胚体と前方羊膜をつなぐ羊膜襟の形成と機能（英文）

鳥類を含む有羊膜類では、陸上生活へ適応するため、発生中に胚体外膜が発達する。その一つである羊膜は、胚体外外胚葉と胚体外中胚葉の二層で構成され、胚を包み保護する役割を持つ。ニワトリ胚ではst.10で胚頭部腹側にある胚体外組織から羊膜褶と呼ばれるひだが形成され、st.19にかけてそれが胚の背側を徐々に覆っていくことで、羊膜が形成される。羊膜褶の形成がどのように開始されるかを調べるため、st.10のニワトリ胚の切片を作成し観察した。すると、咽頭付近の腹側で胚体の外・中胚葉と将来羊膜褶を形成する胚体外外・中胚葉が、側方でそれぞれ結合した特徴的な構造が形成されることを発見した。この構造を羊膜襟と名付け、その形成過程と機能を調べた。st.10の胚では、羊膜襟が咽頭から心臓付近にかけてV字状に形成されており、それによって胚腹側と胚体外組織との間に外胚葉で囲まれた頭部下腔と呼ばれる空間が生じている。これらの構造がいつ形成されるかを調べるため、他のステージの胚の切片を作成し観察した。すると、st.7+まではこの羊膜襟と頭部下腔は存在せず、st.8-で形成されることが確認できた。また、st.8-では、羊膜襟は浅いU字の形状をしており、st.9付近にかけて深いV字状に変化していくことが分かった。このことから、羊膜褶の形成に先立ち、羊膜襟はst.8-で形成され、st.9付近にかけその形態を変化させることが分かった。羊膜襟の形成と形態変化がどのような細胞挙動により起こっているのかを調べるため、胚体と胚体外の境界に位置する外胚葉の細胞のラベル実験を行った。st.6の胚を用い、前腸門のすぐ前方にある外胚葉をDiOで、前腸門の側方にある外胚葉をDiIでラベルし、タイムラプスで観察を行った。すると、まず胚体が細くなると同時にDiOラベルされた細胞が頭尾軸に沿って放射状に広がった。次に前腸門が狭まるに伴い内胚葉が後方へ伸長するが、ラベルされた外胚葉はほぼ同じ位置に留まっていた。その後、DiOラベルされた細胞が放射状から頭尾軸に平行な方向へと伸長方向を変えるとともにDiIラベルされた細胞が前方へ移動することで、V字状の羊膜襟の形態が形成されていた。st.9まで発生させると、DiOラベルされた細胞は羊膜襟の後端と頭部下腔全体に、DiIラベルされた細胞は羊膜襟の前端に寄与した。以上の結果から、羊膜襟は、胚体が細長く伸長する中で、腹側外胚葉はst.8から後方へ伸長せず、後方へ伸長する内胚葉から離れること、さらに頭部下腔の正中付近での細胞の再配置が起こることによって形成されることが分かった。次に、羊膜襟の機能を調べるため、st.9前後の胚の羊膜襟を切断して24時間培養し、その後の胚の形態を観察した。その結果、コントロールと比較して心臓が小さい胚や背側の羊膜形成が遅れる胚、羊膜襟付近で異常な屈曲がある胚が見られた。有羊膜類は脳や心臓が大きく発達する。また、先行研究により羊膜褶が胚を覆うためには頭部が胚体外の組織に沈み込むことが重要であるとされている。そのためこれらの表現型は、羊膜襟が切断されたことにより、胚前方を支え、沈み込みを補助する構造がなくなったことによるものであると考えた。このことから、羊膜襟は胚と胚体を結合することで、心臓や頭部の立体構造の形成が行われても、胚前方が正常な位置に留まるよう維持していると考えている。首都大学東京, 2019-03-25, 修士（理学）首都大学東

A CASE OF CORONAVIRUS DISEASE 2019 COMPLICATED BY VENTILATORASSOCIATED PNEUMONIA, LUNG ABSCESS, AND STAPHYLOCOCCUS AUREUS BACTEREMIA

Complications of healthcare-associated infections have been reported in patients with coronavirus disease 2019 (COVID-19). We encountered a case of ventilator-associated pneumonia and lung abscess, complicated with Staphylococcus aureus bacteremia and multiple abscesses, in a patient with COVID-19. Streptococci and anaerobes were cultured from the sputum, which was considered to be the causative organism of the lung abscess. In the management of severe COVID-19, care should be taken to prevent complications of healthcare-associated infections; when secondary respiratory tract infections are suspected, the presence of lung abscess and anaerobic culture should be considered

Coronary Artery Disease/Effects of Ablation on Cardiac Reserve

The effects of catheter ablation on exercise tolerance and quality of life in patients with atrial fibrillation (AF) have been reported. We assessed cardiac function in more detail using the leg positive pressure (LPP) technique and found that contractile reserve is particularly important in relation to exercise tolerance and prognosis. In this study, we used the LPP technique to examine changes in contractile reserve immediately after ablation and 6 months later. We prospectively enrolled patients who underwent catheter ablation for AF at 2 institutes. We performed LPP stress echocardiography 2 to 3 days after (FU-1) and 6 months after (FU-2) ablation to examine changes in cardiac function indexes. The primary end point was improvement in contractile reserve. Ultimately, 109 patients (mean age 67.4 ± 9.6 years; 70% men) underwent 2 sessions of LPP stress echocardiography. The median CHA2DS2-VASC score was 2 (interquartile range 13). From FU-1 to FU-2, the change in the stroke volume index after the LPP maneuver increased in patients with paroxysmal and persistent AF with low CHA2DS2-VASC scores (both p <0.05). Regardless of AF subtype, contractile reserve at FU-2 improved in patients with low CHA2DS2-VASC scores compared with that at FU-1. In contrast, patients with high CHA2DS2-VASC scores had no change. In conclusion, patients with AF with a low CHA2DS2-VASC score had improved contractile reserve after ablation, whereas patients with high scores did not show any improvement. Aggressive interventions in patients with high scores may lead to better management after catheter ablation

RV Strain in PH due to Left Heart Disease

Background: Recent studies showed that the combined pre- and post-capillary pulmonary hypertension (CpcPH) had worse outcomes compared with isolated post-capillary (Ipc) PH. However, the prognostic factors including right ventricular (RV) function have not been well documented. The aim of this study was to assess the differentiation of PH phenotypes using echocardiography, and the association between RV longitudinal strain and cardiac events. Methods and Results: We prospectively recruited consecutive patients who had undergone right heart catheterization. The primary endpoint was cardiovascular death or readmission due to heart failure. One hundred thirty-seven patients with Group 2 PH were included. A RV longitudinal strain of 17% was sensitive (85%) and specific (70%) to determine the CpcPH. During a median period of 31 months, 43 patients had the primary endpoint during follow-up. In a multivariate analysis, RV longitudinal strain was associated with the primary endpoint in both CpcPH and IpcPH (hazard ratio: HR: 0.84, p =0.003 and HR: 0.86, p =0.001). Conclusions: Lower RV longitudinal strain was independently associated with worse outcomes in CpcPH and IpcPH. RV longitudinal strain may play a prognostic role among PH phenotypes

更新された左室拡張機能評価勧告と心不全入院患者における心血管イベント

Background: Evaluation of diastolic dysfunction is crucial in determining elevated left atrial pressure. However, a validation of the long-term prognostic value of the newly proposed algorithm updated in 2016 has not been performed. The aim of the present study was to investigate the relative value of the updated 2016 diastolic dysfunction grading system for the incidence of readmission in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods: Two hundred thirty-two patients hospitalized with HF were retrospectively evaluated. Subjects were divided into two subgroups: those with HFrEF (n = 127) and those with HFpEF (n = 105). Readmission risk scores were calculated using the Yale Center for Outcomes Research and Evaluation HF, LACE index, and HOSPITAL scores. The primary end point was readmission following HF and cardiac death. Results: Over a period of 24 months, 86 patients were either readmitted or died. Multivariate Cox analysis was performed on both the HFrEF and HFpEF groups. In the HFrEF group, both the 2009 and 2016 algorithms had superior incremental value for the association of the primary end point to several readmission risk scores. In the HFpEF group, only the 2016 algorithm led to significant improvement in association with the primary end point. The 2016 algorithm had incremental value over several readmission risk scores alone. Conclusions: The recommendations of the 2016 algorithm can be useful for readmission and cardiac mortality risk assessment in patients with HFrEF and HFpEF. The use of echocardiography to estimate elevated left atrial pressure appears to identify a higher risk group and may allow a more tailored approach to therapy