The Combination of Prognostic Nutritional Indicator and Serum Carcinoembryonic Antigen is Useful in Predicting Postoperative Recurrence in Stage II Colorectal Cancer

[Background] The efficacy of adjuvant chemotherapy in stage II colorectal cancer (CRC) patients has not been clearly demonstrated. Therefore, identification of robust prognostic factors is crucial for the assessment of recurrence risk in stage II CRC and appropriate adjuvant treatment, in clinical practice. [Methods] We enrolled 135 colorectal adenocarcinoma patients who underwent proctocolectomies and had histologically diagnosed stage II CRC. [Results] Receiver operating characteristic (ROC) analysis, to evaluate the predictive ability of certain serum factors for CRC recurrence, indicated that the prognostic nutritional indicator (PNI), followed by serum carcinoembryonic antigen (CEA) level, were the strongest predictive metrics. Based on cutoff values from ROC analyses, patients were divided as follows; CEAHigh (≥ 4.55 ng/mL), CEALow (< 4.55 ng/mL), PNIHigh (≥ 47.72), and PNILow (< 47.72). The recurrence rates of patients with CEAHigh and PNILow, CEAHigh and PNIHigh, CEALow and PNILow, and CEALow and PNIHigh were 34.3%, 0%, 6.8%, and 2.6%, respectively (a significant difference at P < 0.0001). Logistic regression analysis revealed that the combination of serum CEA level and PNI was an independent predictive indicator of tumor recurrence after operation in stage II CRC patients. The 5-year disease specific survival rates of patients with CEALowPNIHigh, CEAHighPNIHigh, CEALowPNILow, CEAHighPNILow were 100%, 100%, 97.4%, and 77.5%, respectively (P < 0.0001). [Conclusion] The combination of CEA and PNI was useful in predicting postoperative recurrence in stage II CRC patients

Thoracic Esophagus Cancer Revealing a Tracheal Diverticulum

Tracheal diverticulum is rarely encountered in a clinical setting since almost all patients are asymptomatic. However, its presence may become a problem during esophageal cancer operations in terms of anesthesia and lymph node dissection of superior mediastinum lymphadenectomy. A 70?year?old man with esophageal cancer was referred to our hospital. During thoracoscopic subtotal esophagectomy, we found a cystic lesion connected to the right posterior wall of the trachea. We evaluated the preoperative computed tomography scan during surgery and made a diagnosis of tracheal diverticulum because of the presence of paratracheal air cysts, which had not been noticed preoperatively. It was resected by a linear stapler and the postoperative course of the patient was uneventful. A careful preoperative evaluation of computed tomography and operation are necessary to avoid injury of tracheal diverticulum during thoracoscopic esophagectomy for esophageal cancer revealing a tracheal diverticulum

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