Synthesis and pharmacological characterization of potent, selective, and orally bioavailable isoindoline class dipeptidyl peptidase IV inhibitors

Focused structure-activity relationships of isoindoline class DPP-IV inhibitors have led to the discovery of 4b as a highly selective, potent inhibitor of DPP-IV. In vivo studies in Wistar/ST rats showed that 4b was converted into the strongly active metabolite 4l in high yield, resulting in good in vivo efficacy for antihyperglycemic activity

Results of surgical resection for patients with thymoma according to World Health Organization histology and Masaoka staging

Thymomas are relatively rare tumors. In this study, we investigated the clinical features of patients who underwent surgical resection for thymoma. This study clinicopathologically evaluated 54 consecutive patients who underwent a surgical resection of thymoma in our department between 1994 and 2006. A complete resection was performed in 52 patients, while two patients underwent an incomplete resection due to pleural dissemination. Combined resection with adjacent organs was performed for the lung (n = 6), pericardium (n = 5), and large vessels (brachiocephalic vein in three, superior vena cava in two). The concomitant autoimmune diseases were observed in 20 patients (37%), and they included myasthenia gravis in 17 patients, macroglobulinemia in one, pemphigus vulgaris in one, and stiff person syndrome in one patient. The histologic types of the World Health Organization classification diagnosed as type A in four patients, type AB in 14, type B1 in eight, type B2 in 15, and type B3 in 11. There were 27, 17, eight, and two patients with Masaoka stages I, II, III, and IV, respectively. Four patients died, and the causes of death included recurrence of thymoma in two, gastric carcinoma in one, and respiratory failure due to myasthenia gravis in one patient. The overall survival rate at 10 years was 94.6% in patients with stages I and II disease and 77.1% in patients with stages III and IV disease. Long-term survival can be expected not only for patients at early stages, as well as for patients with stages III and IV disease if surgical resection is completed macroscopically

Results of surgical resection for patients with thymoma according to World Health Organization histology and Masaoka staging

Objectives: Thymomas are relatively rare tumors. In this study, we investigated the clinical features of patients who underwent surgical resection for thymoma. Patients and methods: This study clinicopathologically evaluated 54 consecutive patients who underwent a surgical resection of thymoma in our department between 1994 and 2006. Results: A complete resection was performed in 52 patients, while two patients underwent an incomplete resection due to pleural dissemination. Combined resection with adjacent organs was performed for the lung (n=6), pericardium (n=5), and large vessels (brachiocephalic vein in three, superior vena cava in two). The concomitant autoimmune diseases were observed in 20 patients (37%), and they included myasthenia gravis in 17 patients, macroglobulinemia in one, pemphigus vulgaris in one, and stiff person syndrome in one patient. The histologic types of the World Health Organization classification diagnosed as type A in four patients, type AB in 14, type B1 in eight, type B2 in 15, and type B3 in 11. There were 27, 17, eight, and two patients with Masaoka stages I, II, III, and IV, respectively. Four patients died, and the causes of death included recurrence of thymoma in two, gastric carcinoma in one, and respiratory failure due to myasthenia gravis in one patient. The overall survival rate at 10 years was 94.6% in patients with stages I and II disease and 77.1% in patients with stages III and IV disease. Conclusions: Long-term survival can be expected not only for patients at early stages, as well as for patients with stages III and IV disease if surgical resection is completed macroscopically

Dementia and Car Driving - Looking back on the five years since the establishment of the driver’s license outpatient clinic, consider the future prospects -

　認知症の重症度とともに運転事故の危険性は高まることから，中等度以上の認知症では運転 すべきでないという点についての世界的コンセンサスは得られているが，専門学会ごとに認知症の 運転中止基準は異なる．当院では2017年４月よりものわすれ外来とは別に運転免許外来を新設し， 時間をかけた丁寧な診療と告知，指導，運転免許返納後の生活確保・支援ができるよう，多職種で 受診者に対応してきた．2021年７月までの当外来受診者は64人（のべ117人）で，ほとんどが免許更新時の第１分類該当や交通違反のための受診であった．当外来にて施行した神経心理検査の平均点は，MMSE-J 21.3/30，DASC-21 28.4，CDR 0.6と全般的認知機能低下が比較的軽度な者が多かったが，FAB 10.9/18，TMT-A 102.4s，TMT-B 261s と注意，前頭葉機能，視覚情報処理や遂行機能の低下は明らかであった．当外来を受診した患者には上記の検査結果を踏まえて全例に運転免許返納を推奨したが，全患者が運転継続を強く希望し，運転中止に至った例は20例のみで，残りのうち更に20例は半年毎に当院を再診し現在も運転継続している．この20例は，MMSE-J 22.3/30， DASC-21 26.2，CDR 0.5とやはり全般的認知機能は比較的保たれており，19例（95％）を軽度認知障害と診断している．全般的認知機能が比較的保たれている軽度認知障害の患者は現実的に運転 できていることから，都市部と異なりインフラ整備が十分には整っていない地域での運転の重要性 を鑑みると，社会インフラの整備，限定免許や安全運転技術などのサポート体制の強化など高齢者の運転継続の可能性についても模索すべきであると考えられる．　There is a global consensus that people with moderate or severe dementia should not drive because the risk of driving accidents increases with the severity of dementia. However, the proposed criteria for prohibiting dementia patients from driving a car differ by academic societies. In April 2017, we established a specialized clinic to evaluate eligibility to hold a driver’s license. Multidisciplinary staff collaborate to provide medical examinations, notification, guidance, and support for everyday activities for those who have returned their driver’s license. 　By July 2021, 64 people had visited this clinic (117 visits including re-examinations). Most were classified as having possible dementia (the first category) by the official driving aptitude test failure or more traffic violations. Their average score in the neuropsychological tests were as follows; Mini Mental State Examination-Japanese (MMSE-J) is 21.3/30, Dementia Assessment Sheet in Community-based Integrated Care System (DASC-21) is 28.4, Clinical Dementia Rating (CDR) is 0.6, Frontal Assessment Battery (FAB) is 10.9/18, Trail Making Test (TMT)-A is 102.4s, and TMT-B is 261s. Many of the group had relatively mild cognitive decline, especially in attention, frontal lobe function, visuospatial processing, and executive function domains. We recommended that all people to return their driver’s licenses. However, only 20 followed our recommendation. Rest 20 are still driving with regular visit every 6 months. In these 20 cases, MMSE-J is 22.3/30, DASC-21 is 26.2, CDR is 0.6 and overall cognitive function was relatively maintained, and 19 cases (95%) were diagnosed as Mild cognitive impairment. 　Our data showed that patients with mild cognitive impairment can drive practically. Considering that insufficient public transportation system in suburban areas, continue driving is essential for elderly people to maintain their everyday life. It is important to find the way to continue driving in cognitively declined elderly people with limited licenses or driving assistant system in super-aged society