Clinical utility of the Bosniak classification version 2019:Diagnostic value of adding magnetic resonance imaging to computed tomography examination

Purpose: To assess the impact of the updated Bosniak classification (BC2019) for cystic renal masses (CRMs) on interobserver agreement between radiologists and urologists and the diagnostic value of adding MRI to CT examination (combined CT/MRI). Method: This study included 103 CRMs from 83 consecutive patients assessed using contrast-enhanced CT and MRI between 2010 and 2016. Nine readers in three groups (three radiologists, three radiology residents, and three urologists) reviewed CT alone and the combined CT/MRI using BC2019. Bosniak category was determined by consensus in each group for diagnosing malignancy, with a cut-off category of ?>= III. Interobserver agreement was assessed using Fleiss' kappa values. The effect of CT or combined CT/MRI on the diagnosis of malignancy was assessed using McNemar's test. Results: Interobserver agreement of BC2019 for CT alone was substantial for radiologists and residents, moderate for urologists (0.77, 0.63, and 0.58, respectively). Interobserver agreement of BC2019 for combined CT/MRI was substantial for all three groups (radiologists: 0.78; residents: 0.65; and urologists: 0.61). Among residents, the sensitivity/specificity/accuracy rates of combined CT/MRI vs. CT alone were 82.1/74.7/76.7% vs. 75.0/66.7/68.9%, and specificity and accuracy were significantly higher for combined CT/MRI than that for CT alone (p = 0.03 and 0.008, respectively). Similarly, sensitivity/specificity/accuracy values were significantly higher for combined CT/MRI among urologists (78.6/73.3/74.8% vs. 64.3/64.0/64.1%, p = 0.04/0.04/0.008). However, sensitivity/specificity/accuracy did not significantly differ between the two among radiologists (89.3/74.7/78.6% vs. 85.7/73.3/76.7%, p = 0.32/0.56/0.32). Conclusions: Combined CT/MRI is useful for diagnosing malignancy in patients with CRMs using BC2019, especially for non-expert readers

Clinical significance of nuclear non-phosphorylated beta-catenin in acute myeloid leukaemia and myelodysplastic syndrome

Wnt signaling activates the canonical pathway and induces the accumulation of non-phosphorylated beta-catenin (NPBC) in the nucleus. Although this pathway plays an important role in the maintenance of haematopoietic stem cells as well as in oncogenesis, the significance of nuclear NPBC remains unclear in malignant haematopoiesis. This study examined the expression of nuclear NPBC in bone marrow specimens from 54 and 44 patients with de novo acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), respectively. On immunohistochemistry with an anti-NPBC antibody, the nuclei were positively stained in 22 and 18 of AML and MDS specimens, respectively. Staining of nuclear NPBC was associated with AML subtypes (M6 and M7), low complete remission (CR) rate, and poor prognosis. Nuclear NPBC was also associated with a high score when using the International Prognostic Scoring System (IPSS) for MDS and with −7/−7q and complex karyotypes. These findings suggest that in situ detection of nuclear NPBC by immunohistochemistry could provide new insights into the pathogenesis and prognosis of AML and MDS

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

〈Case Reports〉Control of the platelet count for emergency ascending aortic repair in a patient with idiopathic thrombocytopenic purpura.

[Abstract]We report an acute type A dissection case with refractory idiopathic thrombocytopenic purpura (ITP). A 72-year-old woman treated as ITP patient, whose platelet count was decreased to 2,000/mm3, was transfered to our institute, due to the acute Stanford A aortic dissection complicated with pericardial effusion. She was treated with high-dose γ-globulin therapy (HDGT) and platelet transfusion immediately after admission under pulse steroid therapy. Her platelet count was recovered to 47,000/mm3 36 hours after the onset of acute dissection while maintaining lower systemic blood pressure. Then, we decided to per-form ascending aortic replacement. HDGT and platelet transfusion were continued during the operation. The replacement was completed with-out hemostatic problems, maintaining the plate-let count at >50,000/mm3. HDGT and platelet transfusion should be started as soon as possible after the urgency of the operation of ITP patients become apparent. The operation must be per-formed promptly without hesitation

Changes in lung sounds during asthma progression in a guinea pig model

Background: Lung sound analysis is useful for objectively evaluating airways even in children with asymptomatic asthma. However, the relationship between lung sounds and morphological changes in the airways has not been elucidated. We examined the relationship between lung sounds and chronic morphological changes in the airways during the progression of asthma from onset in guinea pigs. Methods: Eleven male guinea pigs were examined; of these, seven were used as asthma models and four as controls. The asthma models were sensitized and repeatedly challenged by inhaling albumin chicken egg. We measured lung sounds and lung function twice a week for 21 weeks. After the final antigen challenge, the lungs were excised for histological examination. We measured the ratio of airway wall thickness to the total airway area and the ratio of the internal area to the total airway area in the trachea, third bronchi, and terminal bronchioles. Results: Among the lungs sounds, the difference between the two groups was greatest with respect to inspiratory sound intensity. The ratio of airway wall thickness to the total airway area of the terminal bronchioles was greater in the asthma models than in the controls, and it correlated best with the changes in inspiratory sound intensity in the 501–1000-Hz range (r = 0.76, p < 0.003). Conclusions: Lung sound intensity in the middle frequency range from 501 to 1000 Hz correlated with peripheral airway wall thickness. Inspiratory sound intensity appeared to be an indicator of morphological changes in small airways in asthma