免疫抑制剤投与中に急性呼吸促迫症候群を合併した粟粒結核の１例

症例は75歳，女性．MPO-ANCA 関連血管炎に対して半年間，ステロイド薬が投与されていた．４日前から発熱，呼吸困難が出現，意識障害も伴ってきたため，当院を受診した．画像上，両側肺にびまん性の中枢側に有意な浸潤影とすりガラス陰影を認め，急性呼吸促迫症候群（ARDS）の合併を疑われた．人工呼吸管理となり，挿管中に採取した喀痰抗酸菌検査で塗抹陽性，結核菌PCR陽性の結果が得られ，血液や尿からも結核菌が検出され，粟粒結核によるARDS と診断した．治療は入院後の第３病日からINH ＋ RFP ＋ EB による抗結核療法を開始し，人工呼吸管理および血液透析をしながら経過観察をしていたが，播種性血管内凝固症候群も併発し，第14病日に死亡した．ARDS を合併する粟粒結核の症例も散見されることから，鑑別診断に粟粒結核も念頭におきながら診療することが重要と思われた．A 75-year-old woman, who was treated with corticosteroid therapy for six months for MPO-ANCA related vasculitis, visited to our hospital with fever, dyspnea and consciousness disturbance four days ago. She was diagnosed with acute respiratory distress syndrome (ARDS) from radiological findings such as diffuse bilateral hilar dominant infiltration shadow and ground-glass opacity. She was admitted to the intensive care unit (ICU) and put on mechanical ventilation for acute respiratory failure. The aspiration sputum after incubation turned out to be positive for acid-fast bacilli, which were identified as Mycobacterium tuberculosis (MTB) using a polymerase chain reaction test. As the same results in the clinical specimens of peripheral blood and urine were obtained, we made final diagnosis of miliary tuberculosis complicated with ARDS. Although we initiated the anti-tuberculosis treatment using INH, RFP, EB with mechanical ventilation and hemodialysis treatment, she died of multiple organ failure complicated with disseminated intravascular coagulation (DIC). Due to the fact, that we have encountered few cases of miliary tuberculosis complicated with ARDS, it is important that we suspect severe miliary tuberculosis in patients with immunosuppressive treatment

急速に増大する腫瘤影を呈した肺Mycobacterium avium症の1例

症例は66歳,男性.慢性閉塞性肺疾患とい草塵肺で経過観察をしていた.6カ月前の胸部CTでは明らかな異常を認めなかったが,新たに左上葉の気腫性病変周囲に腫瘤性病変を認めた.気管支鏡検査にて,局所検体からM.avium が検出されたものの生検で肉芽腫病変を認めなかったため,CTガイド下肺生検を実施した結果,肺MAC症と最終診断した.近年,孤立性腫瘤形成型肺MAC症の症例を散見するようになってきているが,本症例のごとく短期間で急速に増大することもあることから,抗酸菌を含めた肺感染症に対する積極的な検査が必要と思われる.A 66-year-old man was admitted to our hospital for follow-up on chronic obstructive pulmonary disease with a recent-showing abnormal chest shadow. He had received a periodic chest computed tomography (CT) six months prior due to a past history of COPD and Igusa pneumoconiosis. Although there was no mass shadow on the chest CT six months ago, a solitary tumorous shadow appeared surrounding the emphysematous lesions in the left upper lobe. M. avium was detected from local specimens viabronchoscopic examination, but because a granulomatous lesion was not observed, we performed a CT-guided lung biopsy and made a final diagnosis of pulmonary MAC disease. We recently observed that pulmonary MAC disease presents as a solitary tumorous shadow. However, as there are cases of pulmonary MAC disease presenting as a rapidly growing tumorous shadow within a short time, it is necessary to perform aggressive examinations for infectious diseases including an acid-fast bacilli examination

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

Direct Monitoring of γ-Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized (13) C-Labeled Molecular Probe.

The γ-glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, γ-Glu-[1-(13) C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) (13) C magnetic resonance (MR). The properties of γ-Glu-[1-(13) C]Gly are suitable for in vivo HP (13) C metabolic analysis since the chemical shift between γ-Glu-[1-(13) C]Gly and its metabolic product, [1-(13) C]Gly, is large (4.3 ppm) and the T1 of both compounds is relatively long (30 s and 45 s, respectively, in H2 O at 9.4 T). We also demonstrate that γ-Glu-[1-(13) C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin

Direct Monitoring of γ-Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized (13) C-Labeled Molecular Probe

The γ-glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, γ-Glu-[1-(13) C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) (13) C magnetic resonance (MR). The properties of γ-Glu-[1-(13) C]Gly are suitable for in vivo HP (13) C metabolic analysis since the chemical shift between γ-Glu-[1-(13) C]Gly and its metabolic product, [1-(13) C]Gly, is large (4.3 ppm) and the T1 of both compounds is relatively long (30 s and 45 s, respectively, in H2 O at 9.4 T). We also demonstrate that γ-Glu-[1-(13) C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin