The authors experienced a case of fatal cerebellar, and brainstem infarction accompanying clamping of the left subclavian artery during operation for thoracic aortic aneurysm. Autopsy of this case revealed that right vertebral artery became markedly hypoplastic distal to the posteroinferior cere bellar artery, and left vertebral and basilar arteries were occluded by thrombus formation. These findings indicate that clamping of the dominant left subclavian artery is responsible for severe vertebrobasilar ischemia producing the fatal brain infarction. Since the occurrence of this devastating complication, we have performed pancerebral angiography and balloon occlusion test of the left subclavian artery in patients who might undergo proximal clamping of the aortic arch between the left carotid artery and the left subclavian artery during operations for thoracic aortic aneurysm. Selective perfusion of the left subclavian artery is then planned for those with abnormal vertebrobasilar communications producing neurological signs.

Left ventricular hypertrophy in patients with aortic valve disease has long been recognized as a significant risk factor for aortic valve replacement. Higher operative mortality in such patients has been attributed to poor myocardial preservation. In these patients improvement of left ventricular subendocardial blood flow during reperfusion seems to be mandatory to avoid subendocardial injury. Therefore, we attempted to increase subendocardial blood flow during reperfusion by terminal warm blood cardioplegia (TWBCP) followed by controlled aortic root reperfusion (CARR) in patients requiring isolated aortic valve replacement. The patients with TWBCP and CARR had a tendency towards severe left ventricular hypertrophy and more advanced NYHA function class compared to those with hypothermic cardioplegia alone. Nevertheless, the patients with TWBCP and CARR showed significantly better recovery of left ventricular function, i.e., spontaneous recovery of beating and higher cardiac index as well as left ventricular stroke work index, despite significantly less catecholamine support. These resuls suggest that TWBCP followed by CARR may offer significant benefits over unmodified reperfusion during aortic valve replacement for patients with severe left ventricular hypertrophy.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate, a synthetic disease-modifying antirheumatic drug (DMARD), and biologic DMARD has revolutionized treatment of RA. Clinical remission is now realistic targets, achieved by a large proportion of RA patients, and rapid and appropriate induction of remission by intensive treatment with biological DMARD and methotrexate is prerequisite to halt joint damage and functional disabilities. However, biological DMARD is limited to intravenous or subcutaneous uses and orally available small but strong molecules have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active patients with methotrexatenaive, inadequately responsive to methotrexate or tumor necrosis factor (TNF)-inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. Meanwhile, association of tofacitinib on carcinogenicity and malignancy is under debate and further investigation on post-marketing survey would be warranted. On the other hand, discontinuation of a biological DMARD without disease flare is our next goal and desirable from the standpoint of risk reduction and cost effectiveness, especially for patients with clinical remission. Recent reports indicate that more than half of early RA patients could discontinue TNF-targeted biological DMARD without clinical flare and functional impairment after obtaining clinical remission. Contrarily, for established RA, fewer patients sustained remission after the discontinuation of biological DMARD and "deep remission" at the discontinuation was a key factor to keep the treatment holiday of biological DMARD.
Administration, Oral ; Antirheumatic Agents/*administration & dosage/adverse effects ; Arthritis, Rheumatoid/diagnosis/*drug therapy/metabolism/physiopathology ; Biological Products/administration & dosage ; Disability Evaluation ; Drug Administration Schedule ; Humans ; Janus Kinases/antagonists & inhibitors/metabolism ; Molecular Targeted Therapy ; Predictive Value of Tests ; Protein Kinase Inhibitors/administration & dosage ; Recovery of Function ; Remission Induction ; Signal Transduction/drug effects ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors/metabolism