化学療法施行中のオピオイド使用による便秘に対するルビプロストンの有用性

　当科において2014年10月から2016年２月に入院で化学療法を施行し，がん性疼痛に対して使用したオピオイドにより誘発された便秘に対してルビプロストンを投与した全症例を対象とした．対照群は，当院のルビプロストン採用以前の2012年４月から2014年９月まで，化学療法施行中にオピオイドを使用した患者に緩下薬を使用していた全症例とした．ルビプロストンを追加してからの排便回数と食事量の変化を後方視的に解析した．対照群の排便回数と食事量の変化は，新たな緩下薬（センノシド，ピコスルファートナトリウム，または大建中湯）の追加または酸化マグネシウムを増量した前後を基準とした．ルビプロストン使用群７人，未使用の対照群12人で，オキシコドン換算の使用量中央値（範囲）は対照群で10.0（10.0～62.9）mg，ルビプロストン群で39.3（10.0～125.7）mg であった（P=0.103）．ルビプロストン群ではその投与翌日に７例中６人，対照群においては12例中３例で排便が認められた（P<0.05）．ルビプロストン群においては排便があった翌日の食事摂取量は７例中６例，対照群は12例中３例で改善していた（P<0.05）．化学療法施行中にもオピオイドによる便秘に対するルビプロストンが有用であることが示唆された．　Lubiprostone is a useful treatment for opioid-induced constipation (OIC); however, it is not known whether the treatment is suitable for OIC in patients undergoing cancer chemotherapy. This study evaluated hospitalized patients receiving cancer chemotherapy in whom OIC was treated with lubiprostone between October 2014 and February 2016. The control group consisted of OIC + chemotherapy patients who were hospitalized between April 2012 and September 2014, before lubiprostone was approved for use at our hospital. Frequency of stool and food intake were retrospectively evaluated before and after treatment with lubiprostone (lubiprostone group; n=7) or other laxative agent (control group; n=12). Other laxative agents included sennoside, sodium picosulfate, daikenchuto or magnesia. The lubiprostone and control groups both received oxycodone (median [range]: 39.3 [10.0-125.7] mg vs 10.0 [10.0-62.9] mg; P=0.103). The day following treatment, defecation was observed in 6 of 7 patients in the lubiprostone group and 3 of 12 patients in the control group (P<0.05). Dietary intake also increased in 6 of 7 patients in the lubiprostone group and 3 of 12 patients in the control group (P<0.05). Therefore, lubiprostone may be an effective treatment for OIC during chemotherapy

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

A surgical case of pulmonary adenocarcinoma in the right upper lobe associated with a systemic artery‐to‐pulmonary artery fistula

Abstract A 52‐year‐old female never‐smoker with an abnormal shadow in the right lung detected on radiography was referred to our institution. Contrast‐enhanced computed tomography revealed an irregular nodule in the upper lobe of the right lung, suggestive of a pulmonary vascular abnormality. Angiography revealed a direct communication between the right internal mammary artery (IMA) and the right upper lobe pulmonary artery branches, with dilated and tortuous vascular proliferation. As multiple branch arteries were seen flowing into the upper lobe from the IMA, transcatheter selective embolization of these vessels and right upper lobectomy by video‐assisted thoracoscopic surgery were performed. Contrary to the clinical diagnosis, the pathological finding was a pulmonary adenocarcinoma of the right upper lobe. Additional lymph node dissection was performed later. We report an extremely rare and unprecedented case of pulmonary adenocarcinoma fed by the right IMA, with a literature review

Do Elderly Lung Cancer Patients Aged ≥75 Years Benefit from Immune Checkpoint Inhibitors?

Lung cancer patients &ge;75 years represent nearly 40% of all lung cancer patients and continue to increase. If elderly patients have a good performance status and adequate organ function, they can be treated the same as non-elderly patients. However, few comparative studies limited to elderly patients (&ge;75 years) have been conducted. We review the evidence on using immune check inhibitors for the treatment of elderly patients (&ge;75 years old) with advanced non-small cell lung cancer. Prospective randomized or non-randomized, retrospective, registrational, insurance-based, and community-based studies have shown that elderly (&ge;75 years) and non-elderly patients are similarly treated with immune check inhibitors effectively and safely. However, such analyses have not shown that immune check inhibitors are significantly more effective than chemotherapy alone. In addition, patient selection might be critically performed to administer immune check inhibitors in the elderly because they are more likely to have a poor performance status with comorbidities, which lead to little benefit, even in non-elderly patients. There is a need for more evidence showing the benefit of immune check inhibitors in non-small cell lung cancer patients &ge;75 years

Ceftriaxone-associated pancreatitis captured on serial computed tomography scans

A 74-year-old man was treated with ceftriaxone for 5 days and subsequently experienced epigastric pain. Computed tomography (CT) was performed 7 and 3 days before epigastralgia. Although the first CT image revealed no radiographic signs in his biliary system, the second CT image revealed dense radiopaque material in the gallbladder lumen. The third CT image, taken at symptom onset, showed high density in the common bile duct and enlargement of the pancreatic head. This is a very rare case of pseudolithiasis involving the common bile duct, as captured on a series of CT images