Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."

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2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Principles and Practice of Sleep Medicine

Since the introduction of the first edition of International Classification of Sleep Disorders: Diagnostic and Coding Manual(ICSD-1)in 1990,national and international meetings were held to openly discuss the ongoing developments of sleep disorders and a new International Classification of Sleep Disorders: Diagnostic and Coding Manual(ICSD-2)was published in 2005.Compared with ICSD-1,the classification of ICSD-2 was developed in a manner compatible with new International Classification of Diseases(ICD-9 and ICD-10)and formed a coordinated system of International Classification of Diseases.The updated version was characterized by the significant improvements of its logicality and clinical practicability,and was more consistent with the International Classification of Disease.The contents of ICSD-2 were introduced in this article.

Brief introduction to second edition of International Classification of Sleep Disorders:Diagnostic and Coding Manual

OX40 (CD134) and its binding partner, OX40L (CD252), are members of the TNFR/TNF superfamily and are expressed on activated CD4 and CD8 T cells as well as a number of other lymphoid and non-lymphoid cells. Costimulatory signals from OX40 to a conventional T cell promote division and survival, augmenting the clonal expansion of effector and memory populations as they are being generated to antigen. OX40 additionally suppresses the differentiation and activity of Treg, further amplifying this process. OX40 and OX40L also regulate cytokine production from T cells, antigen-presenting cells, NK cells, and NKT cells, and modulate cytokine receptor signaling. In line with these important modulatory functions, OX40/OX40L interactions have been found to play a central role in the development of multiple inflammatory and autoimmune diseases, making them attractive candidates for intervention in the clinic. Conversely, stimulating OX40 has shown it to be a candidate for therapeutic immunization strategies for cancer and infectious disease. This review provides a broad overview of the biology of OX40, and the intracellular signals from OX40, that impact many aspects of immune function, and have promoted OX40 as one of the most prominent costimulatory molecules known to control T cells.

The Significance of OX40 and OX40L to T cell Biology and Immune Disease

Second-generation chimeric antigen receptors (CARs) retarget and reprogramme T cells to augment their antitumour efficacy. The combined activating and co-stimulatory domains incorporated in these CARs critically determine the function, differentiation, metabolism and persistence of engineered T cells. CD19-targeted CARs that incorporate CD28 or 4-1BB signalling domains are the best known to date. Both have shown remarkable complete remission rates in patients with refractory B cell malignancies. Recent data indicate that CD28-based CARs direct a brisk proliferative response and boost effector functions, whereas 4-1BB-based CARs induce a more progressive T cell accumulation that may compensate for less immediate potency. These distinct kinetic features can be exploited to further develop CAR-based T cell therapies for a variety of cancers. A new field of immunopharmacology is emerging.

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The pharmacology of second-generation chimeric antigen receptors

Intracranial Aneurysm Is Associated with High Intracranial Artery Tortuosity.

BACKGROUND AND PURPOSE Since the long-term survival rate has improved in laryngeal cancer patients who receive radiotherapy, concerns about postradiation complications (including carotid atherosclerosis) have increased. We followed changes in the common carotid artery (CCA) after radiotherapy and identified the underlying risk factors. METHODS Consecutive patients with laryngeal cancer who underwent radiotherapy between January 1999 and December 2009 and who had received computed tomography (CT) both pre- and postradiotherapy were enrolled. Changes in the wall thickness and in the vessel and lumen areas as well as the presence of calcification or atherosclerosis were investigated. Demographics and risk factors were compared between patients with and without atherosclerosis at follow-up CT. RESULTS In total, 125 patients were enrolled. The wall thickness had increased and the lumen area had decreased several months after radiotherapy. These changes were not associated with vascular risk factors and were not progressive. Calcification and atherosclerosis were observed in 37 (29.6%) and 71 (56.8%) patients, respectively. Diabetes was associated with calcification (p=0.02). The prevalence of hyperlipidemia was higher in patients with atherosclerosis (28.2% vs. 11.1%, p=0.02) and for a longer period postradiation [62.7±32.1 vs. 40.0±24.2 months (mean±SD), p<0.001]. Atherosclerosis occurred mostly in the middle portion of the CCA (n=31, 24.6%), followed by the proximal CCA at the intrathoracic level (n=26, 20.6%) and the distal CCA (n=6, 4.8%). Positive remodeling was also observed, but this was less common in patients with calcification (p=0.02). CONCLUSIONS Various types of postradiation changes occur in the CCA and can be easily observed in postradiation CT. The prevalence and burden of postradiation atherosclerosis increased in a close relationship with baseline cholesterol levels and the time after radiotherapy. Postradiation atherosclerosis was observed at unusual sites of the CCA.

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Changes in the Common Carotid Artery after Radiotherapy: Wall Thickness, Calcification, and Atherosclerosis

Japanese encephalitis virus (JEV) envelope (E) protein holds great promise for use in the development of a recombinant vaccine. Purified recombinant E (rE) protein may be useful for numerous clinical applications; however, there are limitations in using the Escherichia coli expression system for producing high-quality rE protein. Therefore, in this study, the yeast expression system was used to generate the rE protein. For protein production using the yeast system, the full-length JEV E gene was cloned into Pichia pastoris. SDS-PAGE and immunoblotting analysis demonstrated that the rE protein had a molecular mass of 58 kDa and was glycosylated. The predicted size of the mature unmodified E protein is 53 kDa, suggesting that post-translational modifications resulted in the higher molecular mass. The rE protein was purified to greater than 95% purity using combined ammonium sulfate precipitation and a SP-Sepharose Fast Flow column. This purified rE protein was evaluated for immunogenicity and protective efficacy in mice. The survival rates of mice immunized with the rE protein were significantly increased over that of Hyphantria cunea nuclear polyhedrosis virus E protein (HcE). Our results indicate that the rE protein expressed in the P. pastoris expression system holds great promise for use in the development of a subunit vaccine against JEV.

Protective immunity of Pichia pastoris-expressed recombinant envelope protein of Japanese encephalitis virus.

Myasthenia gravis (MG), an autoimmune neuromuscular disorder, occurs owing to autoantibodies against acetylcholine receptors. MG symptoms can be triggered by various vaccines. Many studies have evaluated the safety and adverse events of the human papillomavirus (HPV) vaccine. Here, we present a life-threatening case of ocular and bulbar MG symptoms after HPV vaccination and a brief literature review. A 23-year-old woman presented with binocular diplopia, ptosis, dysarthria, and dysphagia, which occurred on the 3rd day after the second HPV vaccine administration. She was diagnosed with MG based on history, clinical features, and test results. Her symptoms deteriorated on the 3rd day after admission, and she was transferred to the intensive care unit with mechanical ventilation. On the 7th day after admission, due to discomfort in the right chest, pulmonary embolism was suspected. A tracheostomy was performed on the 14th day of mechanical ventilation. In the 4th week, the tracheostomy tube was removed; all symptoms had completely resolved at discharge. She was followed up for 5 months without recurrence or further treatment. HPV vaccination may cause MG owing to unexpected abnormal autoimmune responses. Additional studies are needed to clarify the possible causal relationship between the HPV vaccine and neurological complications and to evaluate the safety of the vaccine.

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Myasthenia gravis following human papillomavirus vaccination: a case report.

The carotid artery plays a major role in stroke aetiology and is a good indicator of atherosclerosis. However, the clinical significance of internal carotid artery (ICA) anatomy remains unclear in patients with ischaemic stroke. This study examined the relationship between ICA angle and risk of ischaemic stroke. ICA angles of patients with acute ischaemic stroke were retrospectively compared with those of control patients between March 2014 and July 2014. Controls consisted of those with headaches but without ischaemic stroke. In both groups, ICA angles were measured using Maximum Intensity Projection images from computed tomography angiography, and the relationship between ICA angle and risk of ischaemic stroke was analysed. Of 128 screened patients with acute ischaemic stroke, 27 were enrolled, and 29 with headache were enrolled as controls. No differences were found in baseline characteristics between the two groups, but intracranial stenosis was more frequent in patients with stroke than in controls. Bilateral ICA angles were significantly larger in patients with stroke than in controls. Multiple logistic regression models showed that the right ICA angle was associated with risk of ischaemic stroke. Measuring the ICA angle may help assess the risk of ischaemic stroke.

/pdf/clinical-significance-of-the-internal-carotid-artery-angle-49pb391vg3.pdf

Hyun Goo Kang

Papers

Intracranial Aneurysm Is Associated with High Intracranial Artery Tortuosity.

Changes in the Common Carotid Artery after Radiotherapy: Wall Thickness, Calcification, and Atherosclerosis

Protective immunity of Pichia pastoris-expressed recombinant envelope protein of Japanese encephalitis virus.

Myasthenia gravis following human papillomavirus vaccination: a case report.

Clinical significance of the internal carotid artery angle in ischemic stroke.