Decoding Bone Marrow Fibrosis in Myelodysplastic Syndromes

BackgroundBone marrow fibrosis (BMF), a poor prognostic factor in myelodysplastic syndromes (MDS), in the context of new risk stratifications of MDS has not been fully explored. We examined the relationship between BMF in MDS and survival outcomes, and explored the landscape of somatic gene mutations in the setting of BMF.Patients and MethodsWe retrospectively evaluated 2624 MDS patients for BMF who were divided into 2 groups: grade 0-2 BMF (96%) and severe/grade 3 BMF (4%) based on analysis presented. Commonly MDS tested acquired somatic mutations were also compared between those 2 groups of patients with available next-generation sequencing data.ResultsOnly grade 3 BMF was associated with worse overall survival independent from the Revised International Prognostic Scoring System (IPSS-R) (hazard ratio = 1.6; 95% confidence interval, 1.2-1.9; P < .005). More patients with severe BMF were classified as MDS-EB1 and -EB2 by the World Health Organization 2016 classification, a higher-risk International Prognostic Scoring System score, and a high/very high IPSS-R risk category than patients with grade 0-2 BMF. A complex karyotype, higher bone marrow myeloblasts, lower platelets, and higher rate of elevated lactate dehydrogenase were observed more often in patients with severe BMF. No differences in response to hypomethylating agents or lenalidomide were observed. Among somatic gene mutations tested in MDS, TP53 mutation and SETBP1 were more frequent in patients with grade 3 BMF.ConclusionThe presence of grade 3 BMF is associated with reduced overall survival independent from IPSS-R; however, BMF grade did not affect response to hypomethylating agent or lenalidomide treatment. TP53 and SETBP1 mutations occurred with greater frequency among patients with severe fibrosis.     

Oral-lung microbiome interactions in lung diseases

The proximity and continuity of the oral cavity and the lower respiratory tract allows the oropharyngeal microbiome to be a major determinant of the lung microbiome. In addition, host-pathogen interactions related to the oropharyngeal microbiome or its metabolites could propagate systemic inflammation or modulate host defense mechanisms that could affect other organs, including the lung. There is increasing appreciation of the pathophysiologic significance of the lung microbiome, not only in the classical infection-related diseases, pneumonia, bronchiectasis, and cystic fibrosis, but also in chronic noninfectious lung diseases, such as chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis. In this review, we will explore the relationship of the oral microbiome with lung diseases, such as pneumonia, chronic obstructive pulmonary disease, asthma, and cystic fibrosis.     

实时剪切波弹性成像在拉米夫定治疗乙肝纤维化过程中的疗效评估作用

目的探讨实时剪切波弹性成像在评估拉米夫定治疗乙肝纤维化临床疗效中的作用。方法选取2017年1月～2018年1月我院收治的80例乙肝纤维化患者,根据随机数字法分为对照组和观察组,每组40例。对照组采用常规治疗,观察组在对照组的基础上给予拉米夫定进行治疗,治疗6个月。比较两组治疗前后肝功能、肝纤维化指标,利用实时剪切波弹性成像评估两组治疗前后肝脏弹性模量值及肝穿刺活检情况,并进行比较。结果两组治疗后AST、ALT、TBIL水平均明显低于治疗前,差异有统计学意义(P0.05);观察组治疗后AST、ALT、TBIL水平均明显低于对照组,差异有统计学意义(P0.05);两组治疗后HA、LN、PⅢPN-P、CL-Ⅳ水平及杨氏弹性模量值均显著低于治疗前,差异有统计学意义(P0.05);观察组治疗后HA、LN、PⅢPN-P、CL-Ⅳ水平及杨氏弹性模量值均显著低于对照组,差异有统计学意义(P0.05);与治疗前相比,两组治疗后肝穿刺活检结果均有好转,尤其是汇管区、肝小叶内炎症及肝纤维化改善明显。结论实时剪切波弹性成像作为肝脏硬度定量检测的无创性技术,可用于拉米夫定治疗乙肝纤维化临床疗效评估的重要方法。     

CSF-1R inhibition attenuates ischemia-induced renal injury and fibrosis by reducing Ly6C+ M2-like macrophage infiltration

Acute kidney injury (AKI) to chronic kidney disease (CKD) progression has become a life-threatening disease. However, an effective therapeutic strategy is still needed. The pathophysiology of AKI-to-CKD progression involves chronic inflammation and renal fibrosis driven by macrophage activation, which is physiologically dependent on colony-stimulating factor-1 receptor (CSF-1R) signaling. In this study, we modulated macrophage infiltration through oral administration of the CSF-1R inhibitor GW2580 in an ischemia–reperfusion (I/R)-induced AKI model to evaluate its therapeutic effects on preventing the progression of AKI to CKD. We found that GW2580 induced a significant reduction in the number of macrophages in I/R-injured kidneys and attenuated I/R-induced renal injury and subsequent interstitial fibrosis. By flow cytometry, we observed that the reduced macrophages were primarily Ly6C⁺ inflammatory macrophages in the GW2580-treated kidneys, while there was no significant difference in the number and percentage of Ly6C⁻CX3CR1⁺ macrophages. We further found that these reduced macrophages also demonstrated some characteristics of M2-like macrophages, which have been generally regarded as profibrotic subtypes in chronic inflammation. These results indicate the existence of phenotypic and functional crossover between Ly6C⁺ and M2-like macrophages in I/R kidneys, which induces AKI worsening to CKD. In conclusion, therapeutic GW2580 treatment alleviates acute renal injury and subsequent fibrosis by reducing Ly6C⁺ M2-like macrophage infiltration in ischemia-induced AKI.     

经前侧入路达芬奇机器人辅助肺段切除术的临床分析

目的总结经前侧入路达芬奇机器人辅助肺段切除术治疗肺部结节的临床价值。方法回顾性分析2018年6月至2019年10月于我科行前侧入路达芬奇机器人辅助肺段切除术77例患者的临床资料,其中男22例、女55例,年龄53(30~71)岁。对患者症状、一般情况、术前影像学资料、切除肺段分布、手术时间、出血量、淋巴结清扫数、术后带管时间、引流量、术后住院时间、术后并发症以及围术期死亡等指标进行分析。结果所有患者均顺利完成手术,无中转开胸,无严重并发症,无围术期死亡。术后病理48例为早期肺癌,29例为良性肿瘤。机器人Docking时间4(1~30)min,机器人腔内操作时间76(30~170)min,出血量30(20~400)mL,术后胸腔闭式引流管引流时间4(2~15)d,术后总引流量780(200~3980)mL;术后住院时间7(3~19)d。结论经前侧入路机器人辅助肺段切除治疗肺部结节安全、便捷和有效,值得临床推广应用。