A Clinical Study of Photodynamic Therapy for Superficial Esophageal Carcinoma by YAG-OPO Laser

A cooperative clinical study of photodynamic therapy (PDT) for superficial esophageal carcinoma was conducted at 6 medical institution. PHE (2mg/kg) with high tumor affinity was used as the oncotropic compound. The light source was a pulse wave YAG-OPO laser with high penetration into the tissue. Irradiation was performed at an energy density of 60–180 J/cm2 48–72 h after PHE administration. Eight lesions in 6 patients were treated. All were type 0-II superficial carcinomas. The depth of invasion was EP–MM for 6 lesions and SM for 2 lesions. A complete response (CR) was achieved in all patients after one session of PDT. Five adverse events, including anemia and fever, were reported by 4 patients, but all were WHO grade 2 or lower and transient. PDT using PHE and YAG-OPO laser was therefore considered effective as a curative therapy for superficial esophageal carcinoma

Cooperative Clinical Trial of Photodynamic Therapy for Early Gastric Cancer With Photofrin Injection® and YAG-OPO Laser

Background and Objective: Photodynamic therapy (PDT) treats malignant tumors using photosensitizers and light. We employed a new pulse laser as the excitation light source for PDT, i.e. an optical parametric oscillator (OPO) system pumped by a Q-switched Nd:YAG laser, because it provides extremely high peak power

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

Un estudio piloto para evaluar la seguridad y eficacia de la insuflación de dióxido de carbono durante la disección submucosa endoscópica colorrectal con el paciente bajo sedación consciente

15 páginasBackground Endoscopic submucosal dissection (ESD) is accepted as one of the treatments for en bloc resection of large superficial colorectal lesions. This procedure is performed by using air insufflation, is time consuming, and is associated with severe abdominal discomfort. The safety and efficacy of carbon dioxide (CO2) insufflation during colonoscopy already has been assessed in some trials. Objective To assess the safety and efficacy of CO2 insufflation instead of air insufflation during colorectal ESD with the patient under conscious sedation. Design A case-control series with a historical control. Patients A total of 35 consecutive patients were enrolled in this study. Another 35 consecutive patients who previously received colorectal ESDs by using air insufflation were included as a historical control. Interventions Arterial partial pressure of CO2 (pCO2) was measured before and after each procedure with the total dose of midazolam used as an index of abdominal discomfort. Main Outcome Measurements and Results The mean (standard deviation [SD]) operation time was 90 ± 57 minutes in the CO2 group and 100 ± 80 minutes in the control group (not significant). In the CO2 group, the mean (SD) dose of midazolam was significantly lower than that of the control group; 5.6 ± 4.9 mg and 9.7 ± 5.9 mg, respectively (P = .005). Blood analysis revealed a slight pCO2 elevation in the CO2 group; however, only 2 patients complained of mild abdominal discomfort. Limitations Abdominal discomfort and pCO2 were not evaluated in the control group. Conclusions This study strongly suggests that CO2 insufflation is safe and effective during lengthy colonic endoscopic procedures, eg, ESD, with the patient under conscious sedation.Fondo La disección submucosa endoscópica (DES) se acepta como uno de los tratamientos para la resección en bloque de grandes lesiones colorrectales superficiales. Este procedimiento se realiza mediante insuflación de aire, requiere mucho tiempo y se asocia con molestias abdominales graves. La seguridad y eficacia de la insuflación de dióxido de carbono (CO2) durante la colonoscopia ya se ha evaluado en algunos ensayos. Objetivo Evaluar la seguridad y eficacia de la insuflación de CO2 en lugar de la insuflación de aire durante la ESD colorrectal con el paciente bajo sedación consciente. Diseño Una serie de casos y controles con un control histórico. Pacientes Un total de 35 pacientes consecutivos se inscribieron en este estudio. Se incluyeron como control histórico otros 35 pacientes consecutivos que previamente recibieron ESD colorrectal mediante insuflación de aire. Intervenciones La presión arterial parcial de CO2 (pCO2) se midió antes y después de cada procedimiento con la dosis total de midazolam utilizada como índice de malestar abdominal. Principales medidas de resultado y resultados El tiempo quirúrgico medio (desviación estándar [DE]) fue de 90 ± 57 minutos en el grupo de CO2 y de 100 ± 80 minutos en el grupo de control (no significativo). En el grupo de CO2, la dosis media (DE) de midazolam fue significativamente menor que la del grupo de control; 5,6 ± 4,9 mg y 9,7 ± 5,9 mg, respectivamente (p = 0,005). El análisis de sangre reveló una ligera elevación de pCO2 en el grupo de CO2; sin embargo, solo 2 pacientes se quejaron de molestias abdominales leves. Limitaciones En el grupo control no se evaluaron las molestias abdominales ni la pCO2. Conclusiones Este estudio sugiere fuertemente que la insuflación de CO2 es segura y eficaz durante procedimientos endoscópicos colónicos prolongados, por ejemplo, ESD, con el paciente bajo sedación consciente