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Objective-To evaluate endothelial repair processes in denuded pial vessels to clarify mechanisms for reconstructing endothelium (because endothelial repair of the cerebral artery after its damage is critical for the prevention of thrombosis, the maintenance of vascular tone, and the protection of the brain by the blood-brain barrier). Methods and Results-Endothelial cells (ECs) in a 350-m-long segment of the middle cerebral artery were damaged through a photochemical reaction. Tie2-green fluorescent protein transgenic mice were used for the identification of ECs. Six hours after the endothelial damage, ECs were detached from the luminal surface of the damaged artery, which was then covered with a platelet carpet. Within 24 hours, recovery of the denuded artery started at both edges, with EC elongation and migration. The repair rate was faster at the proximal edge than at the distal edge. Reendothelialization with EC proliferation peaked at 2 to 3 days and ended at 5 days, together with normalization of EC length, with no apparent involvement of foreign progenitor cells. Conclusion-Our in vivo study demonstrated a stepwise reendothelialization process by resident ECs of the pial artery.The prevention of thrombosis, vasospasm, and treatment for blood-brain barrier dysfunction should be considered during the reendothelialization period. Key Words: Tie2 Ⅲ reendothelialization Ⅲ pial artery Ⅲ confocal laser microscopy Ⅲ photochemical reaction B ecause endothelial damage and subsequent exposure of subendothelial tissue in the cerebral artery quickly induces a luminal thrombus and disturbs cerebral blood flow, urgent endothelial repair is critical to minimize ischemic damage, especially after rupture of an atherosclerotic plaque, commonly observed at the carotid artery and the intracranial cerebral arteries. Reendothelialization is also essential to recover normal vascular tone controlled by vasodilatory mediators, such as nitric oxide released from the endothelium. Furthermore, loss of the endothelial tight junction results in breakdown of the blood-brain barrier, causing vasogenic edema. Therefore, restoration of endothelial function in the cerebral vessel is an urgent process for the brain.Endothelial damage of the cerebral artery is a key mechanism involved in the pathophysiology of various brain diseases, including stroke, atherosclerosis, 1 diabetes mellitus, 2 dyslipidemia, 3 hypertension, 4 vasculitis, 5 multiple sclerosis, 6 radiation necrosis, 7 and drug adverse effects. 8 Some markers of endothelial damage are good indicators for the future incidence of cardiovascular events, including stroke. 9 Carotid endarterectomy, a treatment for carotid stenosis, removes atheroma and endothelial cells (ECs), exposing subendothelial tissue. 10 In these conditions, endothelial repair is one of the major targets of treatment.Histological evaluation of reendothelialization and neointima formation after mechanical carotid denudation was previously reported. 11-13 However, the dynamic and minute process of endothelial repair...

To clarify the clinical features of moyamoya disease in Japan, 941 patients with definite moyamoya disease were analyzed from the databases constructed by the Research Committee on Moyamoya Disease, established by the Ministry of Health, Labour and Welfare. Moyamoya disease occurs much more frequently among women than men, with a female-to-male ratio of 1.98. A family history of the disease was observed in 14.9%. The age at onset was characterized by two peaks: one at 5-9 years and another lower peak at around 40 years. Initial clinical features were transient ischemic attack in 46%, infarction in 20%, hemorrhage in 21%, headache in 6%, and epilepsy in 4%. The distribution of the age at onset showed one peak at around 40 years in patients with hemorrhage but two peaks in patients with ischemia.

A 60-year-old man presented with dyspnea four days after the second dose of the coronavirus disease (COVID-19) vaccine. Imaging revealed extensive ground-glass opacification. Blood tests were notable for elevated KL-6 levels. Bronchoalveolar lavage fluid analysis showed increased lymphocyte-dominant inflammatory cells and decreased CD4/CD8 ratio. These findings were consistent with the diagnosis of drug-induced interstitial lung disease (DIILD). To the best of our knowledge, this has never been reported in previous literature. Treatment with glucocorticoids relieved his symptoms. This paper highlights that although extremely rare, COVID-19 vaccine could cause DIILD, and early diagnosis and treatment are crucial to improve patient outcomes.

Our results indicate that capillary remodeling, pial artery dilatation and collateral growth without angiogenesis are sufficient mechanisms to restore normal cerebral blood flow after unilateral CCA occlusion.

Rationale and aimsMonotherapy with antiplatelet agents is only modestly effective in secondary prevention of ischemic stroke (IS), particularly in patients with multiple risk factors such as cervicocephalic arterial stenosis, diabetes, and hypertension. While dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduced IS recurrence, particularly in the early stages after IS, it increased the risk of bleeding. Compared with aspirin, cilostazol prevented IS recurrence without increasing the incidence of serious bleeds. In patients with intracranial arterial stenosis, no significant increase in bleeding events was observed for DAPT with cilostazol and aspirin, compared to that for aspirin monotherapy. DAPT involving cilostazol may therefore be safer than conventional DAPT. These findings prompted us to conduct the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com; ClinicalTrials.gov identifier: NCT01995370) to evaluate the safety and efficacy of DAPT involving cilostazol for secondary IS prevention, in comparison with that of antiplatelet monotherapy.DesignThe CSPS.com is a multicenter, randomized, open-label, parallel-group trial. A total of 4000 high-risk patients with noncardioembolic IS will be randomized 8–180 days after onset to receive aspirin or clopidogrel monotherapy, or DAPT with cilostazol and aspirin or clopidogrel for at least one-year.Study outcomesThe primary outcome is IS recurrence. Secondary outcomes are composite occurrences of any stroke, death from any cause, myocardial infarction, vascular death, and other vascular events.DiscussionThe CSPS.com is expected to provide evidence indicating whether secondary IS prevention in high-risk patients can be improved by using DAPT involving cilostazol.

Background The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. Methods The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. Results Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4–8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). Conclusions This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

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