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Chest X-Ray Comparison Between Drug-Resistant and Drug-Sensitive Pulmonary Tuberculosis in Children 儿童耐药性肺结核与药物敏感性肺结核胸部 X 光片比较
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-09-25 DOI: 10.1111/crj.70010
Saffanah Az Zuhriyyah, Harry Galuh Nugraha, Djatnika Setiabudi, Prayudi Santoso, Heda Melinda Nataprawira

Introduction

Chest X-ray (CXR) remains one of the tools used in diagnosing tuberculosis (TB). However, few studies about such tools exist, specifically in children in Indonesia. We aim to investigate and compare the CXR findings of children with pulmonary drug-resistant TB (DR-TB) and drug-sensitive TB (DS-TB) that could help in the evaluation and management of TB cases in children.

Methods

Retrospective analysis with cross-sectional approach was conducted in children (<18 years old) diagnosed with pulmonary DR-TB and DS-TB from January 2018 to December 2021. Documented data were collected from the Paediatric Respirology Registry and Tuberculosis Information System at Dr. Hasan Sadikin General Hospital Bandung. Characteristics of children, CXR findings, and TB severity were assessed and compared using the chi-square and Fisher's exact tests with significance levels set at p value <0.05.

Results

Sixty-nine children (DR-TB 31 children vs. DS-TB 38 children) were assessed. Of the 31 children with DR-TB, 65% were classified as multidrug-resistant TB (MDR-TB), followed by rifampicin-resistant TB (RR-TB), pre-extensively drug-resistant TB (pre-XDR-TB), and extensively drug-resistant TB (XDR-TB). The most common CXR findings in DR-TB are consolidation (68%), fibrosis (42%), and cavity (29%), whereas in DS-TB, it is pleura effusion (37%). Severe TB accounts for 50% of DR-TB (p = 0.008).

Conclusions

Consolidation, fibrosis, cavities, and findings of severe TB are most common in DR-TB. Pleural effusion is the most common in DS-TB. These findings have the potential to be considered in further examination of children with pulmonary DR-TB and DS-TB; hence, more extensive studies are needed to confirm these results.

导言 胸部 X 光(CXR)仍然是诊断肺结核(TB)的工具之一。然而,有关此类工具的研究很少,尤其是针对印度尼西亚儿童的研究。我们旨在调查和比较耐药肺结核(DR-TB)和药敏肺结核(DS-TB)患儿的胸部 X 光检查结果,以帮助评估和管理儿童肺结核病例。 方法 对 2018 年 1 月至 2021 年 12 月期间诊断为肺部 DR-TB 和 DS-TB 的儿童(<18 岁)进行横断面回顾性分析。记录数据来自万隆哈桑-萨迪金博士综合医院的儿科呼吸内科登记处和结核病信息系统。采用卡方检验(chi-square)和费雪精确检验(Fisher's exact)对儿童特征、CXR结果和结核病严重程度进行评估和比较,显著性水平设定为P值<0.05。 结果 共评估了 69 名儿童(DR-TB 31 名,DS-TB 38 名)。在31名DR-TB患儿中,65%被归类为耐多药结核病(MDR-TB),其次是耐利福平结核病(RR-TB)、前广泛耐药结核病(pre-XDR-TB)和广泛耐药结核病(XDR-TB)。在 DR-TB 中,最常见的 CXR 检查结果是合并症(68%)、纤维化(42%)和空洞(29%),而在 DS-TB 中则是胸腔积液(37%)。重症肺结核占 DR-TB 的 50%(P = 0.008)。 结论 合并、纤维化、空洞和重症肺结核在 DR-TB 中最为常见。胸腔积液在 DS-TB 中最为常见。在对肺部 DR-TB 和 DS-TB 儿童进行进一步检查时,有可能会考虑到这些结果;因此,需要进行更广泛的研究来证实这些结果。
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引用次数: 0
Detection of the Fatty Acid Metabolism-Linked Genes in Lung Adenocarcinoma as Biomarkers for Clinical Prognosis and Immunotherapeutic Targets 检测肺腺癌中的脂肪酸代谢相关基因,作为临床预后和免疫治疗靶点的生物标记物
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-09-25 DOI: 10.1111/crj.70013
Jingwei Shi, Rusong Yang, Xinyi Jiang, Kangle Zhu, Zhengcheng Liu

Background

Lung cancer, on a global scale, leads to the most common cases of cancer mortalities. Novel therapeutic approaches are urgently needed to disrupt this lethal disease. The rapid development of tumor immunology combining breakthroughs involving fatty acid metabolism brings possibilities. Directing fatty acid metabolism is supposed to help discover potential prognostic biomarkers and treatment targets for lung cancer.

Methods

Through searching the GSE140797 dataset, we identified genes related to fatty acid metabolism as well as fatty acid metabolism-related differentially expressed genes (DEGs). We applied various methods to ascertain the independent prognostic value of the DEGs. The methods we utilized entail prognostic analysis, differential expression analysis, as well as univariate and multivariate Cox regression analyses. The lasso Cox regression model was utilized in examining how DEGs correlate with the immune score, immune checkpoint, ferroptosis, methylation, and OCLR score. The expression levels of ACAT1 and ACSL3 in tissues derived from normal lung and lung adenocarcinoma (LUAD) tissues were compared by qRT-PCR.

Results

In this study, ACSL3 and ACAT1 were identified as fatty acid metabolism-related genes utilizing independent prognostic value and as a result, the risk prognostic model was built using these factors. qRT-PCR results implied that ACSL3 and ACAT1 expressions were upregulated and downregulated, correspondingly in tumor tissues. Additional evaluations suggested that ACSL3 and ACAT1 were affirmed to be remarkably correlated with the immune score, methylation, immune checkpoint, OCLR score, and ferroptosis.

Conclusions

ACSL3 and ACAT1 were effective prognostic biomarkers and potential immunotherapeutic targets in LUAD.

背景肺癌在全球范围内导致最常见的癌症死亡病例。目前迫切需要新的治疗方法来阻断这一致命疾病。肿瘤免疫学的快速发展与脂肪酸代谢方面的突破相结合,带来了各种可能性。引导脂肪酸代谢有助于发现肺癌的潜在预后生物标志物和治疗靶点。 方法 通过搜索 GSE140797 数据集,我们发现了与脂肪酸代谢相关的基因以及与脂肪酸代谢相关的差异表达基因(DEGs)。我们采用了多种方法来确定 DEGs 的独立预后价值。我们采用的方法包括预后分析、差异表达分析以及单变量和多变量 Cox 回归分析。在研究 DEGs 与免疫评分、免疫检查点、铁突变、甲基化和 OCLR 评分的相关性时,我们使用了 lasso Cox 回归模型。通过 qRT-PCR 技术比较了 ACAT1 和 ACSL3 在正常肺组织和肺腺癌(LUAD)组织中的表达水平。 结果 本研究发现,ACSL3 和 ACAT1 是具有独立预后价值的脂肪酸代谢相关基因,因此利用这些因子建立了风险预后模型。其他评估结果表明,ACSL3 和 ACAT1 与免疫评分、甲基化、免疫检查点、OCLR 评分和铁变态反应显著相关。 结论 ACSL3 和 ACAT1 是 LUAD 的有效预后生物标志物和潜在免疫治疗靶点。
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引用次数: 0
Is It Time to (Re)define the N-Category for Metastatic Lymph Nodes in Non–Small Cell Lung Cancer? 是时候(重新)定义非小细胞肺癌转移淋巴结的 N 分类了吗?
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-09-25 DOI: 10.1111/crj.70016
Koen C. H. A. Verkoulen, Jean H. T. Daemen, Aimée J. P. M. Franssen, Juliette H. R. J. Degens, Karel W. E. Hulsewé, Yvonne L. J. Vissers, Erik R. de Loos
<p>In a recent issue of <i>The Clinical Respiratory Journal</i>, Guo et al. published a study that evaluated the correlation between the rate and number of resected metastatic lymph nodes and survival in patients undergoing an anatomical resection for non–small cell lung cancer (NSCLC) [<span>1</span>]. To date, nodal staging is key in the work-up and treatment guidance for NSCLC as it is an important determinant of survival [<span>2, 3</span>]. As opposed to some other cancer types, nodal staging for lung cancer is based on the anatomic location of the respective regional and mediastinal lymph node stations rather than the number of metastasis [<span>4-6</span>]. Hence, the ongoing debate concerning the potential prognostic value of the number and rate of lymph node metastases in NSCLC continues. Over the last decade, numerous studies have aimed to address this issue [<span>7-10</span>]. However, they are generally limited by their retrospective design and inherent bias, as well as methodological disparity [<span>11</span>]. How does the current report add to the evidence collected for over more than a decade?</p><p>Guo et al. carried out the first population-based study concerning this subject. They revealed that both the number and rate of positive lymph nodes after lymphadenectomy concomitant to an anatomical lung parenchyma resection are a predictor for overall survival, independent of the anatomical location of the nodal station that is affected, being either N1 or N2. These results are in line with prior retrospective studies and a recently published meta-analysis [<span>8, 10, 12</span>]. However, the number and rate of metastatic lymph nodes was only examined in postoperative patients that underwent lymphadenectomy, in whom the lymph nodes were completely dissected (defined as examination of more than 15 dissected lymph nodes) instead of biopsied stations. Thus, these results are only applicable as a prognostic tool and in treatment decision-making processes for postoperative patients. To be of an even greater importance for treatment plan composition, for example, one should repeat this study for preoperative clinical lymph node staging (cTNM) using minimally invasive staging techniques like endosonographic lymph node staging (EUS/EBUS) or surgical video-assisted mediastinoscopy (VAM) or video-assisted mediastinoscopic lymphadenectomy (VAMLA). However, a recent publication showed in a noninferiority study that VAMLA might not be of added value in patients that underwent systemic EUS/EBUS [<span>13</span>]. Additionally, VAM/VAMLA or EUS is mainly used to assess N2 nodes. Hence, the vast majority of metastatic N1 nodes cannot be evaluated through these techniques. These drawbacks illustrate the challenges of the current TNM classification, and lymph node staging, especially for clinical lymph node staging. The sensitivity of preoperative lymph node staging modalities like (PET)-CT scan and EUS/EBUS ranges from 20% to 70%, resulting in a
欧洲和美国的术前淋巴结分期指南存在差异。修订后的欧洲胸外科医师协会纵隔分期指南建议至少清扫 4L-R 和 7 号淋巴结[20],而美国胸科医师学会指南则建议至少清扫 2L-R、4L-R 和 7 号淋巴结[21]。包括荷兰指南在内的一些国家指南甚至没有明确指出应切除的具体部位[22]。Guo 等人建议至少清扫 16 个检查淋巴结,并排除了 16 个检查淋巴结的患者。但另一项研究建议切除 10 个淋巴结,而不是 Guo 等人提出的 16 个[7]。另一项研究发现,在解剖性肺切除术中,如果切除的淋巴结越多,生存率越高[23]。相反,根据一项荟萃分析[24],迄今为止,淋巴结清扫比取样更有利于提高总生存率。因此,这些研究报告中关于解剖肺切除术中淋巴结检查的差异导致了术中淋巴结清扫的混乱。日常实践也凸显了这种不一致;从荷兰全国肺癌审计中可以推断出,只有少数患者的术中淋巴结取样是根据指南进行的[25]。要实现这种重新定义,就必须在淋巴结分期方面制定更少异质性、更精确的国际指南,并尽可能遵守和报告这些指南。改变 TNM 分期可能与临床相关,并有助于未来的研究工作。在第 9 版 TNM 分类系统中,国际肺癌研究协会提出了不同的概念,如前面提到的结节区概念以及淋巴结转移的数量和确切位置[11]。这些概念的整合可能会成为更适合患者的治疗方法,从而获得更好的生存结果。无论 TNM 分类的 N 描述符是否会改变,提高现行指南的标准化程度并遵守这些指南,都将是朝着改进结节分期和适合患者的治疗模式方向迈出的良好的第一步。由于这是一篇特邀社论,没有使用任何人类或动物数据,因此本稿件草案不适用伦理审批或患者/动物同意书。作者对工作的所有方面负责,确保与工作任何部分的准确性或完整性有关的问题得到妥善调查和解决。作者无利益冲突需要声明,他们都为本手稿的撰写做出了贡献。
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引用次数: 0
Comparison Between Endobronchial-Guided Transbronchial Biopsy and Computed Tomography–Guided Transthoracic Lung Biopsy for the Diagnosis of Central Pulmonary Lesions 支气管内引导经支气管活检与计算机断层扫描引导经胸肺活检在诊断肺中心病变方面的比较
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-09-24 DOI: 10.1111/crj.70015
Cheng Zhang, Senlin Zhu, Yanliang Yuan, Shenhui Dai

Background

Lung cancer is one of the most common malignant tumors at present. This study aimed to compare the diagnostic accuracy, complication rates, and predictive values of computed tomography (CT)–guided percutaneous transthoracic needle biopsy (PTNB) and electronic bronchoscopy–guided transbronchial lung biopsy (TBLB) for patients with central pulmonary lesions (CPLs) with a diameter ≥ 3 cm.

Methods

We retrospectively included 110 patients with CPLs with a diameter ≥ 3 cm who underwent preoperative PTNB and TBLB examinations and ultimately underwent surgery to remove CPLs and obtained pathological results. Detailed information was collected in order to compare whether there was a difference between two groups. Data were processed using SPSS software (Version 26.0; IBM Corp). Data were compared by t-test or chi-square test. p < 0.05 was considered statistically significant.

Results

All patients underwent surgical treatment at the department of thoracic surgery and obtained a final pathological diagnosis. The rate of positive predictive value (PPV) was comparable between the two methods, and the negative predictive value (NPV) was significantly higher in the PTNB group compared with the TBLB group (p < 0.05). In addition, PTNB was more sensitive and accurate than TBLB (p < 0.05). However, the PTNB group had a higher probability of complications, and TBLB was a relatively safer examination method.

Conclusion

PTNB demonstrated a higher accuracy and sensitivity than TBLB in the treatment of CPLs with a diameter ≥ 3 cm, but the complication rates of PTNB are relatively high. These methods exhibited different diagnostic accuracies and therefore should be selected based on different medical conditions.

背景:肺癌是目前最常见的恶性肿瘤之一:肺癌是目前最常见的恶性肿瘤之一。本研究旨在比较计算机断层扫描(CT)引导下经皮经胸针活检(PTNB)和电子支气管镜引导下经支气管肺活检(TBLB)对直径≥3 厘米的肺中心病变(CPLs)患者的诊断准确性、并发症发生率和预测值:我们回顾性地纳入了 110 例直径≥ 3 cm 的 CPL 患者,这些患者在术前接受了 PTNB 和 TBLB 检查,最终接受了手术切除 CPL 并获得了病理结果。收集详细信息是为了比较两组之间是否存在差异。数据使用 SPSS 软件(26.0 版;IBM 公司)处理。数据比较采用 t 检验或卡方检验:所有患者均在胸外科接受手术治疗,并获得最终病理诊断。两种方法的阳性预测值(PPV)率相当,与 TBLB 组相比,PTNB 组的阴性预测值(NPV)明显更高(P 结论:PTNB 显示出更高的准确性和阴性预测值:在治疗直径≥ 3 厘米的 CPL 时,PTNB 的准确性和灵敏度均高于 TBLB,但 PTNB 的并发症发生率相对较高。这些方法表现出不同的诊断准确性,因此应根据不同的病情进行选择。
{"title":"Comparison Between Endobronchial-Guided Transbronchial Biopsy and Computed Tomography–Guided Transthoracic Lung Biopsy for the Diagnosis of Central Pulmonary Lesions","authors":"Cheng Zhang,&nbsp;Senlin Zhu,&nbsp;Yanliang Yuan,&nbsp;Shenhui Dai","doi":"10.1111/crj.70015","DOIUrl":"10.1111/crj.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung cancer is one of the most common malignant tumors at present. This study aimed to compare the diagnostic accuracy, complication rates, and predictive values of computed tomography (CT)–guided percutaneous transthoracic needle biopsy (PTNB) and electronic bronchoscopy–guided transbronchial lung biopsy (TBLB) for patients with central pulmonary lesions (CPLs) with a diameter ≥ 3 cm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively included 110 patients with CPLs with a diameter ≥ 3 cm who underwent preoperative PTNB and TBLB examinations and ultimately underwent surgery to remove CPLs and obtained pathological results. Detailed information was collected in order to compare whether there was a difference between two groups. Data were processed using SPSS software (Version 26.0; IBM Corp). Data were compared by <i>t</i>-test or chi-square test. <i>p</i> &lt; 0.05 was considered statistically significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All patients underwent surgical treatment at the department of thoracic surgery and obtained a final pathological diagnosis. The rate of positive predictive value (PPV) was comparable between the two methods, and the negative predictive value (NPV) was significantly higher in the PTNB group compared with the TBLB group (<i>p</i> &lt; 0.05). In addition, PTNB was more sensitive and accurate than TBLB (<i>p</i> &lt; 0.05). However, the PTNB group had a higher probability of complications, and TBLB was a relatively safer examination method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PTNB demonstrated a higher accuracy and sensitivity than TBLB in the treatment of CPLs with a diameter ≥ 3 cm, but the complication rates of PTNB are relatively high. These methods exhibited different diagnostic accuracies and therefore should be selected based on different medical conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 9","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Linoleic Acid Promotes Mitochondrial Biogenesis and Alleviates Acute Lung Injury 亚油酸促进线粒体生物生成并缓解急性肺损伤
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-09-23 DOI: 10.1111/crj.70004
Jie Liu, Yu Jiang, Qiuhong Zhang, Yin Qin, Kexin Li, Yu Xie, Tingting Zhang, Xiaoliang Wang, Xi Yang, Li Zhang, Gang Liu

Introduction

Acute lung injury (ALI) is a critical and lethal medical condition. This syndrome is characterized by an imbalance in the body's oxidation stress and inflammation. Linoleic acid (LA), a polyunsaturated fatty acid, has been extensively studied for its potential health benefits, including anti-inflammatory and antioxidant activities. However, the therapeutic effects of LA on ALI remain unexplored.

Methods

Lipopolysaccharide (LPS), found in gram-negative bacteria's outer membrane, was intraperitoneally injected to induce ALI in mice. In vitro model was established by LPS stimulation of mouse lung epithelial 12 (MLE-12) cells.

Results

LA treatment demonstrated a significant amelioration in LPS-induced hypothermia, poor state, and pulmonary injury in mice. LA treatment resulted in a reduction in the concentration of bronchoalveolar lavage fluid (BALF) protein and an increase in myeloperoxidase (MPO) activity in LPS-induced mice. LA treatment reduced the generation of white blood cells. LA treatment reduced cell-free (cfDNA) release and promote adenosine triphosphate (ATP) production. LA increased the levels of superoxide dismutase (SOD) and glutathione (GSH) but decreased the production of malondialdehyde (MDA). LA treatment enhanced mitochondrial membrane potential. LA attenuated LPS-induced elevations of inflammatory cytokines in both mice and cells. Additionally, LA exerted its protective effect against LPS-induced damage through activation of the peroxisome proliferator-activated receptor γ coactivator l alpha (PGC-1α)/nuclear respiratory factor 1 (NRF1)/transcription factor A of the mitochondrion (TFAM) pathway.

Conclusion

LA may reduce inflammation and stimulate mitochondrial biogenesis in ALI mice and MLE-12 cells.

简介急性肺损伤(ALI)是一种严重的致命性疾病。这种综合征的特点是体内氧化压力和炎症失衡。亚油酸(LA)是一种多不饱和脂肪酸,因其潜在的健康益处,包括抗炎和抗氧化活性,已被广泛研究。然而,亚油酸对 ALI 的治疗效果仍有待探索:方法:腹腔注射革兰氏阴性细菌外膜中的脂多糖(LPS)诱发小鼠 ALI。通过 LPS 刺激小鼠肺上皮细胞 12(MLE-12)建立体外模型:结果:LA治疗明显改善了LPS诱导的小鼠低体温、不良状态和肺损伤。在 LPS 诱导的小鼠中,LA 治疗导致支气管肺泡灌洗液(BALF)蛋白浓度降低,髓过氧化物酶(MPO)活性升高。LA 治疗减少了白细胞的生成。LA 可减少细胞游离 DNA(cfDNA)的释放,促进三磷酸腺苷(ATP)的产生。LA 增加了超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的水平,但减少了丙二醛(MDA)的产生。LA 可增强线粒体膜电位。LA 可减轻 LPS 诱导的小鼠和细胞炎症细胞因子的升高。此外,LA 通过激活过氧化物酶体增殖激活受体 γ 辅激活因子 l alpha(PGC-1α)/核呼吸因子 1(NRF1)/线粒体转录因子 A(TFAM)途径,对 LPS 诱导的损伤发挥保护作用:LA可减轻ALI小鼠和MLE-12细胞的炎症反应并刺激线粒体的生物生成。
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引用次数: 0
Immunotherapy Improves the Survival of Stage 4 Non–Small Cell Lung Cancer Patients at the US Population Level: The Real-World Evidence 免疫疗法提高了美国非小细胞肺癌 4 期患者的生存率:真实世界的证据
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-09-14 DOI: 10.1111/crj.70000
Yuxuan Wei, Rui Zhang, Ruikang Yin, Shijie Wang, Jianglong Han, Ruyan Chen, Zhenming Fu

Introduction

Immunotherapy has revolutionized the management of lung cancer and improved lung cancer survival in trials, but its real-world impact at the population level remains unclear.

Methods

Using data obtained from eight Surveillance, Epidemiology, and End Results (SEER) registries from 2004 through 2019, we addressed the long-term trends in the incidence, incidence-based mortality (IBM), and survival of lung cancer patients in the United States.

Results

The incidence and IBM of both non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) all significantly decreased steadily from 2004 to 2019. The 1-year survival (1-YS) of both NSCLC and SCLC improved over time, with the best improvement observed for Stage 4 NSCLC. Two significant turning points of Stage 4 NSCLC 1-YS were observed over the years: 0.63% (95% confidence interval [CI]: 0.33%–0.93%) from 2004 to 2010, 0.81% (95% CI: 0.41%–1.21%) from 2010 to 2014 and a striking 2.09% (95% CI: 1.70%–2.47%) from 2014 to 2019. The same two turning points in 1-YS were pronounced for Stage 4 NSCLC in women, which were coincident with the introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immunotherapy. However, for Stage 4 NSCLC in men, only one significant turning point in the 1-YS starting in 2014 was found, which might only correspond to immunotherapy. Significant period effects in reduced IBM were also observed for both Stage 4 AD and Stage 4 SQCC during the period.

Conclusion

This SEER analysis found that immunotherapy improved the survival of Stage 4 NSCLC patients at the population level in the United States. This real-world evidence confirms that immunotherapy has truly revolutionized the management of lung cancer.

引言 免疫疗法在肺癌治疗方面带来了革命性的变化,并在试验中提高了肺癌的生存率,但其在人群中的实际影响仍不清楚。 方法 我们利用从 2004 年到 2019 年的 8 个监测、流行病学和最终结果(SEER)登记处获得的数据,研究了美国肺癌患者的发病率、基于发病率的死亡率(IBM)和生存率的长期趋势。 结果 从 2004 年到 2019 年,非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)的发病率和 IBM 均显著稳步下降。随着时间的推移,非小细胞肺癌和小细胞肺癌的 1 年生存率(1-YS)都有所提高,其中第 4 期非小细胞肺癌的提高幅度最大。多年来,NSCLC 四期的 1 年生存率出现了两个重要转折点:2004年至2010年为0.63%(95%置信区间[CI]:0.33%-0.93%),2010年至2014年为0.81%(95%置信区间:0.41%-1.21%),2014年至2019年为惊人的2.09%(95%置信区间:1.70%-2.47%)。1-YS的两个转折点同样明显地出现在女性NSCLC四期患者中,这两个转折点与表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)和免疫疗法的引入相吻合。然而,在男性 NSCLC 4 期患者中,只发现了一个从 2014 年开始的 1-YS 显著转折点,这可能只与免疫疗法有关。在此期间,4 期 AD 和 4 期 SQCC 也观察到了 IBM 降低的显著时期效应。 结论 SEER 的这项分析发现,在美国,免疫疗法在人群水平上提高了 NSCLC 4 期患者的生存率。这一真实世界的证据证实,免疫疗法确实为肺癌的治疗带来了革命性的变化。
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引用次数: 0
Atezolizumab-Induced Immune-Related Pneumonia on Rounded Atelectasis 阿特珠单抗诱发的圆形气胸免疫相关肺炎
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-09-03 DOI: 10.1111/crj.70008
Satoru Yanagisawa, Takaya Yui, Hiroki Takechi, Satoshi Wasamoto
<p>Dear editor:</p><p>An 82-year-old man with a heavy smoking history (35 pack-years) was diagnosed with right upper lung small cell lung cancer (extensive-disease, cT1cN3M1c: cStage IVB, LYM, OSS, HEP) in June 2023. He was a retired electrician who had been exposed to construction dust and asbestos fibers for decades. Chest computed tomography (CT) revealed partially calcified pleural plaques and posterior left lower lobe rounded atelectasis (RA) with “comet tail sign” [<span>1</span>] (Figure 1A,B). Retrospectively, the RA appeared to remain the same shape and size since 2017. Positron emission tomography revealed <sup>18</sup>F-fluorodeoxyglucose uptake in the right upper lobe primary tumor, but not in the pleural plaque or RA (Figure 1C–E). Subsequently, the patient was treated with carboplatin/etoposide plus atezolizumab as first-line chemotherapy in July 2023. Soon after atezolizumab infusion, he developed a transient fever; thereafter, he gradually complained of worsening dyspnea on exertion, with mild desaturation. On day 9 after chemotherapy induction, chest CT showed a new-onset consolidative shadow on the left lower lung that appeared around the preexisting RA (Figure 2A,B). The laboratory test results, including infectious serology and culture results, were unremarkable. Additional inflammatory serologies (antinuclear and antineutrophil cytoplasmic antibodies) were negative. Due to hypoxemia, further diagnostic studies, such as bronchoscopy, could not be conducted. We suspected that the lesion was consistent with atezolizumab-induced interstitial lung disease (immune-related adverse event [irAE]) and started intravenous prednisolone (40 mg daily). After the initiation of steroid treatment, his hypoxemia and lung shadow were almost completely cleared (Figure 2C,D), which supported the diagnosis of irAE pneumonia in RA. We decided to refrain from atezolizumab treatment and continued carboplatin/etoposide therapy alone without recurrence of irAEs.</p><p>RA [<span>2</span>], also known as “folded lung” or “Blesovsky's syndrome,” is a subtype of lung atelectasis caused by invagination of the redundant visceral pleura [<span>3</span>]. Although most RA are believed to be associated with asbestos lung exposure [<span>4</span>], it is sometimes difficult to differentiate RA from other asbestos exposure-associated malignant diseases such as lung cancer and malignant pleural mesothelioma [<span>5</span>]. RA usually maintains the same volume and even shrinks on serial scans [<span>4-6</span>], which supports the benign feature of the lesion and justifies careful follow-up without intervention. However, there are some reports of RA that gradually enlarge and eventually necessitate surgical biopsy or excision [<span>7</span>]. Although the precise mechanism of RA enlargement is yet to be elucidated, persistent chronic pleural inflammation may be associated. In our case, subpleural consolidation around the RA expanded after the initiation of atezo
亲爱的编辑:一位有严重吸烟史(35 包年)的 82 岁男性于 2023 年 6 月被诊断为右上肺小细胞肺癌(广泛病变,cT1cN3M1c:c IVB 期,LYM,OSS,HEP)。他是一名退休电工,数十年来一直接触建筑粉尘和石棉纤维。胸部计算机断层扫描(CT)显示部分钙化胸膜斑块和左下叶后部圆形脑积水(RA),并伴有 "彗尾征"[1](图 1A、B)。回想起来,自2017年以来,RA的形状和大小似乎保持不变。正电子发射断层扫描显示右上叶原发肿瘤摄取18F-氟脱氧葡萄糖,但胸膜斑块或RA未摄取18F-氟脱氧葡萄糖(图1C-E)。随后,患者于2023年7月接受了卡铂/依托泊苷加阿特珠单抗的一线化疗。输注阿特珠单抗后不久,他出现了一过性发热;此后,他逐渐主诉劳累时呼吸困难加重,并伴有轻度饱和度降低。化疗诱导后第9天,胸部CT显示左下肺出现新发合并影,出现在原有RA周围(图2A,B)。实验室检查结果,包括感染血清学和培养结果,均无异常。其他炎症血清学检查(抗核抗体和抗中性粒细胞胞浆抗体)均为阴性。由于低氧血症,无法进行进一步的诊断检查,如支气管镜检查。我们怀疑该病变与阿特珠单抗诱发的间质性肺病(免疫相关不良事件[irAE])一致,并开始静脉注射泼尼松龙(每天40毫克)。开始类固醇治疗后,他的低氧血症和肺部阴影几乎完全消失(图2C,D),这支持了RAirAE肺炎的诊断。RA[2]又称 "折叠肺 "或 "Blesovsky综合征",是由多余的内脏胸膜内陷引起的肺大泡的一种亚型[3]。虽然大多数 RA 被认为与石棉肺暴露有关[4],但有时很难将 RA 与其他与石棉暴露有关的恶性疾病(如肺癌和恶性胸膜间皮瘤)区分开来[5]。在连续扫描中,RA 的体积通常保持不变,甚至会缩小[4-6],这支持了病变的良性特征,因此有理由在不进行干预的情况下进行仔细随访。不过,也有一些 RA 逐渐增大,最终需要手术活检或切除的报道[7]。虽然 RA 扩大的确切机制尚未阐明,但持续的慢性胸膜炎症可能与此有关。在我们的病例中,开始使用阿特珠单抗治疗后,RA 周围的胸膜下合并症扩大,可能是 RA 周围的胸膜损伤导致了虹膜急性外膜炎肺炎的发生。Sakata 等人报道了滑石粉胸膜穿刺术后发生的 nivolumab 诱导的严重间质性肺炎[8]。他们推测,nivolumab 可能夸大了滑石粉诱导的胸膜间皮细胞损伤,化学炎症最终导致了严重的间质性肺炎。尽管石棉相关的RA通常被认为是一种陈旧性炎症改变,但它可能是一种潜伏期,有可能在使用免疫检查点抑制剂(ICIs)后发作。总之,这是一例阿特珠单抗诱发的irAE肺炎,发生在一名RA患者身上。由于石棉暴露与 RA 相关,因此适当诊断药物诱导的肺炎非常重要,因为这可能会夸大已存在的 RA。此外,在接受 ICIs 治疗后,与 RA 相关的胸膜炎症可能会变得明显。所有作者均审阅了本稿件,并同意提交本稿件。
{"title":"Atezolizumab-Induced Immune-Related Pneumonia on Rounded Atelectasis","authors":"Satoru Yanagisawa,&nbsp;Takaya Yui,&nbsp;Hiroki Takechi,&nbsp;Satoshi Wasamoto","doi":"10.1111/crj.70008","DOIUrl":"10.1111/crj.70008","url":null,"abstract":"&lt;p&gt;Dear editor:&lt;/p&gt;&lt;p&gt;An 82-year-old man with a heavy smoking history (35 pack-years) was diagnosed with right upper lung small cell lung cancer (extensive-disease, cT1cN3M1c: cStage IVB, LYM, OSS, HEP) in June 2023. He was a retired electrician who had been exposed to construction dust and asbestos fibers for decades. Chest computed tomography (CT) revealed partially calcified pleural plaques and posterior left lower lobe rounded atelectasis (RA) with “comet tail sign” [&lt;span&gt;1&lt;/span&gt;] (Figure 1A,B). Retrospectively, the RA appeared to remain the same shape and size since 2017. Positron emission tomography revealed &lt;sup&gt;18&lt;/sup&gt;F-fluorodeoxyglucose uptake in the right upper lobe primary tumor, but not in the pleural plaque or RA (Figure 1C–E). Subsequently, the patient was treated with carboplatin/etoposide plus atezolizumab as first-line chemotherapy in July 2023. Soon after atezolizumab infusion, he developed a transient fever; thereafter, he gradually complained of worsening dyspnea on exertion, with mild desaturation. On day 9 after chemotherapy induction, chest CT showed a new-onset consolidative shadow on the left lower lung that appeared around the preexisting RA (Figure 2A,B). The laboratory test results, including infectious serology and culture results, were unremarkable. Additional inflammatory serologies (antinuclear and antineutrophil cytoplasmic antibodies) were negative. Due to hypoxemia, further diagnostic studies, such as bronchoscopy, could not be conducted. We suspected that the lesion was consistent with atezolizumab-induced interstitial lung disease (immune-related adverse event [irAE]) and started intravenous prednisolone (40 mg daily). After the initiation of steroid treatment, his hypoxemia and lung shadow were almost completely cleared (Figure 2C,D), which supported the diagnosis of irAE pneumonia in RA. We decided to refrain from atezolizumab treatment and continued carboplatin/etoposide therapy alone without recurrence of irAEs.&lt;/p&gt;&lt;p&gt;RA [&lt;span&gt;2&lt;/span&gt;], also known as “folded lung” or “Blesovsky's syndrome,” is a subtype of lung atelectasis caused by invagination of the redundant visceral pleura [&lt;span&gt;3&lt;/span&gt;]. Although most RA are believed to be associated with asbestos lung exposure [&lt;span&gt;4&lt;/span&gt;], it is sometimes difficult to differentiate RA from other asbestos exposure-associated malignant diseases such as lung cancer and malignant pleural mesothelioma [&lt;span&gt;5&lt;/span&gt;]. RA usually maintains the same volume and even shrinks on serial scans [&lt;span&gt;4-6&lt;/span&gt;], which supports the benign feature of the lesion and justifies careful follow-up without intervention. However, there are some reports of RA that gradually enlarge and eventually necessitate surgical biopsy or excision [&lt;span&gt;7&lt;/span&gt;]. Although the precise mechanism of RA enlargement is yet to be elucidated, persistent chronic pleural inflammation may be associated. In our case, subpleural consolidation around the RA expanded after the initiation of atezo","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 9","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bronchoscopic Interventional Therapy Combined With Pembrolizumab in the Treatment of Pulmonary Large Cell Neuroendocrine Carcinoma: A Case Report 支气管镜介入疗法联合 Pembrolizumab 治疗肺大细胞神经内分泌癌:病例报告。
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-09-03 DOI: 10.1111/crj.70009
Yingyi Fan, Yingying Wang, Yanrong Ji, Shuang Li, Jian Zhang, Xingliang Hao

This study reports a significant clinical outcome following the use of bronchoscopic interventional therapy combined with pembrolizumab for treating pulmonary large cell neuroendocrine carcinoma (LCNEC), showcasing a novel approach in managing this aggressive cancer.

这项研究报告了使用支气管镜介入疗法联合 pembrolizumab 治疗肺大细胞神经内分泌癌(LCNEC)后取得的显著临床疗效,展示了一种治疗这种侵袭性癌症的新方法。
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引用次数: 0
Analysis of Depression and Anxiety Scores Following Initiation of Elexacaftor/Tezacaftor/Ivacaftor in Adults With Cystic Fibrosis 囊性纤维化成人患者开始使用 Elexacaftor/Tezacaftor/Ivacaftor 后的抑郁和焦虑评分分析
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-08-29 DOI: 10.1111/crj.70007
Harish Pudukodu, Margret Z. Powell, Agathe Ceppe, Scott H. Donaldson, Jennifer L. Goralski, Nathaniel A. Sowa

Objective

Elexacaftor/tezacaftor/ivacaftor (E/T/I) has provided life-changing pharmacotherapy for many people with cystic fibrosis (CF), but conflicting literature exists regarding the effect on mental health. While some reports suggest E/T/I may induce adverse psychiatric symptoms, others report improvements in mental health symptoms. To add to this growing body of knowledge, we retrospectively analyzed depression and anxiety symptoms before and after E/T/I initiation in adults with CF at a single large US CF center.

Method

Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores recorded in a database were studied. Patients with scores collected before and after E/T/I initiation were included. Regression analyses described associations between score changes and age, race, ethnicity, sex, CFTR variant, and prior depression and/or anxiety diagnoses. Secondary analyses examined possible confounding effects of the COVID-19 pandemic.

Results

There was no change in mean GAD-7 (0.5 ± 5.3, p = 0.41) or PHQ-9 (−0.02 ± 6.0, p = 0.97) scores following initiation of E/T/I (N = 86). A trend between a prior diagnosis of depression and worsening in PHQ-9 post-E/T/I was observed (OR 3.58; p = 0.054).

Conclusions

Treatment with E/T/I does not lead to changes in depression or anxiety symptoms at the population level in this single center cohort study. A prior diagnosis of depression trended towards an increased odds of worsening PHQ-9 scores after E/T/I initiation.

目的 Elexacaftor/tezacaftor/ivacaftor(E/T/I)为许多囊性纤维化(CF)患者提供了改变生活的药物治疗,但关于其对心理健康的影响,存在相互矛盾的文献。一些报告显示 E/T/I 可能会诱发不良精神症状,而另一些报告则显示精神健康症状有所改善。为了增加这方面的知识,我们在美国一家大型 CF 中心对成年 CF 患者开始使用 E/T/I 前后的抑郁和焦虑症状进行了回顾性分析。 方法 对数据库中记录的患者健康问卷-9(PHQ-9)和广泛性焦虑症-7(GAD-7)评分进行研究。研究对象包括在使用 E/T/I 之前和之后收集到分数的患者。回归分析描述了分数变化与年龄、种族、民族、性别、CFTR 变体以及既往抑郁和/或焦虑诊断之间的关联。二次分析研究了 COVID-19 大流行可能造成的混杂影响。 结果 在开始使用 E/T/I 后,GAD-7(0.5 ± 5.3,p = 0.41)或 PHQ-9 (-0.02 ± 6.0,p = 0.97)平均得分没有变化(N = 86)。E/T/I治疗后,先前的抑郁症诊断与PHQ-9恶化之间存在趋势(OR 3.58; p = 0.054)。 结论 在这项单中心队列研究中,E/T/I 治疗不会导致人群抑郁或焦虑症状发生变化。既往诊断为抑郁症的患者在开始使用 E/T/I 后 PHQ-9 评分恶化的几率呈上升趋势。
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引用次数: 0
A methylation-related lncRNA-based prediction model in lung adenocarcinomas 基于甲基化相关 lncRNA 的肺腺癌预测模型
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-08-26 DOI: 10.1111/crj.13753
Kun Yang, Hao Liu, Jun Hai Li
<div> <section> <h3> Background</h3> <p>The collaboration between methylation and the lung adenocarcinoma (LUAD) occurrence and development is closes. Long noncoding RNA (lncRNA), as a regulatory factor of various biological functions, can be used for cancer diagnosis. Our study aimed to construct a robust methylation-related lncRNA signature of LUAD.</p> </section> <section> <h3> Methods</h3> <p>In the Cancer Genome Atlas (TCGA) dataset, we download the RNA expression data and clinical information of LUAD cases. To develop the best prognostic signature based on methylation-related lncRNAs, Cox regression analyses were utilized. Using Kaplan–Meier analysis, overall survival rates were compared between risk category included both low- and high-risk patients. To categorize genes according to their functional significance, GSEA (Subramanian et al, 2005) was used. Single-sample gene set enrichment analysis (ssGSEA) was used to further reveal the potential molecular mechanism of the methylation-related lncRNA prognostic model in immune infiltration. Using TRLnc (http://www.licpathway.net/TRlnc) and lncRNASNP to analyse the SNP sites and TRLnc of these 18 lncRNAs. LncSEA website was used to analyse 18 lncRNA in the process of tumour development and development. Go was used to analyse the enriched pathways enriched by TFs (transcription factors), Cerna networks, and proteins bound to each other of these 18 lncRNAs. The ‘prophetic’ package was used to analyse the value of this prognostic model in guiding personalized immunotherapy.</p> </section> <section> <h3> Results</h3> <p>In this study, we identified 18 methylation-related lncRNAs (AP002761.1, AL118558.3, CH17-340M24.3, AL353150.1, AC004687.1, LINC00996, AF186192.1, HSPC324, AC087752.3, FAM30A, AC106047.1, AC026355.1, ABALON, LINC01843, AL606489.1, NKILA, AP001453.2, GSEC) to establish a methylation-related lncRNA signature that can detect patients prognosis in LUAD. The enriched pathways enriched by proteins interacting with 18 lncRNAs are mainly EMT, hypoxia, stemness and proliferation, among which LINC00996 and AF186192.1 are regulated by multiple tumour associated transcription factors, such as TP53 and TP63, and fam30a and mRNA form a Cerna network. There are 2319 SNP loci in LINC00996, 36 of which are risk SNP loci and 205 SNP loci in af186192.1; AF186192.1 affects 95 conserved miRNAs and 123 non-conserved miRNAs, promotes the binding of 149 pairs of miRNAs: lncRNAs and inhibits the binding of 95 pairs of miRNAs: lncRNAs. The ROC curve demonstrated that the established methylation-related lncRNA signature was more effective in predicting the prognosis of patients in LUAD than the clinicopatholog
背景:甲基化与肺腺癌(LUAD)的发生和发展之间的关系已接近尾声。长非编码 RNA(lncRNA)作为多种生物功能的调控因子,可用于癌症诊断。我们的研究旨在构建与甲基化相关的LUAD lncRNA特征:在癌症基因组图谱(TCGA)数据集中,我们下载了LUAD病例的RNA表达数据和临床信息。为了建立基于甲基化相关lncRNA的最佳预后特征,我们采用了Cox回归分析。通过Kaplan-Meier分析,比较了不同风险类别(包括低风险和高风险患者)的总生存率。为了根据基因的功能意义对其进行分类,采用了 GSEA(Subramanian 等人,2005 年)。单样本基因组富集分析(ssGSEA)被用来进一步揭示甲基化相关lncRNA预后模型在免疫浸润中的潜在分子机制。利用TRLnc(http://www.licpathway.net/TRlnc)和lncRNASNP分析这18个lncRNA的SNP位点和TRLnc。利用 LncSEA 网站分析肿瘤发生和发展过程中的 18 个 lncRNA。Go 用于分析这 18 个 lncRNA 的 TF(转录因子)、Cerna 网络和相互结合的蛋白质所富集的通路。预言 "软件包用于分析这一预后模型在指导个性化免疫疗法方面的价值:在这项研究中,我们发现了18个与甲基化相关的lncRNA(AP002761.1、AL118558.3、CH17-340M24.3、AL353150.1、AC004687.1、LINC00996、AF186192.1、HSPC324、AC087752.3、FAM30A、AC106047.1、AC026355.1、ABALON、LINC01843、AL606489.1、NKILA、AP001453.2、GSEC)来建立一个甲基化相关的lncRNA特征,以检测LUAD患者的预后。与18个lncRNA相互作用的蛋白质所富集的通路主要是EMT、缺氧、干性和增殖,其中LINC00996和AF186192.1受TP53和TP63等多种肿瘤相关转录因子调控,fam30a与mRNA形成Cerna网络。LINC00996中有2319个SNP位点,其中36个为风险SNP位点,af186192.1中有205个SNP位点;AF186192.1影响95个保守miRNA和123个非保守miRNA,促进149对miRNA:lncRNA的结合,抑制95对miRNA:lncRNA的结合。ROC曲线显示,已建立的甲基化相关lncRNA特征在预测LUAD患者预后方面比临床病理参数更有效。我们的研究证实,基于甲基化相关lncRNA的风险评分模型分出的高危组患者的OS较短。根据GSEA,高危组主要富集了肿瘤和免疫相关通路。ssGSEA显示,LUAD患者的预测特征与免疫状态之间存在明显关联。此外,主成分分析(PCA)证明了我们的特征具有预后和预测价值。甲基化相关lncRNA预测特征与常规化疗药物IC50之间的相关性可为LUAD患者提供个性化的化疗方案。甲基化相关lncRNA特征能有效预测LUAD患者的DFS。
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Clinical Respiratory Journal
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