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."

/pdf/2020-esc-guidelines-for-the-diagnosis-and-management-of-38dpic1xu8.pdf

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.

/pdf/the-pharmacology-of-second-generation-chimeric-antigen-npa77pm6ks.pdf

The pharmacology of second-generation chimeric antigen receptors

Central Skull Base Osteomyelitis Presenting Only With a Severe Headache.

Transient global amnesia caused by cryptogenic ischemic stroke

to progress after more than a decade. Another unusual point is the late-onset presentation for the familial disease. Early-onset disease is a prominent feature of familial forms of both SLE and DLE, as expected. Late-onset familial cases are rarely reported. Even after genome-wide association studies, it is estimated that genetic variation identified so far explains just approximately 8% of genetic SLE risk. So the genetic behavior of SLE is largely unknown. Patients with suspected SLE are classified into SLE with the aid of Systemic Lupus International Collaborating Clinics criteria. Besides research-related concerns, the set of these classification criteria is, indeed, an important clinical tool, especially for the non-rheumatologist physician. However, controversies exist about the applicability of these criteria in older adults, as advanced age, itself, is an atypical condition with infrequent presenting clinical scenarios in this age group. Although non-specific symptoms, such as weight loss, arthralgias, myalgias, weakness, pyrexia, cognitive and affective dysfunction, presentation with interstitial lung disease, sicca and cytopenias, and neurocognitive impairment with peripheral neuropathy, are much more common than in early-/adult-onset disease, late-onset lupus patients have less frequent seizures, psychosis, renal impairment, cutaneous findings and arthritis. As classification criteria are based on more frequent and more specific clinical and laboratory findings for inclusion–exclusion purposes, they do not include more probable presenting signs of elderly-onset disease. Instead of a criteria-based approach, a combination of clinical findings, although atypical, plus some disease-specific clues from laboratory, imaging or biopsy with a holistic approach might direct to a diagnosis in older adults. However, it is important not to forget that the prevalences of idiopathic pulmonary fibrosis, sicca symptoms and non-specific ANA positivity increase by age. Probably because of immunosenescence, older adults are more prone to immunosuppresive sideeffects, such as infections and malignancies. This issue should be of major concern while treating older adults with autoimmune diseases. In conclusion, familial DLE or SLE might present in older adults. Cases with DLE can progress to SLE even after a decade. Presenting symptoms and signs might be atypical in elderly-onset SLE cases.

Chronic myeloid leukemia presenting as multiple cranial nerve palsy.

Background Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory condition characterized by high serum IgG4 concentrations and tissue infiltration by IgG4-positive plasma cells. Reports have demonstrated that IgG4-RD affects various organs, including the pancreas, kidney, lung, thyroid, and lacrimal and salivary glands. In the nervous system, hypertrophic pachymeningitis and hypophysitis are mainly related to IgG4-RD; however, the peripheral neuropathy involvement is unusual. Case presentation We report on a 69-year-old woman with multiple mononeuropathy, weight loss and kidney mass in the setting of IgG4-RD. Biopsies of the kidney mass showed lymphoplasmacytic sclerosing inflammation with numerous IgG4-positive plasma cells. IgG4 and IgG4/IgG ratios in the blood were elevated. The patient was treated with high dose methylprednisolone with improvement in her neuropathy. Conclusions IgG4-RD is a relatively recently reported systemic fibrous inflammatory disease caused by the infiltration of IgG4-positive plasma cells in various organs. In the nervous system, symptomatic peripheral nerve invasion is very rare. However, as demonstrated in our case, IgG4-RD may present with primarily peripheral nerve disease.

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Immunoglobulin G4-related disease presenting with peripheral neuropathy: a case report.

Background and Purpose Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients. Design The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset. Endpoints The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran–Mantel–Haenszel shift test. The secondary endpoints include functional independence (mRS 0–2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days. Conclusion This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).

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The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz (RODIN) Trial: Protocol for a Double-Blinded Clinical Trial of Nelonemdaz in Patients with Hyperacute Ischemic Stroke and Endovascular Thrombectomy

Hyun Goo Kang

Papers

Central Skull Base Osteomyelitis Presenting Only With a Severe Headache.

Transient global amnesia caused by cryptogenic ischemic stroke

Chronic myeloid leukemia presenting as multiple cranial nerve palsy.

Immunoglobulin G4-related disease presenting with peripheral neuropathy: a case report.

The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz (RODIN) Trial: Protocol for a Double-Blinded Clinical Trial of Nelonemdaz in Patients with Hyperacute Ischemic Stroke and Endovascular Thrombectomy