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Study Protocol of the Korean EGFR Registry: A Multicenter Prospective and Retrospective Cohort Study in Nonsmall Cell Lung Cancer Patients With EGFR Mutation. 韩国EGFR登记研究方案:EGFR突变的非小细胞肺癌患者的多中心前瞻性和回顾性队列研究。
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-01-01 DOI: 10.1111/crj.70043
Chang Dong Yeo, Dong Won Park, Seong Hoon Yoon, Eun Young Kim, Jeong Eun Lee, Shin Yup Lee, Chang-Min Choi, In-Jae Oh, Do Jin Kim, Jeong Seon Ryu, Jae Cheol Lee, Young-Chul Kim, Tae Won Jang, Kye Young Lee, Seung Hun Jang, Seung Joon Kim

Introduction: The provision of treatment for epidermal growth factor receptor (EGFR)-mutated nonsmall cell lung cancer (NSCLC) patients has increased in Korea. However, multicenter studies on the clinicopathologic dataset and treatment outcomes, using a large-scale dataset, have not been conducted. The current study is a prospective and retrospective multicenter observational cohort study that registers all stages of EGFR-mutated NSCLC patients.

Methods: The Korean EGFR Registry was designed to enroll 2000 patients with all stages of EGFR-mutated NSCLC from 40 university hospitals across Korea. This study, encompassing both retrospective and prospective cohorts, aims to analyze clinical characteristics, treatment modalities, and outcomes in these patients. Data collection will include patient demographics, smoking history, quality of life assessments, pathological data, and treatment outcomes, with follow-up until December 2026. The primary endpoint is disease-free survival in patients who have undergone radical therapy (surgery and radiotherapy) or progression-free survival in those receiving targeted therapy (first, second, and subsequent lines), chemotherapy (first and subsequent lines), combination therapy, and palliative/maintenance therapy according to stages of EGFR-mutated NSCLC. The study will explore the diagnostic methods for EGFR mutations, clinical outcomes based on treatment modalities, and metastatic patterns in EGFR-mutated NSCLC patients. Moreover, it will investigate various aspects, including the safety and efficacy of a new third-generation EGFR tyrosine kinase inhibitor (TKI), lazertinib, approved for both first- and second-line treatments.

Discussion: This study is expected to provide valuable insights into the epidemiology, risk factors, progression, and treatment outcomes of EGFR-mutated NSCLC in Korea. The Korean EGFR Registry will contribute significantly to the understanding of the complex dynamics of EGFR-mutated NSCLC, aiding in the development of more effective and personalized treatment strategies.

在韩国,对表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)患者的治疗增加了。然而,尚未使用大规模数据集对临床病理数据集和治疗结果进行多中心研究。目前的研究是一项前瞻性和回顾性的多中心观察队列研究,登记了所有阶段的egfr突变的非小细胞肺癌患者。方法:韩国EGFR登记处旨在从韩国40所大学医院招募2000名所有阶段的EGFR突变的非小细胞肺癌患者。本研究包括回顾性和前瞻性队列,旨在分析这些患者的临床特征、治疗方式和结果。数据收集将包括患者人口统计、吸烟史、生活质量评估、病理数据和治疗结果,随访至2026年12月。根据egfr突变的NSCLC的分期,主要终点是接受根治性治疗(手术和放疗)的患者的无病生存期或接受靶向治疗(一线、二线和后续线)、化疗(一线和后续线)、联合治疗和姑息/维持治疗的患者的无进展生存期。该研究将探讨EGFR突变的诊断方法、基于治疗方式的临床结果以及EGFR突变的NSCLC患者的转移模式。此外,它将研究各个方面,包括新的第三代EGFR酪氨酸激酶抑制剂(TKI) lazertinib的安全性和有效性,该抑制剂已被批准用于一线和二线治疗。讨论:本研究有望为韩国egfr突变的非小细胞肺癌的流行病学、危险因素、进展和治疗结果提供有价值的见解。韩国EGFR登记处将对了解EGFR突变的非小细胞肺癌的复杂动态做出重大贡献,有助于制定更有效和个性化的治疗策略。
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引用次数: 0
Significance of Combining Bronchoalveolar Lavage Fluid With Targeted Next-Generation Sequencing in the Pathogen Detection-Based Diagnosis of Pulmonary Infections. 支气管肺泡灌洗液联合靶向新一代测序在肺部感染病原体检测诊断中的意义。
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-01-01 DOI: 10.1111/crj.70046
Jiangbo Liu, Bo Yang, Yu Wu, Guihong Yang, Xiaojiu Zha, Wei Jiang

Objective: In this study, we investigated the application value of bronchoalveolar lavage fluid (BALF) combined with targeted next-generation sequencing (tNGS) in the pathogen detection-based diagnosis of patients with lung infections.

Method: A retrospective analysis was conducted on patients who underwent tracheoscopy and conventional microbiological tests (CMTs) on BALF, coupled with metagenomic next-generation sequencing (mNGS) or tNGS. This investigation encompassed individuals with suspected lung infections at Tianjin First Central Hospital from March 2023 to July 2023. Diagnostic rates based on pathogens detected via tNGS were compared with CMTs within the tNGS group. Additionally, diagnostic rates obtained through tNGS were compared with mNGS between the two groups.

Results: The data of a total of 169 patients (78 in the tNGS group and 91 in the mNGS group) were collected, and 145 patients (67 in the tNGS group and 78 in the mNGS group) were finally diagnosed with lung infections. The comprehensive positive pathogen detection-based diagnosis rate for tNGS was 86.6%, with a single-pathogen lung infection diagnosis rate of 85.7% and a mixed-pathogen pulmonary infection diagnosis rate of 88.0%. In contrast, the overall positive pathogen detection-based diagnosis rate for CMTs was 38.8%, comprising a single-pathogen pulmonary infection diagnosis rate of 28.6% and a mixed-pathogen pulmonary infection diagnosis rate of 20.0%. The difference in positive diagnosis rate was deemed statistically significant (p < 0.05). In the mNGS group, the overall pathogen detection-based diagnosis rate was 89.7%, with a single-pathogen pulmonary infection diagnosis rate of 84.9%, and a 100% diagnosis rate for mixed-pathogen pulmonary infections. There was no statistically significant difference in the positive diagnosis rate when compared with the tNGS group (p > 0.05).

Conclusion: In patients with pulmonary infections, the diagnosis rate based on BALF pathogen detection using tNGS exceeded that of CMTs, showing no statistically significant difference compared to mNGS.

目的:探讨支气管肺泡灌洗液(BALF)联合靶向新一代测序(tNGS)在肺部感染患者病原体检测诊断中的应用价值。方法:回顾性分析经气管镜检查和常规微生物检测(CMTs)联合新一代宏基因组测序(mNGS)或tNGS检测BALF的患者。该调查包括2023年3月至2023年7月在天津市第一中心医院疑似肺部感染的个体。通过tNGS检测病原体的诊断率与tNGS组内的cmt进行比较。此外,比较两组间通过tNGS和mNGS获得的诊断率。结果:共收集到169例患者的资料(tNGS组78例,mNGS组91例),最终诊断为肺部感染的患者145例(tNGS组67例,mNGS组78例)。基于综合阳性病原体检测的tNGS诊断率为86.6%,其中单一病原体肺部感染诊断率为85.7%,混合病原体肺部感染诊断率为88.0%。相比之下,cmt的总体阳性病原体检测诊断率为38.8%,其中单一病原体肺部感染诊断率为28.6%,混合病原体肺部感染诊断率为20.0%。阳性诊断率差异有统计学意义(p < 0.05)。结论:在肺部感染患者中,tNGS检测BALF病原体的诊断率高于CMTs,与mNGS比较无统计学差异。
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引用次数: 0
New Insights on Continuous Renal Replacement Therapy for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis. 持续肾脏替代治疗急性呼吸窘迫综合征的新见解:系统回顾和荟萃分析。
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-01-01 DOI: 10.1111/crj.70045
Siyao Zeng, Shanpeng Cui, Yue Li, Zhipeng Yao, Yunlong Li, Yang Cao, Lianghe Wen, Ming Li, Junbo Zheng, Hongliang Wang

Background: In recent times, the applications of continuous renal replacement therapy (CRRT) beyond kidney-related conditions have been progressively increasing, and its implementation in randomized controlled trials (RCTs) specifically for acute respiratory distress syndrome (ARDS) has been documented. This meta-analysis compiles all existing RCTs to assess whether CRRT benefits ARDS.

Methods: We searched 12 databases in English and Chinese and two clinical trial centers up to November 28, 2023. The main outcome indicator is the mortality rate. Secondary outcome indicators include incidence of ventilator-associated pneumonia (VAP), ICU length of stay, mechanical ventilation time, oxygenation index (OI) at 24 h (h), OI at 48 h, OI at 72 h, OI at 7 days (d), partial pressure of oxygen (PaO2) at 72 h, Acute Physiology and Chronic Health Evaluation II (APACHE II) score at 24 h, APACHE II score at 48 h, APACHE II score at 72 h, APACHE II score at 7 d, extravascular lung water indexes (EVLWI) at 72 h, TNF-α at 24 h, TNF-α at 7 d, IL-6 at 24 h, IL-6 at 48 h, IL-6 at 72 h, and IL-6 at 7 d. Statistical measures utilized include risk ratios (RR), weighted mean difference (WMD), and 95% confidence intervals (95% CI).

Results: We summarized 36 studies, including 2123 patients. It was found that for ARDS, using CRRT in addition to conventional therapy can reduce the mortality rate (I2 = 0%; RR: 0.40; 95% CI: 0.30-0.53; p < 0.01), the incidence of VAP (I2 = 0%; RR: 0.44; 95% CI: 0.33-0.59; p < 0.01), ICU length of stay, mechanical ventilation time, and EVLWI at 72 h, as well as APACHE II score, TNF-α, and IL-6 at various time points. Additionally, it can increase OI during different time intervals and PaO2 at 72 h.

Conclusions: Low-quality evidence suggests that compared with conventional therapy alone, the use of CRRT may be associated with a lower mortality rate, the incidence of VAP, ICU length of stay, mechanical ventilation time, EVLWI, APACHE II score, TNF-α, and IL-6 and may be related to better respiratory function. CRRT may be beneficial for ARDS patients. Future multicenter, well-designed, high-quality RCTs are needed to substantiate these findings.

背景:近年来,持续肾替代疗法(CRRT)在肾脏相关疾病以外的应用逐渐增加,并在急性呼吸窘迫综合征(ARDS)的随机对照试验(rct)中得到了证实。本荟萃分析汇编了所有现有的随机对照试验,以评估CRRT是否有益于ARDS。方法:检索截至2023年11月28日的12个中英文数据库和2个临床试验中心。主要的结果指标是死亡率。次要结局指标包括与机械通气相关肺炎(VAP)的发生率、ICU住院时间、机械通气时间、氧合指数(OI) 24小时(h),在48 h, OI OI 72 h, OI在7天(d),氧气分压(PaO2)在72 h,急性生理和慢性健康评估II (APACHE II)评分在24 h, APACHE II评分在48 h, APACHE II评分在72 h, APACHE II分数在7 d,肺血管外的水指数(EVLWI)在72 h,肿瘤坏死因子-α在24 h, TNF -α7 d,IL-6 24 h, IL-6 48 h, IL-6 72 h, IL-6 7 d。采用的统计方法包括风险比(RR)、加权平均差(WMD)和95%置信区间(95% CI)。结果:我们总结了36项研究,包括2123例患者。结果发现,对于ARDS,在常规治疗的基础上应用CRRT可降低死亡率(I2 = 0%;RR: 0.40;95% ci: 0.30-0.53;p 2 = 0%;RR: 0.44;95% ci: 0.33-0.59;72小时时的p2。结论:低质量证据表明,与单独使用常规治疗相比,CRRT的使用可能与更低的死亡率、VAP发生率、ICU住院时间、机械通气时间、EVLWI、APACHE II评分、TNF-α和IL-6有关,并可能与更好的呼吸功能有关。CRRT可能对ARDS患者有益。未来需要多中心、设计良好、高质量的随机对照试验来证实这些发现。
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引用次数: 0
Effect of Refined Nursing on Wound Complications After Thoracoscopic Surgery for Lung Cancer. 精细护理对肺癌胸腔镜术后创面并发症的影响。
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-01-01 DOI: 10.1111/crj.70039
Yanxia Dong, Guangqin Ma, Shuaishuai Wu, Shuling Zhang

Introduction: Lung cancer thoracoscopic postoperative wound complications bring great pain and inconvenience to patients.

Methods: To provide clinical nurses with a more scientific and effective nursing plan, this study evaluated the effect of refined nursing on wound complications after thoracoscopic surgery for lung cancer. Two-hundred thirty patients undergoing thoracoscopic radical resection for lung cancer were randomly divided into two groups according to the random number table method. The study group received refined nursing intervention (115 cases), and the control group received routine nursing intervention (115 cases). The effects of the two groups' nursing modes on the wound complications (pleural effusion, incision infection, lung leakage, and wound bleeding) after thoracoscopic surgery for lung cancer were compared.

Results: According to the study results, the study group experienced a shorter intraoperative blood loss, lower extubation time, shorter hospital stay, and lower wound complication rate than the control group (p < 0.05). Compared to the control group, the study group had significantly lower Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and visual analog scale (VAS) scores, and higher the short form 36 health survey questionnaire (SF-36) scores (p < 0.05).

Conclusion: Compared with the control group, the implementation of refined nursing intervention for patients with thoracoscopic radical resection of lung cancer has fewer postoperative wound complications and can improve patients' nursing satisfaction and quality of life, which is worthy of clinical promotion and application.

肺癌胸腔镜术后伤口并发症给患者带来极大的痛苦和不便。方法:为给临床护士提供更科学有效的护理方案,本研究评估了精细化护理对肺癌胸腔镜术后创面并发症的影响。采用随机数字表法将230例胸腔镜肺癌根治术患者随机分为两组。研究组采用精细化护理干预(115例),对照组采用常规护理干预(115例)。比较两组护理模式对肺癌胸腔镜术后创面并发症(胸腔积液、切口感染、肺漏、创面出血)的影响。结果:研究结果显示,研究组术中出血量、拔管时间、住院时间、伤口并发症发生率均低于对照组(p)。与对照组相比,对胸腔镜肺癌根治术患者实施精细化护理干预,术后创面并发症较少,可提高患者的护理满意度和生活质量,值得临床推广应用。
{"title":"Effect of Refined Nursing on Wound Complications After Thoracoscopic Surgery for Lung Cancer.","authors":"Yanxia Dong, Guangqin Ma, Shuaishuai Wu, Shuling Zhang","doi":"10.1111/crj.70039","DOIUrl":"https://doi.org/10.1111/crj.70039","url":null,"abstract":"<p><strong>Introduction: </strong>Lung cancer thoracoscopic postoperative wound complications bring great pain and inconvenience to patients.</p><p><strong>Methods: </strong>To provide clinical nurses with a more scientific and effective nursing plan, this study evaluated the effect of refined nursing on wound complications after thoracoscopic surgery for lung cancer. Two-hundred thirty patients undergoing thoracoscopic radical resection for lung cancer were randomly divided into two groups according to the random number table method. The study group received refined nursing intervention (115 cases), and the control group received routine nursing intervention (115 cases). The effects of the two groups' nursing modes on the wound complications (pleural effusion, incision infection, lung leakage, and wound bleeding) after thoracoscopic surgery for lung cancer were compared.</p><p><strong>Results: </strong>According to the study results, the study group experienced a shorter intraoperative blood loss, lower extubation time, shorter hospital stay, and lower wound complication rate than the control group (p < 0.05). Compared to the control group, the study group had significantly lower Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and visual analog scale (VAS) scores, and higher the short form 36 health survey questionnaire (SF-36) scores (p < 0.05).</p><p><strong>Conclusion: </strong>Compared with the control group, the implementation of refined nursing intervention for patients with thoracoscopic radical resection of lung cancer has fewer postoperative wound complications and can improve patients' nursing satisfaction and quality of life, which is worthy of clinical promotion and application.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 1","pages":"e70039"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016900","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
Bronchiectasis Exacerbation Increases the Risk of Adverse Renal Outcomes-Results From a Large Territory-Wide Cohort Study. 支气管扩张加剧增加肾脏不良后果的风险——来自一项大型区域性队列研究的结果。
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-01-01 DOI: 10.1111/crj.70029
Wang Chun Kwok, Chung Ki Tsui, Leung Sze Him Isaac, Chun Ka Emmanuel Wong, Terence Chi Chun Tam, James Chung Man Ho, Desmond Yat Hin Yap

Introduction: Bronchiectasis exacerbation (BE) is associated with unfavorable sequelae in other organs such as the cardiovascular system; data regarding its impact on adverse term renal outcomes, however, is lacking.

Methods: A territory-wide retrospective cohort study was conducted in Hong Kong between 1/1/1993 and 31/12/2017. All patients with bronchiectasis followed in the public healthcare system in 2017 were classified as "Exacerbators" or "Non-Exacerbators," and their adverse renal outcomes (renal progression [decrease in eGFR by 30 mL/min lasted for more than 12 months during follow up], acute kidney injury [AKI], and annual rate of eGFR decline) in the ensuing 7 years were compared. Results were also analyzed in the 1:1 propensity score matched (PSM) cohort.

Results: A total of 7929 patients (1074 "Exacerbators" group and 6855 "Non-exacerbators") were followed for 6.2 ± 1.6 years. A total of 1570 patients (19.8%) had renal progression, and 935 (11.8%) patients developed AKI. "Exacerbators" showed significantly increased risk of renal progression (adjusted odds ratio [aOR] 1. 27 [95% CI 1.08-1.50, p = 0.003]), more rapid eGFR decline (-3.67 [-1.74 to -6.54] vs. -3.03 [-1.56 to -5.12] mL/min/1.73 m2/year, p = 0.004) and AKI (aOR 1.99; 95% CI 1.44-2.73, p < 0.001) than the "Non-exacerbators." Annual number of BE was associated with renal progression (aOR 1.45; 95% CI 1.22-1.72, p < 0.001) and AKI (aOR 2.00; 95% CI 1.38-2.91, p < 0.001). Results were consistent in the analysis with the PSM cohort.

Conclusions: Renal progression and AKI are common among patients with bronchiectasis, and BE is an independent risk factor for adverse renal outcomes.

简介:支气管扩张加剧(BE)与其他器官如心血管系统的不良后遗症有关;然而,关于其对不良长期肾脏预后影响的数据缺乏。方法:于1993年1月1日至2017年12月31日在香港进行了一项区域性回顾性队列研究。2017年在公共卫生系统随访的所有支气管扩张患者被分类为“加重者”或“非加重者”,并比较他们在随后7年的不良肾脏结局(肾脏进展[随访期间eGFR下降30 mL/min持续超过12个月]、急性肾损伤[AKI]和eGFR年下降率)。结果也在1:1倾向评分匹配(PSM)队列中进行分析。结果:7929例患者(急性加重组1074例,非急性加重组6855例)共随访6.2±1.6年。共有1570例(19.8%)患者发生肾脏进展,935例(11.8%)患者发生AKI。“加重剂”显示肾脏进展的风险显著增加(调整优势比[aOR])。27 [95% CI 1.08-1.50, p = 0.003]), eGFR下降更快(-3.67[-1.74至-6.54]vs -3.03[-1.56至-5.12]mL/min/1.73 m2/年,p = 0.004)和AKI (aOR 1.99;结论:肾进展和AKI在支气管扩张患者中很常见,BE是肾脏不良结局的独立危险因素。
{"title":"Bronchiectasis Exacerbation Increases the Risk of Adverse Renal Outcomes-Results From a Large Territory-Wide Cohort Study.","authors":"Wang Chun Kwok, Chung Ki Tsui, Leung Sze Him Isaac, Chun Ka Emmanuel Wong, Terence Chi Chun Tam, James Chung Man Ho, Desmond Yat Hin Yap","doi":"10.1111/crj.70029","DOIUrl":"10.1111/crj.70029","url":null,"abstract":"<p><strong>Introduction: </strong>Bronchiectasis exacerbation (BE) is associated with unfavorable sequelae in other organs such as the cardiovascular system; data regarding its impact on adverse term renal outcomes, however, is lacking.</p><p><strong>Methods: </strong>A territory-wide retrospective cohort study was conducted in Hong Kong between 1/1/1993 and 31/12/2017. All patients with bronchiectasis followed in the public healthcare system in 2017 were classified as \"Exacerbators\" or \"Non-Exacerbators,\" and their adverse renal outcomes (renal progression [decrease in eGFR by 30 mL/min lasted for more than 12 months during follow up], acute kidney injury [AKI], and annual rate of eGFR decline) in the ensuing 7 years were compared. Results were also analyzed in the 1:1 propensity score matched (PSM) cohort.</p><p><strong>Results: </strong>A total of 7929 patients (1074 \"Exacerbators\" group and 6855 \"Non-exacerbators\") were followed for 6.2 ± 1.6 years. A total of 1570 patients (19.8%) had renal progression, and 935 (11.8%) patients developed AKI. \"Exacerbators\" showed significantly increased risk of renal progression (adjusted odds ratio [aOR] 1. 27 [95% CI 1.08-1.50, p = 0.003]), more rapid eGFR decline (-3.67 [-1.74 to -6.54] vs. -3.03 [-1.56 to -5.12] mL/min/1.73 m<sup>2</sup>/year, p = 0.004) and AKI (aOR 1.99; 95% CI 1.44-2.73, p < 0.001) than the \"Non-exacerbators.\" Annual number of BE was associated with renal progression (aOR 1.45; 95% CI 1.22-1.72, p < 0.001) and AKI (aOR 2.00; 95% CI 1.38-2.91, p < 0.001). Results were consistent in the analysis with the PSM cohort.</p><p><strong>Conclusions: </strong>Renal progression and AKI are common among patients with bronchiectasis, and BE is an independent risk factor for adverse renal outcomes.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 1","pages":"e70029"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967463","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
Explainable Machine Learning Predictions for the Benefit From Chemotherapy in Advanced Non-Small Cell Lung Cancer Without Available Targeted Mutations 无靶向突变的晚期非小细胞肺癌化疗获益的可解释机器学习预测
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-18 DOI: 10.1111/crj.70044
Zhao Shuang, Xiong Xingyu, Cheng Yue, Yu Mingjing

Background

Non-small cell lung cancer (NSCLC) is a global health challenge. Chemotherapy remains the standard therapy for advanced NSCLC without mutations, but drug resistance often reduces effectiveness. Developing more effective methods to predict and monitor chemotherapy benefits early is crucial.

Methods

We carried out a retrospective cohort study of NSCLC patients without targeted mutations who received chemotherapy at West China Hospital from 2009 to 2013. We identified variables associated with chemotherapy outcomes and built four predictive models by machine learning. Shapley additive explanations (SHAP) interpreted the best model's predictions. The Kaplan–Meier method assessed key variables' impact on 5-year overall survival.

Results

The study enrolled 461 NSCLC patients. Eight variables were selected for the model: differentiation, surgery history, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), total bilirubin (TBIL), total protein (TP), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH). The extreme gradient boosting (Xgboost) model exhibited superior discriminatory ability in predicting complete response (CR) probabilities to chemotherapy, with an AUC of 0.78. SHAP plots showed surgery history and high differentiation were related to CR benefits from chemotherapy. Absence of surgery, higher NLR, higher PLR, and higher LDH were all independent prognostic factors for poor survivals in NSCLC patients without mutations receiving chemotherapy.

Conclusions

By machine learning, we developed a predictive model to assess chemotherapy benefits in NSCLC patients without targeted mutations, utilizing eight readily available and non-invasive clinical indicators. Demonstrating satisfactory predictive performance and clinical practicability, this model may help clinicians identify patients' tendency to benefit from chemotherapy, potentially improving their prognosis.

背景:非小细胞肺癌(NSCLC)是一个全球性的健康挑战。化疗仍然是晚期非小细胞肺癌无突变的标准治疗方法,但耐药往往降低疗效。开发更有效的方法来早期预测和监测化疗的效果是至关重要的。方法:对2009 - 2013年在华西医院接受化疗的非靶向突变NSCLC患者进行回顾性队列研究。我们确定了与化疗结果相关的变量,并通过机器学习建立了四个预测模型。Shapley加性解释(SHAP)解释了最佳模型的预测。Kaplan-Meier方法评估了关键变量对5年总生存率的影响。结果:该研究纳入了461例非小细胞肺癌患者。模型选取了8个变量:分化、手术史、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、总胆红素(TBIL)、总蛋白(TP)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)。极端梯度增强(Xgboost)模型在预测化疗完全缓解(CR)概率方面表现出优越的判别能力,AUC为0.78。SHAP图显示手术史和高分化与化疗的CR获益有关。没有手术,更高的NLR,更高的PLR和更高的LDH都是接受化疗的非突变NSCLC患者生存不良的独立预后因素。结论:通过机器学习,我们开发了一个预测模型来评估无靶向突变的非小细胞肺癌患者的化疗益处,利用8个现成的非侵入性临床指标。该模型表现出令人满意的预测性能和临床实用性,可以帮助临床医生确定患者从化疗中获益的倾向,从而潜在地改善其预后。
{"title":"Explainable Machine Learning Predictions for the Benefit From Chemotherapy in Advanced Non-Small Cell Lung Cancer Without Available Targeted Mutations","authors":"Zhao Shuang,&nbsp;Xiong Xingyu,&nbsp;Cheng Yue,&nbsp;Yu Mingjing","doi":"10.1111/crj.70044","DOIUrl":"10.1111/crj.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Non-small cell lung cancer (NSCLC) is a global health challenge. Chemotherapy remains the standard therapy for advanced NSCLC without mutations, but drug resistance often reduces effectiveness. Developing more effective methods to predict and monitor chemotherapy benefits early is crucial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We carried out a retrospective cohort study of NSCLC patients without targeted mutations who received chemotherapy at West China Hospital from 2009 to 2013. We identified variables associated with chemotherapy outcomes and built four predictive models by machine learning. Shapley additive explanations (SHAP) interpreted the best model's predictions. The Kaplan–Meier method assessed key variables' impact on 5-year overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study enrolled 461 NSCLC patients. Eight variables were selected for the model: differentiation, surgery history, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), total bilirubin (TBIL), total protein (TP), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH). The extreme gradient boosting (Xgboost) model exhibited superior discriminatory ability in predicting complete response (CR) probabilities to chemotherapy, with an AUC of 0.78. SHAP plots showed surgery history and high differentiation were related to CR benefits from chemotherapy. Absence of surgery, higher NLR, higher PLR, and higher LDH were all independent prognostic factors for poor survivals in NSCLC patients without mutations receiving chemotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>By machine learning, we developed a predictive model to assess chemotherapy benefits in NSCLC patients without targeted mutations, utilizing eight readily available and non-invasive clinical indicators. Demonstrating satisfactory predictive performance and clinical practicability, this model may help clinicians identify patients' tendency to benefit from chemotherapy, potentially improving their prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856830","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
Concomitant ALK Fusion and TP53/EGFR Mutation Lead to Adverse Prognostic Outcome 伴随ALK融合和TP53/EGFR突变导致不良预后。
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-16 DOI: 10.1111/crj.70041
Mingyuan Du, Cuiwei Liu, Leichong Chen, Zhenyu Li, Sijia Zhang, Rui Meng

Lung cancer treatment has evolved at the molecular level. Detecting the presence of driver genes in lung cancer fundamentally alters the choice of therapeutic regimens and the outcome of this disease. ALK fusion mutation is one of the most important mutations in nonsmall cell lung cancer (NSCLC). Also, it often has other coexisting mutation types. TP53 is the most common coexisting mutation type, whereas the EGFR/ALK coexisting mutation type is extremely rare. There is still no definite conclusion about the impact of the multimutation and best treatment options for NSCLC patients with advanced multimutation. In this study, we report three cases of NSCLC with ALK fusion mutations as well as ALK combined with TP53 mutations and ALK combined with EGFR mutations. Combining cases from our oncology center and previous literature, we found that NSCLC patients with coexisting ALK fusion mutations and other mutations have poorer response to targeted therapy and poorer prognosis, and we also compared the efficacy rates of various types of coexisting mutations for different treatment regimens. Therefore, this review can help to evaluate the prognosis of NSCLC patients with coexisting mutations and the efficacy of targeted therapies and to find more favorable treatment options for patients with this type of coexisting mutations.

肺癌的治疗已经在分子水平上得到了发展。检测肺癌驱动基因的存在从根本上改变了治疗方案的选择和这种疾病的结果。ALK融合突变是非小细胞肺癌(NSCLC)中最重要的突变之一。此外,它经常有其他共存的突变类型。TP53是最常见的共存突变类型,而EGFR/ALK共存突变类型极为罕见。关于多突变的影响和晚期多突变NSCLC患者的最佳治疗方案仍没有明确的结论。在本研究中,我们报道了3例ALK融合突变、ALK合并TP53突变和ALK合并EGFR突变的NSCLC。结合我们肿瘤中心的病例和既往文献,我们发现同时存在ALK融合突变和其他突变的NSCLC患者对靶向治疗的反应较差,预后较差,我们也比较了不同类型共存突变在不同治疗方案下的有效率。因此,本综述有助于评估共存突变NSCLC患者的预后和靶向治疗的疗效,为这类共存突变患者寻找更有利的治疗方案。
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引用次数: 0
Dramatic Response to Ensartinib in Metastatic Neuroendocrine Tumors With a Novel CEP44-ALK Fusion: A Case Report and Literature Review 新型 CEP44-ALK 融合的转移性神经内分泌肿瘤对恩沙替尼的显著反应:病例报告和文献综述。
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-12 DOI: 10.1111/crj.70040
Haiyang Chen, Yingxi Wu, Xuan Wu, Kai Wang, Qingxin Xia, Qiming Wang

Neuroendocrine tumor (NET) is a deadly malignancy disease that can be found anywhere in the body. The lack of tumor-specific treatment led to the worse prognosis of NET. Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), such as alectinib and crizotinib, have been used in the treatment of NET patients with ALK rearrangement. However, the response to ensatinib in NET patients with rare ALK fusion has been rarely reported. Here, we report a 55-year-old Chinese female patient with NET (atypical carcinoid tumor) and a novel CEP44-ALK rearrangement identified by next-generation sequencing (NGS). NGS can provide more information on mutation landscape for rare neuroendocrine tumors to guide treatment and assist in clinical decisions by presenting molecular changes. The patient received ensartinib (225 mg/day) for 18 months until disease progression in June 2024 and achieved a radiographic partial response. Although patients with ALK fusions showed response to ensatinib in nonsmall cell lung cancer (NSCLC), this study first reports a metastatic NET case with a novel CEP44-ALK rearrangement that responded favorably to ensartinib.

神经内分泌肿瘤(NET)是一种可在身体任何部位发现的致命恶性肿瘤。缺乏肿瘤特异性治疗导致NET预后较差。间变性淋巴瘤激酶-酪氨酸激酶抑制剂(ALK- tkis),如阿勒替尼和克唑替尼,已被用于治疗ALK重排的NET患者。然而,罕见ALK融合的NET患者对恩沙替尼的反应很少有报道。在这里,我们报告了一位55岁的中国女性NET(非典型类癌)患者,通过下一代测序(NGS)发现了一种新的CEP44-ALK重排。NGS可以为罕见神经内分泌肿瘤提供更多的突变景观信息,通过分子变化来指导治疗和辅助临床决策。患者接受恩沙替尼(225mg /天)治疗18个月,直到2024年6月疾病进展,并获得放射学部分缓解。尽管ALK融合患者在非小细胞肺癌(NSCLC)中对恩沙替尼有反应,但本研究首次报道了一例转移性NET病例,该病例具有一种新的CEP44-ALK重排,对恩沙替尼有良好的反应。
{"title":"Dramatic Response to Ensartinib in Metastatic Neuroendocrine Tumors With a Novel CEP44-ALK Fusion: A Case Report and Literature Review","authors":"Haiyang Chen,&nbsp;Yingxi Wu,&nbsp;Xuan Wu,&nbsp;Kai Wang,&nbsp;Qingxin Xia,&nbsp;Qiming Wang","doi":"10.1111/crj.70040","DOIUrl":"10.1111/crj.70040","url":null,"abstract":"<p>Neuroendocrine tumor (NET) is a deadly malignancy disease that can be found anywhere in the body. The lack of tumor-specific treatment led to the worse prognosis of NET. Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), such as alectinib and crizotinib, have been used in the treatment of NET patients with ALK rearrangement. However, the response to ensatinib in NET patients with rare ALK fusion has been rarely reported. Here, we report a 55-year-old Chinese female patient with NET (atypical carcinoid tumor) and a novel CEP44-ALK rearrangement identified by next-generation sequencing (NGS). NGS can provide more information on mutation landscape for rare neuroendocrine tumors to guide treatment and assist in clinical decisions by presenting molecular changes. The patient received ensartinib (225 mg/day) for 18 months until disease progression in June 2024 and achieved a radiographic partial response. Although patients with ALK fusions showed response to ensatinib in nonsmall cell lung cancer (NSCLC), this study first reports a metastatic NET case with a novel CEP44-ALK rearrangement that responded favorably to ensartinib.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819986","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
Causal Association Between Monounsaturated Fatty Acids and Lung Cancer: A Two-Sample Mendelian Randomization Study 单不饱和脂肪酸与肺癌之间的因果关系:一项双样本孟德尔随机研究。
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-10 DOI: 10.1111/crj.70038
Shaofeng Zhang, Jia Jiang, Xiping Wu, Jiayi Liu, Wei Lei, Siqin Chen, Yaling Zeng, Xiang Liu, Qiang Xiao

Objective

This study aims to investigate the potential causal relationship between monounsaturated fatty acids (MUFAs) and lung cancer.

Methods

Genetic data on MUFAs and pathological subtypes of lung cancer were extracted from genome-wide association studies (GWAS). The primary analysis utilized inverse-variance weighted analysis (IVW), with additional methods including the weighted median method, MR-Egger regression method, and weighted model method. Sensitivity analysis was conducted to assess the robustness of the findings.

Results

The inverse variance–weighted (IVW) analysis of monounsaturated fatty acids in relation to lung adenocarcinoma yielded an odds ratio (OR) of 1.059 with a 95% confidence interval of 0.960 to 1.168 and a p value of 0.252. Similarly, for lung squamous cell carcinoma, the IVW analysis produced odd ratios of 0.884, 95% confidence intervals of 0.747 to 1.045, and a p value of 0.148. In the case of small cell lung cancer, the odds ratio was 0.936, the 95% confidence interval was 0.751 to 1.166, and the p value was 0.554.

Conclusion

It can be concluded that there is no direct causal relationship between monounsaturated fatty acids and the development of lung cancer.

目的:探讨单不饱和脂肪酸(MUFAs)与肺癌之间的潜在因果关系。方法:从全基因组关联研究(GWAS)中提取MUFAs与肺癌病理亚型的遗传数据。主要分析采用反方差加权分析(IVW),附加方法包括加权中位数法、MR-Egger回归法和加权模型法。进行敏感性分析以评估研究结果的稳健性。结果:单不饱和脂肪酸与肺腺癌相关的逆方差加权(IVW)分析得出优势比(OR)为1.059,95%置信区间为0.960 ~ 1.168,p值为0.252。同样,对于肺鳞状细胞癌,IVW分析的奇比为0.884,95%可信区间为0.747 ~ 1.045,p值为0.148。对于小细胞肺癌,比值比为0.936,95%可信区间为0.751 ~ 1.166,p值为0.554。结论:单不饱和脂肪酸与肺癌的发生无直接的因果关系。
{"title":"Causal Association Between Monounsaturated Fatty Acids and Lung Cancer: A Two-Sample Mendelian Randomization Study","authors":"Shaofeng Zhang,&nbsp;Jia Jiang,&nbsp;Xiping Wu,&nbsp;Jiayi Liu,&nbsp;Wei Lei,&nbsp;Siqin Chen,&nbsp;Yaling Zeng,&nbsp;Xiang Liu,&nbsp;Qiang Xiao","doi":"10.1111/crj.70038","DOIUrl":"10.1111/crj.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to investigate the potential causal relationship between monounsaturated fatty acids (MUFAs) and lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genetic data on MUFAs and pathological subtypes of lung cancer were extracted from genome-wide association studies (GWAS). The primary analysis utilized inverse-variance weighted analysis (IVW), with additional methods including the weighted median method, MR-Egger regression method, and weighted model method. Sensitivity analysis was conducted to assess the robustness of the findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The inverse variance–weighted (IVW) analysis of monounsaturated fatty acids in relation to lung adenocarcinoma yielded an odds ratio (OR) of 1.059 with a 95% confidence interval of 0.960 to 1.168 and a <i>p</i> value of 0.252. Similarly, for lung squamous cell carcinoma, the IVW analysis produced odd ratios of 0.884, 95% confidence intervals of 0.747 to 1.045, and a <i>p</i> value of 0.148. In the case of small cell lung cancer, the odds ratio was 0.936, the 95% confidence interval was 0.751 to 1.166, and the <i>p</i> value was 0.554.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>It can be concluded that there is no direct causal relationship between monounsaturated fatty acids and the development of lung cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808736","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
Rapid Response to Penpulimab Combined With Anlotinib and Chemotherapy in a Thoracic SMARCA4-UT Without PD-L1 Expression: A Case Report and Review of Literature Penpulimab联合Anlotinib和化疗对无PD-L1表达的胸部SMARCA4-UT的快速反应:1例报告和文献回顾
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2024-12-08 DOI: 10.1111/crj.70036
Yuanhang Wang, Kelei Zhao, Jingjing Zhang, Xiaohan Yuan, Yanting Liu, Jinghang Zhang, Ping Lu, Min Zhang

SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) in the chest is a high-grade malignant tumor that grows rapidly and often carries a poor prognosis. Unfortunately, there are currently no effective treatment available until now. Here, we report a case of SMARCA4-UT in a patient who showed a swift response to a combination treatment of penpulimab, anlotinib, and chemotherapy. A 55-year-old man was diagnosed with thoracic SMARCA4-UT along with metastases to multiple lymph nodes, the pleura, and bones. Immunohistochemical (IHC) testing indicated the absence of PD-L1 expression in tumor cells. He was given sintilimab and anlotinib as first line treatment. However, a follow-up chest CT revealed progressive disease (PD) after the first cycle treatment. Subsequently, the second line regimen was modified to etoposide and cisplatin (EP) combined with anlotinib and penpulimab. The effectiveness evaluation revealed partial remission (PR) following two cycles of the second-line regimen treatment. Notably, the patient's progress-free survival (PFS) exceeds 7 months and the overall survival up to 12 months. Our case implies that a combination of chemotherapy, anlotinib, and penpulimab might offer a promising therapeutic approach for PD-L1-negative thoracic SMARCA4-UT.

胸部smarca4缺陷未分化肿瘤(SMARCA4-UT)是一种生长迅速且预后差的高级别恶性肿瘤。不幸的是,目前还没有有效的治疗方法。在这里,我们报告了一例SMARCA4-UT患者,他对喷普利单抗、安洛替尼和化疗的联合治疗表现出迅速的反应。一名55岁男性被诊断为胸椎SMARCA4-UT,并伴有多发性淋巴结、胸膜和骨骼转移。免疫组化(IHC)检测显示肿瘤细胞中PD-L1表达缺失。给予辛替单抗和安洛替尼作为一线治疗。然而,随访胸部CT显示第一周期治疗后疾病进展(PD)。随后,二线方案被修改为依托泊苷和顺铂(EP)联合安洛替尼和彭普利单抗。有效性评估显示,经过两个周期的二线方案治疗后部分缓解(PR)。值得注意的是,患者的无进展生存期(PFS)超过7个月,总生存期长达12个月。我们的病例表明,化疗、安洛替尼和喷普利单抗联合治疗pd - l1阴性的胸部SMARCA4-UT可能是一种有希望的治疗方法。
{"title":"Rapid Response to Penpulimab Combined With Anlotinib and Chemotherapy in a Thoracic SMARCA4-UT Without PD-L1 Expression: A Case Report and Review of Literature","authors":"Yuanhang Wang,&nbsp;Kelei Zhao,&nbsp;Jingjing Zhang,&nbsp;Xiaohan Yuan,&nbsp;Yanting Liu,&nbsp;Jinghang Zhang,&nbsp;Ping Lu,&nbsp;Min Zhang","doi":"10.1111/crj.70036","DOIUrl":"10.1111/crj.70036","url":null,"abstract":"<p>SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) in the chest is a high-grade malignant tumor that grows rapidly and often carries a poor prognosis. Unfortunately, there are currently no effective treatment available until now. Here, we report a case of SMARCA4-UT in a patient who showed a swift response to a combination treatment of penpulimab, anlotinib, and chemotherapy. A 55-year-old man was diagnosed with thoracic SMARCA4-UT along with metastases to multiple lymph nodes, the pleura, and bones. Immunohistochemical (IHC) testing indicated the absence of PD-L1 expression in tumor cells. He was given sintilimab and anlotinib as first line treatment. However, a follow-up chest CT revealed progressive disease (PD) after the first cycle treatment. Subsequently, the second line regimen was modified to etoposide and cisplatin (EP) combined with anlotinib and penpulimab. The effectiveness evaluation revealed partial remission (PR) following two cycles of the second-line regimen treatment. Notably, the patient's progress-free survival (PFS) exceeds 7 months and the overall survival up to 12 months. Our case implies that a combination of chemotherapy, anlotinib, and penpulimab might offer a promising therapeutic approach for PD-L1-negative thoracic SMARCA4-UT.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796607","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
期刊
Clinical Respiratory Journal
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