Human bone marrow-derived mesenchymal stromal cells cultured in serum-free media demonstrate enhanced antifibrotic abilities via prolonged survival and robust regulatory T cell induction in murine bleomycin-induced pulmonary fibrosis.

BACKGROUND: Mesenchymal stromal cells (MSCs) are a potential therapeutic tool for pulmonary fibrosis. However, ex vivo MSC expansion using serum poses risks of harmful immune responses or unknown pathogen infections in the recipients. Therefore, MSCs cultured in serum-free media (SF-MSCs) are ideal for clinical settings; however, their efficacy in pulmonary fibrosis is unknown. Here, we investigated the effects of SF-MSCs on bleomycin-induced pulmonary inflammation and fibrosis compared to those of MSCs cultured in serum-containing media (S-MSCs). METHODS: SF-MSCs and S-MSCs were characterized in vitro using RNA sequence analysis. The in vivo kinetics and efficacy of SF-MSC therapy were investigated using a murine model of bleomycin-induced pulmonary fibrosis. For normally distributed data, Student's t test and one-way repeated measures analysis of variance followed by post hoc Tukey's test were used for comparison between two groups and multiple groups, respectively. For non-normally distributed data, Kruskal-Wallis and Mann-Whitney U tests were used for comparison between groups, using e Bonferroni's correction for multiple comparisons. All tests were two-sided, and P < 0.05 was considered statistically significant. RESULTS: Serum-free media promoted human bone marrow-derived MSC expansion and improved lung engraftment of intravenously administered MSCs in recipient mice. SF-MSCs inhibited the reduction in serum transforming growth factor-ß1 and the increase of interleukin-6 in both the serum and the bronchoalveolar lavage fluid during bleomycin-induced pulmonary fibrosis. SF-MSC administration increased the numbers of regulatory T cells (Tregs) in the blood and lungs more strongly than in S-MSC administration. Furthermore, SF-MSCs demonstrated enhanced antifibrotic effects on bleomycin-induced pulmonary fibrosis, which were diminished by antibody-mediated Treg depletion. CONCLUSIONS: SF-MSCs significantly suppressed BLM-induced pulmonary inflammation and fibrosis through enhanced induction of Tregs into the lungs and corrected the dysregulated cytokine balance. Therefore, SF-MSCs could be a useful tool for preventing pulmonary fibrosis progression without the demerits of serum use.

Gemcitabine maintenance therapy after gemcitabine and platinum drug chemotherapy for naive stage IIIB/IV squamous cell lung cancer: a phase II study.

Platinum doublet is the standard chemotherapy regimen for unresectable nonsmall-cell lung cancer (NSCLC) without a driver mutation. However, for squamous cell lung cancer, the most effective cytotoxic regimen is not yet established. Combination therapy of gemcitabine with a platinum agent is a highly effective treatment among the platinum doublet regimens and is promising as a treatment for advanced squamous cell lung carcinoma. In this study, we prospectively evaluated the efficacy of gemcitabine + platinum combination therapy followed by maintenance gemcitabine monotherapy in untreated advanced squamous cell lung cancer. Patients with squamous cell lung cancer received four cycles of gemcitabine + platinum combination therapy every 3 or 4 weeks. After the induction therapy, gemcitabine maintenance therapy was administered every 3 or 4 weeks until disease progression or unacceptable toxicity. Of 18 patients enrolled, the median progression-free survival was 3.9 months. Only six patients received maintenance chemotherapy with gemcitabine. The median survival time of all enrolled patients was 18.1 months. Cytopenia of any grade occurred in at least 70% of the enrolled patients. However, severe adverse events were observed in only a few cases. Gemcitabine maintenance therapy after gemcitabine plus platinum agents is a suggested treatment for unresectable squamous cell lung cancer. While the overall toxicity profile of this therapy is acceptable, attention should be paid to bone marrow suppression.

Extent of pulmonary fibrosis on high-resolution computed tomography is a prognostic factor in patients with pleuroparenchymal fibroelastosis.

BACKGROUND: Several prognostic factors for pleuroparenchymal fibroelastosis (PPFE) have recently been reported. However, detailed high-resolution computed tomography (HRCT) findings have not yet been evaluated as prognostic factors. This study retrospectively investigated whether HRCT findings are prognostic factors in patients with PPFE compared to those with idiopathic pulmonary fibrosis (IPF). METHODS: Patients with PPFE and IPF diagnosed at our hospital between January 2008 and December 2016 were enrolled. Clinical and HRCT characteristics were obtained. In addition to our patients, we also analyzed data of PPFE patients whose cause of death had been identified in previous studies. RESULTS: We enrolled 15 patients with PPFE and 75 patients with IPF. Consolidation and maximum pleural thickening were significantly higher in patients with PPFE than in those with IPF (both P < .001). Fibrosis score, honeycomb area, and traction bronchiectasis were not significantly different between these patient groups but were significant prognostic factors in patients with PPFE in univariate analysis (P = .021, P = .017, and P = .014, respectively). The proportions of deaths by acute exacerbation or lung cancer were significantly lower in patients with PPFE than in those with IPF (P < .001 and P = .001, respectively), whereas death by respiratory failure was significantly more frequent in PPFE patients (P < .001). CONCLUSIONS: HRCT findings, such as fibrosis score, honeycomb area, and traction bronchiectasis, were independent prognostic factors in patients with PPFE. Respiratory failure, but not acute exacerbation and lung cancer, was the main cause of death in patients with PPFE.

Pulmonary arteriovenous malformation exhibiting recanalization >10 years after coil embolization: Two case reports.

RATIONALE: Some patients with pulmonary arteriovenous malformation (PAVM) present with hypoxemia and life-threatening complications, including stroke and cerebral abscess. Catheter embolization is currently the preferred treatment for PAVM. However, previous studies have revealed that the incidence of PAVM recanalization is approximately 10% 5 to 7 years after embolization. In contrast, there are no studies where recanalization has occurred over 10 years after embolization. PATIENT CONCERNS: Herein, we report 2 cases diagnosed with cerebral embolism due to PAVM recanalization 13 years and 30 years after catheter treatment, in case I and II, respectively. DIAGNOSES: Both cases were diagnosed with PAVM recanalization on chest computed tomography (CT) examination performed after cerebral embolism development. Furthermore, pulmonary artery angiography revealed blood flow from the pulmonary artery to the vein in the PAVM, confirming PAVM recanalization. INTERVENTIONS: Coil re-embolization was performed for the all recanalized PAVM. OUTCOMES: All the target lesions were successfully re-embolized in both cases. However, in case I, the second recanalization of embolized PAVM was confirmed 1 year after coil re-embolization. Consequently, the third embolization was performed in case I. In contrast to case I, the patient in case II was followed up without recanalization for 2 years after embolization. LESSONS: We described the first 2 cases diagnosed with PAVM recanalization >10 years after the first catheter embolization. These cases suggest that patients with PAVMs should undergo life-long follow-up after catheter embolization.

High preoperative C-reactive protein level is a risk factor for acute exacerbation of interstitial lung disease after non-pulmonary surgery.

Several studies have investigated the incidence of and risk factors for acute exacerbation (AE) in patients with interstitial lung disease (ILD) after lung resection surgery. However, the incidence and risk factors for AE-ILD after non-pulmonary surgery are not known. The aim of this study was to investigate the incidence of and risk factors for AE-ILD after non-pulmonary surgery.Eighty patients who were diagnosed with ILD on preoperative chest computed tomography (CT) imaging and underwent non-pulmonary surgery under general anesthesia at Hiroshima University Hospital between September 2011 and September 2017 were enrolled. We retrospectively compared the preoperative patient characteristics, laboratory findings, and factors associated with anesthetic management between the patients who developed AE-ILD and those who did not.The incidence of AE-ILD after non-pulmonary surgery was 6.3% and the mortality rate was 80%. Univariate logistic analysis showed that a usual interstitial pneumonia pattern on computed tomography, a high C-reactive protein (CRP) level, a long operating time, high blood loss, and blood transfusion during surgery were significant risk factors for AE-ILD. In multivariate analysis, only a high CRP level (odds ratio 2.556, 95% confidence interval 1.110-5.889, P = .028) was identified as an independent risk factor for AE-ILD after non-pulmonary surgery.The risk of AE-ILD should be kept in mind in patients with ILD and a high CRP level before non-pulmonary surgery. These patients should also be monitored carefully for development of AE-ILD after surgery.