. One patient withdrew consent and ended his hospital visit. One patient received additional radiotherapy before surgery. Histopathological responses of grade 3, grade 2, grade 1b, and grade 1a were observed in two (5.4%), 14 (37.8%), 10 (27.0%), and seven (18.9%) patients, respectively, and the primary endpoint was met. Of the 37 eligible patients, 11 (29.7%) developed FN in the first cycle. CONCLUSIONS: Since the histopathological responses were as expected, DCF with prophylactic pegfilgrastim is considered to be effective as preoperative chemotherapy. However, the prophylactic use of pegfilgrastim on day 7 was insufficient to prevent FN.

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  26. Premorbid angiotensin converting enzyme inhibitors or angiotensin II receptor blockers in patients with sepsis. Reviewed International journal

    Daisuke Hasegawa, Young Im Lee, Narut Prasitlumkum, Lakshay Chopra, Kazuki Nishida, Robert L Smith, Ryota Sato

    The American journal of emergency medicine   Vol. 62   page: 69 - 77   2022.12

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    OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of the premorbid use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB) on short-term mortality in patients with sepsis. DATA SOURCES: Embase, the Cochrane Central Register of Controlled Trials, and MEDLINE were searched for studies based on the below eligibility criteria. The protocol was registered at the PROSPERO (CRD42022309129). STUDY SELECTION: Eligibility criteria were as follows: (1) randomized controlled trials, cohort studies, cross-sectional studies, (2) patients with sepsis aged ≥16 years, and (3) received premorbid ACEI/ARB, or not. DATA EXTRACTION: The patient and study characteristics and outcomes were extracted. All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as ≤30-day, in-hospital, or intensive care unit (ICU)- mortality. The secondary outcome was acute kidney injury (AKI). DATA SYNTHESIS: Fifteen studies (N = 96,159) met the eligibility criteria. Of these, eleven studies (N = 40,360) reported unadjusted short-term mortalities. The pooled odds ratio (OR) of short-term mortality with the premorbid use of ACEI/ARB was as follows: OR, 0.86; 95% confidence interval (CI), 0.67 to 1.11; P = 0.24, I2 = 88%. Five studies reported an adjusted OR of short-term mortality with the premorbid use of ACEI/ARB as follows: OR, 0.74; 95%CI, 0.59 to 0.93; P < 0.01, I2 = 93%. Seven studies reported the pooled adjusted OR of AKI with the premorbid use of ACEI/ARB as follows: OR: 1.57, 95%CI: 1.26-1.96, p < 0.01, I2 = 69%. CONCLUSION: In this meta-analysis, the premorbid ACEI/ARB was associated with significantly lower short-term mortality in patients with sepsis despite the significantly higher risk of AKI.

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  27. Comment on: Favourable complete remission of anti-OJ antibody-positive myositis after lung cancer resection. Reviewed International journal

    Yoshinao Muro, Kazuki Nishida, Yuta Yamashita, Haruka Koizumi, Takuya Takeichi, Minoru Satoh, Masashi Akiyama

    Rheumatology (Oxford, England)   Vol. 61 ( 8 ) page: e232 - e234   2022.8

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  28. The finger-to-nose test improved diagnosis of cerebrovascular events in patients presenting with isolated dizziness in the emergency department. Reviewed

    Kazuki Nishida, Takuya Usami, Nana Matsumoto, Mitsuaki Nishikimi, Kunihiko Takahashi, Shigeyuki Matsui

    Nagoya journal of medical science   Vol. 84 ( 3 ) page: 621 - 629   2022.8

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    It is difficult to identify patients with isolated dizziness caused by cerebrovascular events. The estimated risk of cerebrovascular events in isolated dizziness patients is not completely understood. We aimed to evaluate the association of the finger-to-nose test (FNT) in diagnosing cerebrovascular events in isolated dizziness patients in emergency departments (EDs). We combined 2 datasets from a single center for consecutive isolated dizziness patients, with the same inclusion and exclusion criteria. Those who met any of the following criteria were excluded: no FNT data, age < 16 years, and psychological trauma. The primary outcome was cerebrovascular event, which was defined as cerebral stroke due to cerebral infarction, cerebral hemorrhage, vertebral artery dissection, or transient ischemic attack. In the combined dataset, there were 357 patients complaining of isolated dizziness and 31 cerebrovascular events. After adjusted by 5 previously reported risk factors for cerebrovascular event, (age, hypertension, hyperlipidemia, diabetes mellitus, nystagmus), a multivariable logistic model analysis showed that the existence of FNT abnormalities was significantly associated with cerebrovascular events (odds ratio, 25.3; 95% confidence interval, 7.3-88.2; p < 0.001). There was a significant increase in predictive accuracy, with an AUC increase of 0.116 in the in a ROC analysis (p = 0.023). The existence of FNT abnormalities is considered as a strong risk factor that could be useful for predicting cerebrovascular events in isolated dizziness patients. We recommend the FNT for screening isolated dizziness patients in EDs to judge whether they need to undergo further diagnostic evaluation.

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  29. Predictive factors for massive hemorrhage in women with retained products of conception: a prospective study. Reviewed International journal

    Reina Sonehara, Tomoko Nakamura, Akira Iwase, Kazuki Nishida, Sachiko Takikawa, Mayuko Murakami, Sayako Yoshita, Ayako Muraoka, Natsuki Miyake, Natsuki Nakanishi, Satoko Osuka, Maki Goto, Hiroaki Kajiyama

    Scientific reports   Vol. 12 ( 1 ) page: 11859 - 11859   2022.7

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    Retained products of conception (RPOC) is a common cause of postpartum bleeding, which may be life-threatening; however, no evidence-based guidelines exist to assist in evaluating the risk of massive hemorrhage in women with RPOC. In this prospective study, we aimed to evaluate the predictive factors for massive hemorrhage in women with RPOC. The primary and secondary endpoints were to validate the usefulness of power Doppler color scoring (PDCS) in evaluating hypervascularity and to identify other predictive factors (such as maximum RPOC diameter and serum βhCG and Hb level at first visit), respectively. Among the 51 women with RPOC included in this study, 16 (31.5%) experienced massive hemorrhage during follow-up. None of the women with PDCS 1 or 2 (18) experienced massive hemorrhage, whereas 16 (48.5%) women with PDCS 3 or 4 (33) did. Multiple logistic regression analysis showed that the odds ratio [95% confidence interval] (P value) for PDCS, assisted reproductive technology (ART), and low serum hemoglobin (Hb) levels were 22.39 [2.25 - 3087.92] (P = 0.004), 5.72 [1.28 - 33.29] (P = 0.022), and 4.24 [0.97 - 22.99] (P = 0.056), respectively. Further, the decision tree method identified PDCS, ART, and low serum Hb levels as potential predictive factors for massive hemorrhage. This study identified PDCS as useful predictor of massive hemorrhage in women with RPOC. With additional inclusion of factors such as ART and low serum Hb levels, the risk of massive hemorrhage may be effectively evaluated, leading to better management of women of reproductive age.

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  30. Prediction of Prehospital Change of the Cardiac Rhythm From Nonshockable to Shockable in Out-of-Hospital Patients With Cardiac Arrest: A Post Hoc Analysis of a Nationwide, Multicenter, Prospective Registry. Reviewed International journal

    Ryo Emoto, Mitsuaki Nishikimi, Muhammad Shoaib, Kei Hayashida, Kazuki Nishida, Kazuya Kikutani, Shinichiro Ohshimo, Shigeyuki Matsui, Nobuaki Shime, Taku Iwami

    Journal of the American Heart Association   Vol. 11 ( 12 ) page: e025048   2022.6

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    Background Predicting a spontaneous rhythm change from nonshockable to shockable before hospital arrival in patients with out-of-hospital cardiac arrest can help emergency medical services develop better strategies for prehospital treatment. The aim of this study was to identify predictors of spontaneous rhythm change before hospital arrival in patients with out-of-hospital cardiac arrest and develop a predictive scoring system. Methods and Results We retrospectively reviewed data of eligible patients with out-of-hospital cardiac arrest with an initial nonshockable rhythm registered in a nationwide registry between June 2014 and December 2017. We performed a multivariable analysis using a Cox proportional hazards model to identify predictors of a spontaneous rhythm change, and a ridge regression model for predicting it. The data of 25 804 patients were analyzed (derivation cohort, n=17 743; validation cohort, n=8061). The rhythm change event rate was 4.1% (724/17 743) in the derivation cohort, and 4.0% (326/8061) in the validation cohorts. Age, sex, presence of a witness, initial rhythm, chest compression by a bystander, shock with an automated external defibrillator by a bystander, and cause of the cardiac arrest were all found to be independently associated with spontaneous rhythm change before hospital arrival. Based on this finding, we developed and validated the Rhythm Change Before Hospital Arrival for Nonshockable score. The Harrell's concordance index values of the score were 0.71 and 0.67 in the internal and external validations, respectively. Conclusions Seven factors were identified as predictors of a spontaneous rhythm change from nonshockable to shockable before hospital arrival. We developed and validated a score to predict rhythm change before hospital arrival.

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  31. Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade Reviewed International journal

    Yuki Miyai, Daisuke Sugiyama, Tetsunari Hase, Naoya Asai, Tetsuro Taki, Kazuki Nishida, Takayuki Fukui, Toyofumi Fengshi Chen-Yoshikawa, Hiroki Kobayashi, Shinji Mii, Yukihiro Shiraki, Yoshinori Hasegawa, Hiroyoshi Nishikawa, Yuichi Ando, Masahide Takahashi, Atsushi Enomoto

    Life Science Alliance   Vol. 5 ( 6 )   2022.6

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    Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.

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  32. Impact of Serum Zinc Level and Oral Zinc Supplementation on Clinical Outcomes in Patients Undergoing Infrainguinal Bypass for Chronic Limb-Threatening Ischemia.

    Akio Kodama, Kimihiro Komori, Akio Koyama, Tomohiro Sato, Shuta Ikeda, Takuya Tsuruoka, Yohei Kawai, Kiyoaki Niimi, Masayuki Sugimoto, Hiroshi Banno, Kazuki Nishida

    Circulation journal : official journal of the Japanese Circulation Society   Vol. 86 ( 6 ) page: 995 - 1006   2022.5

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    BACKGROUND: Zinc (Zn) has been reported to play an important role in wound healing (WH). Nevertheless, the effect of Zn in chronic limb-threatening ischemia (CLTI) patients is unclear. This study investigated the effect of Zn on the clinical outcomes of CLTI patients undergoing bypass surgery.Methods and Results:This study reviewed 111 consecutive patients who underwent an infrainguinal bypass from 2012 to 2020. Patients with Zn deficiency (serum Zn level <60 μg/dL) received oral Zn supplementation and maintained a normal level until WH. This study aimed to explore: (1) the effect of Zn deficiency; and (2) Zn supplementation in Zn-deficient patients on the clinical outcomes of this cohort. Patients with Zn deficiency, Zn supplementation, and no Zn supplementation despite Zn deficiency accounted for 48, 21, and 42 patients, respectively. (1) Zn deficiency was associated with WH (HR, 0.47; 95% CI, 0.29-0.78: P=0.003), major adverse limb events (MALE) (HR, 2.53; 95% CI, 1.26-5.09: P=0.009), and major amputation or death (HR, 3.17; 95% CI, 1.51-6.63: P=0.002). (2) Zn supplementation was positively related to WH (HR, 2.30; 95% CI, 1.21-4.34: P=0.011). This result was confirmed using propensity score matching (HR, 2.24; 95% CI, 1.02-4.87: P=0.043). CONCLUSIONS: The current study revealed that Zn level was associated with clinical outcomes in CLTI patients after bypass surgery. Oral Zn supplementation could improve WH in these patients.

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  33. Fecal incontinence and oral regurgitation during duodenal endoscopic submucosal dissection using the water-pressure method. Reviewed International journal

    Yoshihisa Takada, Takashi Hirose, Kazuki Nishida, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima, Mitsuhiro Fujishiro

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   Vol. 34 ( 3 ) page: 526 - 534   2022.3

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    OBJECTIVES: Endoscopic submucosal dissection (ESD) in the duodenum is challenging. The water pressure method (WP-ESD) has been developed with a decreased rate of perforation. However, details about perioperative adverse events of WP-ESD are unknown. The purpose of this study was to clarify the frequency and related factors of fecal incontinence and oral regurgitation during WP-ESD. METHODS: A chart-based retrospective analysis was performed on 43 patients who underwent duodenal WP-ESD. The saline volume given into the body was calculated in all cases. All adverse events during WP-ESD until six weeks were extracted, and factors related to intraoperative fecal incontinence or oral regurgitation were analyzed. The frequency of fecal incontinence and oral regurgitation was also compared to those of 83 conventional ESD cases. RESULTS: In WP-ESD, intraoperative fecal incontinence occurred in 12 (28%), oral regurgitation in six (14%), and aspiration pneumonia in one patient. For fecal incontinence, the infusion speed (saline volume divided by resection time) ≧17ml/min was a significant factor in multivariable analysis. For oral regurgitation, only tumor size was the significant factor in univariate analysis (P=0.027). Significant difference was observed in the frequency of fecal incontinence between WP-ESD and conventional ESD (28% vs 0%, P<0.001), but no difference was observed in oral regurgitation or aspiration pneumonia. CONCLUSIONS: Intraoperative fecal incontinence is a unique adverse event of WP-ESD related to the infusion speed. WP-ESD was not a risk of oral regurgitation, but we should be aware of the risk in large tumor cases.

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  34. Evaluation of lower extremity gait analysis using Kinect V2® tracking system. Reviewed International journal

    Takuya Usami, Kazuki Nishida, Hirotaka Iguchi, Taro Okumura, Hiroaki Sakai, Ruido Ida, Mitsuya Horiba, Shuuto Kashima, Kento Sahashi, Hayato Asai, Yuko Nagaya, Hideki Murakami, Yoshino Ueki, Gen Kuroyanagi

    SICOT-J   Vol. 8   page: 27 - 27   2022

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    INTRODUCTION: Microsoft Kinect V2® (Kinect) is a peripheral device of Xbox® and acquires information such as depth, posture, and skeleton definition. In this study, we investigated whether Kinect can be used for human gait analysis. METHODS: Ten healthy volunteers walked 20 trials, and each walk was recorded by a Kinect and infrared- and marker-based-motion capture system. Pearson's correlation and overall agreement with a method of meta-analysis of Pearson's correlation coefficient were used to assess the reliability of each parameter, including gait velocity, gait cycle time, step length, hip and knee joint angle, ground contact time of foot, and max ankle velocity. Hip and knee angles in one gait cycle were calculated in Kinect and motion capture groups. RESULTS: The coefficients of correlation for gait velocity (r = 0.92), step length (r = 0.81) were regarded as strong reliability. Gait cycle time (r = 0.65), minimum flexion angle of hip joint (r = 0.68) were regarded as moderate reliability. The maximum flexion angle of the hip joint (r = 0.43) and maximum flexion angle of the knee joint (r = 0.54) were regarded as fair reliability. Minimum flexion angle of knee joint (r = 0.23), ground contact time of foot (r = 0.23), and maximum ankle velocity (r = 0.22) were regarded as poor reliability. The method of meta-analysis revealed that participants with small hip and knee flexion angles tended to have poor correlations in maximum flexion angle of hip and knee joints. Similar trajectories of hip and knee angles were observed in Kinect and motion capture groups. CONCLUSIONS: Our results strongly suggest that Kinect could be a reliable device for evaluating gait parameters, including gait velocity, gait cycle time, step length, minimum flexion angle of the hip joint, and maximum flexion angle of the knee joint.

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  35. A Diagnostic Predictive Model of Bronchoscopy with Radial Endobronchial Ultrasound for Peripheral Pulmonary Lesions. Reviewed International journal

    Takayasu Ito, Yuji Matsumoto, Shotaro Okachi, Kazuki Nishida, Midori Tanaka, Tatsuya Imabayashi, Takaaki Tsuchida, Naozumi Hashimoto

    Respiration; international review of thoracic diseases   Vol. 101 ( 12 ) page: 1148 - 1156   2022

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    BACKGROUND: Several factors have been reported to affect the diagnostic yield of bronchoscopy with radial endobronchial ultrasound (R-EBUS) for peripheral pulmonary lesions (PPLs). However, it is difficult to accurately predict the diagnostic potential of bronchoscopy for each PPL in advance. OBJECTIVES: Our objective was to establish a predictive model to evaluate the diagnostic yield before the procedure. METHOD: We retrospectively analysed consecutive patients who underwent diagnostic bronchoscopy with R-EBUS between April 2012 and October 2015. We assessed the factors that were predictive of successful bronchoscopic diagnosis of PPLs with R-EBUS using a multivariable logistic regression model. The accuracy of the predictive model was evaluated using the receiver operator characteristic area under the curve (ROC AUC). Internal validation was analysed using 10-fold stratified cross-validation. RESULTS: We analysed a total of 1,634 lesions; the median lesion size was 25.0 mm. Of these, 1,138 lesions (69.6%) were successfully diagnosed. In the predictive logistic model, significant factors affecting the diagnostic yield were lesion size, lesion structure, bronchus sign, and visible on chest X-ray. The predictive model consisted of seven factors: lesion size, lesion lobe, lesion location from the hilum, lesion structure, bronchus sign, visibility on chest X-ray, and background lung. The ROC AUC of the predictive model was 0.742 (95% confidence interval: 0.715-0.769). Internal validation using 10-fold stratified cross-validation revealed a mean ROC AUC of 0.734. CONCLUSIONS: The predictive model using the seven factors revealed a good performance in estimating the diagnostic yield.

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  36. 17O-labeled water distribution in the human inner ear: Insights into lymphatic dynamics and vestibular function. Reviewed International journal

    Tadao Yoshida, Shinji Naganawa, Masumi Kobayashi, Satofumi Sugimoto, Naomi Katayama, Tsutomu Nakashima, Yutaka Kato, Kazushige Ichikawa, Hiroshi Yamaguchi, Kazuki Nishida, Michihiko Sone

    Frontiers in neurology   Vol. 13   page: 1016577 - 1016577   2022

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    We evaluated the inner ear distribution of 17O-labeled saline administered to the human tympanic cavity. Magnetic resonance imaging was performed after intratympanic administration in five healthy volunteers and one patient with cochlear endolymphatic hydrops. In all volunteers, 17O-labeled water permeated the cochlear basal turn and vestibule at 30 min and disappeared gradually within 2-4 h. All participants experienced positional vertigo lasting a few hours to a few days. Visualization of 17O-labeled water distribution in the endolymphatic space of the posterior ampulla showed indistinct separation of endolymph and perilymph in the cochlea and most of the vestibule in all participants. Intralabyrinthine distribution of 17O-labeled water differed from that in previous reports of intratympanically administered gadolinium-based contrast agent. 17O-labeled water in the endolymphatic space may cause heavier endolymph and positional vertigo. These results of this study may add new insights for investigating the distribution and the effects of molecules in the inner ear after the intratympanic administration in living humans.

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  37. Effect of IV High-Dose Vitamin C on Mortality in Patients With Sepsis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Reviewed International journal

    Ryota Sato, Daisuke Hasegawa, Narut Prasitlumkum, Miki Ueoka, Kazuki Nishida, Kunihiko Takahashi, Michitaka Nasu, Siddharth Dugar

    Critical care medicine   Vol. 49 ( 12 ) page: 2121 - 2130   2021.12

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    OBJECTIVES: The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials to investigate whether IV high-dose vitamin C improves the short-term mortality of patients with sepsis. DESIGN: This study is a systematic review and meta-analysis of randomized controlled trials. We searched EMBASE, the Cochrane Central Register of Controlled Trials, and MEDLINE for randomized controlled trials that met inclusion criteria. The protocol was registered at the University hospital Medical Information Network Clinical Trials Registry (UMIN000040528). All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as 28-day, 30-day, or in-hospital mortality. PATIENTS: Two authors independently evaluated the following eligibility criteria: 1) randomized controlled trial, 2) patients with sepsis aged ≥18 years, and 3) received intravenous high-dose vitamin C in addition to standard of care, or standard of care alone. Then, two authors independently extracted the selected patient and study characteristics and outcomes from studies that met above eligibility criteria. MEASUREMENTS AND MAIN RESULTS: Eleven randomized controlled trials (n = 1,737 patients) were included in this meta-analysis. High-dose IV vitamin C was not associated with a significantly lower short-term mortality (risk ratio, 0.88; 95% CI, 0.73-1.06; p = 0.18; I2 = 29%) but was associated with a significantly shorter duration of vasopressor use (standardized mean difference, -0.35; 95% CI, -0.63 to -0.07; p < 0.01; I2 = 80%) and a significantly greater decline in the Sequential Organ Failure Assessment score at 72-96 hours (standardized mean difference, -0.20; 95% CI, -0.32 to -0.08; p < 0.01; I2 = 16%). One study reported significant association with hypernatremia, but adverse effects were rare, and high-dose vitamin C is deemed relatively safe. CONCLUSIONS: In this meta-analysis, the use of IV high-dose vitamin C in patients with sepsis was not associated with lower short-term mortality although it was associated with significantly shorter duration of vasopressor use and greater decline in the Sequential Organ Failure Assessment score at 72-96 hours.

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  38. Prevalence of pulmonary embolism in patients with acute exacerbations of COPD: A systematic review and meta-analysis Reviewed International journal

    Ryota Sato, Daisuke Hasegawa, Kazuki Nishida, Kunihiko Takahashi, Mary Schleicher, Neal Chaisson

    The American Journal of Emergency Medicine   Vol. 50   page: 606 - 617   2021.12

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    STUDY OBJECTIVE: Identification of pulmonary embolism (PE) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) carries significant therapeutic implications. We aimed to investigate the prevalence of PE in patients with AECOPD. METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and Embase. We registered the protocol at the PROSPERO (CRD42021230481). Two authors independently evaluated whether titles and abstracts met the eligibility criteria, which were as follows: (1), prospective study or cross-sectional study in case the protocol for workup of PE was specified in advance, (2) patients with AECOPD aged ≥ 18 years, and (3) investigated the prevalence of PE or venous thromboembolism (VTE). Two authors independently extracted the selected patient and study characteristics and outcomes. We presented the results of all analyses with the use of random-effects models. The primary outcome was the prevalence of PE. RESULTS: We included 16 studies (N = 4093 patients) in this meta-analysis. The prevalence of PE in patients with AECOPD was 12% [95% confidence interval (CI), 9 to 16%]. Substantial heterogeneity was observed (I2 = 94.8%). The pooled mortality was higher in patients with PE than those without (odds ratio 5.30, 95%CI: 2.48-11.30, p-value < 0.001). CONCLUSION: In this meta-analysis, the prevalence of PE in patients with AECOPD was 12% and the mortality of patients with PE was higher than those without. This suggests an acute necessity to develop validated diagnostic strategies for identifying PE in patients with AECOPD.

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  39. Effect of Premorbid Beta-Blockers on Mortality in Patients With Sepsis: A Systematic Review and Meta-Analysis Reviewed International journal

    Daisuke Hasegawa, Ryota Sato, Narut Prasitlumkum, Kazuki Nishida

    Journal of Intensive Care Medicine   Vol. 37 ( 7 ) page: 088506662110529 - 088506662110529   2021.11

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    <jats:sec><jats:title>Objective</jats:title><jats:p> The aim of this study was to conduct a systematic review and meta-analysis to investigate the impact of premorbid beta-blockers on mortality in patients with sepsis. </jats:p></jats:sec><jats:sec><jats:title>Data Sources</jats:title><jats:p> We searched EMBASE, the Cochrane Central Register of Controlled Trials, and MEDLINE for eligible studies. The protocol was registered at the PROSPERO (CRD42021256813). </jats:p></jats:sec><jats:sec><jats:title>Study Selection</jats:title><jats:p> Two authors independently evaluated the following inclusion criteria: (1) randomized controlled trials, cohort studies, cross-sectional studies; (2) patients with sepsis aged ≥18 years, and (3) premorbid beta-blocker use. </jats:p></jats:sec><jats:sec><jats:title>Data Extraction</jats:title><jats:p> Two authors extracted the patients’ characteristics and outcomes independently. All analyses were performed using the random-effects models. The primary outcome was short-term mortality, defined as mortality within 30 days, in-hospital or intensive care unit mortality. </jats:p></jats:sec><jats:sec><jats:title>Data Synthesis</jats:title><jats:p> Ten studies (n = 24 748 patients) were included. The pooled odds ratio (OR) of short-term mortality associated with the premorbid use of beta-blockers was 0.85 (95% confidence interval [CI], 0.69-1.04; P = .12; I<jats:sup>2</jats:sup> = 50%). Five studies reported an adjusted OR of short-term mortality. The pooled adjusted OR of short-term mortality associated with the premorbid use of beta-blockers was 0.73 (95% CI, 0.65-0.83; P &lt; .001; I<jats:sup>2</jats:sup> = 0%). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Premorbid beta-blockers were associated with a lower short-term mortality in patients with sepsis. </jats:p></jats:sec>

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  40. The rCAST score is useful for estimating the neurological prognosis in pediatric patients with post-cardiac arrest syndrome before ICU admission: External validation study using a nationwide prospective registry. Reviewed International journal

    Yuma Yasuda, Mitsuaki Nishikimi, Kota Matsui, Atsushi Numaguchi, Kazuki Nishida, Ryo Emoto, Shigeyuki Matsui, Naoyuki Matsuda

    Resuscitation   Vol. 168   page: 103 - 109   2021.11

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    INTRODUCTION: The objective of this cohort study was to investigate whether the revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia score (rCAST), which we previously developed as a prognostic score for adult patients with post-cardiac arrest syndrome (PCAS), is also applicable to pediatric patients. METHODS: Pediatric PCAS patients were included from an out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM). We validated the predictive accuracy of the rCAST for the neurological outcomes at 30 and 90 days. We also evaluated the probability of a good neurological outcome in each of the three specified severity categories based on the rCAST (low severity: ≤5.5; moderate severity: 6.0-14.0; high severity: ≥14.5). RESULTS: Among the 737 pediatric patients with OHCA, the data of 179 pediatric PCAS patients in whom return of spontaneous circulation was achieved were analyzed. The areas under the curve (AUC) of the rCAST for predicting the neurological outcomes at 30 days and 90 days were 0.95 (95% CI: 0.90-0.99) and 0.96 (0.91-1.00), respectively. The proportions of patients with a good neurological outcome at 30 days were 100% (12/12) in the low severity group, 36.1% (13/36) in the moderate severity group, and 2.3% (3/131) in the high severity group. CONCLUSIONS: The AUC of the rCAST for pediatric PCAS patients was found to be greater than 0.9 in the external validation, which corresponds to excellent predictive accuracy. There was no patient with good neurological outcome among the patients with more than 17.0 points (extremely high severity group).

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  41. Hypofibrinogenemia can be estimated by the predictive formula in aortic surgery Reviewed

    Nishi, Toshihiko, Mutsuga, Masato, Akita, Toshiaki, Narita, Yuji, Fujimoto, Kazuro, Tokuda, Yoshiyuki, Nishida, Kazuki, Matsui, Shigeyuki, Nishiwaki, Kimitoshi, Usui, Akihiko

    General Thoracic and Cardiovascular Surgery   Vol. 69 ( 10 ) page: 1376 - 1382   2021.10

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    OBJECTIVE: Aortic surgery often causes massive bleeding due to hypofibrinogenemia. Predicting hypofibrinogenemia is useful for developing a hemostasis strategy, including preparing for blood transfusion. We made a formula for predicting the serum fibrinogen level (SFL) at the termination of cardiopulmonary bypass (CPB) in aortic surgery and examined its validity. METHODS: We performed a retrospective observational study that consisted of 267 patients (group A) who underwent aortic surgery from July 2013 to December 2016 and made a formula for predicting the SFL at the termination of CPB in group A by a multiple linear regression analysis. The validity of this formula was then examined in another 60 patients (group B) who underwent aortic surgery from January 2017 to December 2017. RESULTS: We developed the following predictive formula: SFL at the termination of CPB (mg/dL) = 14.7 + 0.44 × preoperative SFL (mg/dL) + (- 0.14) × CPB time (min) + 0.64 × preoperative body weight (kg) + (- 17.3) × lateral thoracotomy (Yes/No, Yes: 1, No: 0). In group B, the predictive formula proved to be statistically valid in group B (R2 = 0.531, p < 0.001). CONCLUSION: The SFL at the termination of CPB in aortic surgery can be predicted by the preoperative SFL, body weight, CPB time and surgical approach. The predictive formula is useful for developing a hemostasis strategy, including preparing for blood transfusion.

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  42. Clinical impact of visually assessed right ventricular dysfunction in patients with septic shock. Reviewed International journal

    Hiroaki Hiraiwa, Daisuke Kasugai, Masayuki Ozaki, Yukari Goto, Naruhiro Jingushi, Michiko Higashi, Kazuki Nishida, Toru Kondo, Kenji Furusawa, Ryota Morimoto, Takahiro Okumura, Naoyuki Matsuda, Shigeyuki Matsui, Toyoaki Murohara

    Scientific reports   Vol. 11 ( 1 ) page: 18823 - 18823   2021.9

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    We retrospectively analyzed data from the Medical Information Mart for Intensive Care-III critical care database to determine whether visually-assessed right ventricular (RV) dysfunction was associated with clinical outcomes in septic shock patients. Associations between visually-assessed RV dysfunction by echocardiography and in-hospital mortality, lethal arrhythmia, and hemodynamic indicators to determine the prognostic value of RV dysfunction in patients with septic shock were analyzed. Propensity score analysis showed RV dysfunction was associated with increased risk of in-hospital death in patients with septic shock (adjusted odds ratio [OR] 2.15; 95% confidence interval [CI] 1.99-2.32; P < 0.001). In multivariate logistic regression analysis, RV dysfunction was associated with in-hospital death (OR 2.19; 95% CI 1.91-2.53; P < 0.001), lethal arrhythmia (OR 2.19; 95% CI 1.34-3.57; P < 0.001), and tendency for increased blood lactate levels (OR 1.31; 95% CI 1.14-1.50; P < 0.001) independent of left ventricular (LV) dysfunction. RV dysfunction was associated with lower cardiac output, pulmonary artery pressure index, and RV stroke work index. In patients with septic shock, visually-assessed RV dysfunction was associated with in-hospital mortality, lethal arrhythmia, and circulatory insufficiency independent of LV dysfunction. Visual assessment of RV dysfunction using echocardiography might help to identify the short-term prognosis of patients with septic shock by reflecting hemodynamic status.

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  43. Outcome Related to Level of Targeted Temperature Management in Postcardiac Arrest Syndrome of Low, Moderate, and High Severities: A Nationwide Multicenter Prospective Registry. Reviewed International journal

    Mitsuaki Nishikimi, Takayuki Ogura, Kazuki Nishida, Kei Hayashida, Ryo Emoto, Shigeyuki Matsui, Naoyuki Matsuda, Taku Iwami

    Critical care medicine   Vol. 49 ( 8 ) page: e741 - e750   2021.8

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    OBJECTIVES: The optimal target temperature during targeted temperature management for patients after cardiac arrest remains under debate. The aim of this study was to evaluate the association between targeted temperature management at lower target temperatures and the neurologic outcomes among patients classified by the severity of postcardiac arrest syndrome. DESIGN: A multicenter observational study from the out-of-hospital cardiac arrest registry of the Japanese Association for Acute Medicine, which is a nationwide prospective registry of out-of-hospital cardiac arrest patients. SETTING: A total of 125 critical care medical centers or hospitals with an emergency care department across Japan. PATIENTS: A total of 1,111 out-of-hospital cardiac arrest patients who had received targeted temperature management. MEASUREMENTS AND MAIN RESULTS: We divided all 1,111 postcardiac arrest syndrome patients treated with targeted temperature management into two groups: those who received targeted temperature management at a lower target temperature (33-34°C) and those who received targeted temperature management at a higher target temperature (35-36°C). In regard to classification of the patients, we divided the patients into three categories of severity (low, moderate, and high severities) using the risk classification tool, post-Cardiac Arrest Syndrome for Therapeutic hypothermia, which was previously validated. The primary outcome was the percentage of patients with a good neurologic outcome at 30 days, and the secondary outcome was the survival rate at 30 days. Multivariate analysis showed that targeted temperature management at 33-34°C was significantly associated with a good neurologic outcome and survival at 30 days in the moderate severity (odds ratio, 1.70 [95% CI, 1.03-2.83] and 1.90 [95% CI, 1.15-3.16], respectively), but not in the patients of low or high severity (pinteraction = 0.033). Propensity score analysis also showed that targeted temperature management at 33-34°C was associated with a good neurologic outcome in the moderate-severity group (p = 0.022). CONCLUSIONS: Targeted temperature management at 33-34°C was associated with a significantly higher rate of a good neurologic outcome in the moderate-severity postcardiac arrest syndrome group, but not in the low- or high-severity group.

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  44. Relative platelet reductions provide better pathophysiologic signatures of coagulopathies in sepsis. Reviewed International journal

    Daisuke Kasugai, Masayuki Ozaki, Kazuki Nishida, Yukari Goto, Kunihiko Takahashi, Shigeyuki Matsui, Naoyuki Matsuda

    Scientific reports   Vol. 11 ( 1 ) page: 14033 - 14033   2021.7

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    In sepsis-associated coagulopathies and disseminated intravascular coagulation, relative platelet reductions may reflect coagulopathy severity. However, limited evidence supports their clinical significance and most sepsis-associated coagulopathy criteria focus on the absolute platelet counts. To estimate the impact of relative platelet reductions and absolute platelet counts on sepsis outcomes. A multicenter retrospective observational study was performed using the eICU Collaborative Research Database, comprising 335 intensive care units (ICUs) in the United States. Patients with sepsis and an ICU stay > 2 days were included. Estimated effects of relative platelet reductions and absolute platelet counts on mortality and coagulopathy-related complications were evaluated. Overall, 26,176 patients were included. Multivariate mixed-effect logistic regression analysis revealed marked in-hospital mortality risk with larger platelet reductions between days one and two, independent from the resultant absolute platelet counts. The adjusted odds ratio (OR) [95% confidence intervals (CI)] for in-hospital mortality was 1.28[1.23-1.32], 1.86[1.75-1.97], 2.99[2.66-3.36], and 6.05[4.40-8.31] for 20-40%, 40-60%, 60-80%, and > 80% reductions, respectively, when compared with a < 20% decrease in platelets (P < 0.001 for each). In the multivariate logistic regression analysis, platelet reductions ≥ 11% and platelet counts ≤ 100,000/μL on day 2 were associated with high coagulopathy-related complications (OR [95%CI], 2.03 and 1.18; P < 0.001 and P < 0.001), while only platelet reduction was associated with thromboembolic complications (OR [95%CI], 1.43 [1.03-1.98], P < 0.001). The magnitude of platelet reductions represent mortality risk and provides a better signature of coagulopathies in sepsis; therefore, it is a plausible criterion for sepsis-associated coagulopathies.

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  45. Usefulness of Respiratory Mechanics and Laboratory Parameter Trends as Markers of Early Treatment Success in Mechanically Ventilated Severe Coronavirus Disease: A Single-Center Pilot Study Reviewed International journal

    Daisuke Kasugai, Masayuki Ozaki, Kazuki Nishida, hiroaki hiraiwa, Naruhiro Jingushi, Atsushi Numaguchi, Norihito Omote, Yuichiro Shindo, Yukari Goto

    Journal of Clinical Medicine   Vol. 10 ( 11 ) page: 2513 - 2513   2021.6

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    Whether a patient with severe coronavirus disease (COVID-19) will be successfully liberated from mechanical ventilation (MV) early is important in the COVID-19 pandemic. This study aimed to characterize the time course of parameters and outcomes of severe COVID-19 in relation to the timing of liberation from MV. This retrospective, single-center, observational study was performed using data from mechanically ventilated COVID-19 patients admitted to the ICU between 1 March 2020 and 15 December 2020. Early liberation from ventilation (EL group) was defined as successful extubation within 10 days of MV. The trends of respiratory mechanics and laboratory data were visualized and compared between the EL and prolonged MV (PMV) groups using smoothing spline and linear mixed effect models. Of 52 admitted patients, 31 mechanically ventilated COVID-19 patients were included (EL group, 20 (69%); PMV group, 11 (31%)). The patients' median age was 71 years. While in-hospital mortality was low (6%), activities of daily living (ADL) at the time of hospital discharge were significantly impaired in the PMV group compared to the EL group (mean Barthel index (range): 30 (7.5-95) versus 2.5 (0-22.5), p = 0.048). The trends in respiratory compliance were different between patients in the EL and PMV groups. An increasing trend in the ventilatory ratio during MV until approximately 2 weeks was observed in both groups. The interaction between daily change and earlier liberation was significant in the trajectory of the thrombin-antithrombin complex, antithrombin 3, fibrinogen, C-reactive protein, lymphocyte, and positive end-expiratory pressure (PEEP) values. The indicator of physiological dead space increases during MV. The trajectory of markers of the hypercoagulation status, inflammation, and PEEP were significantly different depending on the timing of liberation from MV. These findings may provide insight into the pathophysiology of COVID-19 during treatment in the critical care setting.

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  46. The predictive value of airway occlusion pressure at 100 msec (P0.1) on successful weaning from mechanical ventilation: A systematic review and meta-analysis Reviewed International journal

    Sato, Ryota, Hasegawa, Daisuke, Hamahata, Natsumi T., Narala, Swetha, Nishida, Kazuki, Takahashi, Kunihiko, Sempokuya, Tomoki, Daoud, Ehab G.

    Journal of Critical Care   Vol. 63   page: 124 - 132   2021.6

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    PURPOSE: The predictive value of airway occlusion pressure at 100 milliseconds (P0.1) on weaning outcome has been controversial. We performed a meta-analysis to investigate the predictive value of P0.1 on successful weaning from mechanical ventilation. MATERIALS AND METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE, and two authors independently screened articles. The pooled sensitivity, specificity and the summary receiver operating characteristic (sROC) curve were estimated. Diagnostic odds ratio (DOR) was calculated using meta-regression analysis. RESULTS: We included 12 prospective observational studies (n = 1089 patients). Analyses of sROC curves showed the area under the curve of 0.81 (95% confidence interval (CI): 0.77 to 0.84) for P0.1. The pooled sensitivity and specificity were 86% (95% CI, 72 to 94%) and 58% (95% CI, 37% to 76%) with substantial heterogeneity respectively. DOR was 20.09 (p = 0.019, 95%CI: 1.63-247.15). After filling the missing data using the trim-and-fill method to adjust publication bias, DOR was 36.23 (p = 0.002, 95%CI: 3.56-372.41). CONCLUSION: This meta-analysis suggests that P0.1 is a useful tool to predict successful weaning. To determine clinical utility, a large prospective study investigating the sensitivity and specificity of P0.1 on weaning outcomes from mechanical ventilation is warranted.

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  47. Effect of Ultrashort-Acting β-Blockers on Mortality in Patients With Sepsis With Persistent Tachycardia Despite Initial Resuscitation: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Reviewed International journal

    Daisuke Hasegawa, Ryota Sato, Narut Prasitlumkum, Kazuki Nishida, Kunihiko Takahashi, Tomoaki Yatabe, Osamu Nishida

    Chest   Vol. 159 ( 6 ) page: 2289 - 2300   2021.6

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    BACKGROUND: Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation. RESEARCH QUESTION: Do ultrashort-acting β-blockers such as esmolol and landiolol improve mortality in patients with sepsis with persistent tachycardia despite initial resuscitation? STUDY DESIGN AND METHODS: This was a systematic review and meta-analysis. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with esmolol or landiolol. We updated our search on April 20, 2020. Two independent reviewers assessed whether titles and abstracts met the following eligibility criteria: (1) RCT, (2) patients with sepsis and septic shock ≥ 18 years of age, and (3) treatment with either esmolol/landiolol or placebo/no interventions. Two authors independently extracted selected patient and study characteristics and outcomes. The results of all analyses are presented using random effect models. RESULTS: Seven RCTs with a pooled sample size of 613 patients were included. Of these, six RCTs with 572 patients reported 28-day mortality. Esmolol or landiolol use in patients with sepsis and septic shock was significantly associated with lower 28-day mortality (risk ratio, 0.68; 95% CI, 0.54-0.85; P < .001). Unimportant heterogeneity was observed (I2 = 31%). The absolute risk reduction and number of patients to be treated to prevent one death were 18.2% and 5.5, respectively. INTERPRETATION: The use of ultrashort-acting β-blockers such as esmolol and landiolol in patients with sepsis with persistent tachycardia despite initial resuscitation was associated with significantly lower 28-day mortality. TRIAL REGISTRY: UMIN Clinical Trials Registry; No.: UMIN000040174; URL: https://www.umin.ac.jp/ctr/index.htm.

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  48. Failure of non-invasive respiratory support after 6 hours from initiation is associated with ICU mortality Reviewed International journal

    Nishikimi, M., Nishida, K., Shindo, Y., Shoaib, M., Kasugai, D., Yasuda, Y., Higashi, M., Numaguchi, A., Yamamoto, T., Matsui, S., Matsuda, N.

    PLoS ONE   Vol. 16 ( 4 ) page: e0251030   2021

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    A previous study has shown that late failure (> 48 hours) of high-flow nasal cannula (HFNC) was associated with intensive care unit (ICU) mortality. The aim of this study was to investigate whether failure of non-invasive respiratory support, including HFNC and non-invasive positive pressure ventilation (NPPV), was also associated with the risk of mortality even if it occurs in the earlier phase. We retrospectively analyzed 59 intubated patients for acute respiratory failure due to lung diseases between April 2014 and June 2018. We divided the patients into 2 groups according to the time from starting non-invasive ventilatory support until their intubation: ≤ 6 hours failure and > 6 hours failure group. We evaluated the differences in the ICU mortality between these two groups. The multivariate logistic regression analysis showed the highest mortality in the > 6 hours failure group as compared to the ≤ 6 hours failure group, with a statistically significant difference (p < 0.01). It was also associated with a statistically significant increased 30-day mortality and decreased ventilator weaning rate. The ICU mortality in patients with acute respiratory failure caused by lung diseases was increased if the time until failure of HFNC and NPPV was more than 6 hours.

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  49. Endocytoscopy Is Useful for the Diagnosis of Superficial Nonampullary Duodenal Epithelial Tumors. Reviewed International journal

    Takashi Hirose, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Kazuki Nishida, Takio Yokoi, Hiroki Kawashima, Mitsuhiro Fujishiro

    Digestion   Vol. 102 ( 6 ) page: 895 - 902   2021

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    INTRODUCTION: Endoscopic criteria for the diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs) are lacking. The aim of this study was to explore the usefulness of endocytoscopy (ECS) in the duodenum. METHODS: A total of 77 ECS images stained by methylene blue and 58 images with double staining of methylene blue and crystal violet were obtained from 20 patients. Images were classified into 3 grades based on nuclear and villi atypia: EC A, B, and C. Diagnostic performance of ECS classification to predict histology and interobserver agreement was evaluated. The performance was compared between staining methods and ×520 or ×936 zoom. RESULTS: With methylene blue staining, high rates of accuracy, sensitivity, specificity, and positive predictive value (PPV) over 90% were achieved for tumor and nontumor diagnosis as assessed by EC A versus EC B. High rates of accuracy, sensitivity, PPV, and negative predictive value over 90% were achieved for the differentiation between the diagnosis of the Vienna category 3 and 4/5 as assessed by EC B versus C. The accuracy rate of interpreting ECS images with ×936 zoom among 10 endoscopists was 82%, and the interobserver agreement rate was 0.803 (Kendall's coefficient of concordance). In the ×936 zoom group, methylene blue staining was significantly associated with higher accuracy rate (odds ratio 1.76 [1.06-2.92], p value 0.0297). No benefit was observed by double staining. CONCLUSIONS: ECS diagnosis with methylene blue provides a high accuracy rate and good interobserver agreement to predict histology of SNADETs.

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  50. Banding with lesser trochanter fragment using nonabsorbable tape in trochanteric femoral fractures Reviewed International journal

    Takuya Usami, Naoya Takada, Kazuki Nishida, Hiroaki Sakai, Hidetoshi Iwata, Isato Sekiya, Yoshino Ueki, Hideki Murakami, Gen Kuroyanagi

    SICOT-J   Vol. 7   page: 33 - 33   2021

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    INTRODUCTION: Trochanteric femoral fracture is one of the most common fractures in the elderly. Trochanteric femoral fracture with involvement of the lesser trochanter is considered unstable and recognized as having a poor prognosis. However, fixation of lesser trochanter fragment is scarce because of technical difficulties. In this study, we reported the simple surgical procedure and the effect of using nonabsorbable tape in lesser trochanter fixation. METHODS: From January 2014 to December 2017, 114 patients treated with proximal intramedullary nailing for trochanteric fractures with the lesser trochanter fragment were reviewed. Among patients enrolled in this study, 73 were followed up until radiographic bone union, of which 26 were treated with lesser trochanter fragment banding (group B) and 47 without banding (group N). Radiographs and/or computed tomography images were used to evaluate bone union of the lesser trochanter fragment at three months postoperatively. RESULTS: The bone union of the lesser trochanter fragment was achieved in 24 cases (92%) in group B and 30 cases (64%) in group N. Compared with group N, group B showed a significantly increased number of mild and moderate deformities but decreased number of severe deformity and nonunion (P < 0.001). Postoperative complications were not observed in both groups. CONCLUSIONS: From the viewpoint of increasing lesser trochanteric bone union ratio, fixation of the lesser trochanter fragment using nonabsorbable tape in the treatment of trochanteric fractures could be an effective procedure.

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  51. Impact of Blood Type O on Mortality of Sepsis Patients: A Multicenter Retrospective Observational Study Reviewed International journal

    Hasegawa, Daisuke, Nishida, Kazuki, Kawaji, Takahiro, Hara, Yoshitaka, Shimomura, Yasuyo, Moriyama, Kazuhiro, Niimi, Daisuke, Kuriyama, Naohide, Shintani, Ayumi, Komura, Hidefumi, Nishida, Osamu

    Diagnostics   Vol. 10 ( 10 ) page: 826 - 826   2020.10

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    ABO blood groups have been implicated as potential risk factors for various diseases. However, no study has investigated the association between sepsis mortality and ABO blood types. We aimed to evaluate the impact of these blood types on mortality in patients with sepsis and septic shock. This retrospective observational study was conducted at two general hospitals in Japan. Patients diagnosed with sepsis or septic shock were included and divided into four groups based on blood type (O, A, B, and AB). The association between type O vs. other types and 28- and 90-day mortalities was evaluated using multivariate logistic regression analysis adjusted for age, sex, and Sequential (Sepsis-related) Organ Failure Assessment score. This study included 415 patients, of whom 131 (31.6%), 171 (41.2%), 81 (19.5%), and 32 (7.7%) had type O, A, B, and AB, respectively. Blood type O was not associated with 28-day (odds ratio: 1.7 p = 0.08) or 90-day mortality (odds ratio: 1.53, p = 0.091). However, type O was significantly associated with higher 90-day mortality (odds ratio: 3.26, p = 0.009) in patients with septic shock. The role of ABO blood type in risk stratification for septic shock and the mechanisms that potentially affect the prognosis of sepsis patients need further investigation.

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  52. Comparative Analysis of Three Machine-Learning Techniques and Conventional Techniques for Predicting Sepsis-Induced Coagulopathy Progression Reviewed International journal

    Hasegawa, Daisuke, Yamakawa, Kazuma, Nishida, Kazuki, Okada, Naoki, Murao, Shuhei, Nishida, Osamu

    Journal of Clinical Medicine   Vol. 9 ( 7 ) page: 2113 - 2113   2020.7

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    Sepsis-induced coagulopathy has poor prognosis; however, there is no established tool for predicting it. We aimed to create predictive models for coagulopathy progression using machine-learning techniques to evaluate predictive accuracies of machine-learning and conventional techniques. A post-hoc subgroup analysis was conducted based on the Japan Septic Disseminated Intravascular Coagulation retrospective study. We used the International Society on Thrombosis and Haemostasis disseminated intravascular coagulation (DIC) score to calculate the ΔDIC score as ((DIC score on Day 3) - (DIC score on Day 1)). The primary outcome was to determine whether the predictive accuracy of ΔDIC was more than 0. The secondary outcome was the actual predictive accuracy of ΔDIC (predicted ΔDIC-real ΔDIC). We used the machine-learning methods, such as random forests (RF), support vector machines (SVM), and neural networks (NN); their predictive accuracies were compared with those of conventional methods. In total, 1017 patients were included. Regarding DIC progression, predictive accuracy of the multiple linear regression, RF, SVM, and NN models was 63.7%, 67.0%, 64.4%, and 59.8%, respectively. The difference between predicted ΔDIC and real ΔDIC was 2.05, 1.54, 2.24, and 1.77 for the multiple linear regression, RF, SVM, and NN models, respectively. RF had the highest predictive accuracy.

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  53. EFFECT OF SUSTAINED HIGH-EFFICIENCY DAILY DIAFILTRATION USING A MEDIATOR-ADSORBING MEMBRANE ON 28-DAY MORTALITY IN SEPTIC SHOCK PATIENTS Reviewed International journal

    Hasegawa Daisuke, Nishida Kazuki, Kasugai Daisuke, Kawaji Takahiro, Moriyama Kazuhiro, Nishida Osamu

    SHOCK   Vol. 53   page: 31 - 32   2020.6

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  54. High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial pneumonia: a retrospective observational study Reviewed

    Omote, Norihito, Matsuda, Naoyuki, Hashimoto, Naozumi, Nishida, Kazuki, Sakamoto, Koji, Ando, Akira, Nakahara, Yoshio, Nishikimi, Mitsuaki, Higashi, Michiko, Matsu, Shigeyuki, Hasegawa, Yoshinori

    Nagoya Journal of Medical Science   Vol. 82 ( 2 ) page: 301 - 313   2020.5

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    High-flow nasal cannula (HFNC) oxygen is a therapy that has demonstrated survival benefits in acute respiratory failure (ARF). However, the role of HFNC in ARF due to interstitial pneumonia (IP) is unknown. The aim of this study was to compare the effects of HFNC therapy and non-invasive positive pressure ventilation (NPPV) in ARF due to IP. This retrospective observational study included 32 patients with ARF due to IP who were treated with HFNC (n = 13) or NPPV (n = 19). The clinical characteristics, intubation rate and 30-day mortality were analyzed and compared between the HFNC group and the NPPV group. Predictors of 30-day mortality were evaluated using a logistic regression model. HFNC group showed higher mean arterial blood pressure (median 92 mmHg; HFNC group vs 74 mmHg; NPPV group) and lower APACHEII score (median 22; HFNC group vs 27; NPPV group) than NPPV group. There was no significant difference in the intubation rate at day 30 between the HFNC group and the NPPV group (8% vs 37%: p = 0.069); the mortality rate at 30 days was 23% and 63%, respectively. HFNC therapy was a significant determinant of 30-day mortality in univariate analysis, and was confirmed to be an independent significant determinant of 30-day mortality in multivariate analysis (odds ratio, 0.148; 95% confidence interval, 0.025-0.880; p = 0.036). Our findings suggest that HFNC therapy can be a possible option for respiratory management in ARF due to IP. The results observed here warrant further investigation of HFNC therapy in randomized control trials.

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  55. Relationship Between Serum Norepinephrine Levels at ICU Admission and the Risk of ICU-Acquired Delirium: Secondary Analysis of the Melatonin Evaluation of Lowered Inflammation of ICU Trial. Reviewed International journal

    Yuma Yasuda, Mitsuaki Nishikimi, Kazuki Nishida, Kunihiko Takahashi, Atsushi Numaguchi, Michiko Higashi, Shigeyuki Matsui, Naoyuki Matsuda

    Critical care explorations   Vol. 2 ( 2 ) page: e0082   2020.2

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    Abnormal secretion of catecholamines is well known to cause delirium. In particular, disturbances of catecholamine balance can cause ICU-acquired delirium. The aim of this study was to evaluate the association between the serum levels of catecholamines and the risk of occurrence of ICU-acquired delirium separately in patients who had/had not received exogenous catecholamines before ICU admission. Design:A secondary analysis of the data of 81 patients enrolled in our previous randomized clinical trial. Setting:ICU of an academic hospital. Patients:ICU patients in whom the serum levels of catecholamines were measured at ICU admission. Interventions:None. Measurements and Main Results:We evaluated the association between the serum levels of catecholamines measured at ICU admission and the risk of ICU-acquired delirium separately in patients who had received exogenous catecholamines at ICU admission (Ex[+] group) and those who had not received exogenous catecholamines (Ex[-] group). The serum levels of norepinephrine measured at ICU admission were significantly associated with the risk of ICU-acquired delirium in the Ex(-) group (odds ratio, 2.58; 95% CI, 1.02-6.52; p = 0.046), but not in the Ex(+) group (odds ratio, 1.02; 95% CI, 0.88-1.18; p = 0.823). Furthermore, there was a statistically significant interaction effect between the serum levels of norepinephrine and the use/nonuse of exogenous catecholamines at ICU admission in relation to the risk of occurrence of ICU-acquired delirium (p interaction = 0.017). Conclusions:The serum levels of norepinephrine measured at admission were associated with the risk of occurrence of ICU-acquired delirium in patients who had not received exogenous catecholamines at ICU admission, whereas no such association was observed in those who had received exogenous catecholamines previously. Thus, the association between the serum levels of catecholamines measured at admission and the risk of ICU-acquired delirium differed between patients who had/had not received exogenous catecholamines at ICU admission.

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  56. Galapagosization of sepsis management in Japan: a nationwide survey of current practices Reviewed International journal

    Yamakawa, Kazuma, Hasegawa, Daisuke, Yasuda, Hideto, Sakamoto, So, Nishida, Kazuki, Yatabe, Tomoaki, Egi, Moritoki, Ogura, Hiroshi, Nishida, Osamu

    Acute Medicine & Surgery   Vol. 7 ( 1 ) page: e561   2020.1

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  57. Maximum Norepinephrine Dosage Within 24 Hours as an Indicator of Refractory Septic Shock: A Retrospective Study Reviewed International journal

    Kasugai, Daisuke, Hirakawa, Akihiko, Ozaki, Masuyuki, Nishida, Kazuki, Ikeda, Takao, Takahashi, Kunihiko, Matsui, Shigeyuki, Uenishi, Norimichi

    Journal of Intensive Care Medicine   Vol. 35 ( 11 ) page: 088506661986073 - 088506661986073   2020

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    BACKGROUND: The management of refractory septic shock remains a major challenge in critical care and its early indicators are not fully understood. We hypothesized that the maximum norepinephrine dosage within 24 hours of intensive care unit (ICU) admission may be a useful indicator of early mortality in patients with septic shock. METHODS: In this retrospective single-center observational study, patients with septic shock admitted to the emergency ICU of an academic medical center between April 2011 and March 2017 were included. Individuals with cardiac arrest and those with do-not-resuscitate orders before admission were excluded. We analyzed if the maximum norepinephrine dosage within 24 hours of ICU admission (MD24) was associated with 7-day mortality. RESULTS: Among 152 patients with septic shock, 20 (15%) did not survive by day 7. The receiver operating characteristic curve analysis for predicting 7-day mortality revealed a cutoff of MD24 of 0.6 μg/kg/min (sensitivity 47%, specificity 93%). In the multivariable regression analysis, a higher MD24 was significantly associated with 7-day mortality (odds ratio: 7.20; 95% confidence interval [CI]: 2.02-25.7; P = .002) but not with 30-day mortality. Using the inverse probability of treatment weighting method in a propensity scoring analysis, a higher MD24 was significantly associated with 7-day (hazard ratio [HR]: 8.9; 95% CI: 3.2-25.0; P < .001) and 30-day mortality (HR: 2.7; 95% CI: 1.2-5.8; P = .012). CONCLUSIONS: An MD24 ≥0.6 μg/kg/min was significantly associated with 7-day mortality in patients with septic shock and may therefore be a useful indicator of refractory septic shock.

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  58. EFFECT OF SUSTAINED HIGH-EFFICIENCY DAILY DIAFILTRATION USING A MEDIATOR-ADSORBING MEMBRANE ON 28-DAY MORTALITY IN SEPTIC SHOCK PATIENTS

    Hasegawa, Daisuke, Nishida, Kazuki, Kasugai, Daisuke, Kawaji, Takahiro, Moriyama, Kazuhiro, Nishida, Osamu

    Shock     2020

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  59. Clinical Frailty Scale Score Before ICU Admission Is Associated With Mobility Disability in Septic Patients Receiving Early Rehabilitation. Reviewed International journal

    Hiroki Nakajima, Mitsuaki Nishikimi, Miho Shimizu, Kazuhiro Hayashi, Takayuki Inoue, Kazuki Nishida, Kunihiko Takahashi, Shigeyuki Matsui, Yoshihiro Nishida, Naoyuki Matsuda

    Critical care explorations   Vol. 1 ( 12 ) page: e0066   2019.12

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    To clarify the relationship between mobility disability at the time of discharge from the ICU and clinical factors evaluated at ICU admission in septic patients. Design: A single-center, retrospective, observational study. Setting: Ten-bed, the emergency and medical ICU. Patients: We analyzed the data of septic patients who were admitted to our ICU between September 2012 and September 2016 and received early rehabilitation. Interventions: None. Measurements and Main Results: The patients were categorized into two groups based on their scores on the ICU mobility scale at the time of discharge from the ICU: the mobility disability group (ICU mobility scale score < 9) and the no mobility disability group (ICU mobility scale score ≥ 9). Of the 110 eligible patients, 63 met the inclusion criteria; of these, 46 patients (73%) were classified into the mobility disability group, and 17 patients (27%) were classified into the no mobility disability group. The age (median, 72 vs 64 yr; p = 0.024), prevalence of patients with clinical frailty scale scores of greater than or equal to 5 (54% vs 12%; p = 0.003), Sequential Organ Failure Assessment score (median, 9.0 vs 6.0; p = 0.006) and rate of vasopressin use (26% vs 0%; p = 0.026) were significantly higher in the mobility disability group as compared with the no mobility disability group. Among the candidate variables for which values recorded before/at the time of ICU admission were available, the clinical frailty scale score was identified as the only independent, statistically significant predictor of mobility disability at ICU discharge (odds ratio, 7.77; 95% CI, 1.37-44.21; p = 0.021). The positive predictive value and negative predictive value of clinical frailty scale scores greater than or equal to 5 for mobility disability at ICU discharge were 92.6% and 41.7%, respectively. Conclusions: The clinical frailty scale score was associated with increased mobility disability at ICU discharge in septic patients receiving early rehabilitation.

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  60. Clinical features and treatment outcome of desmoid-type fibromatosis: based on a bone and soft tissue tumor registry in Japan Reviewed

    Nishida, Yoshihiro, Kawai, Akira, Toguchida, Junya, Ogose, Akira, Ae, Keisuke, Kunisada, Toshiyuki, Matsumoto, Yoshihiro, Matsunobu, Tomoya, Takahashi, Kunihiko, Nishida, Kazuki, Ozaki, Toshifumi

    International Journal of Clinical Oncology   Vol. 24 ( 11 ) page: 1498 - 1505   2019.11

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    BACKGROUND: Treatment modality of desmoid-type fibromatosis (DF) has changed from surgery with a wide surgical margin to conservative treatment. In this study, tumor characteristics of DF, transition of the treatment modality, and clinical outcome of surgical treatment were analyzed based on data obtained from the bone and soft tissue tumor registry established in Japan. METHODS: Data were collected as registration data and follow-up data. Five hundred and thirty registered cases of DF were identified, including 223 cases with follow-up data with or without surgical treatment. RESULTS: The number of registered patients increased gradually. The frequency of surgical treatment was gradually reduced year by year. The 3-year local recurrence free survival (LRFS) was 77.7%, with tumor location and size tending to correlate with LRFS. Interestingly, there was no significant difference in LRFS between wide and marginal margin (P = 0.34). CONCLUSIONS: The treatment modality has shifted from surgical to conservative treatment, with risk factors for surgical treatment similar to those noted in previous studies. The National registry system is crucial for a rare disease such as DF, and in the future, a population based registry system should be established to better comprehend the actual status of DF.

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  61. Steeper Macular Curvature in Eyes With Non-Highly Myopic Retinitis Pigmentosa Reviewed International journal

    Komori, Shiori, Ueno, Shinji, Ito, Yasuki, Sayo, Akira, Meinert, Monika, Kominami, Taro, Inooka, Daiki, Kitagawa, Masahiro, Nishida, Kazuki, Takahashi, Kunihiko, Matsui, Shigeyuki, Terasaki, Hiroko

    Investigative Ophthalmology & Visual Science   Vol. 60 ( 8 ) page: 3135 - 3141   2019.7

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    Purpose: A posterior staphyloma has been reported to be present in some eyes with retinitis pigmentosa (RP), and the purpose of this study was to determine the macular curvature of non-highly myopic RP eyes. Methods: This was a retrospective, observational study. The medical charts of the right eyes of 143 patients with RP and 60 controls whose axial length ranged from 21.5 mm to 26.0 mm were reviewed. The mean curvature of Bruch's membrane within 6 mm of the central macula obtained from the horizontal optical coherence tomographic images were evaluated as the mean macular curvature index (MMCI). The relationships between the MMCI and other clinical factors were assessed. Results: The mean MMCI of RP patients (-13.73 ± 9.63 × 10-5 μm-1) was significantly lower than that of the controls (-6.63 ± 5.63 × 10-5 μm-1). This indicated a deeper concave shape of the macula in RP eyes (P < 0.001). The MMCI was significantly correlated with the age (r = 0.20; P = 0.016) and the axial length (r = -0.24; P = 0.004). Further analysis suggested a nonlinear effect of the ellipsoid zone width on the macular curvature in the RP eyes. Conclusions: There is a high incidence of steeper macular curvatures even in non-highly myopic RP eyes, and the steepness was also affected by the degree of photoreceptor degeneration.

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  62. External validation of a risk classification at the emergency department of post-cardiac arrest syndrome patients undergoing targeted temperature management Reviewed International journal

    Nishikimi, Mitsuaki, Ogura, Takayuki, Nishida, Kazuki, Takahashi, Kunihiko, Nakamura, Mitsunobu, Matsui, Shigeyuki, Matsuda, Naoyuki, Iwami, Taku

    Resuscitation   Vol. 140   page: 135 - 141   2019.7

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    INTRODUCTION: There are no established risk classification for post-cardiac arrest syndrome (PCAS) patients at the Emergency Department (ED) undergoing targeted temperature management (TTM). The aim of this study was to externally validate a simplified version of our prognostic score, the "post-Cardiac Arrest Syndrome for Therapeutic hypothermia score" (revised CAST [rCAST]) and estimate the predictive accuracy of the risk classification based on it. METHODS: For the external validation, we used data from an out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM), which is a multicenter, prospective registry of OHCA patients across Japan. Eligible patients were PCAS patients treated with TTM at 33-36 °C between June 2014 and December 2015. We validated the accuracy of rCAST for predicting the neurological outcomes at 30 and 90 days. RESULTS: Among the 12,024 OHCA patients, the data of 460 PCAS patients treated by TTM were eligible for the validation. The areas under the curve of rCAST for predicting the neurological outcomes at 30 and 90 days were 0.892 and 0.895, respectively. The estimated sensitivity and specificity of the risk categories for the outcomes were as follows: 0.95 (95% CI: 0.92-0.98) and 0.47 (0.40-0.55) for the low (rCAST: ≤5.5), 0.62 (0.56-0.68) and 0.48 (0.40-0.55) for the moderate (rCAST: 6.0-14.0), and 0.57 (0.51-0.63) and 0.95 (0.91-0.98) for the high severity category (rCAST: ≥14.5). CONCLUSIONS: The rCAST was useful for predicting the neurological outcomes with high accuracy in PCAS patients, and the three grades was developed for a risk classification based on the rCAST.

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  63. Differential effect of lactate in predicting mortality in septic patients with or without disseminated intravascular coagulation: a multicenter, retrospective, observational study (vol 7, 2, 2019) Reviewed International journal

    Hasegawa, Daisuke, Nishida, Kazuki, Hara, Yoshitaka

    Journal of Intensive Care   Vol. 7 ( 1 ) page: 2 - 2   2019

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    Background: We examined whether high lactate level in septic patients was associated with 90-day mortality based on the patients' disseminated intravascular coagulation (DIC) status. Methods: We conducted a multicenter, retrospective, observational study of patients admitted to the intensive care unit (ICU) with a suspicion of severe infection and diagnosed with sepsis. Regression analyses were performed to estimate the interaction effect between DIC status and the lactate level. Then, the association between the lactate level and 90-day mortality was assessed in the DIC and non-DIC subgroups. Results: The data of 415 patients were analyzed. We found a significant interaction between DIC status and the lactate level for predicting 90-day mortality (p interaction = 0.04). Therefore, we performed a subgroup analysis and found that high lactate concentration was significantly associated with 90-day mortality in the DIC group (odds ratio = 2.31, p = 0.039) but not in the non-DIC group. Conclusions: In patients with DIC, a high lactate level significantly predicted 90-day mortality; no such association was found in the non-DIC group. Thus, DIC status may serve as a possible effect modifier of lactate level in predicting mortality in patients with sepsis.

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  64. Timing of administration of epinephrine predicts the responsiveness to epinephrine in norepinephrine-refractory septic shock: a retrospective study Reviewed

    Kasugai, Daisuke, Nishikimi, Mitsuaki, Nishida, Kazuki, Higashi, Michiko, Yamamoto, Takanori, Numaguchi, Atsushi, Takahashi, Kunihiko, Matsui, Shigeyuki, Matsuda, Naoyuki

    Journal of Intensive Care   Vol. 7 ( 1 ) page: 20 - 20   2019

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    Background:Currently, the appropriate method of management of patients with refractory septic shock remains unclear. This study aimed to evaluate the factors associated with response to epinephrine in norepinephrine-refractory septic shock. Methods:A retrospective single-center observational study was performed using data from adult patients (≥ 18 years old) admitted to our emergency and medical intensive care unit (ICU) from January 2014 to December 2017 who had received epinephrine to treat norepinephrine-refractory septic shock. The response was considered positive if there was increase in mean arterial pressure of 10 mmHg or decrease in arterial lactate level 3 h after epinephrine administration. Results:Forty-one patients were included: 24 responders (59%) and 17 non-responders (41%). Responders showed higher rate of survival from shock (92% vs. 18%; P < 0.001), and 28-day survival (83% vs. 18%; P < 0.001). In multivariable analysis, time of epinephrine administration after ICU admission (odds ratio [OR] 0.48; 95% confidence interval [CI] 0.27-0.87; P = 0.011) and SOFA score (OR 0.19; 95% CI 0.04-0.88; P = 0.034) were associated with epinephrine response. Time of epinephrine administration was also significantly associated with survival from shock (OR 0.42; P = 0.005) and 28-day survival (OR 0.14; P = 0.006), while SOFA score did not. Using inverse probability of treatment weighing (IPTW) adjustment of propensity score, epinephrine administration later than 24 h after ICU admission was associated with poor response (OR 0.07; 95% CI 0.02-0.21; P < 0.001). Conclusions:Early administration of epinephrine after ICU admission (i.e., within 24 h) is associated with better hemodynamic status in patients with refractory septic shock.

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  65. Differential Effects of Mild Therapeutic Hypothermia Against Normothermia for Post-Cardiac Arrest Syndrome According to the Severity Scale

    Nishikimi, Mitsuaki, Ogura, Takayuki, Nishida, Kazuki, Iwami, Taku

    Circulation     2019

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  66. Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice Reviewed International journal

    Funahashi, Satomi, Okazaki, Yasumasa, Nishiyama, Takahiro, Ohyoshi, Hidekazu, Yasui, Hiroyuki, Nishida, Kazuki, Matsui, Shigeyuki, Toyokuni, Shinya

    Free Radical Research   Vol. 52 ( 9 ) page: 1030 - 1039   2018.9

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    Exposure to asbestos fiber is central to mesothelial carcinogenesis, for which iron overload in or near mesothelial cells is a key pathogenic mechanism. Alternatively, iron chelation therapy with deferasirox or regular phlebotomy was significantly preventive against crocidolite-induced mesothelial carcinogenesis in rats. However, the role of iron transporters during asbestos-induced carcinogenesis remains elusive. Here, we studied the role of divalent metal transporter 1 (DMT1; Slc11a2), which is a Fe(II) transporter, that is present not only on the apical plasma membrane of duodenal cells but also on the lysosomal membrane of every cell, in crocidolite-induced mesothelial carcinogenesis using DMT1 transgenic (DMT1Tg) mice. DMT1Tg mice show mucosal block of iron absorption without cancer susceptibility under normal diet. We unexpectedly found that superoxide production was significantly decreased upon stimulation with crocidolite both in neutrophils and macrophages of DMT1Tg mice, and the macrophage surface revealed higher iron content 1 h after contact with crocidolite. Intraperitoneal injection of 3 mg crocidolite ultimately induced malignant mesothelioma in ∼50% of both wild-type and DMT1Tg mice (23/47 and 14/28, respectively); this effect was marginally (p = 0.069) delayed in DMT1Tg mice, promoting survival. The promotional effect of nitrilotriacetic acid was limited, and the liver showed significantly higher iron content both in DMT1Tg mice and after crocidolite exposure. The results indicate that global DMT1 overexpression causes decreased superoxide generation upon stimulation in inflammatory cells, which presumably delayed the promotional stage of crocidolite-induced mesothelial carcinogenesis. DMT1Tg mice with low-stamina inflammatory cells may be helpful to evaluate the involvement of inflammation in various pathologies.

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  67. Differential effect of mild therapeutic hypothermia depending on the findings of hypoxic encephalopathy on early CT images in patients with post-cardiac arrest syndrome Reviewed International journal

    Nishikimi, Mitsuaki, Ogura, Takayuki, Nishida, Kazuki, Takahashi, Kunihiko, Fukaya, Kenji, Liu, Keibun, Nakamura, Mitsunobu, Matsui, Shigeyuki, Matsuda, Naoyuki

    Resuscitation   Vol. 128   page: 11 - 15   2018.7

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    INTRODUCTION: The aim of this study was to evaluate the differential effects of mild therapeutic hypothermia (MTH) in post-cardiac arrest syndrome (PCAS) patients depending on the presence/absence of hypoxic encephalopathy (HE) in the early brain CT images obtained before the initiation of MTH. METHODS: We conducted a retrospective review of the data of a total of 129 patients with PCAS who were treated by MTH (34 °C) or normothermia treatment (NT) (35 °C or 36 °C), and had undergone brain CT examination prior to the initiation of these treatments. We divided the subjects into 4 groups, namely, the HE(-)/MTH, HE(-)/NT, HE(+)/MTH, and HE(+)/NT groups, for evaluating the interaction effect between the two variables. Then, we compared the neurological outcomes between the HE(-)/MTH and HE(-)/NT groups by multivariate logistic analysis. Good outcome was defined as a Cerebral Performance Category score of ≤2 at 30 days. RESULTS: The percentages of subjects with a good outcome in the HE(-)/MTH and HE(-)/NT group were 68.9% (42/61) and 36.1% (13/36), respectively (p = .003), while those in the HE(+)/MTH and HE(+)/NT groups were lower, at 7.4% (2/27) and 20.0% (1/5), respectively (p = .410), suggesting a statistically significant interaction effect between the two variables (pinteraction = 0.002). In the HE(-) group, MTH was associated with a higher odds ratio of a good outcome as compared to NT (OR 6.80, 95% CI 1.19-38.96, p = .031). CONCLUSIONS: The effect of MTH in patients with PCAS differed depending on the presence/absence of evidence of HE on the early CT images.

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  68. Treatment of patients with sepsis in a closed intensive care unit is associated with improved survival: a nationwide observational study in Japan Reviewed International journal

    Ogura, Takayuki, Nakamura, Yoshihiko, Takahashi, Kunihiko, Nishida, Kazuki, Kobashi, Daisuke, Matsui, Shigeyuki

    Journal of Intensive Care   Vol. 6 ( 1 ) page: 57 - 57   2018

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    Background: The aim of this study is to investigate the association between treatment in a closed ICU and survival at discharge in patients with sepsis. Methods: This is a post hoc analysis utilizing data from the Japan Septic Disseminated Intravascular Coagulation study, including data from patients with sepsis from 2011 to 2013. Multiple logistic regression analysis was used to estimate the association between ICU policy and survival at discharge, and propensity score matching analysis was performed including the same covariates as a sensitivity analysis. Multiple linear regression analysis for the length of ICU stay in surviving patients was also performed with adjustments for the same covariates. Results: Two thousand four hundred ninety-five patients were analyzed. The median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 22 [17-29], the median Sequential Organ Failure Assessment (SOFA) score was 9 [7-12], and the overall mortality was 33%. There were 979 patients treated in 17 open ICUs and 1516 patients in 18 closed ICUs. In comparison, the APACHE II score and SOFA scores were significantly higher in patients in closed ICUs (closed vs open = 23 [18-29] vs 21 [16-28]; p < .001, 9 [7-13] vs 9 [6-12]; p = 0.004). There was no difference in the unadjusted mortality (closed vs open; 33.1% vs 33.2%), but in multiple logistic regression analysis, treatment in a closed ICU is significantly associated with survival at discharge (odds ratio = 1.59, 95% CI [1.276-1.827], p = .001). The sensitivity analysis (702 pairs of the matching) showed a significantly higher survival rate in the closed ICU (71.8% vs 65.2%, p = 0.011). The length of ICU stay of patients in closed ICUs was significantly shorter (20% less). Conclusion: This Japanese nationwide analysis of patients with sepsis shows a significant association between treatment in a closed ICU and survival at discharge, and a 20% decrease in ICU stay.

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  69. Longitudinal study of visual field changes determined by Humphrey Field Analyzer 10-2 in patients with Retinitis Pigmentosa Reviewed International journal

    Sayo, Akira, Ueno, Shinji, Kominami, Taro, Nishida, Kazuki, Inooka, Daiki, Nakanishi, Ayami, Yasuda, Shunsuke, Okado, Satoshi, Takahashi, Kunihiko, Matsui, Shigeyuki, Terasaki, Hiroko

    Scientific Reports   Vol. 7 ( 1 ) page: 16383 - 16383   2017.11

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    The aim of this study is to determine the progress of the visual field defects obtained by the Humphrey Field Analyzer 10-2 program (HFA 10-2) in patients with retinitis pigmentosa (RP). The medical records of 45 eyes of 45 RP patients who had at least 3 visual field tests were reviewed. Linear mixed models were used to follow the changes of the mean deviation and the average sensitivity of 4, 12, and 20 points in three concentric squares, designated as S4, S12, and S20. The median follow-up time was 3.86 years [range: 1.93 to 9.86, IQR (Interquartile range): 3.01 to 4.93]. The median number of the visual field tests was 3 (range: 3 to 15, IQR: 3 to 4). The mean change of the MD was -0.46 dB/year (-5.80%/year). When the patients were grouped by the average initial MD, the less advanced group had slower progressions than the more advanced group in S4, S12, and S20. These results should be useful in understanding the pathological changes of RP in the central visual field.

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  70. Risk Classification of Post-Cardiac Arrest Syndrome Based on the CAST: Is Targeted Temperature Management at 34 degrees C Recommended in the Moderate-Risk Group?

    Nishikimi, Mitsuaki, Ogura, Takayuki, Nishida, Kazuki, Liu, Keibun, Nakamura, Mitsunobu, Sakamoto, Tetsuya, Matsuda, Naoyuki

    Circulation     2017

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Books 1

  1. 臨床試験の事典

    丹後, 俊郎, 松井, 茂之( Role: Contributor)

    朝倉書店  2023.1  ( ISBN:9784254322644

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MISC 8

  1. 院外心停止例での体温管理療法に関する無作為化比較試験

    内藤 宏道, 錦見 満暁, 岡田 遥平, 前山 博輝, 木口 雄之, 西田 一貴, 松井 茂之, 黒田 泰弘, 西山 慶, 石見 拓, 中尾 篤典

    日本脳低温療法・体温管理学会誌   Vol. 25 ( 1 ) page: 12 - 13   2022.9

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  2. Weekly point-prevalence surveillanceを用いた医療関連感染対策の有効性評価

    豊留 有香, 西田 一貴, 井口 光孝, 森岡 悠, 手塚 宜行, 岡 圭輔, 矢田 吉城, 長田 ゆかり, 安立 なぎさ, 八木 哲也

    日本環境感染学会総会プログラム・抄録集   Vol. 36回   page: 274 - 274   2021.9

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  3. Microsoft Xbox Kinect V2を用いた歩行解析の信頼性評価

    宇佐美 琢也, 黒柳 元, 西田 一貴, 鹿島 崇人, 堀場 充哉, 佐橋 健斗, 浅井 勇人, 坂井 宏章, 井口 普敬, 植木 美乃, 村上 英樹

    日本整形外科学会雑誌   Vol. 95 ( 8 ) page: S1836 - S1836   2021.8

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  4. 大腿骨転子部骨折手術において小転子締結は骨癒合に影響するか 小転子骨癒合形態の後ろ向き比較研究

    宇佐美 琢也, 高田 直也, 西田 一貴, 林 義一, 柴田 芳宏, 勝田 康裕, 生田 憲史, 柴田 淳, 岩田 英敏, 稲本 捷悟, 太田 恭平, 関谷 勇人

    日本整形外科学会雑誌   Vol. 94 ( 3 ) page: S815 - S815   2020.3

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  5. 機械学習を用いた敗血症患者のDIC進展予測モデル

    長谷川大祐, 西田一貴, 西田修

    日本血栓止血学会学術標準化委員会シンポジウム   Vol. 14th   2020

  6. 医学統計はじめの一歩

    西田 一貴

    日本急性血液浄化学会雑誌   Vol. 9 ( Suppl. ) page: 111 - 111   2018.9

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  7. 救急外来で中枢性めまいをとらえるために 中枢性めまいの予測スコアの検討

    松本 奈々, 西田 一貴, 長谷川 義高, 宇佐美 琢也, 横山 大輔, 川出 洋平, 越山 彩香, 須網 和也, 稲本 捷悟

    日本農村医学会雑誌   Vol. 66 ( 3 ) page: 284 - 284   2017.9

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  8. 蘇生後脳症に対する軽度低体温療法のCT像による有効性の検討

    錦見 満暁, 小倉 崇以, 西田 一貴, 中村 光伸, 劉 啓文, 徳山 秀樹, 松田 直之

    日本救急医学会雑誌   Vol. 28 ( 9 ) page: 622 - 622   2017.9

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KAKENHI (Grants-in-Aid for Scientific Research) 4

  1. 心停止後症候群に対する33℃と35℃の目標温度管理の神経学的予後に関する比較

    Grant number:21K09075  2021.4 - 2026.3

    科学研究費助成事業  基盤研究(C)

    内藤 宏道, 頼藤 貴志, 中尾 篤典, 西田 一貴, 錦見 満曉

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    重症神経障害を呈する心停止後症候群の予後は不良であり,治療法は確立されていない。脳温を低下させる管理法が,神経障害のある心停止後症候群の唯一の治療法ともいえるが,目標とすべき温度は国際ガイドラインで32℃から36℃のうちいずれかを選択し持続することが推奨されるのみで,判断は現場にまかされている。これまでに心停止後症候群の重症度を加味したRCTは実施されていない。本研究は,意識障害呈する心停止後症候群患者に対し,より低い低体温療法と常温管理に近い低体温療法を行い,さらに重症度を加味した上で神経学的予後の違いを検証する多施設RCTである。
    重症神経障害を呈する心停止後症候群(PCAS)の予後は不良であり、治療法は確立されていない。脳温を低下させる管理法が、神経障害のある心停止後症候群の唯一の治療法ともいえるが、至適な管理目標温度は定まっていない。
    2021年8月に発表されたTTM-2試験はこれまでで最大規模の無作為化比較試験(RCT)である。33℃を目標とする低体温療法群と37.8℃以上の発熱に介入を行う常温療法群に180日生存に関して差は認められなかった。さらに、他の最近の研究で、低体温療法は、中等度程度のPCAS患者(すなわち介入を必要としない軽症患者でなく、また、救命不能であるほどの虚血障害を負った最重症患者でない)で効果を発揮する可能性が示された。新たに発表された、この2つの研究を受け、本研究では、院外心停止・自己心拍再開後に意識障害を呈する患者のうち、もっとも効果が高いと推測される重症度(中等症)の患者選択を行い、低体温療法(34℃)または常温療法(37℃)を行った後、30日神経学的予後の違いを検証する。
    現在、研究計画が岡山大学倫理委員会に承認され、34施設で症例の組込みを行っている(適宜追加予定)。研究専用Electronic Data Captureを構築しランダム化およびデータの登録を行っている。定期的な多施設での研究ミーティングを実施し、問題点や研究体制の確認を行っている。モニタリング・データマネジメントを開始し、大きな問題は生じていない。2023年3月31日の時点で、49例の症例が登録されている。380例の症例登録が目標であり、190例の時点で中間解析を行う。
    5年の研究期間の2年目が終了した。現在、症例登録を行っているが、症例の登録数は2023年3月31日の時点で、49例に留まっている。
    参加施設は現時点で、旭川医科大学、岡山大学病院、京都医療センター、久留米大学病院、国際医療福祉大学成田病院、国立病院機構熊本医療センター、済生会宇都宮病院、佐賀大学医学部附属病院、札幌医科大学附属病院、JA広島総合病院、順天堂大学医学部附属浦安病院、聖隷浜松病院、千葉大学医学部附属病院、津山中央病院、長崎みなとメディカルセンター、奈良県立医科大学、新潟大学医歯学総合病院、広島市立広島市民病院、広島大学病院、福岡大学病院、八尾徳洲会総合病院、山口大学医学部附属病院、りんくう総合医療センター、獨協医科大学病院、大阪府済生会千里病院、京都第二赤十字病院、島根県立中央病院、島根大学医学部附属病院、愛媛大学医学部附属病院、大分大学医学部附属病院、熊本赤十字病院、長崎医療センター、済生会熊本病院、富山県立中央病院の34施設である。組み込み数が目標数の約半数程度で推移しているため、各参加施設で適応となった症例をできるだけ組み込んでいくことが課題である。
    症例の組込みが目標数の半数程度で推移しているため、組み込み数を各病院で増やすこと。また、あらたな組み込み病院の研究協力を検討している。専用メーリングリストを開設し、定期的なミーティングを実施している。データマネジメント、モニタリングを適切に行い、目標症例に残り3年間で到達できるように研究グループの調整を行っていくことが重要と考えている。目標症例数(380例)の半分に到達した時点での中間解析を予定している。
    また、本年度はプロトコル論文の作成を行う予定である。

  2. ビッグデータと凝固プロファイリングによる敗血症性凝固障害主要メカニズムの解明

    Grant number:22K09180  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    春日井 大介, 西田 一貴

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    Authorship:Coinvestigator(s) 

    本研究では敗血症性凝固障害発症・重症化のリスク因子の解明及び重症化に寄与する主要メカニズムを明らかにする。国内外の2つの大規模なデータベースを利用して、敗血症性凝固障害の発症・重症化予測因子を明らかにし、機械学習により凝固障害の重症化を予測する精度の高いモデルを構築する。次に、、包括的凝固機能プロファイル測定を活用した主要な凝固障害のフェノタイプ毎のモニタリング方法を探索的に明らかにする。

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  3. 膵癌早期診断を目的とした、IPMNの病変及び周囲背景膵における遺伝子変異解析

    Grant number:22K08010  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    大野 栄三郎, 石川 卓哉, 加藤 あす香, 川嶋 啓揮, 西田 一貴, 飯田 忠, 水谷 泰之

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    Authorship:Coinvestigator(s) 

    膵癌早期診断は喫緊の課題であるが、未だに高リスク群の絞り込みは不十分である。膵管内乳頭粘液性腫瘍(IPMN)は自身の悪性化に加え、通常型膵癌が高頻度に発生すると報告されている。本研究では、サーベイランス中の膵嚢胞症例中、手術例(膵癌または悪性IPMN疑い)における、切除病変の遺伝子変異プロファイルと周囲正常膵実質内の膵管上皮内腫瘍性病変(PanIN)の発症頻度および背景膵実質内膵管上皮における遺伝子変異プロファイルを同時に解析し、IPMN症例における膵管癌発生の超高リスク群の特徴を解明する。更にその結果を蓄積された臨床情報、画像情報、血液検体と対比し、膵発癌予測の新規バイオマーカーを探索する。
    本研究では膵管内乳頭粘液性腫瘍(IPMN)および膵癌に対して外科的切除が行われた症例の、主病変部及び背景膵実質における遺伝子変異プロファイルを対比することにより、IPMN患者群における膵がん発癌高リスク群の絞り込みを行うことにある。2022年度には自身が研究代表者を務めるIPMN多施設共同観察研究のデータ取集およびIPMN患者における発癌率の解析を実施し、2023年4月の日本消化器病学会総会にて報告した。解析結果としてIPMNが膵発癌の危険因子である点を明らかにした。IPMNおよび膵癌組織における背景膵に対する遺伝子変異解析については、研究代表者が名古屋大学医学部から藤田医科大学医学部へ異動したこともあり、解析症例の収集やレーザーマイクロダイセクションを実施する研究体制の準備のために時間を費やした。2022年度にはこれまで切除を実施したIPMN(良性例)、IPMN(非浸潤癌)、IPMN微小浸潤癌、IPMN由来浸潤癌、PDAC(IPMN非合併例)、PDAC(IPMN併存例)症例を各5-10例通出し、術前の画像所見との対比を実施した。実際の外科切除症例のパラフィン包埋組織からのDNA抽出、デジタルPCRを用いた遺伝子解析は2023年度より順次開始する予定である。また藤田医科大学においてIPMN経過観察症例に対するctDNAを含むバイオマーカー探索を実施するための前向き研究を計画し、IRBの承認を得て症例の集積を開始している。
    2022年10月に研究代表者の施設異動があったため。異動先の藤田医科大学においても目的の研究実施体制は整い、2023年度に実験解析を開始する予定である。
    膵嚢胞観察研究は現在も遂行中である。IPMNを始めとする1000例を超えるコホートからの膵発癌症例の抽出は今後も継続して実施する予定である。
    IPMN及び膵がん切除症例を対象とした、遺伝子変異プロファイル解析研究については、名古屋大学の症例に加えて藤田医科大学における症例を追加して研究を開始する体制の準備が整った状況である。2023年度は抽出した症例の病理プレパラートより膵管病変部のレーザーマイクロダイセクションにて組織採取、DNAの抽出、当科で所持するデジタルPCRによる解析を実施する予定である。

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  4. Effectiveness of P0.1 in Determining the Timing of Mechanical Ventilation Weaning: A Diagnostic Meta-Analysis

    Grant number:20K23222  2020.9 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    Nishida Kazuki

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    Authorship:Principal investigator 

    Grant amount:\2860000 ( Direct Cost: \2200000 、 Indirect Cost:\660000 )

    In the treatment of patients with severe respiratory failure, the appropriate use and timing of weaning from mechanical ventilation is crucial, yet an accurate predictive indicator has not been established. In response to this issue, we examined the efficacy of airway occlusion pressure (P0.1). P0.1 can be measured during treatment and could potentially predict the timing of weaning based on its threshold. However, as the threshold of P0.1 varies between studies, a clear decision criterion needs to be established. Thus, we conducted a diagnostic meta-analysis and evaluated its diagnostic power. As a result, we were able to show that P0.1 significantly predicts the possibility of weaning. This achievement is expected to contribute to improving the success rate of mechanical ventilation treatment.

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