Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non–Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors

IntroductionPneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non–small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those without, few data are available on the prognosis of those treated with PD-1 inhibitors who developed immune-related pneumonitis (IRP). Additionally, the robust risk factors of IRP have not been well elucidated.Patients and MethodsA retrospective review of patients with recurrent or advanced NSCLC who took a PD-1 inhibitor (nivolumab or pembrolizumab monotherapy) between January 2016 and March 2018 was undertaken. Radiologic findings such as unilateral infiltration were also defined as IRP as long as they were deemed relevant to PD-1 inhibitors.ResultsTwenty-seven (16%) of 170 patients developed IRP. Although 22 (81%) of 27 patients with IRP recovered with drug cessation with or without corticosteroid therapy, 8-week landmark analysis showed the overall survival after administration of the PD-1 inhibitor was significantly shorter in patients with IRP than in those without (8.7 vs. 23.0 months, P = .015). Patients with IRP tended to not receive next-line treatment and choose best supportive care after cessation of PD-1 inhibitor therapy. In the multivariate analysis, pembrolizumab (vs. nivolumab) and low serum albumin were independent risk factors for IRP.ConclusionDevelopment of IRP was correlated with poor prognosis in patients with NSCLC. Further study is necessary for establishing the best prediction and management strategies for IRP.     

Invasive pulmonary aspergillosis secondary to microwave ablation: a multicenter retrospective study

Purpose: Invasive pulmonary aspergillosis (IPA) is a life-threatening complication of microwave ablation (MWA) during the treatment of primary or metastatic lung tumors. The purpose of this study was to investigate the clinical, radiological and demographic characteristics and treatment responses of patients with IPA after MWA.

Materials and methods: From January 2011 to January 2016, all patients who were treated by MWA of their lung tumors from six health institutions were enrolled in this study. Patients with IPA secondary to MWA were identified and retrospectively evaluated for predisposing factors, clinical treatment, and outcome.

Results: The incidence of IPA secondary to lung MWA was 1.44% (23/1596). Of the 23 patients who developed IPA, six died as a consequence, resulting in a high mortality rate of 26.1%. Using computed tomography (CT), pulmonary cavitation was the most common finding and occurred in 87.0% (20/23) of the patients. Sudden massive hemoptysis was responsible for one-third of the deaths (2/6). Most patients (22/23) received voriconazole as an initial treatment, and six patients with huge cavities underwent intracavitary lavage. Finally, 17 patients (73.9%) achieved treatment success.

Conclusions: Lung MWA may be an additional host risk factor for IPA, particularly in elderly patients with underlying diseases and in patients who have recently undergone chemotherapy. Early and accurate diagnosis of IPA after MWA is critical for patient prognosis. Voriconazole should be given as the first-line treatment as early as possible. Bronchial artery embolization or intracavitary lavage may be required in some patients.     

Progress in clinical trial of histone deacetylase （HDAC） inhibitors for non-small cell lung cancers

Histone deacetylase （HDAC） inhibitors, which represent a structurally diverse group of molecules, have emerged as a novel therapeutic class of molecules with significant anticancer potential. Vorinostat and romidepsin, known as the first generation of HDAC inhibitors, were approved in the United States for the treatment of T-cell lymphomas. Preliminary activity of HDAC inhibitors has also been observed in non-small cell lung cancer （NSCLC） in combination with the existing treatment regimens, of which is the focus of the current review.     

Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

B cell and B cell-related pathways for novel cancer treatments

B cells are recognized as the main effector cells of humoral immunity which suppress tumor progression by secreting immunoglobulins, promoting T cell response, and killing cancer cells directly. Given these properties, their anti-tumor immune response in the tumor micro-environment (TME) is of great interest. Although T cell-related immune responses have become a therapeutic target with the introduction of immune checkpoint inhibitors, not all patients benefit from these treatments. B cell and B cell-related pathways (CCL19, −21/CCR7 axis and CXCL13/CXCR5 axis) play key roles in activating immune response through humoral immunity and local immune activation via tertiary lymphoid structure (TLS) formation. However they have some protumorigenic works in the TME. Thus, a better understanding of B cell and B cell-related pathways is necessary to develop effective cancer control. In this review, we summarize recent evidences regarding the roles of B cell and B cell-related pathways in the TME and immune response and discuss their potential roles for novel cancer treatment strategies.     

Lung age is related to carotid structural alterations in hypertensive subjects

Hypertensive patients exhibit higher cardiovascular risk and reduced lung function compared with the general population. Whether this association stems from the coexistence of two highly prevalent diseases or from direct or indirect links of pathophysiological mechanisms is presently unclear. This study investigated the association between lung function and carotid features in non-smoking hypertensive subjects with supposed normal lung function. Hypertensive patients (n = 67) were cross-sectionally evaluated by clinical, hemodynamic, laboratory, and carotid ultrasound analysis. Forced vital capacity, forced expired volume in 1 second and in 6 seconds, and lung age were estimated by spirometry. Subjects with ventilatory abnormalities according to current guidelines were excluded. Regression analysis adjusted for age and prior smoking history showed that lung age and the percentage of predicted spirometric parameters associated with common carotid intima-media thickness, diameter, and stiffness. Further analyses, adjusted for additional potential confounders, revealed that lung age was the spirometric parameter exhibiting the most significant regression coefficients with carotid features. Conversely, plasma C-reactive protein and matrix-metalloproteinases-2/9 levels did not influence this relationship. The present findings point toward lung age as a potential marker of vascular remodeling and indicate that lung and vascular remodeling might share common pathophysiological mechanisms in hypertensive subjects.     

Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine

The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of “multilevel cycle” helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results.     

肺泡表面活性物质联合鼻塞式持续气道正压通气治疗早产儿肺透明膜病的应用研究

目的 分析早产儿肺透明膜病经肺泡表面活性物质联合鼻塞式持续气道正压通气治疗的效果。方法 选取黄山市人民医院2014年11月-2017年11月收治的肺透明膜病早产儿50例,依据不同治疗方法分为两组,24例施予鼻塞式持续气道正压通气治疗者为对照组,26例予以肺泡表面活性物质联合鼻塞式持续气道正压通气治疗者为试验组,比较两组血气分析指标、呼吸力学与并发症发生情况。结果 治疗后,试验组血氧饱和度(SpO₂)、血氧分压(PaO₂)、二氧化碳分压(PaCO₂)、氢离子浓度指数(pH)优于对照组,且试验组呼吸时间常数(RCexp)、呼气峰流量(PEF)均较对照组高,差异均有统计学意义(P均<0.05);试验组并发症发生率为低于对照组(7.69% vs. 28.00%),差异有统计学意义(P<0.05)。结论 通过肺泡表面活性物质联合鼻塞式持续气道正压通气治疗早产儿肺透明病,可有效改善其血气分析指标,并提升RCexp、PEF,达到减少并发症、改善预后的效果,值得推广。