Análisis de las comorbilidades en pacientes con colitis ulcerosa: una herramienta para prevenir las exacerbaciones en casos de colitis ulcerosa

There have been previous studies, especially in Western countries and even in some areas in Asia, about extra-intestinal manifestations (EIMs) and its link with the outcome of inflammatory bowel disease (IBD), which includes Crohn’s disease (CD), and ulcerative colitis (UC). This link is crucial when discussing a patient’s prognosis and important when dealing with UC management. The aim of this study was to clarify the most common comorbidities associated with UC, emphasizing immunologic comorbidities in Japan. This study was a retrospective analysis performed at Nagoya University Hospital. The data collection started in March, 2019, and continued for two years. We retrieved the medical records of 105 patients with UC diagnosis, from which the data of 176 EIMs were extracted and analyzed. Results showed that EIMs with UC in the active phase accounted for 43.7% of total EIMs. Twenty-six patients with immune-mediated inflammatory disease frequently had an active phase (odds ratio [OR] 3.84, 99% CI, 1.44–10.27). Comorbidities showing an active manifestation of symptoms and UC in the active phase were significantly correlated in patients with immunological comorbidities, such as peripheral arthritis (r = 0.97, p < 0.01) and rheumatoid arthritis (RA) (r = 0.99, p < 0.01), as well as in patients with primary sclerosis cholangitis (PSC) (r = 0.98, p < 0.01). In conclusion, this analysis suggests the importance of having full comprehension of how immunological comorbidities affect the natural development of UC, which is of vital importance to prevent further UC complications and properly adjust the management of the disease.Se trata de un análisis retrospectivo que estudia múltiples comorbilidades de índole inmunológico que se da en pacientes con colitis ulcerosa. Este estudio se llevó a cabo en el hospital universitario de la Universidad de Nagoya. Se recolectó datos de 105 pacientes con colitis ulcerosa, de los cuales 176 comorbilidades extraintestinales fueron analizadas. Se encontró que comorbilidades con manifestación activa de síntomas y con colitis ulcerosa en fase activa fueron significativamente correlacionadas en pacientes con comorbilidades inmunológicas, tales como artritis periféricas (r=O.97, P<O.OI ), artritis reumatoide (r=O.99, P<O.OI ), así como pacientes con colangitis esclerosa primaria (r=O.98, P<O.OI ). En conclusión, este análisis sugiere la importancia de tener plena comprensión de cómo las comorbilidades inmunológicas afectan el desarrollo natural de la colitis ulcerosa, lo cual es de vital importancia para prevenir mayores complicaciones de la colitis ulcerosa y ajustar adecuadamente el manejo de la enfermedad.Japón. Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología (Monbukagakusho)Artículo de investigació

Stent-Related Adverse Events as Related to Dual Antiplatelet Therapy in First- vs Second-Generation Drug-Eluting Stents

[Background] There are limited data on the long-term stent-related adverse events as related to the duration of dual antiplatelet therapy (DAPT) in second-generation (G2) drug-eluting stents (DES) compared with first-generation (G1) DES. [Objectives] This study sought to compare the long-term stent-related outcomes of G2-DES with those of G1-DES. [Methods] The study group consisted of 15, 009 patients who underwent their first coronary revascularization with DES from the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) Registry Cohort-2 (first-generation drug-eluting stent [G1-DES] period; n = 5, 382) and Cohort-3 (second-generation drug eluting stent [G2-DES] period; n = 9, 627). The primary outcome measures were definite stent thrombosis (ST) and target vessel revascularization (TVR). [Results] The cumulative 5-year incidences of definite ST and TVR were significantly lower in the G2-DES group than in the G1-DES group (0.7% vs 1.4%; P < 0.001; and 16.2% vs 22.1%; P < 0.001, respectively). The lower adjusted risk of G2-DES relative to G1-DES for definite ST and TVR remained significant (HR: 0.53; 95% CI: 0.37-0.76; P < 0.001; and HR: 0.74; 95% CI: 0.68-0.81; P < 0.001, respectively). In the landmark analysis that was based on the DAPT status at 1 year, the lower adjusted risk of on-DAPT status relative to off-DAPT was significant for definite ST beyond 1 year in the G1-DES stratum (HR: 0.42; 95% CI: 0.24-0.76; P = 0.004) but not in the G2-DES stratum (HR: 0.66; 95% CI: 0.26-1.68; P = 0.38) (Pinteraction = 0.14). [Conclusions] G2-DES compared with G1-DES were associated with a significantly lower risk for stent-related adverse events, including definite ST and TVR. DAPT beyond 1 year was associated with a significantly lower risk for very late ST of G1-DES but not for that of G2-DES

A Report on Overseas Teaching Practicum by Graduate Students in Elementary/Secondary Schools in the United States（Ⅺ）

This paper reports on the 11th overseas teaching practicum in the U.S. 12 students joined this year’s program and they observed and conducted lessons in English in three local public schools in North Carolina after careful and repeated preparation sessions in Japan. Many of them did lessons on crosscultural understandings and a few taught subject contents. Through the trail to convey messages in English, their foreign language, students learned the role of verbal and nonverbal language and the more universal way to explain topics to children who are unfamiliar with what re taught. And they also learned and noticed the cultural differences and similalities between the two countries. It seemed that students realized that the two countries share many things in common such as what chidren are like, teachers’ attitude toward children and challenges they are facing, and people’s kindness. These learning was no substitute experience for the participants and it is hoped that their experience will be passed to the next generation when they become teachers

Effect of Heart Failure on Long‐Term Clinical Outcomes After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Severe Coronary Artery Disease

[Background] Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long‐term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). [Methods and Results] Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO‐Kyoto PCI/CABG registry Cohort‐3, we identified the current study population of 3380 patients with three‐vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow‐up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P=0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28–2.42; P<0.001) and no excess mortality risk in patients without heart failure (HR, 1.04; 95% CI, 0.80–1.34; P=0.77). [Conclusions] There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure

Percutaneous coronary intervention using new-generation drug-eluting stents versus coronary arterial bypass grafting in stable patients with multi-vessel coronary artery disease: From the CREDO-Kyoto PCI/CABG registry Cohort-3

AIMS: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease. METHODS AND RESULTS: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001). CONCLUSIONS: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Numerical analysis of the space charge effect in a MWPC

A numerical calculation code was developed by employing a two-dimensional continuum model for the detailed design of MWPC (Multi-Wire Proportional Chamber) detectors. The temporal evolutions of electron and ion density distributions were evaluated for the time period required by ions to travel between the anode and the cathode. The temporal evolution of the electric field was also calculated to take into account the space charge effect caused by ions. The output signals of an anode, which were multiplied by electron avalanche, were estimated from an electron flux into anodes. By comparing the gain curve evaluated from the output signals with that obtained by theoretical calculations, we confirmed that the numerical code is capable of quantitative estimations of the gas gain. From these results, we discuss the dependence of the output signal on the space charge effect, and the relations between the ion distribution and the space charge effect