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Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients. Methods A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed. Results In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01–1.07; IL-8, HR = 1.04, 95% CI 1.01–1.08; MIP-1α, HR = 1.19, 95% CI 1.00–1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02–1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01–1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls. Conclusions CTACK is a novel prognostic biomarker of IPF. Trial registration None (because of no healthcare intervention)

Background Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. Methods A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. Results Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. Conclusions Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings.

背景．肺原発淡明細胞癌は組織学的に明るい胞体を有する腫瘍細胞が多数を占める癌で，発生頻度は全肺癌に対して0.3∼3.4%である．症例．66歳，男性．慢性腎不全で維持透析中に左片麻痺が出現し，頭部CTで多発腫瘤，胸部単純X線写真で左肺尖腫瘤を認めた．左片麻痺で低下したactivity of daily livingの改善と診断の目的で脳腫瘍を摘出した．脳腫瘍はhematoxylin and eosin染色で明るい胞体を有し，免疫組織化学的に腎癌で高率に発現するcluster of differentiation 10（CD 10）が一部発現していた．病理組織，免疫組織学的検討の結果から淡明細胞性腫瘍の病理組織像を呈する腎癌の脳転移と考えたが画像上腎腫瘤は明らかでなかった．interferon治療を開始したが左肺尖腫瘤は増大し，CTガイド下経皮肺生検を行い組織学的に再検討したところ肺原発淡明細胞癌と考えた．第102病日に永眠され，剖検では肺腫瘍が肉眼的に最も大きく，腎腫瘍は認めなかった．肺腫瘍，遠隔転移病巣の病理組織像は，明るい胞体を伴った腫瘍細胞が大部分を占め，癌真珠，細胞間橋形成，腺管構造形成などの分化傾向は認めず，大細胞癌の特殊型である肺原発淡明細胞癌と診断した．結論．我々は剖検所見から大細胞癌の特殊型である淡明細胞癌と診断した1剖検例を報告した．

A 66-year-old man with hepatocellular carcinoma (HCC) and suspicion of lung metastasis consulted us because of an abnormal chest shadow as seen on a radiograph. He had been treated with sorafenib for 2 months. A chest CT scan showed cavitating nodules in the left upper lobe that were present before therapy with sorafenib, and infiltrative shadows in the subpleural areas of the right upper lobe. The shadows were diagnosed, at least in part, as pulmonary tuberculosis by using a nucleic acid amplification test for Mycobacterium tuberculosis in the sputum that yielded a positive result. Treatment with antituberculosis drugs resulted in a good clinical response. However, the patient died of HCC. We concluded that the nodule in the right upper lobe was old pulmonary tuberculosis, because it did not change during the course of the disease and because the cavities in the left upper lobe were active lesions. Sorafenib is a molecularly targeted agent that has been proven effective for treating advanced HCC with extrahepatic metastasis. It may also cause necrosis within lung metastases as an anti-tumor effect. Therefore, pulmonary tuberculosis, including reactivation, should be considered in the differential diagnosis when treating a patient with sorafenib.

A 64-year-old woman underwent allogeneic peripheral blood-derived stem cell transplantation for acute lymphocytic leukemia. She complained of dyspnea and was admitted to hospital 116 days after transplantation. Because of positive serum testing for the Aspergillus antigen and antibody, and ground-glass opacity in the right upper lobe on high-resolution computed tomography (HRCT), we made a diagnosis of pulmonary aspergillosis and administered an antifungal agent. Although tests for the Aspergillus antibody became negative and the ground-glass opacities disappeared, her dyspnea persisted. Progressive bronchiectasis was seen on HRCT, predominantly in the lower lobes. A pulmonary function test showed mixed impairment. We made a diagnosis of bronchiolitis obliterans after chronic graft versus host disease (GVHD). Prednisolone and an increased dose of tacrolimus (FK506) were administered, but type II respiratory failure progressed and she died 2 months after admission. On HRCT, each lobe was graded for bronchiectasis using a scale: 0 = normal, 1 = less than 2 x the diameter of an adjacent pulmonary artery, 2 = 2 - 3 x the diameter of an adjacent pulmonary artery, and 3 = more than 3 x the diameter of an adjacent pulmonary artery. A total score was calculated by summing the scores of all the lobes (maximum 15). In this case, the total score increased rapidly from 0 to 13 in 2 months.

SUMMARY The activation of B lymphocytes and formation of immune complexes have been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To investigate the mechanisms of activation of B lymphocytes, we studied the production of B cell growth factor (BCGF) and B cell differentiation factor (BCDF) in patients with IPF and those with interstitial pneumonia associated with collagen vascular diseases (IP-CVD), in comparison with healthy controls. Culture supernatants of peripheral blood mononuclear cells from patients with IPF induced more IgM and IgA production by B lymphocytes than those from healthy controls, indicating a higher production of BCDF in the patients. Culture supernatants of T lymphocytes obtained from bronchoalveolar lavage fluids (BALF) of patients with IPF induced higher proliferation of B lymphocytes than those from healthy controls, indicating a higher production of BCGF. An increase in production of BCGF and BCDF was not observed in patients with IP-CVD. In the light of these results, it was suggested that there may be an imbalance in T lymphocyte subsets that release lymphokines like BCGF and BCDF in patients with IPF, and that the subsets may differ between blood and BALF. It remains to be elucidated whether the activation of B lymphocytes depending on T lymphocytes determines the development of disease in IPF.

In an evaluation of the role of coronary collaterals in the early period of acute myocardial infarction (AMI), 30 patients with acute total coronary occlusion treated with intracoronary thrombolysis 2 to 8 hours after the onset of symptoms were studied. Only 13 patients with well-developed collaterals in the early period of AMI and successful thrombolysis showed improvement of global and regional ejection fraction (EF) from the acute phase to the chronic phase (global EF from 50% to 71%, p less than 0.001; regional EF from 25.4% to 49.2%, p less than 0.001). In patients with no or less well-developed collaterals and successful thrombolysis, global and regional EF were similar to those in patients in whom thrombolysis was unsuccessful. Among the 19 patients with successful thrombolysis, there was no significant correlation between the duration of ischemia and the improvement of regional EF (r = -0.03, difference not significant). These data suggest that the extent of coronary collateral vessels in the early period of AMI is an important determinant of restoration of left ventricular function after intracoronary thrombolysis.