200 results on '"Kawano, Y."'
Search Results
2. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
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Moreau, P., Dimopoulos, M-A, Mikhael, J., Yong, K., Capra, M., Facon, T., Hajek, R., Špička, I., Baker, R., Kim, K., Martinez, G., Min, C-K, Pour, L., Leleu, X., Oriol, A., Koh, Y., Suzuki, K., Risse, M-L, Asset, G., Macé, S., Martin, T., Quach, H., Lim, A., Crowther, H., Sia, H., Hulin, C., Mohty, M., Mikala, G., Nagy, Z., Reinoso Segura, M., Rosinol, L., Yagci, M., Turgut, M., Garg, M., Parmar, G., Augustson, B., Castro, N., Crusoe, E., Pika, T., Delimpasi, S., Ishizawa, K., George, A., Konstantinova, T., De La Rubia, J., Sung-Hyun, K., Maiolino, A., Reiman, A., LeBlanc, R., Ito, S., Tanaka, J., Luchinin, A., Kryuchkova, I., Martinez, J., Shustik, J., Karlin, L., Symeonidis, A., Egyed, M., Petrini, M., Cavo, M., Uchiyama, M., Blacklock, H., Arat, M., Griffin, J., Hunter, H., Buck, T., Anagnostopoulos, A., Konstantopoulos, K., Masszi, T., Bringhen, S., Gamberi, B., Kawano, Y., Jin Seok, K., Ozdogu, H., Ozkalemkas, F., Moreau, P., Dimopoulos, M-A, Mikhael, J., Yong, K., Capra, M., Facon, T., Hajek, R., Špička, I., Baker, R., Kim, K., Martinez, G., Min, C-K, Pour, L., Leleu, X., Oriol, A., Koh, Y., Suzuki, K., Risse, M-L, Asset, G., Macé, S., Martin, T., Quach, H., Lim, A., Crowther, H., Sia, H., Hulin, C., Mohty, M., Mikala, G., Nagy, Z., Reinoso Segura, M., Rosinol, L., Yagci, M., Turgut, M., Garg, M., Parmar, G., Augustson, B., Castro, N., Crusoe, E., Pika, T., Delimpasi, S., Ishizawa, K., George, A., Konstantinova, T., De La Rubia, J., Sung-Hyun, K., Maiolino, A., Reiman, A., LeBlanc, R., Ito, S., Tanaka, J., Luchinin, A., Kryuchkova, I., Martinez, J., Shustik, J., Karlin, L., Symeonidis, A., Egyed, M., Petrini, M., Cavo, M., Uchiyama, M., Blacklock, H., Arat, M., Griffin, J., Hunter, H., Buck, T., Anagnostopoulos, A., Konstantopoulos, K., Masszi, T., Bringhen, S., Gamberi, B., Kawano, Y., Jin Seok, K., Ozdogu, H., and Ozkalemkas, F.
- Abstract
Background Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide–dexamethasone and carfilzomib–dexamethasone for relapsed or refractory multiple myeloma. This phase 3, open-label study compared the efficacy of isatuximab plus carfilzomib–dexamethasone versus carfilzomib–dexamethasone in patients with relapsed multiple myeloma. Methods This was a prospective, randomised, open-label, parallel-group, phase 3 study done at 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients with relapsed or refractory multiple myeloma aged at least 18 years who had received one to three previous lines of therapy and had measurable serum or urine M-protein were eligible. Patients were randomly assigned (3:2) to isatuximab plus carfilzomib–dexamethasone (isatuximab group) or carfilzomib–dexamethasone (control group). Patients in the isatuximab group received isatuximab 10 mg/kg intravenously weekly for the first 4 weeks, then every 2 weeks. Both groups received the approved schedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatment continued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assigned treatment. Safety was assessed in all patients who received at least one dose according to treatment received. The study is registered at ClinicalTrials.gov, NCT03275285. Findings Between Nov 15, 2017, and March 21, 2019, 302 patients with a median of two previous lines of therapy were enrolled. 179 were randomly assigned to the isatuximab group and 123 to the control group. Median progression-free survival was not reached in the isatuximab group compared with 19·15 months (95% CI 15·77–not reached) in the control group, with a hazard ratio of 0·53 (99% CI 0·32–0·89; one-sided p=0·0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in
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- 2021
3. Effects of Line of Vision on Posture, Muscle Activity and Sitting Balance During Tooth Preparation
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Katano, K, Nakajima, K, Saito, M, Kawano, Y, Takeda, T, Fukuda, K, Katano, K, Nakajima, K, Saito, M, Kawano, Y, Takeda, T, and Fukuda, K
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- 2021
4. Terahertz nano-devices and nano-systems
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Kawano, Y., primary
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- 2013
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5. Formation and Structure Control of Reverse Micelles by the Addition of Alkyl Amines and their Applications for Extraction Processes of Proteins
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Shiomori, K., primary, Honbu, T., additional, Kawano, Y., additional, Kuboi, R., additional, and Komasawa, I., additional
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- 2001
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6. Flexible control of autonomous vehicle utilizing hierarchical map and planning
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Niizuma, M., primary, Kawano, Y., additional, Tomizawa, M., additional, Sugiyama, M., additional, and Degawa, S., additional
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- 1993
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7. Application of Liquid Membrane Technique to the Recovery if Fermented Organic Acids
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HANO, T., primary, MATSUMOTO, M., additional, OHTAKE, T., additional, SASAKI, K., additional, HORI, F., additional, and KAWANO, Y., additional
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- 1992
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8. A thoracic CT imaging parameter predicting access difficulty in acute stroke thrombectomy.
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Yamaoka H, Hirai S, Hanazawa R, Yoshimura M, Hayashi T, Kaneoka A, Yamada K, Yoshino Y, Ebiko Y, Yamamura T, Ishikawa M, Sagawa H, Aoyama J, Fujii S, Fujita K, Kawano Y, Hirakawa A, and Sumita K
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- Humans, Male, Female, Aged, Retrospective Studies, Middle Aged, Stroke diagnostic imaging, Stroke surgery, Aged, 80 and over, Aorta, Thoracic diagnostic imaging, Aorta, Thoracic surgery, Thrombectomy methods, Tomography, X-Ray Computed methods
- Abstract
Purpose: The quick establishment of adequate vascular access is essential for the technical success of mechanical thrombectomy (MT). Focusing on shifts in aortic arch geometry and aging-related changes, we propose an imaging parameter for predicting access difficulty using chest CT., Methods: Patients with acute anterior circulation large-vessel occlusion who underwent MT from April 2020 to September 2021 were included in this retrospective multicenter observational study. The distance from the sternum to the ascending aorta (S-AAD) was defined as the surrogate marker of access difficulty. Access was defined as difficult when the time from femoral sheath placement to guiding catheter induction (guiding time: GT) ≥ 30 minutes, and the patients were dichotomized into groups with short GT (sGT: GT < 30 min) and long GT (lGT: GT ≥ 30 min)., Results: One hundred fifteen patients were included. There were 12 patients (10.4 %) in lGT group. The median (IQR) S-AAD was 11.9 mm (6.3, 18.3 mm) in sGT group and 6.6 mm (4.0, 10.3 mm) in lGT group, and a significant difference in S-AAD was observed (P = 0.026). In multivariate analyses, dyslipidemia and S-AAD < 5 mm were significantly associated with difficult access (OR, 5.938 [95 % CI, 1.468, 24.022], P = 0.012 for dyslipidemia; OR, 5.147 [95 % CI, 1.267, 20.917], P = 0.022 for S-AAD < 5 mm)., Conclusion: S-AAD is a simple and reliable imaging parameter to predict access difficulty. This parameter may be helpful in selecting the appropriate devices and access routes in preinterventional practice., Competing Interests: Competing interests The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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9. Uterine prostaglandin DP receptor-induced upon implantation contributes to decidualization together with EP4 receptor.
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Sakamoto R, Fujiwara T, Kawano Y, Aikawa S, Inazumi T, Nakayama O, Kawasaki-Shirata Y, Hashimoto-Iwasaki M, Sugimoto T, Tsuchiya S, Nakao S, Takeo T, Hirota Y, and Sugimoto Y
- Abstract
To investigate the yet-unknown roles of prostaglandins (PGs) in the uterus, we analyzed the expression of various PG receptors in the uterus. We found that three types of Gs-coupled PG receptors, DP, EP2, and EP4, were expressed in luminal epithelial cells from the peri-implantation period to late pregnancy. DP expression was also induced in stromal cells within the mesometrial region, whereas EP4 was expressed in stromal cells within the anti-mesometrial region during the peri-implantation period. The timing of DP induction after embryo attachment correlated well with that of cyclooxygenase-2 (COX-2); however, COX-2-expressing stromal cells were located in the vicinity of the embryo, whereas DP-expressing stromal cells surrounded these cells on the mesometrial side. Specific [
3 H]PGD2 -binding activity was detected in the decidua of uteri, with PGD2 synthesis comparable to that of PGE2 detected in the uteri during the peri-implantation period. Administration of the COX-2-specific inhibitor celecoxib caused adverse effects on decidualization, as demonstrated by the attenuated weight of the implantation sites, which was recovered by the simultaneous administration of a DP agonist. Such a rescuing effect of the DP agonist was mimicked by an EP4 agonist, but not an EP2 agonist. While the importance of DP signaling was shown pharmacologically, DP/EP2 double deficiency did not affect implantation and decidualization, suggesting the contribution of EP4 to these processes. Indeed, administration of an EP4 antagonist substantially affected decidualization in DP/EP2-deficient mice. These results suggest that COX-2-derived PGD2 and PGE2 contribute to decidualization via a coordinated pathway of DP and EP4 receptors., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest regarding the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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10. Contact aspiration for basilar artery occlusion safely reduces the puncture-to-recanalization time.
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Hirota S, Fujita K, Ishiwada T, Takahashi S, Hirai S, Sagawa H, Wakabayashi H, Aoyama J, Fujii S, Yamaoka H, Yoshimura M, Shigeta K, Sato Y, Sawada K, Yamada K, Yamamura T, Ishii Y, Obata Y, Hara M, Kawano Y, Yamamoto S, Nemoto S, and Sumita K
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- Humans, Male, Female, Aged, Middle Aged, Vertebrobasilar Insufficiency surgery, Treatment Outcome, Punctures methods, Aged, 80 and over, Registries, Time-to-Treatment, Basilar Artery surgery, Stents, Suction methods, Thrombectomy methods, Endovascular Procedures methods
- Abstract
Objective: Effective thrombectomies in the posterior circulation remain controversial. Previous reports have demonstrated the superiority of contact aspiration in anterior circulation. Aspiration catheters and stent retrievers are often used alone on a global scale, while combined techniques are commonly used in Japan. This study evaluated the effect of first-line contact aspiration with other strategies for the treatment of basilar artery occlusion., Methods: The primary outcome was the frequency of the first-pass effect, and the secondary outcome was the time from puncture to the first-pass effect. A multicenter observational registry including 16 Japanese stroke centers was used. Between December 2013 and February 2021, enrolled patients underwent endovascular thrombectomy for basilar artery occlusion. The efficacy of contact aspiration compared to other methods (including stent retrievers and combined techniques) was evaluated., Results: Eighty-four patients were included, all of whom had achieved effective recanalization. Twenty-six patients were treated with contact aspiration, 13 with combined technique, and 45 with stent retrievers. The two groups: contact aspiration and non-contact aspiration, had different backgrounds. Both had similar frequencies of effective recanalization and first-pass effects. The contact aspiration group experienced better functional outcomes without statistical significance, while this strategy was significantly associated with a shorter puncture-to-recanalization time (38 vs. 55 minutes, P=0.036). In particular, in the 55 patients with the first-pass effect, multivariate Cox proportional hazard analysis showed that contact aspiration was significantly associated with a shorter time from puncture to first-pass effect, independent of age and etiology of large-artery atherosclerosis (hazard ratio 2.02, 95% confidence intervals 1.10-3.69, P=0.023)., Conclusion: This study suggested that contact aspiration for basilar artery occlusion may shorten the puncture-to-first-pass effect, compared to stent retrievers and combined techniques., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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11. Time-lagged amelioration of vascular endothelial function in malignant hypertension: different organs improved at different rates.
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Hayashi SI, Kawano Y, Morishita R, and Kusano KF
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- Humans, Time Factors, Endothelium, Vascular physiopathology, Hypertension, Malignant drug therapy, Hypertension, Malignant physiopathology
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Competing Interests: Declaration of interests We declare no competing interests.
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- 2024
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12. Response to letter to the editor regarding "Is local anesthesia or general anesthesia preferable for plate removal after clavicle fracture surgery under general anesthesia? A comparative study using a patient questionnaire" by Uraya et al.
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Uraya Y, Kawano Y, Kuroiwa T, Watanabe H, Maeda A, Funahashi T, Shizu K, Suzuki K, and Fujita N
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- Humans, Clavicle surgery, Fracture Fixation, Internal, Surveys and Questionnaires, Anesthesia, General, Anesthesia, Local, Fractures, Bone surgery
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Competing Interests: Declaration of Competing Interest The authors have no financial or other relationships that may lead to conflicts of interest.
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- 2024
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13. Low-adhesion and low-swelling hydrogel based on alginate and carbonated water to prevent temporary dilation of wound sites.
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Teshima R, Osawa S, Yoshikawa M, Kawano Y, Otsuka H, and Hanawa T
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- Mice, Animals, Hydrogels pharmacology, Hydrogels chemistry, Alginates pharmacology, Alginates chemistry, Dilatation, Skin pathology, Tissue Adhesions pathology, Adhesives, Anti-Bacterial Agents chemistry, Carbonated Water
- Abstract
Hydrogel-based wound dressings have been developed for rapid wound healing; however, their adhesive properties have not been adequately investigated. Excessive adhesion to the skin causes wound expansion and pain when hydrogels absorb exudates and swell at wound sites. Herein, we developed a low-adhesion and low-swelling hydrogel dressing using alginate, which is non-adhesive to cells and skin tissue, CaCO
3 , and carbonated water. The alginate/CaCO3 solution rapidly formed a hydrogel upon the addition of carbonated water, and the CO2 in the hydrogel diffused into the atmosphere, preventing acidification and obtaining a pH value suitable for wound healing. Remarkably, the skin adhesion and swelling of the hydrogel were 11.9- to 16.5-fold and 1.9-fold lower, respectively, than those of clinical low-adhesion hydrogel dressings. In vivo wound-healing tests in mice demonstrated its therapeutic efficacy, and the prepared hydrogel prevented temporary wound dilation during early healing. These results illustrate the importance of controlling skin adhesion and swelling in wound dressings and demonstrate the potential clinical applications of this wound-friendly hydrogel dressing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2024
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14. Is local anesthesia or general anesthesia preferable for plate removal after clavicle fracture surgery under general anesthesia? A comparative study using a patient questionnaire.
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Uraya Y, Kawano Y, Kuroiwa T, Maeda A, Funahashi T, Shizu K, Suzuki K, and Fujita N
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- Humans, Male, Female, Surveys and Questionnaires, Adult, Middle Aged, Treatment Outcome, Patient Preference, Clavicle injuries, Clavicle surgery, Anesthesia, General, Fractures, Bone surgery, Bone Plates, Anesthesia, Local, Fracture Fixation, Internal methods, Device Removal
- Abstract
Introduction: Because we have a limited number of surgeries performed under general anesthesia, implant removal after plate fixation for clavicular fracture is often performed under local anesthesia. However, it is unclear whether local anesthesia or general anesthesia is preferred. Therefore, we conducted a questionnaire survey of patients who had undergone implant removal surgery under local or general anesthesia after clavicle fracture surgery to assess their impressions of each procedure and which anesthesia they would prefer if they were to undergo plate removal in the future., Materials and Methods: A questionnaire survey was conducted on 239 patients. Fifty-six patients who had undergone plate fixation of a clavicle fracture in whom plate removal was conducted under local anesthesia in a university hospital, and one hundred and eighty-three patients in whom plate removal was conducted under general anesthesia in a general hospital. All participants had undergone plate fixation for clavicle fractures under general anesthesia. The participants were asked to complete a questionnaire including a question on which method of anesthesia they would prefer should they have to undergo similar surgery in the future., Results: The patients of both groups responded that they would prefer the same method of anesthesia as before to be used (87.1 % of the patients who underwent plate removal under local anesthesia, 78.9 % of the patients underwent plate removal under general anesthesia), with no significant difference between the groups (p > 0.33)., Conclusions: Patients who underwent surgery under local anesthesia preferred local anesthesia if they were to undergo it next, even though most of them felt some pain. Though surgeons tend to focus only on the patient's distress during surgery, they also find that patients are often dissatisfied during the perioperative period, including bed rest and urinary catheters. Although clavicle plate removal may be performed under general anesthesia in many cases, it may be worth considering plate removal under local anesthesia to use general anesthesia surgery effectively, which is limited due to financial problems and facilities. Plate removal under local anesthesia was just as acceptable as general anesthesia for the patients., Competing Interests: Declaration of Competing Interest There are no financial or any other relationships that lead to a conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)
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- 2023
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15. Isatuximab Plus Carfilzomib and Dexamethasone in East Asian Patients With Relapsed Multiple Myeloma: Updated IKEMA Subgroup Analysis.
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Kawano Y, Kim K, Min CK, Koh Y, Ishizawa K, Kim SH, Ito S, Tanaka J, Uchiyama M, Ishida T, Kim JS, Moreau P, Martin T, Tada K, Risse ML, and Suzuki K
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- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Dexamethasone therapeutic use, East Asian People, Recurrence, Multiple Myeloma
- Abstract
Background: The Phase 3 IKEMA study (NCT03275285) demonstrated isatuximab (Isa) in combination with carfilzomib (K) and dexamethasone (d) significantly improved progression-free survival (PFS) in patients with relapsed multiple myeloma (MM) compared with Kd. A post-hoc analysis of East Asian patients in IKEMA evaluated the efficacy and safety of Isa-Kd versus Kd in this population and was previously published., Patients and Methods: Patients with relapsed MM who had received 1 to 3 prior lines of therapy were randomized 3:2 to receive Isa-Kd or Kd. The primary endpoint was PFS, and key secondary endpoints included rate of very good partial response or better (≥VGPR), complete response (CR) rate, and minimal residual disease (MRD) negativity. Of the IKEMA overall population, 46 patients were of East Asian descent. This is an updated analysis of the efficacy and safety of Isa-Kd in East Asian patients, including data through 14 January 2022., Results: Isa-Kd continued to demonstrate improved efficacy and safety versus Kd in East Asian patients with relapsed MM, with improved PFS, rate of ≥VGPR, CR rate, and MRD negativity, that was consistent with the overall IKEMA population. The rate of Grade ≥3 treatment-emergent adverse events was also consistent with the prior analysis and overall IKEMA population., Conclusion: Based on the results of this analysis, Isa-Kd is a novel treatment option for East Asian patients with relapsed MM., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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16. Imaging predictors of clinical outcomes after endovascular treatment in MRI-selected patients with acute basilar artery occlusion.
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Hirai S, Hirakawa A, Fujita K, Ishiwada T, Sasaki M, Yoshimura M, Shigeta K, Sato Y, Yamada K, Ishikawa M, Sagawa H, Aoyama J, Fujii S, Ishii Y, Sawada K, Obata Y, Karakama J, Hara M, Kawano Y, Nemoto S, and Sumita K
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- Humans, Basilar Artery diagnostic imaging, Basilar Artery surgery, Treatment Outcome, Retrospective Studies, Thrombectomy methods, Infarction, Magnetic Resonance Imaging, Vertebrobasilar Insufficiency diagnostic imaging, Vertebrobasilar Insufficiency surgery, Stroke therapy, Endovascular Procedures methods, Arterial Occlusive Diseases diagnostic imaging, Arterial Occlusive Diseases surgery, Arterial Occlusive Diseases etiology
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Purpose: We aimed to investigate the impact of baseline infarct area and collateral status (CS), which are imaging predictors of clinical outcome following stroke, after endovascular treatment (EVT) in MRI-selected patients with acute basilar artery occlusion (BAO)., Methods: Patients with acute BAO who underwent EVT within 24 h after stroke from December 2013 to February 2021 were included in this retrospective, multicenter, observational study. The baseline infarct area was evaluated by the posterior circulation of Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) using diffuse-weighted imaging (DWI), and CS was assessed by measuring the computed tomography angiography of the basilar artery (BATMAN) score and the posterior circulation collateral score (PC-CS) using magnetic resonance angiography (MRA). A Good outcome was defined as a modified Rankin scale score ≤ 3 at 3 months. For each imaging predictor, a multivariate logistic regression analysis was performed to evaluate its impact on good outcomes., Results: A total of 86 patients were analyzed, and 37 (43.0%) had a good outcome. The latter showed significantly higher pc-ASPECTS than those without good outcomes. In multivariate analyses, a pc-ASPECTS ≥ 7 was significantly associated with good outcomes (OR, 2.98 [95% CI, 1.10-8.13], P = 0.032), while PC-CS ≥ 4 (OR, 2.49 [95% CI, 0.92-6.74], P = 0.073) and BATMAN score ≥ 5 (OR, 1.51 [95% CI, 0.58-3.98], P = 0.401) were not., Conclusions: In MRI-selected patients with acute BAO, pc-ASPECTS on DWI was an independent predictor of clinical outcomes after EVT, while the MRA-based CS assessments were not., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2023
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17. Targeting the immune microenvironment in Waldenström macroglobulinemia via halting the CD40/CD40-ligand axis.
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Sacco A, Desantis V, Celay J, Giustini V, Rigali F, Savino FD, Cea M, Soncini D, Cagnetta A, Solimando AG, D'Aliberti D, Spinelli S, Ramazzotti D, Almici C, Todoerti K, Neri A, Anastasia A, Tucci A, Motta M, Chiarini M, Kawano Y, Martinez-Climent JA, Piazza R, and Roccaro AM
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- Humans, Animals, Mice, CD40 Ligand genetics, Phosphatidylinositol 3-Kinases, Ligands, Signal Transduction, Tumor Microenvironment, Waldenstrom Macroglobulinemia pathology, Lymphoma, B-Cell complications
- Abstract
Recent investigations have improved our understanding of the molecular aberrations supporting Waldenström macroglobulinemia (WM) biology; however, whether the immune microenvironment contributes to WM pathogenesis remains unanswered. First, we showed how a transgenic murine model of human-like lymphoplasmacytic lymphoma/WM exhibits an increased number of regulatory T cells (Tregs) relative to control mice. These findings were translated into the WM clinical setting, in which the transcriptomic profiling of Tregs derived from patients with WM unveiled a peculiar WM-devoted messenger RNA signature, with significant enrichment for genes related to nuclear factor κB-mediated tumor necrosis factor α signaling, MAPK, and PI3K/AKT, which was paralleled by a different Treg functional phenotype. We demonstrated significantly higher Treg induction, expansion, and proliferation triggered by WM cells, compared with their normal cellular counterpart; with a more profound effect within the context of CXCR4C1013G-mutated WM cells. By investigating the B-cell-to-T-cell cross talk at single-cell level, we identified the CD40/CD40-ligand as a potentially relevant axis that supports WM cell-Tregs interaction. Our findings demonstrate the existence of a Treg-mediated immunosuppressive phenotype in WM, which can be therapeutically reversed by blocking the CD40L/CD40 axis to inhibit WM cell growth., (© 2023 by The American Society of Hematology.)
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- 2023
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18. Corrigendum to ' Catechol-O-methyltransferase (COMT) Val158Met polymorphism and prepulse inhibition of the change-related cerebral response'[Psychiatry Research: Neuroimaging 323 (2022) 111,484].
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Motomura E, Tanii H, Kawano Y, Inui K, and Okada M
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- 2023
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19. A nationwide survey of human metapneumovirus-associated encephalitis/encephalopathy in Japan.
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Mori A, Kawano Y, Hara S, Numoto S, Kurahashi H, and Okumura A
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- Child, Humans, Child, Preschool, Japan epidemiology, Seizures complications, Metapneumovirus, Brain Diseases epidemiology, Brain Diseases complications, Encephalitis complications, Encephalitis epidemiology
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Background: As there have been no comprehensive reports of human metapneumovirus-associated encephalopathy (hMPVE), this study examined the clinical features of hMPVE in children in Japan., Method: A nationwide survey of children with hMPVE was conducted using a structured research form. An initial survey asked pediatricians about children with hMPVE treated between 2014 and 2018. A second survey obtained patient information from hospitals that responded to the initial survey and those identified as having treated cases from a literature search. We collected demographic data, symptoms of hMPV infection, neurological symptoms, laboratory data, treatment, and outcomes. Outcomes were determined using the Pediatric Cerebral Performance Category Score., Result: Clinical information was available for 16 children. Their median age was 37 months. Six had preexisting neurological disorders. The interval between the onsets of infection and hMPVE was 4 days. Outcomes were good in 11 patients and poor in 5. There were no significant differences in demographic data, neurological symptoms, or laboratory data between the patients with good and poor outcomes. The encephalopathy subtypes were acute encephalopathy with biphasic seizures and late reduced diffusion in 3, clinically mild encephalitis/encephalopathy with a reversible splenial lesion in 3, hemorrhagic shock and encephalopathy syndrome in 2, and others in 8., Conclusion: The outcomes of children with hMPVE were not very different from those of acute encephalopathy due to other viruses. We found no factors associated with poor outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)
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- 2023
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20. Influence of Bilateral Cerebellar Infarction on Functional Outcome After Endovascular Treatment for Basilar Artery Occlusion.
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Ishiwada T, Fujita K, Hirai S, Fujii S, Yamaoka H, Ishikawa M, Yoshimura M, Shigeta K, Sato Y, Sawada K, Yamada K, Yamamura T, Ishii Y, Obata Y, Tone O, Hara M, Kawano Y, Aoyagi M, Nemoto S, Maehara T, and Sumita K
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- Humans, Basilar Artery, Treatment Outcome, Infarction etiology, Ischemic Stroke etiology, Endovascular Procedures adverse effects, Brain Ischemia etiology, Stroke etiology, Arterial Occlusive Diseases etiology
- Abstract
Background and Purpose: To measure the magnitude of the effect of the infarct location measured using the posterior circulation Alberta Stroke Program Early Computed Tomographic Score (pc-ASPECTS) on the functional outcome at 90 days in patients with basilar artery (BA) occlusion undergoing endovascular therapy (EVT)., Methods: Of the acute ischemic stroke patients undergoing EVT for acute posterior circulation large vessel occlusion enrolled in the multicenter observational registry from December 2013 to February 2021, patients with BA occlusion were included. A favorable outcome was defined as achieving a modified Rankin Scale score of 0-3 at 90 days. The effect of pc-ASPECTS including the distribution on favorable outcomes was evaluated., Results: One hundred patients were analyzed. Fifty-one patients (51%) achieved favorable outcome. Patients achieving a favorable outcome were younger, had a lower National Institutes of Health Stroke Scale score before EVT, and had a higher pc-ASPECTS before EVT than those not achieving a favorable outcome. Multivariable logistic analysis showed a significant association between higher pc-ASPECTS and a favorable outcome (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.02-1.52; P = 0.028). Considering the infarct location, bilateral cerebellar infarction was significantly associated with a lower frequency of favorable outcomes than those without cerebellar infarction (OR 0.16; 95% CI 0.04-0.51; P = 0.002)., Conclusions: A higher pc-ASPECTS before EVT could be a predictor of a favorable outcome after EVT for BA occlusion. In particular, the presence of bilateral cerebellar infarction before EVT was significantly associated with a lower likelihood of a favorable outcome., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2023
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21. Preparation and Evaluation of Hydrogel Film Containing Tramadol for Reduction of Peripheral Neuropathic Pain.
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Natori N, Shibano Y, Hiroki A, Taguchi M, Miyajima A, Yoshizawa K, Kawano Y, and Hanawa T
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- Mice, Animals, Hypromellose Derivatives, Water, Analgesics, Methylcellulose, Tramadol, Neuralgia drug therapy
- Abstract
To develop and assess new dosage forms for the alternative to existing oral medication for peripheral neuropathy, a hydrogel film in the skin patch formation containing tramadol hydrochloride (TRA), a water-soluble drug used as an analgesic, was prepared and evaluated. A hydrogel film composed of 20%(w/w) hydroxypropyl methylcellulose (HPMC) irradiated with electron beams had high transparency and elasticity similar to commercially available wound dressings and soft tissues, suggesting that it is a suitable substrate for TRA. The inclusion of TRA was enabled by immersing the HPMC hydrogel film in TRA aqueous solution. The release and skin permeation of TRA from TRA-containing hydrogel films differed depending on the electron beam dose. Moreover, the analgesic effects in mice were confirmed in a dose-dependent manner. This study demonstrated the usefulness of a hydrogel film containing TRA as a new dosage form alternative to the existing oral medication for peripheral neuropathy., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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22. Corrigendum to "Effects of Line of Vision on Posture, Muscle Activity, and Sitting Balance During Tooth Preparation" [International Dental Journal, Volume 71, Issue 5, 2021, pages 399-406].
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Katano K, Nakajima K, Saito M, Kawano Y, Takeda T, and Fukuda K
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- 2022
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23. [Treatment of patients with COVID-19 on Hemodialysis: Efficacy of Remdesivir].
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Nakaya A, Kondo M, Ogura E, Katayama Y, Yoshino E, Hozumi K, Tago S, Teranishi Y, Minamibashi Y, Harada M, Kawano Y, Arai Y, Kobayashi M, Kouyama A, Yoshida K, Shimizu S, Ogura K, and Iwashita K
- Abstract
Background: There is no standard therapy for hemodialysis (HD) patients with COVID-19. Data on remdesivir in HD patients with COVID-19 are scarce., Methods: We retrospectively analyzed 25 HD patients with COVID-19 treated with remdesivir., Results: The median age of the patients was 78 years (range, 45-92 years) and was predominantly male (84%). A total of 44% of the patients had mild disease, 36% had moderate-1, and 20% had moderate-2. The most common symptoms were fever (76%) and coughing (44%). The most common comorbidity was renal failure (100%), followed by hypertension (60%) and cardiac disease (44%). The most frequent biomarker was elevated creatinine (100%), followed by C-reactive protein (80%), lymphopenia (76%), and D-dimer (68%). C-reactive protein levels decreased significantly before and after remdesivir administration (p < 0.001). Two patients showed deterioration, but none died. All patients recovered from COVID-19 and no adverse effects of treatment with remdesivir were observed., Conclusion: Our study suggests the safe use of remdesivir in HD patients with COVID-19., (© 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U.)
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- 2022
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24. VSIG4/CRIg directly regulates early CD8 + T cell activation through its counter-receptor in a narrow window.
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Widyagarini A, Nishii N, Kawano Y, Zhang C, and Azuma M
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- Animals, Interferon-gamma metabolism, Lymphocyte Activation, Mice, Mice, Inbred C57BL, CD28 Antigens genetics, CD8-Positive T-Lymphocytes
- Abstract
T-cell responses are fine-tuned by positive and negative co-signal molecules expressed on immune cells and adjacent tissues. VSIG4 is a newly identified member of the B7 family of ligands, which negatively regulates innate inflammatory and CD4
+ T cell-mediated responses. However, little is known about the direct effects of VSIG4, which are exerted through an unidentified counter-receptor on CD8+ T cells. We investigated the binding of the VSIG4-Ig fusion protein during CD8+ T cell activation, and the functional involvement of VSIG4 pathway, using VSIG4-Ig and VSIG4-transfectants. VSIG4-Ig binding to CD8+ T cells was temporally observed in the CD44high phenotype during initial activation. VSIG4-Ig binding was observed earlier than the induction of PD-1, LAG3, and TIM-3, which are immune checkpoint receptors for exhausted CD8+ T cells. Immobilized VSIG4-Ig inhibited anti-CD3/CD28 mAb-induced CD8+ T cell activation, as indicated by proliferation and IFN-γ production, similar to the downregulation of T-bet and Eomesodermin transcription factors. VSIG4 on FcγR+ P815 or specific antigen-presenting E.G7 cells inhibited the generation of effector CD8+ T cells, as indicated by proliferation, IFN-γ and TNF-α expression, and granule degradation, compared to parental cells. However, the window for the regulatory function of VSIG4 was narrow and dependent on the strength of TCR (and CD28)-mediated signals. Our results suggested that VSIG4 directly delivers co-inhibitory signals via an as-yet unidentified counter-receptor on activated CD8+ T cells. VSIG4-mediated CD8+ T cell tolerance might contribute to the steady-state maintenance of homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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25. The Role for miR-146b-5p in the Attenuation of Dermal Fibrosis and Angiogenesis by Targeting PDGFRα in Skin Wounds.
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Fujisawa C, Hamanoue M, Kawano Y, Murata D, Akishima-Fukasawa Y, Okaneya T, Minematsu T, Sanada H, Tsuburaya K, Isshiki T, Mikami T, Hanawa T, and Akasaka Y
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- Animals, Fibroblasts metabolism, Fibrosis, Rats, Receptor Protein-Tyrosine Kinases metabolism, MicroRNAs metabolism, Receptor, Platelet-Derived Growth Factor alpha genetics, Receptor, Platelet-Derived Growth Factor alpha metabolism, Skin injuries, Wounds and Injuries genetics
- Abstract
As a candidate microRNA antifibrotic effector in skin wounds, miR-146b-5p was upregulated by basic FGF, and PDGFRα was identified as a direct target of miR-146b-5p in fibroblasts. The treatment of fibroblasts with a miR-146b-5p mimic markedly downregulated the expression of PDGFRα and collagen type I. miR-146b-5p mimic transfection in wounds markedly attenuated cutaneous fibrosis, whereas a miR-146b-5p inhibitor strongly promoted fibrosis, with increases in PDGFRα and collagen I levels. These results indicate the positive effects of miR-146b-5p for the suppression of fibrosis, possibly through the inhibition of PDGFRα. The miR-146b-5p inhibitor markedly increased CD34
+ vessel numbers and CD34 expression in wounds. We found miR-146b-5p+ cells in close contact with S100+ adipocytes. Moreover, we discovered the specific colocalization of the exosome marker CD81 and miR-146b-5p in the adipose tissue cells of mimic-transfected wounds, with miR-146b-5p signals being detected in the FSP1+ fibroblastic cells of adipose tissues. Therefore, fibroblastic cells of adipose tissues, which may specifically pick up and contain miR-146b-5p by exosome after transfection, may play an important role in the suppression of fibrosis. In this process, the inhibition of PDGFRα in adipose tissue cells by miR-146b-5p may lead to the loss of their PDGFRα-induced profibrotic activities, thereby suppressing fibrosis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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26. Catechol-O-methyltransferase (COMT) Val158Met Polymorphism and Prepulse Inhibition of the Change-related Cerebral Response.
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Motomura E, Tanii H, Kawano Y, Inui K, and Okada M
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- Acoustic Stimulation methods, Dopamine metabolism, Evoked Potentials, Auditory genetics, Humans, Catechol O-Methyltransferase genetics, Prepulse Inhibition genetics
- Abstract
Change-related potentials elicited by an abrupt sound feature's change are attenuated by a leading weak sound (prepulse inhibition: PPI). We investigated whether the PPI index is associated with the catechol-methyltransferase (COMT) Val158Met polymorphism (rs4680), which is involved in the metabolism of dopamine in the prefrontal cortex. Healthy subjects with normal hearing were recruited (n = 70). A train of 100-Hz clicks 650 ms in duration was used. The test stimulus was an abrupt increase in sound intensity (+10 dB) from the baseline (70 dB) provided at 400 ms after the sound onset. Three consecutive clicks at 30, 40, and 50 ms before the change's onset were greater (+3 or +5 dB) from the baseline as a prepulse. The targeting auditory evoked potential component was Change-N1 peaking approx. 130 ms after the change onset. We calculated the inhibition level as the% inhibition of the Change-N1 amplitude by a prepulse. The %PPI in the Met-carriers was significantly greater than that in the Val/Val-individuals. Our results suggest that dopamine might play a role in the PPI of the change-related response. We propose that this index has the potential to identify an intermediate phenotype in psychiatric disorders such as schizophrenia., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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27. Assessment of the albumin-bilirubin grade as a prognostic factor in patients with non-small-cell lung cancer receiving anti-PD-1-based therapy.
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Takada K, Takamori S, Shimokawa M, Toyokawa G, Shimamatsu S, Hirai F, Tagawa T, Okamoto T, Hamatake M, Tsuchiya-Kawano Y, Otsubo K, Inoue K, Yoneshima Y, Tanaka K, Okamoto I, Nakanishi Y, and Mori M
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- Humans, Neoplasm Recurrence, Local, Prognosis, Programmed Cell Death 1 Receptor antagonists & inhibitors, Prospective Studies, Retrospective Studies, Albumins analysis, Bilirubin analysis, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms diagnosis, Lung Neoplasms drug therapy
- Abstract
Introduction: The albumin-bilirubin (ALBI) grade is a novel indicator of the liver function. Some studies showed that the ALBI grade was a prognostic and predictive biomarker for the efficacy of chemotherapy in cancer patients. The association between the ALBI grade and outcomes in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy, however, is poorly understood., Methods: We retrospectively enrolled 452 patients with advanced or recurrent NSCLC who received anti-programmed cell death protein 1 (PD-1)-based therapy between 2016 and 2019 at three medical centers in Japan. The ALBI score was calculated from albumin and bilirubin measured at the time of treatment initiation and was stratified into three categories, ALBI grade 1-3, with reference to previous reports. We examined the clinical impact of the ALBI grade on the outcomes of NSCLC patients receiving anti-PD-1-based therapy using Kaplan-Meier survival curve analysis with log-rank test and Cox proportional hazards regression analysis., Results: The classifications of the 452 patients were as follows: grade 1, n = 158 (35.0%); grade 2, n = 271 (60.0%); and grade 3, n = 23 (5.0%). Kaplan-Meier survival curve analysis showed that the ALBI grade was significantly associated with progression-free survival and overall survival. Moreover, Cox regression analysis revealed that the ALBI grade was an independent prognostic factor for progression-free survival and overall survival., Conclusion: The ALBI grade was an independent prognostic factor for survival in patients with advanced or recurrent NSCLC who receive anti-PD-1-based therapy. These findings should be validated in a prospective study with a larger sample size., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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28. A novel PDK1 inhibitor, JX06, inhibits glycolysis and induces apoptosis in multiple myeloma cells.
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Kawano Y, Sasano T, Arima Y, Kushima S, Tsujita K, Matsuoka M, and Hata H
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- Antineoplastic Combined Chemotherapy Protocols, Apoptosis genetics, Bortezomib pharmacology, Cell Line, Tumor, Cell Proliferation drug effects, Datasets as Topic, Disulfiram pharmacology, Drug Synergism, Gene Expression Regulation, Neoplastic, Glycolysis genetics, Humans, Ketone Oxidoreductases genetics, Ketone Oxidoreductases metabolism, Mitochondria drug effects, Mitochondria enzymology, Mitochondria pathology, Molecular Targeted Therapy, Multiple Myeloma drug therapy, Multiple Myeloma enzymology, Multiple Myeloma genetics, Multiple Myeloma pathology, Phosphorylation drug effects, Plasma Cells drug effects, Plasma Cells enzymology, Plasma Cells pathology, Pyruvate Dehydrogenase Acetyl-Transferring Kinase antagonists & inhibitors, Pyruvate Dehydrogenase Acetyl-Transferring Kinase metabolism, Antineoplastic Agents pharmacology, Apoptosis drug effects, Disulfiram analogs & derivatives, Enzyme Inhibitors pharmacology, Glycolysis drug effects, Morpholines pharmacology
- Abstract
Pyruvate dehydrogenase kinase 1 (PDK1) is a Ser/Thr kinase that inactivates mitochondrial pyruvate dehydrogenase (PDH), leading to switch of glucose metabolism from mitochondrial oxidation to aerobic glycolysis. We previously reported that PDK1 inhibition is a potent therapeutic strategy in multiple myeloma (MM). However, availability of PDK1 inhibitors, which are effective at low concentrations, are limited at present, making PDK1 inhibition difficult to apply in the clinic. In the present study, we examined the efficacy and mechanism of action of JX06, a novel PDK1 inhibitor, against MM cells. We confirmed that PDK1 is highly expressed in normal plasma cells and MM cells using publicly available gene expression datasets. JX06 suppressed cell growth and induced apoptosis against MM cells from approximately 0.5 μM JX06 treatment reduced PDH phosphorylation, suggesting that JX06 is indeed inhibiting PDK1. Intracellular metabolite analysis revealed that JX06 treatment reduced metabolites associated with glucose metabolism of MM cells. Additionally, JX06 in combination with a well-known proteasome inhibitor, bortezomib, significantly increased MM cell death, which raises the possibility of combination use of JX06 with proteasome inhibitors in the clinic. These findings demonstrate that PDK1 can be potentially targeted by JX06 in MM through glycolysis inhibition, leading to a novel therapeutic strategy in MM., Competing Interests: Declaration of competing interest Yawara Kawano reports a relationship with Janssen Pharmaceuticals Inc that includes: speaking and lecture fees. Yawara Kawano reports a relationship with Takeda Pharmaceutical Co Ltd that includes: speaking and lecture fees. Yawara Kawano reports a relationship with Sanofi that includes: speaking and lecture fees. Yawara Kawano reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Yawara Kawano reports a relationship with Ono Pharmaceutical Co Ltd that includes: speaking and lecture fees., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2022
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29. Effects of Line of Vision on Posture, Muscle Activity and Sitting Balance During Tooth Preparation.
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Katano K, Nakajima K, Saito M, Kawano Y, Takeda T, and Fukuda K
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- Electromyography, Humans, Muscles, Tooth Preparation, Posture, Sitting Position
- Abstract
Objectives: Most dentists maintain awkward and restricted postures for prolonged periods that stress the body while providing direct patient care. Information about working posture must be analysed in a more systematic manner to provide a deeper understanding of the relationship between working posture and work-related musculoskeletal disorders (MSD). Therefore, the present study aimed to clarify the effects of different lines of vision during tooth preparation, such as the direct and the mirror view technique, on-body tilt (angle), muscle activity, and sitting balance, which may correlate with the reduction or prevention of MSD., Methods: A mannequin head with a maxillary right first molar embedded in a model was attached to the dental chair headrest. Two different techniques for tooth preparation were selected: direct view and mirror view. Muscle activity, body tilt (angle), and sitting balance were analysed as independent parameters., Results: Different tooth preparation techniques had a distinct influence on body tilt (angle), muscle activity, and sitting balance. The direct view technique resulted in significantly larger values for all parameters, except for the activity of the spinal column erector muscles than the mirror view technique., Conclusion: Based on these results, the direct view technique for tooth preparation, which is used by most dentists in practice, imposes a burden on the lower back, shoulders, and neck of the dentist., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2021
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30. Weaker prepulse exerts stronger suppression of a change-detecting neural circuit.
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Fujii S, Motomura E, Inui K, Watanabe T, Hakumoto Y, Higuchi K, Kawano Y, Morimoto M, Nakatani K, and Okada M
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- Acoustic Stimulation, Humans, Inhibition, Psychological, Prepulse Inhibition, Evoked Potentials, Auditory, Reflex, Startle
- Abstract
Change-N1 peaking 90-180 ms after changes in a sound feature of a continuous sound is clearly attenuated by a preceding change stimulus (called a "prepulse"). Here, we investigated the effects of a preceding decrease in sound pressure on the degree of inhibition of the subsequent Change-N1 amplitude. Using 100-Hz click train sounds, we obtained Change-N1s from 11 healthy volunteers. The two types of test stimuli were an abrupt 10-dB increase from the baseline (70 dB) and the insertion of a 0.45-ms inter-aural time difference in the middle of the sound. Three consecutive clicks at 30, 40, and 50 ms before the change onset that was used as a prepulse were weaker than the background by 5 or 10 dB. The Change-N1 elicited by the two test stimuli was attenuated more strongly by the weaker prepulse, which was not congruent with the theory that the inhibition of the subsequent sensory/sensory-motor processing depends on the sound pressure level of a prepulse. These results suggest that a change in any type of sound feature elicits a change-related response that is inhibited by any type of preceding change stimulus, which reflects auto-inhibition of the change-responding circuit., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)
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- 2021
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31. Corrigendum to "CEACAM1 specifically suppresses B cell receptor signaling-mediated activation".
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Tsugawa N, Yamada D, Watabe T, Onizawa M, Wang S, Nemoto Y, Oshima S, Tsubata T, Adachi T, Kawano Y, Watanabe M, Blumberg RS, Okamoto R, and Nagaishi T
- Published
- 2021
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32. Progression signature underlies clonal evolution and dissemination of multiple myeloma.
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Shen YJ, Mishima Y, Shi J, Sklavenitis-Pistofidis R, Redd RA, Moschetta M, Manier S, Roccaro AM, Sacco A, Tai YT, Mercier F, Kawano Y, Su NK, Berrios B, Doench JG, Root DE, Michor F, Scadden DT, and Ghobrial IM
- Subjects
- Adaptor Proteins, Signal Transducing antagonists & inhibitors, Adaptor Proteins, Signal Transducing genetics, Animals, Apoptosis, Biomarkers, Tumor genetics, Bone Marrow metabolism, Bone Marrow pathology, CRISPR-Cas Systems, Cell Adhesion, Cell Movement, Cell Proliferation, Clonal Evolution, Disease Progression, Female, HMGA1a Protein antagonists & inhibitors, HMGA1a Protein genetics, Humans, Mice, Mice, SCID, Multiple Myeloma genetics, Multiple Myeloma metabolism, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local metabolism, Prognosis, RNA-Binding Proteins antagonists & inhibitors, RNA-Binding Proteins genetics, Survival Rate, Tumor Cells, Cultured, Adaptor Proteins, Signal Transducing metabolism, Biomarkers, Tumor metabolism, Disease Models, Animal, Gene Expression Regulation, Neoplastic, HMGA1a Protein metabolism, Multiple Myeloma pathology, Neoplasm Recurrence, Local pathology, RNA-Binding Proteins metabolism
- Abstract
Clonal evolution drives tumor progression, dissemination, and relapse in multiple myeloma (MM), with most patients dying of relapsed disease. This multistage process requires tumor cells to enter the circulation, extravasate, and colonize distant bone marrow (BM) sites. Here, we developed a fluorescent or DNA-barcode clone-tracking system on MM PrEDiCT (progression through evolution and dissemination of clonal tumor cells) xenograft mouse model to study clonal behavior within the BM microenvironment. We showed that only the few clones that successfully adapt to the BM microenvironment can enter the circulation and colonize distant BM sites. RNA sequencing of primary and distant-site MM tumor cells revealed a progression signature sequentially activated along human MM progression and significantly associated with overall survival when evaluated against patient data sets. A total of 28 genes were then computationally predicted to be master regulators (MRs) of MM progression. HMGA1 and PA2G4 were validated in vivo using CRISPR-Cas9 in the PrEDiCT model and were shown to be significantly depleted in distant BM sites, indicating their role in MM progression and dissemination. Loss of HMGA1 and PA2G4 also compromised the proliferation, migration, and adhesion abilities of MM cells in vitro. Overall, our model successfully recapitulates key characteristics of human MM disease progression and identified potential new therapeutic targets for MM., (© 2021 by The American Society of Hematology.)
- Published
- 2021
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33. FGF-23 from erythroblasts promotes hematopoietic progenitor mobilization.
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Ishii S, Suzuki T, Wakahashi K, Asada N, Kawano Y, Kawano H, Sada A, Minagawa K, Nakamura Y, Mizuno S, Takahashi S, Matsui T, and Katayama Y
- Subjects
- Animals, Cells, Cultured, Erythroblasts metabolism, Female, Fibroblast Growth Factor-23, Fibroblast Growth Factors genetics, Hematopoiesis, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cells metabolism, Humans, Male, Mice, Inbred C57BL, RNA, Messenger genetics, Up-Regulation, Mice, Erythroblasts cytology, Fibroblast Growth Factors metabolism, Hematopoietic Stem Cells cytology
- Abstract
Fibroblast growth factor 23 (FGF-23) hormone is produced by bone-embedded osteocytes and regulates phosphate homeostasis in kidneys. We found that administration of granulocyte colony-stimulating factor (G-CSF) to mice induced a rapid, substantial increase in FGF-23 messenger RNA in bone marrow (BM) cells. This increase originated mainly from CD45-Ter119+CD71+ erythroblasts. FGF-23 protein in BM extracellular fluid was markedly increased during G-CSF-induced hematopoietic progenitor cell (HPC) mobilization, but remained stable in the blood, with no change in the phosphate level. Consistent with the BM hypoxia induced by G-CSF, low oxygen concentration induced FGF-23 release from human erythroblast HUDEP-2 cells in vitro. The efficient mobilization induced by G-CSF decreased drastically in both FGF-23-/- and chimeric mice with FGF-23 deficiency, only in hematopoietic cells, but increased in osteocyte-specific FGF-23-/- mice. This finding suggests that erythroblast-derived, but not bone-derived, FGF-23 is needed to release HPCs from BM into the circulation. Mechanistically, FGF-23 did not influence CXCL-12 binding to CXCR-4 on progenitors but interfered with their transwell migration toward CXCL-12, which was canceled by FGF receptor inhibitors. These results suggest that BM erythroblasts facilitate G-CSF-induced HPC mobilization via FGF-23 production as an intrinsic suppressor of chemoattraction., (© 2021 by The American Society of Hematology.)
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- 2021
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34. The eldest case of MICPCH with CASK mutation exhibiting gross motor regression.
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Nishio Y, Kidokoro H, Takeo T, Narita H, Sawamura F, Narita K, Kawano Y, Nakata T, Muramatsu H, Hara S, Kaname T, and Natsume J
- Subjects
- Adult, Female, Humans, Motor Skills, Mutation, Neurodevelopmental Disorders genetics, Disease Progression, Guanylate Kinases genetics, Mental Retardation, X-Linked genetics, Microcephaly genetics
- Abstract
Background: MICPCH is manifested as microcephaly associated with pontocerebellar hypoplasia and global developmental delay but developmental regression has never been reported. We describe the detailed clinical history of a woman with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH) with a CASK mutation who exhibited gross motor regression after adolescence., Case: The patient experienced severe motor and intellectual developmental delay with microcephaly from infancy. The initial diagnosis was Rett syndrome based on her clinical features, including hand stereotypes and the absence of structural abnormality on magnetic resonance imaging (MRI) performed at the age of 5 years. Although gross motor abilities developed slowly and she could walk independently, she never acquired speech or understanding of languages. After adolescence, her motor ability gradually regressed so that she was unable to stand without support and moved with a wheelchair. At the age of 31 years, because of her atypical clinical course for Rett syndrome, whole exome sequencing was performed, which revealed a de novo heterozygous c.2068 + 1G > A mutation in the CASK gene (NM_001126055). Brain MRI revealed mild pontocerebellar hypoplasia compatible with the clinical phenotype of MICPCH., Discussion: This case suggests that MICPCH with a CASK mutation might cause developmental regression after adolescence and might be regarded as a neurodegenerative disorder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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35. Efficacy, safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection.
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Suganuma E, Sakata H, Adachi N, Asanuma S, Furuichi M, Uejima Y, Sato S, Abe T, Matsumoto D, Takahashi R, Yamamoto S, Kawano Y, Arai T, and Oh-Ishi T
- Subjects
- Antiviral Agents adverse effects, Child, Child, Preschool, Ganciclovir adverse effects, Humans, Infant, Infant, Newborn, Japan, Valganciclovir adverse effects, Cytomegalovirus Infections drug therapy, Hearing Loss, Sensorineural drug therapy
- Abstract
Objectives: Valganciclovir (VGCV) has been shown to improve sensorineural hearing loss (SNHL) and neurological outcomes in patients with neonatal symptomatic congenital cytomegalovirus (cCMV) infection. However, reports on the pharmacokinetics, efficacy and safety of oral VGCV are limited. The aim of this study is to evaluate the pharmacokinetics of VGCV for use in the treatment of cCMV., Methods: This was a single-center, retrospective observational study conducted at Saitama Children's Medical Center in Japan between 2012 and 2017. CMV DNA copy number, maximum plasma VGCV concentration (Cmax), and adverse events (ADEs) during treatment were evaluated., Results: A total of 26 patients with cCMV who received VGCV were included in this study. The median age at VGCV initiation was 9.5 months (range 0-46). Twenty-one patients (81%) had SNHL at baseline. Of these, five patients (19%) presented with improved SNHL, and none experienced worsened SNHL during treatment. The mean VGCV Cmax was 3.5 μg/mL (range 2-5.3), with no significant variation among individual values, and the values were maintained during treatment. Furthermore, there were no correlations between the Cmax values and age, sex, SNHL improvement or ADEs. Neutropenia (<1000/mm
3 ) was observed in six patients (23%); however, no serious ADEs occurred., Conclusions: VGCV prevented the progression of SNHL without serious ADEs due to its stable pharmacokinetics. This study provides safety and tolerability of VGCV for the treatment of cCMV patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)- Published
- 2021
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36. CEACAM1 specifically suppresses B cell receptor signaling-mediated activation.
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Tsugawa N, Yamada D, Watabe T, Onizawa M, Wang S, Nemoto Y, Oshima S, Tsubata T, Adachi T, Kawano Y, Watanabe M, Blumberg RS, Okamoto R, and Nagaishi T
- Subjects
- Animals, B-Lymphocytes metabolism, Cell Differentiation, Cell Lineage, Cells, Cultured, Cytokines biosynthesis, Female, Mice, Inbred C57BL, Mice, Antigens, CD metabolism, Cell Adhesion Molecules metabolism, Receptors, Antigen, B-Cell metabolism, Signal Transduction
- Abstract
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expressed in T cells may regulate immune responses in the gut. In addition to T cells, B cells are also an important population in the gut-associated lymphoid tissues that orchestrate mucosal homeostasis. However, the role of CEACAM1 in B cells has not been elucidated. We herein analyzed mature B cells to determine the functions of CEACAM1. Flow cytometry revealed high expression of CEACAM1 on B cells in secondary lymphoid tissues. Cytokine production induced by activation of B cell receptor (BCR) signaling was suppressed by CEACAM1 signaling in contrast to that associated with either Toll-like receptor 4 or CD40 signaling. Confocal microscopy revealed co-localization of CEACAM1 and BCR when activated with anti-Igμ F(ab')
2 fragment. Overexpression of CEACAM1 in a murine B cell line, A20, resulted in reduced expressions of activation surface markers with decreased Ca2+ influx after BCR signal activation. Overexpression of CEACAM1 suppressed BCR signal cascade in A20 cells in association with decreased spontaneous proliferation. Our results suggest that CEACAM1 can regulate BCR-mediated mature B cell activation in lymphoid tissues. Therefore, further studies of this molecule may lead to greater insights into the mechanisms of immune responses within peripheral tissues and the potential treatment of inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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37. CXCL17-mediated downregulation of type I collagen via MMP1 and miR-29 in skin fibroblasts possibly contributes to the fibrosis in systemic sclerosis.
- Author
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Shimada S, Makino K, Jinnin M, Sawamura S, Kawano Y, Ide M, Kajihara I, Makino T, Fukushima S, and Ihn H
- Subjects
- Animals, Biopsy, Bleomycin administration & dosage, Bleomycin toxicity, Case-Control Studies, Cells, Cultured, Chemokines, CXC administration & dosage, Chemokines, CXC analysis, Collagen Type I analysis, Disease Models, Animal, Down-Regulation, Female, Fibroblasts, Healthy Volunteers, Humans, Male, Matrix Metalloproteinase 1 analysis, Mice, MicroRNAs analysis, MicroRNAs antagonists & inhibitors, Middle Aged, Primary Cell Culture, RNA Processing, Post-Transcriptional, Recombinant Proteins, Scleroderma, Systemic blood, Scleroderma, Systemic chemically induced, Scleroderma, Systemic genetics, Signal Transduction drug effects, Signal Transduction genetics, Skin cytology, Skin pathology, Chemokines, CXC metabolism, Collagen Type I metabolism, Matrix Metalloproteinase 1 metabolism, MicroRNAs metabolism, Scleroderma, Systemic pathology
- Abstract
Background: Systemic sclerosis (SSc) is characterized by excessive deposition of collagen in the skin and internal organs. Recent studies have shown that chemokine (C-X-C motif) ligands (CXCLs) are involved in the pathogenesis of SSc., Objective: Our aim was to examine the anti-fibrotic potential of CXCL17, a newly discovered chemokine, in cultured skin fibroblasts and in a bleomycin-induced SSc mouse model. Moreover, we examined serum level of CXCL17 in patients with SSc., Methods: Type I collagen expression was evaluated in SSc skin and cultured fibroblasts treated with CXCL17 using immunoblotting and quantitative reverse transcription-PCR. Serum CXCL17 levels were determined using enzyme-linked immunosorbent assay in 63 patients with SSc and 17 healthy subjects. A bleomycin-induced SSc mouse model was used to evaluate the effect of CXCL17 on skin fibrosis., Results: CXCL17 reduced the expression of type I collagen in healthy control fibroblasts. CXCL17 also induced matrix metalloproteinase 1 (MMP1) and miR-29 expression in fibroblasts, indicating that CXCL17 regulates type I collagen expression in part via post-transcriptional mechanisms through MMP1 and miR-29. We found that local injection of CXCL17 attenuated bleomycin-induced skin fibrosis in mice. CXCL17 levels in SSc skin were lower than those in healthy controls, in contrast to the high serum CXCL17 levels in patients with SSc. The low expression of CXCL17 in SSc skin possibly affects type I collagen accumulation in this disease., Conclusion: Our data indicate that understanding CXCL17 signaling may lead to a better therapeutic approach for SSc., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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38. A case of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) strain meningitis and ventriculitis following BCG vaccination.
- Author
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Furuichi M, Mori F, Uejima Y, Sato S, Kurihara J, Kawano Y, and Suganuma E
- Subjects
- BCG Vaccine administration & dosage, Brain diagnostic imaging, Brain microbiology, Cerebral Ventriculitis diagnostic imaging, Cerebral Ventriculitis etiology, Humans, Infant, Magnetic Resonance Imaging, Male, Meningitis diagnostic imaging, Meningitis etiology, Mycobacterium bovis genetics, Mycobacterium bovis isolation & purification, Vaccination adverse effects, BCG Vaccine adverse effects, Cerebral Ventriculitis microbiology, Meningitis microbiology, Mycobacterium bovis immunology
- Abstract
The Bacillus Calmette-Guérin (BCG) vaccine is widely used worldwide. Intracranial manifestation as an adverse event of BCG is extremely rare. A previously healthy 16-month-old boy was referred to our hospital for eye contact difficulties and progressive gait disturbance lasting two months. He was inoculated with BCG at seven months of age. Brain magnetic resonance imaging (MRI) revealed hydrocephalus with widespread and disseminated enhancement lesions with thickening of the third ventricle floor, and brain tissue pathologically showed non-caseous granulomatous inflammation. Immunosuppressive therapies were initiated because of a provisional diagnosis of neurosarcoidosis. Three months later, a positive polymerase chain reaction (PCR) result for the Mycobacterium tuberculosis complex was obtained. Eventually, M. bovis (BCG Tokyo 172 strain) was identified in the cerebrospinal fluid (CSF) and shunt tube culture. The prolonged use of antituberculosis drugs and multiple shunt replacement surgeries were needed for recovery. There was no evidence of immunodeficiency. Unfortunately, he had severe neurological sequelae of bilateral blindness and neurodevelopmental delay. Our purpose in this report was to highlight the potential for intracranial manifestations of adverse reactions related to BCG vaccination. We propose that the CSF PCR assay of Mycobacterium tuberculosis (MTB) complex should be applied repeatedly in children suspected of intractable neurosarcoidosis, with a history of BCG vaccination., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
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39. Multidisciplinary Treatments of True Posterior Inferior Cerebellar Artery Aneurysms: Single-Center Retrospective Study and Treatment Algorithm.
- Author
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Kanemoto Y, Michiwaki Y, Maeda K, Kawano Y, Maehara N, Nagaoka S, and Gi H
- Subjects
- Adult, Aged, Aged, 80 and over, Brain Infarction epidemiology, Brain Stem Infarctions epidemiology, Cerebellar Diseases epidemiology, Disease Management, Female, Humans, Male, Middle Aged, Postoperative Complications epidemiology, Retrospective Studies, Vertebral Artery, Algorithms, Aortic Dissection surgery, Cerebellum blood supply, Endovascular Procedures methods, Intracranial Aneurysm surgery, Microsurgery methods, Neurosurgical Procedures methods
- Abstract
Background: True posterior inferior cerebellar artery (PICA) aneurysms outside the vertebral artery-PICA region are rare, with approximately 30 cases reported in just a few papers; no treatment paradigm has been advocated. The objective of this study was to present detailed clinical features and outcomes for several treatments for true PICA aneurysms and suggest an algorithm for treatment strategies., Methods: We retrospectively analyzed outcomes of patients treated for PICA aneurysms with microsurgical and endovascular treatments. We also investigated the influence of several factors on the modified Rankin Scale score., Results: Cases with PICA aneurysms (n = 36) outside the vertebral artery-PICA region were identified angiographically. Aneurysm locations included anterior medullary (n = 7), lateral medullary (n = 10), tonsillomedullary (n = 4), telovelotonsillar (n = 12), and cortical (n = 3) segments of the PICA. Aneurysm morphology was as follows: dissecting: 22; fusiform: 6; and saccular: 8. On multivariate analysis, age (P = 0.028) and lack of vermian infarction (P =0.037) were associated with a significantly better prognosis. Prognosis was not significantly different for the 5 aneurysm locations and among the 4 treatment groups: clipping/coiling, trapping/parent artery occlusion, trapping/parent artery occlusion + bypass, and observation including external ventricular drainage., Conclusions: This study suggests that factors associated with significantly better prognosis include age, clip/coil treatments, and no vermian infarction complication. A treatment algorithm for true PICA aneurysms was supported according to pretreatment H and K grade, PICA segments, aneurysm morphology, and 3 types of ischemia linked to the brainstem, cerebellar hemisphere, or vermis., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
40. Experience of morphine therapy for refractory dyspnea as palliative care in advanced heart failure patients.
- Author
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Kawaguchi J, Hamatani Y, Hirayama A, Nishimura K, Nakai E, Nakamura E, Miyata M, Kawano Y, Takada Y, Anchi Y, Funabashi S, Kuroda K, Azechi M, Takahama H, Anzai T, Yasuda S, Kitaoka H, and Izumi C
- Subjects
- Aged, Aged, 80 and over, Analgesics, Opioid adverse effects, Dyspnea blood, Dyspnea physiopathology, Female, Heart Failure blood, Heart Failure physiopathology, Humans, Male, Middle Aged, Morphine adverse effects, Natriuretic Peptide, Brain blood, Palliative Care, Retrospective Studies, Ventricular Function, Left, Analgesics, Opioid therapeutic use, Dyspnea drug therapy, Heart Failure drug therapy, Morphine therapeutic use
- Abstract
Background: In the field of palliative care, morphine is known to be effective for alleviating dyspnea in cancer patients. However, little is known regarding the safety and efficacy of morphine therapy for refractory dyspnea as palliative care in advanced heart failure (HF) patients., Methods: We retrospectively reviewed consecutive advanced HF patients who were referred to the Palliative Care Team at our institution and administered morphine for refractory dyspnea during hospitalization between September 2013 and December 2018. We investigated the details of morphine usage, vital signs, an 11-point quantitative symptom scale, and adverse events at baseline, 24 h, and 72 h after the start of treatment., Results: Morphine was administered for refractory dyspnea in 43 advanced HF patients [mean age: 73.5 years, male: 28 (65%), New York Heart Association functional class IV: 43 (100%), median left ventricular ejection fraction: 25%, median B-type natriuretic peptide level: 927 pg/ml, concurrent intravenous inotrope: 33 (77%)]. Median initial dose of morphine was 5 mg/day in both oral and intravenous administration and median duration of administration was 5 days. Significant decreases in an 11-point quantitative symptom scale [7 (5, 9) vs. 2 (1, 6); p < 0.01, (data available in 8 patients)] and respiratory rate (22.2 ± 6.1 vs. 19.7 ± 5.2 breaths per minute; p < 0.01) were observed 24 h after the start of morphine administration. Meanwhile, oxygen saturation, blood pressure, and heart rate were not significantly altered after treatment (NS). Common adverse events were delirium (18%) and constipation (8%); however, no lethal adverse event definitely related to morphine therapy occurred during treatment., Conclusions: This single-center retrospective study revealed the clinical practice of morphine therapy and suggested that morphine therapy might be feasible for refractory dyspnea as palliative care in advanced HF patients., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2020
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41. Liver abscess due to Sterigmatomyces halophilus in a boy with acute lymphoblastic leukemia.
- Author
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Imashioya T, Kodama Y, Ooka T, Nakagawa S, Nishikawa T, Tanabe T, Okamoto Y, Imuta N, Kirishima M, Tanimoto A, Koriyama T, Nishi J, and Kawano Y
- Subjects
- Amphotericin B therapeutic use, Antineoplastic Agents adverse effects, Basidiomycota immunology, Biopsy, Bone Marrow Transplantation, Cephalosporins therapeutic use, Chemotherapy-Induced Febrile Neutropenia complications, Chemotherapy-Induced Febrile Neutropenia drug therapy, Chemotherapy-Induced Febrile Neutropenia immunology, Child, Hematopoietic Stem Cell Transplantation, Humans, Liver microbiology, Liver pathology, Liver Abscess diagnosis, Liver Abscess drug therapy, Liver Abscess immunology, Male, Micafungin therapeutic use, Mycoses diagnosis, Mycoses drug therapy, Mycoses immunology, Neoplasm Recurrence, Local immunology, Neoplasm Recurrence, Local therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Treatment Outcome, Cefozopran, Antifungal Agents therapeutic use, Basidiomycota isolation & purification, Liver Abscess microbiology, Mycoses microbiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
We report the first case of liver abscess due to Sterigmatomyces halophilus. Because this pathogen grows poorly in culture medium without added salts, it was identified by sequencing analysis targeting the rRNA gene internal transcribed spacer (ITS) region. This method could be useful for pathogens that cannot be cultured using standard methods., (Copyright © 2019. Published by Elsevier Ltd.)
- Published
- 2019
- Full Text
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42. Vitamin D receptor-mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis.
- Author
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Wakahashi K, Minagawa K, Kawano Y, Kawano H, Suzuki T, Ishii S, Sada A, Asada N, Sato M, Kato S, Shide K, Shimoda K, Matsui T, and Katayama Y
- Subjects
- Animals, Cell Proliferation, Disease Models, Animal, Hematopoietic Stem Cell Transplantation, Heterografts, Humans, Mice, Mice, Knockout, Myofibroblasts pathology, Primary Myelofibrosis complications, Primary Myelofibrosis pathology, Primary Myelofibrosis prevention & control, Signal Transduction, Vitamin D Deficiency, Cell Differentiation, Macrophages pathology, Osteosclerosis etiology, Primary Myelofibrosis etiology, Receptors, Calcitriol metabolism
- Abstract
Myelofibrosis in myeloproliferative neoplasms (MPNs) with mutations such as JAK2V617F is an unfavorable sign for uncontrollable disease progression in the clinic and is complicated with osteosclerosis whose pathogenesis is largely unknown. Because several studies have revealed that macrophages are an indispensable supporter for bone-forming osteoblasts, we speculated that macrophages might play a significant role in the proliferation of collagen-producing myofibroblasts in marrow fibrotic tissues. Here, we show that myelofibrosis critically depends on macrophages whose differentiation is skewed by vitamin D receptor (VDR) signaling. In our novel myelofibrosis model established by transplantation of VDR
+/+ hematopoietic stem/progenitor cells into VDR-/- mice, donor-derived F4/80+ macrophages proliferated together with recipient-derived α-smooth muscle actin-positive myofibroblasts, both of which comprised fibrotic tissues with an indistinguishable spindle-shaped morphology. Interfering VDR signals, such as low vitamin D diet and VDR deficiency in donor cells as well as macrophage depletion prevented myelofibrosis in this model. These interventions also ameliorated myelofibrosis in JAK2V617F-driven murine MPNs likely in a transforming growth factor-β1- or megakaryocyte-independent manner. These results suggest that VDR and macrophages may be novel therapeutic targets for MPNs with myelofibrosis., (© 2019 by The American Society of Hematology.)- Published
- 2019
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43. Ruptured Cerebral Arteriovenous Malformation During Fifth Pregnancy: Case Report and Literature Review.
- Author
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Michiwaki Y, Nakamizo A, Kawano Y, and Tsumoto T
- Abstract
Background: Whether the risk of rupture of a cerebral arteriovenous malformation (AVM) increases during pregnancy remains controversial. Moreover, it is unclear whether the number of pregnancies correlates with AVM rupture risk. We report a case of ruptured AVM during the fifth pregnancy., Case Description: A 34-year-old woman presenting sudden headache and vomiting was admitted to our hospital. Neuroimaging revealed a subarachnoid hemorrhage due to a ruptured AVM in the right temporal lobe. She was pregnant (9 weeks and 1 day), and she had previously experienced 4 normal vaginal deliveries (gravidity and parity G
4 P4 ) without complications. Elective treatment including neuroendovascular and direct surgery was performed, and the AVM was safely resected (at 15 weeks, 6 days of pregnancy). She underwent elective caesarean section without complications 151 days after the AVM resection (at 37 weeks, 1 day of pregnancy), and the baby was healthy., Conclusions: This report suggests that the risk of AVM rupture persists even after multiple deliveries. Intracranial hemorrhage should be suspected in pregnant patients who underwent multiple deliveries, and a rapid diagnosis and appropriate treatment are necessary., (Copyright © 2018. Published by Elsevier Inc.)- Published
- 2019
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44. β-hydroxybutyrate protects hepatocytes against endoplasmic reticulum stress in a sirtuin 1-independent manner.
- Author
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Tagawa R, Kawano Y, Minami A, Nishiumi S, Yano Y, Yoshida M, and Kodama Y
- Subjects
- AMP-Activated Protein Kinases metabolism, Animals, Cell Line, Tumor, Hep G2 Cells, Hepatocytes metabolism, Humans, Mice, Phosphorylation, Tunicamycin pharmacology, 3-Hydroxybutyric Acid pharmacology, Endoplasmic Reticulum Stress drug effects, Hepatocytes drug effects, Sirtuin 1 metabolism
- Abstract
β-hydroxybutyrate (BHB), a major ketone body in mammals, is produced from fatty acids through mitochondrial fatty acid oxidation in hepatocytes. To elucidate the role of BHB in the hepatic endoplasmic reticulum (ER), we examined the effects of BHB on hepatic ER stress induced by tunicamycin. In mouse hepatoma Hepa1c1c7 cells, BHB treatment suppressed the protein expression of ER stress responsive genes and increased cell viability, while reducing the protein expression of apoptosis inducible genes, without causing any alterations in the protein expression of sirtuin 1 (SIRT1) or the phosphorylation of AMP-activated protein kinase. The intraperitoneal administration of BHB also reduced the protein expression of ER stress responsive genes in mouse livers. In human hepatoma HepG2 cells, the protein expression levels of ER stress responsive genes were increased by the partial inhibition of BHB production with siRNA targeting endogenous 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase, whereas they were decreased by promoting BHB production with fenofibrate. These findings revealed that BHB helps to suppress hepatic ER stress via a SIRT1-independent pathway, and it might be possible to manipulate ER stress by regulating BHB production genetically or pharmacologically., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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45. Comparison of accuracy of presepsin and procalcitonin concentrations in diagnosing sepsis in patients with and without acute kidney injury.
- Author
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Nakamura Y, Hoshino K, Kiyomi F, Kawano Y, Mizunuma M, Tanaka J, Nishida T, and Ishikura H
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Sepsis complications, Acute Kidney Injury complications, Limit of Detection, Lipopolysaccharide Receptors metabolism, Peptide Fragments metabolism, Procalcitonin metabolism, Sepsis diagnosis, Sepsis metabolism
- Abstract
Background: Levels of the biomarkers presepsin and procalcitonin are affected by renal function. We evaluated the accuracies of presepsin and procalcitonin levels for diagnosing sepsis in patients with and without acute kidney injury (AKI)., Methods: We evaluated patients with presepsin and procalcitonin data, and classified them into AKI and non-AKI groups based on the Kidney Disease Improving Global Outcomes criteria. Each group was then subdivided according to sepsis status for each stage of AKI. Receiver operating characteristic curve analyses were used to investigate the accuracies of biomarker levels for diagnosing sepsis., Results: In the non-AKI group, the area under the curves (AUCs) for procalcitonin and presepsin levels were 0.897 and 0.880, respectively (p = .525) and optimal cut-off values were 0.10 ng/ml (sensitivity: 85.1%, specificity: 79.1%) and 240 pg/ml (sensitivity: 80.9%, specificity: 83.2%), respectively. In the stage 3 subgroup, the AUC for procalcitonin (0.946) was significantly higher than that for presepsin (0.768, p < .001). The optimal cut-off values for diagnosing sepsis were 4.07 ng/ml (sensitivity: 87.2%, specificity: 93.5%) for procalcitonin and 500 pg/ml (sensitivity: 89.7%, specificity: 59.7%) for presepsin., Conclusions: In patients with severe AKI, the accuracy of the diagnosis of sepsis with procalcitonin was significantly higher than with presepsin., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
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46. Pyogenic liver abscess due to hypervirulent Klebsiella pneumoniae in a 14-year-old boy.
- Author
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Sato S, Aoyama T, Uejima Y, Furuichi M, Suganuma E, Takano T, Ikeda M, Mizoguchi M, Okugawa S, Moriya K, Niimi H, Kitajima I, Kawashima H, and Kawano Y
- Subjects
- Adolescent, Humans, Male, Klebsiella Infections, Klebsiella pneumoniae, Liver Abscess, Pyogenic
- Abstract
A 14-year-old otherwise healthy boy presented with right-sided back pain following high fever. Abdominal computed tomography scan showed a large liver abscess. Klebsiella pneumoniae (KP) was rapidly identified from peripheral blood using the melting temperature mapping (Tm) method, which enables identification of pathogenic microorganisms within four hours after patient sample collection. He was diagnosed with pyogenic liver abscess (PLA) caused by KP on the day of admission. The KP was the hypervirulent (hv) clinical variant (string test positive, serotype K1, sequence type 23, rmpA and magA positive). After intravenous antibiotic therapy and drainage of the abscess, his condition resolved. The highlights of this case report are a healthy child with hypervirulent Klebsiella pneumoniae liver abscess in Japan and the new Tm mapping method for rapid and accurate identification of the pathogenic microorganism., (Copyright © 2018. Published by Elsevier Ltd.)
- Published
- 2019
- Full Text
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47. MUC1/KL-6 expression confers an aggressive phenotype upon myeloma cells.
- Author
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Endo S, Nishimura N, Kawano Y, Ueno N, Ueno S, Tatetsu H, Komohara Y, Takeya M, Hata H, Mitsuya H, Masao M, and Okuno Y
- Subjects
- Animals, Cell Cycle Checkpoints, Cell Line, Tumor, Cell Proliferation, Cell Survival, Female, Gene Knockdown Techniques, Humans, Mice, Middle Aged, Mucin-1 blood, Multiple Myeloma blood, Neoplasm Invasiveness, S Phase, Xenograft Model Antitumor Assays, Mucin-1 metabolism, Multiple Myeloma metabolism, Multiple Myeloma pathology
- Abstract
The sialic glycoprotein, MUC1, is known to be involved in the pathogenesis of various types of cancers. KL-6 is one of the surface antigens of MUC1 and also a marker of interstitial pneumonitis. A fraction of patients with myeloma (3.9%) have elevated serum KL-6 levels without any evidence of interstitial pneumonitis and their myeloma cells have high MUC1 expression. We established a myeloma cell line designated EMM1 from a patient with multiple myeloma accompanied with elevated serum KL-6. EMM1 cells expressed high levels of MUC1 compared with other myeloma cell lines. Knockdown of MUC1 in EMM1 cells induced cell cycle arrest during S phase and apoptosis, suggesting that the MUC1 expression is involved in accelerated growth of EMM1 cells. RNA-seq analysis suggests that MUC1 expression activates k-ras and TNFα-induced NFκB pathways in EMM1 cells. We injected EMM1 cells subcutaneously into Rag2
-/- Jak3-/- Balb/c mice to establish a mouse xenograft model. These mice had aggressive tumor growth that was accompanied by high serum KL-6 levels. In addition, MUC1 knockdown in EMM1 cells led to inhibited tumor growth. These findings demonstrate that MUC1 serves as a potential target for developing drugs for treatment of patients with KL-6+ myeloma, and EMM1 cells and EMM1-engrafted mice are useful tools for the development of such novel agents., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
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48. A case of refractory cytomegalovirus-related thrombocytopenia that achieved complete remission without antiviral therapy.
- Author
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Nishio Y, Kawano Y, Kawada JI, Ito Y, and Hara S
- Subjects
- Cytomegalovirus genetics, Cytomegalovirus isolation & purification, Cytomegalovirus Infections blood, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections drug therapy, DNA, Viral blood, DNA, Viral genetics, Fever, Humans, Immunocompetence immunology, Immunoglobulins, Intravenous therapeutic use, Immunologic Factors administration & dosage, Immunologic Factors therapeutic use, Infant, Male, Platelet Count, Purpura, Thrombocytopenic, Idiopathic blood, Purpura, Thrombocytopenic, Idiopathic diagnosis, Purpura, Thrombocytopenic, Idiopathic drug therapy, Viral Load genetics, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, DNA, Viral immunology, Immunoglobulins, Intravenous administration & dosage, Purpura, Thrombocytopenic, Idiopathic immunology
- Abstract
Cytomegalovirus (CMV) is one of the major infectious etiologies that induce thrombocytopenia. Although immune thrombocytopenic purpura (ITP) in children is often preceded by viral infections, thrombocytopenia associated with active CMV infection is considered CMV-related thrombocytopenia (CMV-thrombocytopenia), which can be distinguished from ITP. CMV-thrombocytopenia is reported to be less responsive to standard therapies for ITP and may require antiviral therapies. We herein report a case of refractory CMV-thrombocytopenia that achieved complete remission without antiviral therapy. A 20-month-old boy presented with a 2-day history of fever and systemic petechiae. There were no abnormal findings except for an extremely low platelet count (8000/μl) on blood examinations. He was clinically diagnosed with ITP, and intravenous immunoglobulin was administered twice, but his platelet count did not increase. CMV infection was suspected serologically, and a high CMV DNA load was detected in serum by real-time quantitative polymerase chain reaction (PCR). Without antiviral treatment, the CMV DNA load decreased below the detection limit on the 11th day of admission, followed by complete remission of the thrombocytopenia. The present case suggests that spontaneous recovery of thrombocytopenia can be expected in immunocompetent patients with CMV-thrombocytopenia in whom decreased CMV DNA load is observed., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
49. Impact of the extent of low-voltage zone on outcomes after voltage-based catheter ablation for persistent atrial fibrillation.
- Author
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Yamaguchi T, Tsuchiya T, Fukui A, Kawano Y, Otsubo T, Takahashi Y, Hirota K, Murotani K, Eshima K, and Takahashi N
- Subjects
- Aged, Anti-Arrhythmia Agents therapeutic use, Atrial Fibrillation mortality, Atrial Fibrillation physiopathology, Catheter Ablation methods, Electrophysiologic Techniques, Cardiac methods, Female, Heart Atria physiopathology, Humans, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Pulmonary Veins physiopathology, Recurrence, Survival Rate, Treatment Outcome, Atrial Fibrillation therapy, Catheter Ablation mortality, Electrophysiologic Techniques, Cardiac mortality
- Abstract
Background: Low-voltage zones (LVZs), as measured by electroanatomic mapping, are thought to be associated with fibrosis. We reported the efficacy of atrial fibrillation (AF) ablation aiming to homogenize left atrial (LA) LVZ. The purpose of this study was to evaluate the impact of LVZ extension outcomes after LVZ homogenization in patients with nonparoxysmal AF., Methods: This prospective observational cohort study included 172 patients with nonparoxysmal AF undergoing their initial ablation. LVZ was defined as an area with bipolar electrograms <0.5mV during sinus rhythm. LVZ extent was calculated as the percentage of LA surface area, and subsequently, LVZ was categorized into stages I (<5%), II (≥5% to <20%), III (≥20% to <30%), and IV (≥30%). Patients with LVZs underwent LVZ ablation aimed at homogenization of ≥80% of LVZs following pulmonary vein isolation. The primary endpoint was atrial tachyarrhythmia recurrence-free survival after a single procedure at 18 months off antiarrhythmic drugs. The association of %LVZ with recurrence-free survival was examined using Cox proportional hazard models., Results: The survival rates were 76%, 74%, 57%, and 28% in patients with stages I, II, III, and IV LVZ, respectively. The difference was significant between stages I and IV (log-rank, p<0.001), while not significant between stages I vs. II and I vs. III (p=0.843, p=0.073, respectively). Cox proportional hazard model revealed that %LVZ was an independent predictor of recurrence-free survival (hazard ratio, 1.025 per 1% increase, p<0.001; unadjusted model). The results were similar after demographic and clinical covariate adjustments and after excluding 12 patients who did not achieve homogenization of ≥80% of LVZ., Conclusions: The extent of LVZ is an independent predictor for recurrence even after LVZ homogenization., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
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50. Long-Term Neurocognitive Outcomes in Patients with Adult Moyamoya Disease.
- Author
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Nakamizo A, Amano T, Michiwaki Y, Kawano Y, Kuwashiro T, Yasaka M, and Okada Y
- Subjects
- Brain diagnostic imaging, Brain physiopathology, Cerebrovascular Circulation, Female, Follow-Up Studies, Humans, Male, Middle Aged, Moyamoya Disease diagnostic imaging, Moyamoya Disease physiopathology, Moyamoya Disease therapy, Prospective Studies, Time Factors, Moyamoya Disease psychology
- Abstract
Objective: Neurocognitive impairment is a frequent complication of moyamoya disease in adults, but the long-term outcomes of neurocognitive function remain unclear. We evaluated neurocognitive functions in a group of patients with a history of moyamoya disease and assessed the relationship between regional cerebral blood flow (rCBF) and neurocognitive functions., Methods: We studied 53 patients with a history of adult moyamoya disease. Neurocognitive functions were evaluated with the Neurobehavioral Cognitive Status Examination (Cognistat) and the Frontal Assessment Battery. The relationship between rCBF and neurocognitive functions were assessed in patients for whom rCBF was measured using single-photon emission computed tomography with
123 I-iodoamphetamine., Results: Patients had a history of moyamoya disease for an average of 10.6 years, with 23 patients managed conservatively and 30 managed using revascularization. Attention, memory, conceptualization, mental flexibility, and inhibitory control were impaired but with no significant difference between conservatively and surgically treated patients. Posterior cerebral artery involvement and frontal lobe infarction were not associated with neurocognitive examination scores in nonrevascularized or revascularized patients. Orientation, comprehension, calculation, conceptualization, and sensitivity to interference correlated with rCBF in the left ventral middle cerebral artery territory (P < 0.01), whereas memory correlated with rCBF in the right dorsal anterior cerebral artery territory (P < 0.01). Conceptualization also correlated with rCBF in the left dorsal anterior cerebral artery territory (P < 0.001)., Conclusions: Our findings indicate that long-standing hypoperfusion in specific brain regions can cause related neurocognitive dysfunction even in mild moyamoya disease managed conservatively., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
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