Publications by authors named "Satoshi Saito"

364 Publications

Feasibility of intensity modulated radiotherapy with involved field radiotherapy for Japanese patients with locally advanced non-small cell lung cancer.

J Radiat Res 2021 Jul 15. Epub 2021 Jul 15.

Department of Radiation Oncology, International Medical Center, Saitama Medical University, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.

The feasibility of intensity modulated radiotherapy (IMRT) with involved field radiotherapy (IFRT) for Japanese patients with locally advanced non-small cell lung cancer (LA-NSCLC) remains unclear. Here we reviewed our initial experience of IMRT with IFRT for Japanese patients with LA-NSCLC to evaluate the feasibility of the treatment. Twenty LA-NSCLC patients who were treated with IMRT with IFRT during November 2019 to October 2020 were retrospectively analyzed. All patients received 60 Gy in 30 fractions of IMRT and were administered concurrent platinum-based chemotherapy. The median patient age was 71 years old and the group included 15 men and 5 women. The patient group included 2 patients with stage IIB, 11 patients with stage IIIA, 5 patients with stage IIIB, and 2 patients with stage IIIC disease. Histological diagnosis was squamous cell carcinoma in 14 patients, adenocarcinoma in 5 patients, and non-small cell lung cancer in 1 patient. The median follow-up period was 8 months. The incidence of grade 3 or greater pneumonitis was 5%, and grade 3 or greater esophagitis was not observed. None of the patients developed regional lymph node, with only recurrence reported so far. These findings indicate that IMRT with IFRT for Japanese patients with LA-NSCLC is feasible in terms of acute toxicity. Further study with a larger number of patients and longer follow-up to clarify the effect of treatment on patient prognosis is required.
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http://dx.doi.org/10.1093/jrr/rrab063DOI Listing
July 2021

Time Dependence of Intra-fractional Motion in Spinal Stereotactic Body Radiotherapy.

In Vivo 2021 Jul-Aug;35(4):2433-2437

Department of Radiation Oncology, Saitama Medical University International Medical Center, Saitama, Japan.

Background/aim: Positional uncertainty in spinal stereotactic body radiotherapy (SBRT) may cause fatal error, therefore, we investigated the intra-fractional spinal motion during SBRT and its time dependency.

Patients And Methods: Thirty-one patients who received SBRT using CyberKnife were enrolled in the study. 2D kV X-ray spine images in two directions were taken before and during treatment. Image acquisition intervals during treatment were set at 35-60 sec. Automatic image matchings were performed between the reference digital reconstructed radiography (DRR) and live images, and the spinal position displacements were logged in six translational and rotational directions. If the displacements exceeded 2 mm or 1 degree, the treatment beam delivery was interrupted and the patient position was corrected by moving couch, and the couch adjustments were also logged. Based on the information, the time-dependent accumulated translational and rotational displacements without any couch adjustments were calculated.

Results: Spinal position displacements in all translational and rotational directions were correlated with elapsed treatment time. Especially, Right-Left displacements of >1 mm and >2 mm were observed at 4-6 and 8-10 min after treatment initiation, respectively. Rotational displacements in the Yaw direction >1° were observed at 10-15 min after treatment initiation.

Conclusion: The translational and rotational displacements systematically increased with elapsed treatment time. It is suggested that the spine position should be checked at least every 4-6 min or the treatment time should be limited within 4-6 minutes to ensure the irradiation accuracy within the millimeter or submillimeter range.
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http://dx.doi.org/10.21873/invivo.12521DOI Listing
June 2021

Incidence and risk factors for pneumonitis among patients with lung cancer who received immune checkpoint inhibitors after palliative thoracic radiotherapy.

J Radiat Res 2021 Jul;62(4):669-675

Departments of Radiation Oncology, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan.

The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P < 0.001). Patients who receive ICI after palliative thoracic RT should be carefully followed-up, especially those who have had obstructive pneumonia or high KL-6 levels.
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http://dx.doi.org/10.1093/jrr/rrab051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273801PMC
July 2021

Conversion from cilostazol to OPC-13015 linked to mitigation of cognitive impairment.

Alzheimers Dement (N Y) 2021 27;7(1):e12182. Epub 2021 May 27.

Department of Neurology National Cerebral and Cardiovascular Center Suita Osaka Japan.

Introduction: Cilostazol may be a novel therapeutic agent for Alzheimer's disease. Its metabolite, OPC-13015, has a stronger inhibitory effect on type 3 phosphodiesterase than cilostazol.

Methods: We prospectively enrolled patients with mild cognitive impairment to whom cilostazol was newly prescribed. Patients underwent the Montreal Cognitive Assessment (MoCA) twice, at a 6-month interval. Plasma cilostazol, OPC-13015, OPC-13213, and OPC-13217 concentrations were determined using liquid chromatography-tandem mass spectrometry.

Results: MoCA score changes from baseline to the 6-month visit were positively correlated with ratios of OPC-13015 to cilostazol and total metabolites (= 19, = .005). Patients with higher ratios of OPC-13015 (≥0.18, median value; = 10) had significantly higher MoCA scores (= .036) than patients with lower ratios (the ratio <0.18, = 9). The absolute value of OPC-13015 concentration in blood was also higher in patients with preserved cognitive function (= .033).

Discussion: Blood OPC-13015 levels may be a predictive biomarker of cilostazol treatment for Alzheimer's disease.
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http://dx.doi.org/10.1002/trc2.12182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158162PMC
May 2021

[Hybrid Treatment for Left Internal Thoracic Artery-Pulmonary Artery Fistula with Aneurysm Complicated with Mitral Regurgitation:Report of a Case].

Kyobu Geka 2021 02;74(2):152-155

Department of Cardiovascular Surgery, Tokyo Women's Medical University, Tokyo, Japan.

A 78-year-old man with mitral regurgitation incidentally diagnosed with aneurysm of the left internal thoracic artery(LITA) and several internal thoracic artery-pulmonary artery( ITA-PA) fistulas originating from the aneurysm. To prevent rupture of the aneurysm, ITA ligation was performed during surgery for the mitral valve. Because of the complex anatomy surrounding the aneurysm, the main duct of the ITA was ligated at the peripheral and center of the aneurysm, then arterial fistulae were resected as many as possible. Postoperative computed tomography (CT), however, showed patent LITA and contrast material in the aneurysm. Second stage coil embolization procedure was performed with successful results. Intravascular treatment is effective for ITA aneurysms or ITA-PA fistulae because we can clearly visualize and confirm blood flow during operation.
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February 2021

Coronary artery bypass using bilateral internal thoracic artery grafts in polyarteritis nodosa.

J Card Surg 2021 Aug 11;36(8):2979-2981. Epub 2021 May 11.

Department of Cardiovascular Surgery, Tokyo Women's Medical University, Tokyo, Japan.

Polyarteritis nodosa (PAN) affects small- and medium-sized arteries but rarely occurs in coronary artery aneurysms and stenosis. For patients with PAN, coronary artery bypass grafting (CABG) can be challenging, especially with respect to graft selection. We performed CABG using a bilateral internal thoracic artery (ITA) graft for a 21-year-old patient with PAN, with successful postoperative outcomes. Arterial grafts have the risk of stenosis in PAN, but the patient's condition was controlled by steroids and immunosuppressants, and angiography showed no stenosis. We decided to use the ITA graft as a bypass conduit and found that long-term follow-up and continuous treatment are necessary.
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http://dx.doi.org/10.1111/jocs.15619DOI Listing
August 2021

Technical Features and Clinical Outcomes of Coronary Venous Left Ventricular Lead Removal and Reimplantation.

Circ J 2021 Jul 2;85(8):1349-1355. Epub 2021 Apr 2.

Department of Cardiology, Tokyo Women's Medical University.

Background: The number of patients undergoing cardiac resynchronization therapy has increased. Consequently, there is increased frequency in the removal and reimplantation of coronary venous (CV) leads due to infection or malfunction.Methods and Results:A total of 345 consecutive patients referred for lead(s) extraction were reviewed. Of these, 34 patients who underwent a CV lead removal were investigated. The indications for CV leads removal were device-related infections in 29 patients and lead malfunctions in 5 patients. The average duration of the CV leads was 4.1±3.8 years. All CV leads were successfully removed without any major complications, except for 1 in-hospital death. Successful CV lead removal by simple traction (ST) was achieved in 21 patients (62%), whereas extraction tools were required in 13 patients (38%). Local infection and CV lead dwell time were significantly associated with successful ST (P=0.04 and P=0.014, respectively). CV lead re-implantation was successfully performed in 25 patients; however, a right-side approach was required in 92%, and occlusion/stenosis of the previous CV was observed in 80% of the patients.

Conclusions: CV lead removal is relatively successful and safe. The presence of local infection and a shorter lead duration may enable successful ST of a CV lead. However, the re-implantation procedure should be well prepared for the complexity related to the right-side approach and occlusion/stenosis of the previous CV.
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http://dx.doi.org/10.1253/circj.CJ-20-1199DOI Listing
July 2021

Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Phase-II Trial: AdrenoMedullin for Ischemic Stroke Study.

J Stroke Cerebrovasc Dis 2021 Jun 1;30(6):105761. Epub 2021 Apr 1.

Department of Neurology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan. Electronic address:

Objectives: Adrenomedullin (AM), a vasoactive peptide, has strong anti-inflammatory and angiogenic properties, which have been reported to ameliorate the consequences of ischemic stroke in several animal models. After a phase I study in healthy volunteers, two phase II trials of AM for inflammatory bowel diseases have been recently completed. The current AdrenoMedullin For Ischemic Stroke (AMFIS) study aims to assess the safety and efficacy of AM in patients with acute ischemic stroke.

Materials And Methods: The AMFIS study is an investigator-initiated, randomized, double-blind, phase-II trial. AM or placebo will be administered to patients with non-cardioembolic ischemic stroke within 24 h after stroke onset. In the first cohort of the AMFIS study, patients will be randomly allocated to the investigation treatment A (30 μg/kg of AM in total for 7 days, n = 20) or placebo group (n = 10). In the second cohort, patients will be assigned to the investigation treatment B (56 μg/kg of AM in total for 7 days, n = 20) or placebo group (n = 10).

Results: Serious adverse events related to the protocol treatment will be evaluated as the primary outcome. All adverse events will be analyzed as the secondary outcome. Regarding efficacy endpoints, the change in National Institutes of Health Stroke Scale and modified Rankin Scale scores will be compared between investigation treatment and placebo groups.

Conclusions: AM is expected to be a safe and effective treatment for ischemic stroke.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105761DOI Listing
June 2021

Complete coronary thrombolysis on continuous-flow left ventricular assist device.

Eur J Cardiothorac Surg 2021 Mar 3. Epub 2021 Mar 3.

Department of Cardiovascular Surgery, Tokyo Women's Medical University, Yuki Ichihara, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

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http://dx.doi.org/10.1093/ejcts/ezab128DOI Listing
March 2021

Taxifolin: A Potential Therapeutic Agent for Cerebral Amyloid Angiopathy.

Front Pharmacol 2021 12;12:643357. Epub 2021 Feb 12.

Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of β-amyloid (Aβ) in the walls of cerebral vessels, leading to complications such as intracerebral hemorrhage, convexity subarachnoid hemorrhage and cerebral microinfarcts. Patients with CAA-related intracerebral hemorrhage are more likely to develop dementia and strokes. Several pathological investigations have demonstrated that more than 90% of Alzheimer's disease patients have concomitant CAA, suggesting common pathogenic mechanisms. Potential causes of CAA include impaired Aβ clearance from the brain through the intramural periarterial drainage (IPAD) system. Conversely, CAA causes restriction of IPAD, limiting clearance. Early intervention in CAA could thus prevent Alzheimer's disease progression. Growing evidence has suggested Taxifolin (dihydroquercetin) could be used as an effective therapy for CAA. Taxifolin is a plant flavonoid, widely available as a health supplement product, which has been demonstrated to exhibit anti-oxidative and anti-inflammatory effects, and provide protection against advanced glycation end products and mitochondrial damage. It has also been shown to facilitate disassembly, prevent oligomer formation and increase clearance of Aβ in a mouse model of CAA. Disturbed cerebrovascular reactivity and spatial reference memory impairment in CAA are completely prevented by Taxifolin treatment. These results highlight the need for clinical trials on the efficacy and safety of Taxifolin in patients with CAA.
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http://dx.doi.org/10.3389/fphar.2021.643357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907591PMC
February 2021

A Nationwide Multi-Center Questionnaire Survey on the Real-World State and Issues Regarding Post-Stroke Complications in Japan.

J Stroke Cerebrovasc Dis 2021 Apr 8;30(4):105656. Epub 2021 Feb 8.

Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan. Electronic address:

Objectives: Post-stroke complications affect stroke survivors across the world, although data on them are limited. We conducted a questionnaire survey to examine the real-world state and issues regarding post-stroke complications in Japan, which represents a super-aged society.

Materials And Methods: In 2018, a nationwide multi-center questionnaire survey was conducted in the top 500 Japanese hospitals regarding the number of stroke patients treated. Three questionnaires regarding post-stroke complications were mailed to the doctors responsible for stroke management.

Results: Responses were obtained from 251 hospitals (50.2%). The chief doctors responsible for stroke management answered the questionnaires. The number of stroke patients in the departments of neurology and neurosurgery was 338.3 ± 195.3 and 295.8 ± 121.8. Hospitals were classified using the categories secondary (n =142) and tertiary hospitals (n = 106); most hospitals were acute hospitals. Dementia was the most common complication (30.9%), followed by dysphagia (29.3%), and apathy (16.3%). Dementia was thought to be more common by neurologists than neurosurgeons, while apathy and bladder-rectal disorder were thought to be more common by neurosurgeons than neurologists (p = 0.001). The most difficult complication to treat was dysphagia (40.4%), followed by dementia (33.9%), epilepsy (4.1%), and fall (4.1%). Dementia was considered to lack clinical evidence regarding treatment (32.8%), followed by dysphagia (25.3%), and epilepsy (14.1%). Epilepsy was considered to lack clinical evidence among hospitals with a larger number of stroke cases (p = 0.044).

Conclusion: This study revealed the current state and issues regarding post-stroke complications in Japan. Clinicians should be aware of the importance of post-stroke complications, although data on them remain unsatisfactory.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105656DOI Listing
April 2021

Nutcracker syndrome due to chronic aortic dissection.

J Card Surg 2021 Mar 1;36(3):1138-1139. Epub 2021 Feb 1.

Department of Cardiovascular Surgery, Tokyo Women's Medical University, Tokyo, Japan.

Nutcracker syndrome (NCS) is known as a status of compression of the left renal vein (LRV) between the abdominal aorta and superior mesenteric artery (SMA). We here report a case of NCS in a Marfan syndrome patient with type B aortic dissection who was presented with sudden gross hematuria. Computed tomography revealed the compression of the LRV sandwiched between the SMA and the dilated dissecting abdominal aorta. The compression was released by surgical intervention and the hematuria was promptly resolved. This report highlights that NCS should be considered as a differential diagnosis of unexplained hematuria in patients with a chronic dissecting aorta.
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http://dx.doi.org/10.1111/jocs.15400DOI Listing
March 2021

Heart transplant candidate with medical complexity in the era of prolonged left ventricular assist device support - A case report.

J Cardiol Cases 2021 Feb 22;23(2):83-86. Epub 2020 Oct 22.

Department of Therapeutic Strategy for Severe Heart Failure, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Heart transplantation improves quality of life and survival in patients with advanced heart failure. However, the shortage of available heart donors and technological advances for left ventricular assist devices (LVAD) have led to longer waiting times for transplantation, and long-term use of LVAD may increase the medical complexity of subsequent transplantation. We present the case of a 35-year-old man who underwent heart transplantation after being supported by an LVAD for 1490 days (∼4 years). He was sensitized with kidney dysfunction and recurrent infections, including candidemia, at the time of transplantation. He underwent a successful heart transplantation with pretransplant plasma exchange, intravenous immunoglobulin administration, early initiation of everolimus, and prompt management of infections. < With a growing number of heart transplant candidates who are supported by left ventricular assist devices for long duration, managing such candidates is becoming increasingly complex and difficult to standardize. The present case had three problems that were linked to each other: (1) anti-HLA antibodies, (2) fungal infection, and (3) pre-transplantation renal dysfunction. Management of heart transplant candidates, including desensitization and immunosuppressive therapies, should be tailored to the individual and the clinical presentation to improve the survival and quality of life.>.
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http://dx.doi.org/10.1016/j.jccase.2020.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817913PMC
February 2021

Impact of anatomical position of the inflow cannula on stroke in patients with left ventricular assist devices.

Int J Artif Organs 2021 Jan 21:391398820988297. Epub 2021 Jan 21.

Department of Cardiovascular Surgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.

Objectives: Stroke is a substantial complication of left ventricular assist device (LVAD) implantation. The relationship between stroke and the anatomical position of the inflow cannula of patients who underwent LVAD implantation was investigated.

Methods: We enrolled 15 patients with advanced-stage heart failure who underwent implantation of continuous-flow-LVAD. Data of patients who suffered a stroke within 6 months after LVAD implantation were retrospectively compared to those who remained free of stroke. The distance between the inflow duct and left ventricular (LV) septum (duct-sep distance) and its ratio to LV diastolic diameter (LVDd) were measured from echocardiography at 1 month after LVAD implantation. Receiver operating characteristic curves for the endpoint of stroke using the duct-sep distance to LVDd ratio was created and the cut-off value was calculated. The incidence of stroke during the 6 months after LVAD implantation according to this ratio was estimated using the Kaplan-Meier method.

Results: At 1 month after LVAD implantation, there were no significant differences in baseline characteristics and echocardiography parameters between the stroke and stroke-free groups. Receiver operating characteristic curve analysis for the endpoint of stroke using the duct-sep distance to LVDd ratio revealed 0.217 as a cut-off value (sensitivity: 80%, specificity: 80%, area under the curve: 0.72). Stroke was more frequent in patients with a duct-sep distance to LVDd ratio ⩾0.217 at 1 month than in those with a lower ratio.

Conclusion: The duct-sep distance to LVDd ratio was associated with the occurrence of stroke, suggesting that inflow cannula position influences the incidence of stroke.
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http://dx.doi.org/10.1177/0391398820988297DOI Listing
January 2021

Transvenous lead extraction in a patient with polysplenia and inferior vena cava defect.

J Cardiol Cases 2021 Jan 2;23(1):41-44. Epub 2020 Oct 2.

Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan.

A 28-year-old woman with polysplenia was referred to our hospital for atrial lead failure. She had undergone an intracardiac repair (ICR) for incomplete atrioventricular septal defect and the implantation of epicardial pacing leads due to complete atrioventricular block at the age of 1 year. When she was 13 years old, an endocardial dual-chamber pacemaker was implanted via the right subclavian vein because of epicardial lead failure. The contrast-enhanced computed tomography scan revealed an inferior vena cava defect with an azygos vein connection to the superior vena cava, occlusion of the right brachiocephalic vein, a defect of the left brachiocephalic vein, and a persistent left superior vena cava ligated at the ICR. Therefore, lead exchange was indicated. During the operation, the temporary pacing lead and the guidewire for emergent deployment of the Bridge Occlusion Balloon® were advanced through the azygos vein and placed at the right ventricle and the hepatic vein, respectively. Both 11-Fr and 13-Fr mechanical rotational dilator sheaths were needed for the lead extraction owing to dense calcification and tight adhesions. The atrial lead was successfully extracted without any complications despite extremely restricted venous access. A new atrial lead was inserted through the space created by the 13-Fr sheath. < Transvenous lead extraction in patients with polysplenia is technically challenging. These patients often undergo pacemaker implantation in childhood, which results in tight adhesions and dense calcifications on the leads, and venous access is extremely restricted. It may be impossible to use a snare and deploy the endovascular balloon to prevent a catastrophic complication from the right femoral vein to the superior vena cava in cases of the inferior vena cava defect.>.
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http://dx.doi.org/10.1016/j.jccase.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783646PMC
January 2021

Mid-regional pro-adrenomedullin is a novel biomarker for arterial stiffness as the criterion for vascular failure in a cross-sectional study.

Sci Rep 2021 01 11;11(1):305. Epub 2021 Jan 11.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

We investigated the potential of mid-regional pro-adrenomedullin (MR-proADM) for use as a novel biomarker for arterial stiffness as the criterion for vascular failure and cardiometabolic disease (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome) compared with high-sensitivity C-reactive protein (hsCRP). Overall, 2169 individuals (702 men and 1467 women) were enrolled. Multiple regression analysis was performed to assess the association of MR-proADM and hsCRP with brachial-ankle pulse wave velocity (baPWV), adjusting for other variables. The diagnostic performance (accuracy) of MR-proADM with regard to the index of vascular failure was tested with the help of receiver operating characteristic curve analysis in the models. MR-proADM was significantly higher in participants with vascular failure, as defined by baPWV and/or its risk factors (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome), than in control groups. Independent of cardiovascular risk factors (age, drinking, smoking, body mass index, systolic blood pressure, lipid and glycol metabolism), MR-proADM was significantly associated with baPWV, and MR-proADM showed higher areas under the curve of baPWV than hsCRP showed. MR-proADM is more suitable for the diagnosis of higher arterial stiffness as the criterion for vascular failure than hsCRP. Because vascular assessment is important to mitigate the most significant modifiable cardiovascular risk factors, MR-proADM may be useful as a novel biomarker on routine blood examination.
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http://dx.doi.org/10.1038/s41598-020-79525-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801498PMC
January 2021

Effect of durvalumab on local control after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer in comparison with chemoradiotherapy alone.

Thorac Cancer 2021 01 1;12(2):245-250. Epub 2020 Dec 1.

Department of Radiation Oncology, International Medical Center, Saitama Medical University, Hidaka, Japan.

Background: Durvalumab after concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (LA-NSCLC) has been found to significantly improve overall survival (OS). However, the effect of durvalumab on local control remains unclear. Here, we evaluated the effect of the durvalumab on local control in comparison with the clinical result of patients treated with CCRT alone.

Methods: A total of 120 LA-NSCLC patients including 76 patients with CCRT alone and 44 patients with CCRT followed by durvalumab were analyzed. Baseline patient characteristics of CCRT alone cohort and durvalumab cohort were compared with student's t test or Mann-Whitney U test for continuous variables and with chi-squared test for categorical variables. Local control (LC), progression free survival (PFS) and OS rates were estimated using the Kaplan-Meier method and compared with the log-rank test.

Results: There were 19 patients with stage II disease and 101 patients with stage III disease. Age, sex, histopathological type, T classification, N classification, clinical stage, tumor volume and dose fractionation schedule were not significantly different between the CCRT alone and durvalumab cohorts. The one-year LC rate was significantly higher in the durvalumab cohort (86%) compared with the CCRT alone cohort (62%) (P = 0.005), whereas no significant difference was observed in either PFS (P = 0.864) or OS (P = 0.443) between the CCRT and durvalumab cohorts.

Conclusions: The one-year LC rate was significantly higher in the durvalumab cohort compared with the CCRT alone cohort. Although the follow-up period was too short to draw definitive conclusions, the study revealed that durvalumab might have a significant effect on LC.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Effect of durvalumab on local control after chemoradiotherapy for locally advanced non-small cell lung cancer is unclear WHAT THIS STUDY ADDS: The one-year local control rate of chemoradiotherapy followed by durvalumab was significantly higher compared with chemoradiotherapy alone.
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http://dx.doi.org/10.1111/1759-7714.13764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812072PMC
January 2021

Results of definitive radiotherapy with concurrent chemotherapy for maxillary sinus carcinomas with neck lymph node metastasis.

J Radiat Res 2021 Jan;62(1):104-109

Departments of Radiation Oncology.

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.
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http://dx.doi.org/10.1093/jrr/rraa120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779343PMC
January 2021

Cerebral Amyloid Angiopathy Presenting as Massive Subarachnoid Haemorrhage: A Case Study and Review of Literature.

Front Aging Neurosci 2020 10;12:538456. Epub 2020 Nov 10.

Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.

Cerebral amyloid angiopathy (CAA) is characterised by the progressive accumulation of β-amyloid (Aβ) in the walls of cerebral capillaries and arteries representing a major cause of haemorrhagic stroke including lobar intracerebral haemorrhage (ICH) and convexity subarachnoid haemorrhage (SAH). Haemorrhaging from CAA predominantly involves smaller arteries rather than arterial aneurysm. Restricted bleeding into the subarachnoid space in CAA results in asymptomatic or mild symptomatic SAH. Herein, we present an autopsied case of massive SAH related to CAA. An 89-year-old male with a history of mild Alzheimer's disease (AD) and advanced pancreatic cancer with liver metastasis developed sudden onset of coma. Head CT illustrated ICH located in the right frontal lobe and right insula, as well as SAH bilaterally spreading from the basal cistern to the Sylvian fissure, with hydrocephalus and brain herniation. He died about 24 h after onset and the post-mortem examination showed no evidence of arterial aneurysm. The substantial accumulation of Aβ in the vessels around the haemorrhagic lesions led to the diagnosis of ICH related to CAA and secondary SAH, which may have been aggravated by old age and malignancy. This case suggests that CAA can cause severe SAH resembling aneurysmal origin and thus may be overlooked when complicated by atypical cerebral haemorrhage.
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http://dx.doi.org/10.3389/fnagi.2020.538456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683384PMC
November 2020

Editorial: Intramural Vascular Cells: Key Therapeutic Targets for Vascular Cognitive Impairment.

Front Aging Neurosci 2020 30;12:615780. Epub 2020 Oct 30.

Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

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http://dx.doi.org/10.3389/fnagi.2020.615780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662129PMC
October 2020

Non-invasive predictors of prognosis of Asian patients with histopathologically-confirmed lean nonalcoholic fatty liver disease.

BMC Gastroenterol 2020 Nov 4;20(1):368. Epub 2020 Nov 4.

Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.

Background: The prognostic factors of morbidity and mortality in patients with lean NAFLD (body mass index < 25.0 kg/m) are unknown.

Methods: In this retrospective study, 446 Japanese patients with histopathologically-confirmed NAFLD (lean NAFLD, n = 170) were followed for liver events, cardiovascular events, type 2 diabetes mellitus, and non-liver malignancies. The median observation period was 4.6 years. We also investigated the predictors of severe fibrosis (stage 3-4) and mortality in lean NAFLD patients.

Results: Glycolipid metabolic markers, liver function tests, NAFLD fibrosis score (NFS), and histological scoring were significantly lower in lean NAFLD patients than in non-lean NAFLD. The incidence of liver cancer was higher while that of T2DM was lower in lean NAFLD. Kaplan-Meier analysis showed no significant difference in overall survival between the lean and non-lean NAFLD. Multivariate analysis of data of lean NAFLD identified NFS ≥ - 1.455 as significant independent predictor of severe fibrosis, while history of liver cancer and NFS ≥ - 1.455 were predictors of overall survival.

Conclusions: Although patients with lean NAFLD have better histopathological and biochemical profile compared to patients with non-lean NAFLD, the prognosis is not different between the two groups. Lean NAFLD patients with NFS ≥ - 1.455 or history of liver cancer should be monitored carefully during follow-up.
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http://dx.doi.org/10.1186/s12876-020-01509-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640447PMC
November 2020

Oral Carriage of Harboring the Gene Relates to an Increased Incidence of Cerebral Microbleeds.

Stroke 2020 12 5;51(12):3632-3639. Epub 2020 Nov 5.

Department of Neurology (S.H., S.S., S.T., H. Ishiyama, T.Y., S.I., H. Ikenouchi, Y.H., M.I.), National Cerebral and Cardiovascular Center, Suita, Japan.

Background And Purpose: Cerebral microbleeds (CMB) are associated with stroke and cognitive impairment. We previously reported a high prevalence of CMB in people with expressing Cnm, a collagen-binding protein in the oral cavity. is a major pathogen responsible for dental caries. Repeated challenge with harboring the gene encoding Cnm induced cerebral bleeding in stroke-prone spontaneously hypertensive rats. The purpose of this longitudinal study is to examine the relationship of -positive to the development of CMB.

Methods: We retrospectively investigated patients with stroke receiving oral microbiological examination and head 3T magnetic resonance imaging evaluations twice in the period 2014 to 2019, allowing >180-day interval. Patients with -positive were compared with those without. Quasi-Poisson regression models were used to explore associations between -positive and the increase in number of CMB between the 2 magnetic resonance imaging scans.

Results: A total of 111 patients were identified; 21 (19%) with -positive and 90 (81%) without. Clinical history, including blood pressure and the use of antithrombotic agents, were comparable between the 2 groups. New CMB were more commonly observed in patients with -positive (52% versus 23%; =0.008). The incidence of CMB was significantly higher in the group with -positive , especially in deep areas, (incidence rate ratios [95% CI], 5.1 [1.9-13.6] for CMB in any brain region; 15.0 [5.4-42.0] for deep CMB), which persisted after adjusting for age, sex, hypertension, and renal impairment (4.7 [1.8-11.9] for CMB in any brain region; 13.9 [4.3-44.5] for deep CMB).

Conclusions: This study demonstrates that -positive is associated with an increased incidence of CMB. Treatment for -positive infection may be a novel microbiota-based therapeutic approach for stroke and cognitive impairment.
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http://dx.doi.org/10.1161/STROKEAHA.120.029607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678651PMC
December 2020

Postprandial cerebral infarction resolved by extracranial-intracranial bypass surgery.

eNeurologicalSci 2020 Dec 14;21:100283. Epub 2020 Oct 14.

Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.

A 51-year-old man with type 2 diabetes mellitus was admitted with a 2-month history of repeated episodes of transient aphasia and right hemiparesis after food intake. His blood pressure (BP) fell when the neurological deficits developed. The fall in BP after each meal was confirmed by 24-h ambulatory blood pressure monitoring (ABPM), which established the diagnosis of postprandial hypotension (PPH). Diffusion-weighted magnetic resonance imaging of the brain showed multiple high-intensity lesions at the borderzone between the anterior and middle cerebral artery (MCA) territories in the left hemisphere. Digital subtraction angiography showed tapered occlusion at the origin of the left internal carotid artery (ICA). Despite sufficient antiplatelet therapy and medication for PPH, the transient symptoms remained. Positron emission tomography scanning using H O showed decreased cerebral blood flow with increased oxygen extraction fraction in the left MCA territory. As the symptomatic left ICA occlusion was intractable, an extracranial-intracranial (EC-IC) bypass surgery was conducted without any perioperative complications. Although PPH remained, cerebrovascular ischemic events including repeated transient ischemic attack disappeared for 2 months after surgery. The coincidence of stroke with ABPM-proved transient hypotension suggested that the brain infarcts were caused by hemodynamic changes related to PPH co-existent with the chronic left ICA occlusion. ABPM is useful in evaluating hemodynamic infarcts associated with BP fluctuation, and should be considered for patients with chronic ICA occlusion. In addition, EC-IC bypass may be a treatment option for symptomatic chronic ICA occlusion due to PPH.
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http://dx.doi.org/10.1016/j.ensci.2020.100283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575838PMC
December 2020

Vertical distribution of radiocesium concentrations among crown positions and year-to-year variation in four major tree species after the Fukushima Daiichi Nuclear Power Plant accident.

J Environ Radioact 2020 Dec 19;225:106447. Epub 2020 Oct 19.

Tohoku Research Center, Forestry and Forest Products Research Institute, Morioka, 020-0123, Japan.

To evaluate the distribution of radiocesium (Cs) among crown positions in trees after the Fukushima Daiichi Nuclear Power Plant accident, we collected foliage and branch samples from different crown positions of four major tree species (Chamaecyparis obtusa, Cryptomeria japonica, Pinus densiflora, and Quercus serrata) from 2011 to 2019 in northeast Japan. We divided the samples into current-year and more than 1-year-old groups (called old foliage and old branches), which sometimes included directly contaminated parts. The Cs activity concentration in dry foliage and branches was measured using a germanium semiconductor detector. There were complex differences in the relative Cs activity concentration among species and organ types (i.e., foliage and branches) among crown positions. The relative Cs activity concentration in current-year foliage was higher in the upper crowns of C. obtusa, but higher in lower crown positions in C. japonica. No differences among crown positions were observed in P. densiflora and Q. serrata. In current-year branches, the relative Cs concentration in Q. serrata was similar among crown positions but higher in the upper crown in P. densiflora. The concentrations in old foliage and old branches in all species tended to be higher in the lower crown. The factors causing these interspecific and organ type differences among crown positions may be related to the organ turnover rate, dilution effect due to different growth rates, and potassium distribution within the crown. No year-to-year variation was observed in most foliage and branches in all species, except for current-year branches of Q. serrata, old foliage in C. japonica and P. densiflora, and old branches in P. densiflora. Our long-term data on the interspecific and inter-organ patterns of contamination, focusing on variation among crown positions and year-to-year trends, might help to improve the estimation of Cs deposition and dynamics in polluted forest ecosystems.
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http://dx.doi.org/10.1016/j.jenvrad.2020.106447DOI Listing
December 2020

Right Ventricle to Pulmonary Artery Conduit With Tricuspid Expanded Polytetrafluoroethylene Valves.

Ann Thorac Surg 2020 Sep 16. Epub 2020 Sep 16.

Department of Cardiovascular Surgery, Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan.

Background: Excellent outcomes of right ventricle to pulmonary artery conduits with expanded polytetrafluoroethylene (ePTFE) valves have been reported. The purpose of this study was to evaluate the outcomes of the different material conduits with tricuspid ePTFE valves.

Methods: Forty-one consecutive patients who received right ventricle to pulmonary artery conduit with tricuspid ePTFE valves for biventricular repair between April 2004 and December 2016 were studied. The conduits made of autologous pericardial roll or xenograft roll were used in 22 patients (group P) and the conduits made of ePTFE tube were used in 19 patients (group G). The conduit reoperation and the conduit dysfunction were analyzed.

Results: During the median follow-up of 5.8 years, no death related to the conduit was observed. There were four reoperations (three in group P and one in group G). Freedom from conduit reoperation at 5 years was 100% in both groups (P = .30). Freedom from more than moderate conduit stenosis at 5 years after operation was not significantly different between groups (46.9% in group P vs 76.3% in group G, P = .23) even though the group G conduits were significantly smaller and freedom from more than moderate conduit regurgitation at 5 years was significantly better in group G (63.3% in group P vs 94.1% in group G, P = .04).

Conclusions: The conduit with ePTFE valves in the ePTFE tubes had better conduit function compared with the conduit with autologous pericardial or xenograft roll, especially in terms of conduit regurgitation.
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http://dx.doi.org/10.1016/j.athoracsur.2020.06.119DOI Listing
September 2020

Seasonal changes in radiocesium and potassium concentrations in current-year shoots of saplings of three tree species in Fukushima, Japan.

J Environ Radioact 2020 Nov 10;223-224:106409. Epub 2020 Sep 10.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-0032, Japan.

We studied seasonal changes in radiocesium (Cs) activity and potassium concentrations in current-year leaves and branches of Pinus densiflora (naturally regenerated saplings), Cryptomeria japonica (planted saplings) and Quercus serrata (planted saplings and coppice shoots) in Fukushima, Japan. We collected current-year shoots from 10 individuals of each species over two growing seasons at intervals of 1-4 months, between June 2016 and December 2017. For the deciduous species Q. serrata, we also collected dead leaves that remained attached to branches in December to investigate reabsorption of Cs. All collected shoots were divided into leaves and branches, oven-dried, and ground; dry weights of each sample were recorded. Cs activity concentrations were measured using a germanium semiconductor detector. Potassium concentrations were quantified using inductively coupled plasma optical emission spectrometry (ICP-OES). Increases in dry weight were observed in both leaves and branches between May/June and August; growth then slowed considerably and virtually ceased after October. Clear seasonal changes in Cs activity concentrations were observed in both 2016 and 2017, regardless of tree species. Concentrations were higher in young leaves and branches during May and June, then decreased and changed relatively little from August to winter. Reduced Cs activity concentrations in dead leaves of Q. serrata were observed only in December 2017 (approximately 15% lower than in October). This reduction may indicate reabsorption of Cs in leaves prior to shedding. The changes in potassium concentrations were similar to those in Cs in both years. Potassium concentrations were higher in young leaves than in mature leaf and branch samples collected later in the year. A reduction of about 50% in the potassium concentrations in dead leaves of Q. serrata was also observed in December. A positive relationship between Cs and potassium concentrations in leaves and branches was observed in all species, except for planted Q. serrata. This relationship may indicate that Cs moves in tree shoots with potassium. Leaf and branch weight correlated negatively with Cs and potassium concentrations. Reduced concentrations may indicate dilution of these elements as a result of biomass increases over the growing season. Our results imply that irrespective of species, Cs exhibits seasonal variations resulting from dilution; these variations correspond with trends in potassium, with higher levels in young organs and decreased levels in older organs.
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http://dx.doi.org/10.1016/j.jenvrad.2020.106409DOI Listing
November 2020

Stereotactic body radiation therapy using CyberKnife for T1N0M0 lung cancer patients with severe pulmonary dysfunction.

J Radiat Res 2020 Nov;61(6):903-907

Departments of Radiation Oncology, International Medical Center, Saitama Medical University, Hidaka, Japan.

We retrospectively investigated the efficacy and safety of stereotactic body radiotherapy (SBRT) for T1N0M0 lung cancer using CyberKnife (CK) among 13 patients with severe pulmonary dysfunction which was defined as forced expiratory volume in 1 s (FEV1.0) of <1 L. The prescribed dose was 54 Gy in 3 fractions but adjusted for some patients if their tumors were in close proximity to the organs at risk (54 Gy/3 fractions: n = 11; 50 Gy/5 fractions: n = 1; 60 Gy/8 fractions: n = 1). During follow up (median follow-up: 27 months), we evaluated local control, overall survival and toxicity, using diagnostic imaging and laboratory tests. The patients' median FEV1.0 was 0.84 L. Of the 13 patients, 3 were diagnosed as having lung cancer histologically and 10 diagnosed clinically. Their 2-year rates for overall survival and local control were 89 and 100%, respectively. So far, we have seen no adverse effects of grade 2 or higher. We concluded that CK-SBRT is effective and well tolerated for T1N0M0 lung cancer, even in patients with severe pulmonary dysfunction, but should be further evaluated with a larger cohort and longer follow-up periods.
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http://dx.doi.org/10.1093/jrr/rraa075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674703PMC
November 2020

Stereotactic Body Radiotherapy for Pulmonary Oligometastasis from Colorectal Cancer.

In Vivo 2020 Sep-Oct;34(5):2991-2996

Department of Radiation Oncology, Saitama Medical University, International Medical Center, Saitama, Japan

Background/aim: A retrospective study was conducted to evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for pulmonary oligometastasis from colorectal cancer (CRC).

Patients And Methods: Patients with pulmonary oligometastasis from CRC who were treated with SBRT between April 2010 and October 2018 were enrolled in this study. All patients underwent SBRT using Cyberknife® with a dose of 54-60 Gy in 3 fractions to 99% of the clinical target volume. The treatment efficacy was evaluated by the local control (LC) and overall survival (OS) rates. The toxicity was evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0.

Results: Twenty-six lesions in 20 patients were treated with SBRT. The median follow-up duration was 19 months (range=6-98 months). Local recurrence occurred in 6 of 26 lesions with a median follow-up of 12 months. The 2-year LC and OS rates were 65.8% and 88.6%, respectively. No patient developed ≥ grade 2 toxicity in the lung and other sites.

Conclusion: Although very high doses were delivered to the tumors with SBRT, the LC of pulmonary metastasis from CRC was not satisfactory when compared to that for stage I primary non-small cell lung cancer reported in the literature.
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http://dx.doi.org/10.21873/invivo.12130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652475PMC
June 2021

Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA): Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease-Opportunities for Therapy.

Alzheimers Dement (Amst) 2020 3;12(1):e12053. Epub 2020 Aug 3.

University of Milano - Bicocca Monza Italy.

Two of the key functions of arteries in the brain are (1) the well-recognized supply of blood via the vascular lumen and (2) the emerging role for the arterial walls as routes for the elimination of interstitial fluid (ISF) and soluble metabolites, such as amyloid beta (Aβ), from the brain and retina. As the brain and retina possess no conventional lymphatic vessels, fluid drainage toward peripheral lymph nodes is mediated via transport along basement membranes in the walls of capillaries and arteries that form the intramural peri-arterial drainage (IPAD) system. IPAD tends to fail as arteries age but the mechanisms underlying the failure are unclear. In some people this is reflected in the accumulation of Aβ plaques in the brain in Alzheimer's disease (AD) and deposition of Aβ within artery walls as cerebral amyloid angiopathy (CAA). Knowledge of the dynamics of IPAD and why it fails with age is essential for establishing diagnostic tests for the early stages of the disease and for devising therapies that promote the clearance of Aβ in the prevention and treatment of AD and CAA. This editorial is intended to introduce the rationale that has led to the establishment of the Clearance of Interstitial Fluid (ISF) and CSF (CLIC) group, within the Vascular Professional Interest Area of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment.
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http://dx.doi.org/10.1002/dad2.12053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396859PMC
August 2020

Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia.

Acta Neuropathol Commun 2020 08 8;8(1):131. Epub 2020 Aug 8.

Faculty of Medicine, University of Southampton, Tremona Road, Southampton, SO16 6YD, UK.

White matter hyperintensities (WMH) occur in association with dementia but the aetiology is unclear. Here we test the hypothesis that there is a combination of impaired elimination of interstitial fluid from the white matter together with a degree of hypoxia in WMH. One of the mechanisms for the elimination of amyloid-β (Aβ) from the brain is along the basement membranes in the walls of capillaries and arteries (Intramural Peri-Arterial Drainage - IPAD). We compared the dynamics of IPAD in the grey matter of the hippocampus and in the white matter of the corpus callosum in 10 week old C57/B16 mice by injecting soluble Aβ as a tracer. The dynamics of IPAD in the white matter were significantly slower compared with the grey matter and this was associated with a lower density of capillaries in the white matter. Exposing cultures of smooth muscle cells to hypercapnia as a model of cerebral hypoperfusion resulted in a reduction in fibronectin and an increase in laminin in the extracellular matrix. Similar changes were detected in the white matter in human WMH suggesting that hypercapnia/hypoxia may play a role in WMH. Employing therapies to enhance both IPAD and blood flow in the white matter may reduce WMH in patients with dementia.
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http://dx.doi.org/10.1186/s40478-020-01009-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414710PMC
August 2020
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