Mixed germ cell tumor infiltrating the pineal gland without elevated tumor markers: illustrative case

BACKGROUND: Tumors in the pineal region consist of various histological types, and correct diagnosis from biopsy specimens is sometimes difficult. The authors report the case of a patient with a mixed germ cell tumor infiltrating into the pineal gland despite showing no elevation of tumor markers. OBSERVATIONS: An 18-year-old man complained of headache and nausea and showed disturbance of consciousness. Magnetic resonance imaging showed hydrocephalus associated with a cystic pineal tumor. The patient underwent tumor biopsy followed by endoscopic third ventriculostomy for hydrocephalus in a local hospital. A pineocytoma was diagnosed, and the patient was referred to the authors' hospital for treatment. Concentrations of placental alkaline phosphatase, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin in cerebrospinal fluid were not elevated. However, the authors' review of the tumor specimen revealed some immature cells infiltrating the pineal gland. These cells were positive for AFP, Sal-like protein 4, and octamer-binding transcription factor 3/4; and the diagnosis was changed to mixed germ cell tumor. Chemoradiotherapy was initiated, followed by surgical removal of the residual tumor. LESSONS: Careful examination of all tumor specimens and immunohistochemical analyses are important for accurate diagnosis of pineal tumors

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

Effect of oral supplementation with branched-chain amino acid granules on serum albumin level in the early stage of cirrhosis: a randomized pilot study.

Summary. The present study was undertaken to examine changes in the levels of amino acids, particularly branched-chain amino acids (BCAAs), following exacerbation of liver cirrhosis and to determine the optimal timing of starting nutritional therapy using BCAA. In patients with well-compensated cirrhosis, both the aminoacid composition and the albumin level were normal. However, as the disease advanced, BCAA first began to decrease, causing amino-acid imbalance, and this change was later followed by a decrease in albumin. We reviewed the criteria for determining indications for treatment with a BCAA formula (Livact), which is currently used after a decrease in albumin level. In patients in whom the BCAA-to-tyrosine ratio (BTR) was less than 4.0 despite normal albumin levels, the use of the BCAA preparation prevented a decrease in albumin. In view of this result, it is advisable to administer the BCAA formula following a reduction in BTR rather than to begin its use following a decrease in albumin

Filler-depletion layer adjacent to interface impacts performance of thermal interface material

When installing thermal interface material (TIM) between heat source and sink to reduce contact thermal resistance, the interfacial thermal resistance (ITR) between the TIM and heat source/sink may become important, especially when the TIM thickness becomes smaller in the next-generation device integration. To this end, we have investigated ITR between TIM and aluminum surface by using the time-domain thermoreflectance method. The measurements reveal large ITR attributed to the depletion of filler particles in TIM adjacent to the aluminum surface. The thickness of the depletion layer is estimated to be about 100 nm. As a consequence, the fraction of ITR to the total contact thermal resistance becomes about 20% when the TIM thickness is about 50 μm (current thickness), and it exceeds 50% when the thickness is smaller than 10 μm (next-generation thickness)

Diffuse Gallium-67 Accumulation in the Left Atrial Wall Detected Using SPECT/CT Fusion Images

Gallium-67 scintigraphy is useful for detecting active inflammation. We show a 66-year-old female patient with atrial fibrillation and diffuse thickening of the left atrial wall due to acute myocarditis, who presented diffuse abnormal accumulation of gallium-67 in the left atrium on single photon emission computed tomography/computed tomography (SPECT/CT) fusion images. In the second gallium-67 scan 2 months after the first scintigraphy, the abnormal accumulation in the heart was no longer visible. Gallium-67 SPECT/CT images helped understanding the disease condition that temporary inflammation in the left atrium caused atrial fibrillation

Additional effects of FDG-PET to thin-section CT for the differential diagnosis of lung nodules: a Japanese multicenter clinical study

Objective This study was a controlled multicenter clinicalstudy on patients with peripheral lung nodules to verify theimprovement in the diagnostic ability of FDG-PET whenused in combination with thin-section CT (TS-CT).Methods Patients with peripheral lung nodules (longmaximal diameter: 10–30 mm) detected using CT wereexamined using TS-CT and FDG-PET for the differentialdiagnosis of benign or malignant lesions. The primaryendpoint was the specificity of the results using a combinationof TS-CT and FDG-PET, compared with the resultsfor TS-CT alone. Images were interpreted by investigatorsat each institution. Blind readings were also performed byan independent image interpretation committee. The goldstandard was a pathological diagnosis determined using asurgical or biopsy specimen obtained after PET; and thepatients in whom a pathological diagnosis could not beobtained were diagnosed based on a follow-up TS-CTperformed more than 6 months later. Adverse reactions toFDG were also evaluated.Results The blind reading results for 82 lesions in 81subjects eligible for analysis among the 90 subjects includedin the study showed a specificity of 91.2% (31/34)(95% CI: 76.3–98.1) for TS-CT ? PET, compared with aspecificity of 67.6% (23/34) (95% CI: 49.5–82.6) for TSCTalone. The specificity was significantly improved by theaddition of the PET findings (p.05). The sensitivityimproved from 89.6% (43/48) for TS-CT to 91.7% (44/48)for TS-CT ? PET; the addition of PET increased the levelof confidence in the diagnosis, but the difference was notsignificant. The results reported by the institutional investigatorswere not significantly different. No serious adversereactions occurred, although two of the 90 subjectsexhibited mild adverse reactions.Conclusions The addition of FDG-PET to TS-CT for thedifferential diagnosis of benign or malignant peripherallung nodules resulted in a significant improvement inspecificity. Although a definitive diagnosis of lung nodulesrequires a histopathological or cytological examination,when combined with TS-CT, FDG-PET can provideadditional diagnostic information and improve thespecificity