Clinical Respiratory Journal最新文献_第9页

Radiological and clinical features of large consolidative-type pulmonary invasive mucinous adenocarcinoma 大面积合并型肺浸润性黏液腺癌的放射学和临床特征。

IF 1.7 4区医学 Q3 Medicine

Clinical Respiratory Journal

Pub Date : 2024-03-26 DOI: 10.1111/crj.13743

Jiaqi Chen, Linlin Qi, Jianwei Wang, Liyan Xue, Qi Xue, Jia Jia, Guochao Zhang, Jianing Liu, Fenglan Li, Shulei Cui

Background

This study aimed to investigate the radiological, pathological, and prognostic characteristics of large consolidative-type pulmonary invasive mucinous adenocarcinomas (IMA).

Methods

We retrospectively reviewed 738 patients who confirmed IMA between January 2010 and August 2022, and two radiologists reviewed imaging data to determine subtypes. We included 41 patients with pathologically large consolidative-type IMA. We analyzed their radiological, pathological, and prognostic characteristics. The recurrence-free survival (RFS) and overall survival (OS) were determined using the Kaplan–Meier method.

Results

Most lesions were located in the lower lobe, with 46.3% patients showing multiple lesions. Halo, angiogram, vacuole, air bronchogram, and dead branch sign were observed in 97.6%, 73.2%, 63.4%, 61.0%, and 61.0% of the cases, respectively. Unevenly low enhancement was observed in 88.89% of patients. T3 and T4 pathological stages were observed in 50.0% and 30.6% of patients, respectively. Lymph node metastasis was observed in 16.7% patients, with no distant metastasis. Spread-through air spaces and intrapulmonary dissemination were observed in 27.8% and 19.4% patients, respectively. Moreover, Kirsten rat sarcoma viral oncogene mutations were found in 68.6% of cases, and no epidermal growth factor receptor mutations were seen. Among all mutation sites, G12V mutation is the most common, accounting for 40%. The average RFS and OS were 19.4 and 66.4 months, respectively, with 3-year RFS and OS rates of 30.0% and 75.0%, respectively. Pleural invasion and lymph node metastasis were independent risk factors for diagnosis.

Conclusion

Halo, vacuole, angiogram, and dead branch signs were frequently observed in consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations are common in consolidative-type IMA, especially site G12V, whereas epidermal growth factor receptor mutations were rare; therefore, gene immunotherapy was more difficult. Most patients were in stage T3–T4; however, lymph node metastasis was rare.

背景：本研究旨在探讨大块整合型肺浸润性粘液腺癌（IMA）的放射学、病理学和预后特征：本研究旨在探讨大块整合型肺浸润性黏液腺癌（IMA）的放射学、病理学和预后特征：我们对2010年1月至2022年8月期间确诊为IMA的738例患者进行了回顾性研究，由两名放射科医生对影像学资料进行了审查，以确定亚型。我们纳入了 41 例病理上巨大的整合型 IMA 患者。我们分析了他们的放射学、病理学和预后特征。采用 Kaplan-Meier 法确定无复发生存期（RFS）和总生存期（OS）：大多数病灶位于下叶，46.3%的患者有多个病灶。分别有97.6%、73.2%、63.4%、61.0%和61.0%的病例观察到光晕、血管影、空泡、气管影和死枝征。88.89%的患者出现不均匀低增强。T3和T4病理分期的患者分别占50.0%和30.6%。16.7%的患者出现淋巴结转移，无远处转移。分别有 27.8% 和 19.4% 的患者出现气隙扩散和肺内播散。此外，68.6%的病例发现 Kirsten 大鼠肉瘤病毒癌基因突变，未发现表皮生长因子受体突变。在所有突变位点中，G12V突变最为常见，占40%。平均RFS和OS分别为19.4个月和66.4个月，3年RFS和OS分别为30.0%和75.0%。胸膜侵犯和淋巴结转移是确诊的独立危险因素：结论：在合并型IMA中经常观察到光晕、空泡、血管造影和枯枝征。Kirsten大鼠肉瘤病毒癌基因突变在整合型IMA中很常见，尤其是G12V位点，而表皮生长因子受体突变则很少见，因此基因免疫治疗较为困难。大多数患者处于T3-T4期，但淋巴结转移罕见。

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引用次数: 0

Prescription patterns of ambrisentan in some cities of Colombia 哥伦比亚部分城市的安利生坦处方模式

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-03-19 DOI: 10.1111/crj.13736

Luis Fernando Valladales-Restrepo, Andrés Gaviria-Mendoza, Manuel Enrique Machado-Duque, Álvaro Vallejos-Narváez, Jorge Enrique Machado-Alba

Introduction

Ambrisentan is a selective type A endothelin receptor antagonist that has shown significant effectiveness and safety in the management of patients with pulmonary hypertension. Its use pattern with real-world evidence in Colombia is unknown.

Objective

The objective of this study is to determine the prescription patterns of ambrisentan in some cities of Colombia.

Methods

A longitudinal descriptive study on the prescription patterns of ambrisentan in patients with pulmonary hypertension (all the groups) was conducted between January 2021 and December 2022 based on a population database of members of the Colombian Health System. Adherence at 1 year was determined using the Medication Possession Ratio (days the drug was dispensed/days from first dispensing to the end of the follow-up period × 100). Descriptive analysis was carried out.

Results

Sixty-seven patients taking ambrisentan were identified in 10 cities of the country. The individuals had a median age of 51.5 years (interquartile range-IQR: 39.8–64.0 years), and 82.1% were women. The drug possession rate was 82.2% (IQR: 65.0–96.8%), and persistence at 1 year was present in 49.3% (n = 33) of the cases. The average dose was 8.8 ± 5.0 mg/day, and 76.1% (n = 51) received it in combination therapy, mainly with phosphodiesterase type 5 inhibitors (61.2%, n = 41).

Conclusions

Adherence to ambrisentan was good, but its persistence at 1 year was low. The dosages of the drug used were in accordance with the recommendations of the clinical practice guidelines, and it was used in combination therapy, especially with phosphodiesterase 5 inhibitors.

导言安布生坦是一种选择性 A 型内皮素受体拮抗剂，在治疗肺动脉高压患者方面具有显著的有效性和安全性。目前尚不清楚该药在哥伦比亚的实际使用情况。目标本研究旨在确定哥伦比亚一些城市的安立生坦处方模式。方法在 2021 年 1 月至 2022 年 12 月期间，根据哥伦比亚卫生系统成员的人口数据库，对肺动脉高压患者（所有组别）的安利生坦处方模式进行了纵向描述性研究。使用药物持有率（配药天数/从首次配药到随访期结束的天数×100）确定一年的依从性。并进行了描述性分析。结果在全国 10 个城市中发现了 67 名服用安利生坦的患者。这些患者的中位年龄为51.5岁（四分位距：39.8-64.0岁），82.1%为女性。藏毒率为 82.2%（IQR：65.0-96.8%），49.3% 的病例（n = 33）在 1 年后仍持续吸毒。平均剂量为 8.8 ± 5.0 毫克/天，76.1%（n = 51）的患者接受联合治疗，主要是与 5 型磷酸二酯酶抑制剂（61.2%，n = 41）联合治疗。结论安利生坦的依从性良好，但1年内的持续性较低。安利生坦的用药剂量符合临床实践指南的建议，而且是在联合治疗中使用，尤其是与5型磷酸二酯酶抑制剂联合使用。

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引用次数: 0

SOX-1 antibodies positive Lambert–Eaton myasthenic syndrome with occult small cell lung cancer: A case report SOX-1抗体阳性的兰伯特-伊顿肌萎缩综合征伴隐匿性小细胞肺癌：病例报告。

IF 1.7 4区医学 Q3 Medicine

Clinical Respiratory Journal

Pub Date : 2024-03-18 DOI: 10.1111/crj.13740

Liming Zhao, Hongyan He, Weixin Han, Yizhe Meng, Lifei Kang, Yanqiang Chen

Lambert–Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX-1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56-year-old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX-1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow-up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long-term follow-up and screening for occult SCLC in LEMS patients with positive SOX-1 antibodies are very important.

兰伯特-伊顿肌萎缩综合征（LEMS）是一种罕见的神经肌肉传递副肿瘤性神经综合征。其症状通常进展缓慢，早期易被误诊。血清 SOX-1 抗体阳性是诊断 LEMS 的依据，对小细胞肺癌（SCLC）具有高度特异性。本文报告了一例 56 岁男性患者的病例，该患者有吸烟史，因双腿近端进行性肌无力入院。通过重复神经刺激（RNS）测试和血清 SOX-1 抗体阳性诊断为 LEMS。胸部计算机断层扫描（CT）和综合 PET/CT 初筛未发现任何肿瘤。经过持续随访，胸部 CT 发现了 SCLC，并在确诊 LEMS 10 个月后通过病理检查确诊。对SOX-1抗体阳性的LEMS患者进行长期随访和隐匿性SCLC筛查非常重要。

引用次数: 0

Primary pulmonary histiocytic sarcoma with high PD-L1 expression benefited from immunotherapy: A case report and bioinformatic analysis PD-L1高表达的原发性肺组织细胞肉瘤受益于免疫疗法：病例报告与生物信息学分析

IF 1.7 4区医学 Q3 Medicine

Clinical Respiratory Journal

Pub Date : 2024-03-07 DOI: 10.1111/crj.13741

Yuanjie Lin, Qian Cao, Aonan Hong, Xiao Liang

Histiocytic sarcoma is an aggressive haematopoietic malignancy accounting for less than 1% of haematolymphoid neoplasms with a diagnosis based on morphology and immunophenotype of tissue biopsies with a very poor prognosis. Here, we report a 45-year-old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Tests demonstrated that TMB was 21 Muts/Mb PD-L1 expression was 90% positive, and the disease has been well-controlled over 3 years using immune checkpoint inhibitors (nivolumab and pembrolizumab). Bioinformatic pan-cancer analysis verified that there was the highest genetic alteration frequency of PD-L1 in which amplification accounted for the majority of sarcoma tumour samples. Following that, we found that the genetic alteration of PD-L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10⁻⁴), progress-free survival (PFS) (p = 4.90 × 10⁻²) and disease-specific survival (DSS) (p = 4.90 × 10⁻²). To our knowledge, this may be the first reported case with high PD-L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely.

组织细胞肉瘤是一种侵袭性造血恶性肿瘤，仅占血淋巴肿瘤的不到 1%，其诊断依据是组织活检的形态学和免疫表型，预后极差。在此，我们报告了一名 45 岁的男性患者，他被诊断为原发性肺组织细胞肉瘤并伴有全身转移，在接受环磷酰胺、多柔比星、长春新碱和泼尼松（CHOP）化疗后病情得到部分缓解（PR），但在上述治疗后不久复发。检测显示，TMB 为 21 Muts/Mb PD-L1 表达 90% 阳性，使用免疫检查点抑制剂（nivolumab 和 pembrolizumab）3 年来，病情得到了很好的控制。生物信息泛癌分析证实，PD-L1 的基因改变频率最高，其中扩增占肉瘤肿瘤样本的大多数。随后，我们发现 PD-L1 基因改变与肉瘤患者的预后不良有关，包括总生存期（OS）（p = 1.51 × 10-4）、无进展生存期（PFS）（p = 4.90 × 10-2）和疾病特异性生存期（DSS）（p = 4.90 × 10-2）。据我们所知，这可能是首例PD-L1高表达的原发性肺组织细胞肉瘤患者，他们可能会明显且安全地受益于nivolumab和pembrolizumab等免疫疗法。

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引用次数: 0

Pulmonary scedosporiosis in an intractable immunocompetent host: A case report and literature review 难治性免疫功能正常宿主的肺孢子虫病：病例报告和文献综述。

IF 1.7 4区医学 Q3 Medicine

Clinical Respiratory Journal

Pub Date : 2024-03-03 DOI: 10.1111/crj.13739

Hong Yu Liang, Chun Hua Han, Wen Juan Xu, Jian Sun, Qiang Wang

Pulmonary scedosporiosis is a rare pulmonary infection that often presents with nonspecific symptoms and radiological findings. In this report, we present a case of localized pulmonary scedosporiosis in an immunocompetent patient and analyze a total of 25 immunocompetent patients with pulmonary scedosporiosis. Through this case and the literature, we highlight the importance of considering pulmonary scedosporiosis in patients with nonspecific clinical symptoms and radiological findings resembling aspergilloma. This case and the literature further emphasize the significance of surgical intervention. Regardless of the use of antifungal drugs, surgery should be conducted as soon as possible.

肺孢子菌病是一种罕见的肺部感染，通常表现为非特异性症状和放射学检查结果。在本报告中，我们介绍了一例免疫功能正常患者的局部肺孢子菌病，并对 25 例免疫功能正常的肺孢子菌病患者进行了分析。通过本病例和文献，我们强调了在临床症状无特异性、放射学检查结果类似曲霉瘤的患者中考虑肺孢子菌病的重要性。本病例和文献进一步强调了手术干预的重要性。无论是否使用抗真菌药物，都应尽快进行手术。

引用次数: 0

The inhibitory effect of apatinib on different small cell lung cancer cells and in lung cancer-bearing mice and patients 阿帕替尼对不同小细胞肺癌细胞以及肺癌小鼠和患者的抑制作用。

IF 1.7 4区医学 Q3 Medicine

Clinical Respiratory Journal

Pub Date : 2024-02-25 DOI: 10.1111/crj.13738

Mingtao Liu, Hui Li, Ranran Guo, Xia Yu, Yu Li

Purpose

To observe the inhibitory effect of the small molecule tyrosine kinase inhibitor apatinib on small cell lung cancer in vitro and vivo.

Material and methods

Three small lung cancer cells were selected CCK-8 and monoclonal assay was used to determine the effect of apatinib on proliferation. The effects on cell cycle and apoptosis were detected by flow cytometry and TUNEL. We observed the inhibitory effect of different doses of apatinib on xenograft tumor. The efficacy and safety of apatinib in 20 patients with advanced small cell lung cancer were observed.

Results

For small cell lung cancer with high expression of VEGFR2, apatinib has a significant inhibitory effect both in vitro and in vivo. It can play an inhibitory role by promoting apoptosis and cell cycle arrest pathways. For small cell lung cancer with low expression of VEGFR, the inhibitory effect on cells in vitro was not significant. It has certain inhibitory effect on nude mouse transplanted tumor and small cell lung cancer patients, but the effect is weaker than that of animal models and patients with small cell lung cancer cells with high expression of VEGFR2.

Conclusion

Apatinib has a significant inhibitory effect on small cell lung cancer with high expression of VEGFR2 and may be a treatment for small cell lung cancer patients.

目的：观察小分子酪氨酸激酶抑制剂阿帕替尼在体外和体内对小细胞肺癌的抑制作用：材料和方法：选取3个小细胞肺癌细胞，用CCK-8和单克隆检测法测定阿帕替尼对细胞增殖的影响。流式细胞术和 TUNEL 检测了阿帕替尼对细胞周期和凋亡的影响。我们观察了不同剂量的阿帕替尼对异种移植瘤的抑制作用。观察了阿帕替尼在20例晚期小细胞肺癌患者中的疗效和安全性：结果：对于VEGFR2高表达的小细胞肺癌，阿帕替尼在体外和体内均有显著的抑制作用。它可以通过促进细胞凋亡和细胞周期停滞途径发挥抑制作用。对于 VEGFR 低表达的小细胞肺癌，阿帕替尼在体外对细胞的抑制作用不明显。对裸鼠移植瘤和小细胞肺癌患者有一定的抑制作用，但效果弱于动物模型和VEGFR2高表达的小细胞肺癌细胞：阿帕替尼对血管内皮生长因子受体2高表达的小细胞肺癌有明显的抑制作用，可作为小细胞肺癌患者的治疗药物。

{"title":"The inhibitory effect of apatinib on different small cell lung cancer cells and in lung cancer-bearing mice and patients","authors":"Mingtao Liu, Hui Li, Ranran Guo, Xia Yu, Yu Li","doi":"10.1111/crj.13738","DOIUrl":"10.1111/crj.13738","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To observe the inhibitory effect of the small molecule tyrosine kinase inhibitor apatinib on small cell lung cancer in vitro and vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and methods</h3>\u0000 \u0000 <p>Three small lung cancer cells were selected CCK-8 and monoclonal assay was used to determine the effect of apatinib on proliferation. The effects on cell cycle and apoptosis were detected by flow cytometry and TUNEL. We observed the inhibitory effect of different doses of apatinib on xenograft tumor. The efficacy and safety of apatinib in 20 patients with advanced small cell lung cancer were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For small cell lung cancer with high expression of VEGFR2, apatinib has a significant inhibitory effect both in vitro and in vivo. It can play an inhibitory role by promoting apoptosis and cell cycle arrest pathways. For small cell lung cancer with low expression of VEGFR, the inhibitory effect on cells in vitro was not significant. It has certain inhibitory effect on nude mouse transplanted tumor and small cell lung cancer patients, but the effect is weaker than that of animal models and patients with small cell lung cancer cells with high expression of VEGFR2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Apatinib has a significant inhibitory effect on small cell lung cancer with high expression of VEGFR2 and may be a treatment for small cell lung cancer patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974726","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

Efficacy of airway stenting and nasogastric tube insertion in airway–esophageal fistula patients with airways compromised by advanced malignancy 对因晚期恶性肿瘤导致气道受损的气道食管瘘患者进行气道支架植入术和鼻胃管插入术的疗效。

IF 1.7 4区医学 Q3 Medicine

Clinical Respiratory Journal

Pub Date : 2024-02-13 DOI: 10.1111/crj.13737

Xue Wu, Guangbing Lu, Lin cheng Luo, Hailong Wei, Qun Yi, Wei Luo

Introduction

Whether airway-compromised airway–esophageal fistula (AEF) patients should undergo combined airway and esophageal stenting is controversial. This study was designed to evaluate the survival prognosis and poststent interventions in AEF patients with airways compromised by advanced malignancy with or without airway stents.

Methods

A retrospective analysis of the medical records, survival times, and poststent interventions of 17 patients with or without airway stents was performed.

Results

The causes of AEF were esophageal cancer (11/17, 64.7%), lung cancer (6/17, 29.4%), and thyroid cancer (1/17, 5.9%). All patients received a nasogastric tube (n = 12) or underwent gastrostomy (n = 5) to resume enteral nutrition. Thirteen patients underwent airway stent insertion (13/17, 76.5%), whereas four patients did not. Four patients with a high risk of stent migration received external stent fixation to the trachea. Three of the patients with stents suffered severe granulation tissue formation and needed repeated bronchoscopy interventions. In the stented group, none of the patients developed stent migration, and the overall median survival time was 9 months, compared with 1.25 months in the nonstented group (P = 0.04). Cox proportional hazards regression revealed that stent insertion, nasogastric tube insertion, and transcatheter bronchial artery chemoembolization were protective factors against death, whereas surgery-related fistula, fistula larger than 2 cm, continued chemotherapy, and age were risk factors for poor survival (P < 0.05).

Conclusion

In airway-compromised AEF patients, airway stents and nasogastric tubes are probably the preferred treatments. Airway stenting is tolerable, and routine weekly poststent bronchoscopy is needed in the first month and depending on respiratory symptoms thereafter.

简介：气道受损的气道食管瘘（AEF）患者是否应接受气道和食管联合支架治疗尚存在争议。本研究旨在评估因晚期恶性肿瘤导致气道受损的气道食管瘘患者使用或不使用气道支架的生存预后和支架后干预措施：方法：对17名使用或未使用气道支架的患者的病历、生存时间和支架后干预措施进行了回顾性分析：AEF的病因是食道癌（11/17，64.7%）、肺癌（6/17，29.4%）和甲状腺癌（1/17，5.9%）。所有患者都接受了鼻胃管（12 例）或胃造口术（5 例），以恢复肠内营养。13名患者接受了气道支架植入术（13/17，76.5%），4名患者没有接受气道支架植入术。四名支架移位风险较高的患者接受了气管外部支架固定。其中 3 名植入支架的患者肉芽组织形成严重，需要反复进行支气管镜检查。在支架组中，没有一名患者发生支架移位，总体中位存活时间为9个月，而无支架组为1.25个月（P = 0.04）。Cox 比例危险度回归显示，支架插入、鼻胃管插入和经导管支气管动脉化疗栓塞是死亡的保护因素，而与手术相关的瘘管、大于 2 厘米的瘘管、持续化疗和年龄则是存活率低的危险因素（P 结论：支架插入、鼻胃管插入和经导管支气管动脉化疗栓塞是死亡的保护因素，而与手术相关的瘘管、大于 2 厘米的瘘管、持续化疗和年龄则是存活率低的危险因素：对于气道受损的 AEF 患者，气道支架和鼻胃管可能是首选治疗方法。气道支架植入术是可以耐受的，支架植入后的第一个月需要每周例行支气管镜检查，之后视呼吸道症状而定。

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引用次数: 0

Distinct age-adjusted D-dimer threshold to rule out acute pulmonary embolism in outpatients and inpatients 用于排除门诊和住院患者急性肺栓塞的不同年龄调整D-二聚体阈值

IF 1.7 4区医学 Q3 Medicine

Clinical Respiratory Journal

Pub Date : 2024-02-11 DOI: 10.1111/crj.13728

Peng Liu, Haixu Yu, Wei Liu, Lin Lin, Ying Qun Ji

Introduction

The diagnosis of acute pulmonary embolism (PE) is combinations of clinical probability assessments, plasma D-dimer (DD) test results, and/or computed tomographic pulmonary angiography (CTPA).

Objective

The aim of this study is to explore the appropriate DD cutoff using the immunoturbidimetric method in outpatients and inpatients.

Methods

We retrospectively enrolled 2689 patients with suspected PE between January 2014 and December 2019. All patients underwent clinical probability assessments, DD tests, and CTPA. We investigated the appropriate cutoff level for plasma DD tests in the correlation analysis and receiver operating characteristic (ROC) curves.

Results

Among all patients, 1263 were confirmed acute PE. The age-adjusted DD level was determined to be age × 10 μg/L (for patients aged >50 years) in outpatients. This cutoff value resulted in a sensitivity of 96.75% and a specificity of 87.02%, with the area under the curve (AUC) of 0.908 and the number needed to treat (NNT) of 1.18. For inpatients, the age-adjusted cutoff values for the biomarker DD demonstrated poor specificity (13.34%) and NNT (9.88). However, when the DD cutoff was adjusted to 2 × the upper limit of normal (ULN), the sensitivity increased to 93.19%, while the specificity remained at 29.55%, with the AUC of 0.610 and the NNT of 4.76. The optimal DD cut-off value was 3010 μg/L (about 5 × ULN), resulting in a sensitivity of 75.22% and specificity of 61.72%, with the AUC of 0.727 and the NNT of 2.7.

Conclusion

Using the immunoturbidimetric method to measure DD, an age-adjusted DD cutoff (age × 10 μg/L, if aged >50 years) should be considered for outpatients with suspected PE. For inpatients, increasing the DD cutoff value to at least 2 × ULN yields the best test performance.

引言急性肺栓塞（PE）的诊断需要结合临床可能性评估、血浆 D-二聚体（DD）检测结果和/或计算机断层扫描肺血管造影（CTPA）。目的本研究旨在探讨门诊和住院患者使用免疫比浊法检测 DD 的合适临界值。方法我们回顾性纳入了 2014 年 1 月至 2019 年 12 月间的 2689 例疑似 PE 患者。所有患者均接受了临床概率评估、DD 检测和 CTPA。我们通过相关性分析和接收器操作特征曲线（ROC）研究了血浆 DD 检测的合适临界值。结果在所有患者中，1263 人确诊为急性 PE。在门诊患者中，年龄调整后的 DD 水平被确定为年龄 × 10 μg/L（50 岁患者）。该临界值的灵敏度为 96.75%，特异度为 87.02%，曲线下面积（AUC）为 0.908，治疗所需次数（NNT）为 1.18。对于住院患者，生物标记物 DD 的年龄调整临界值显示出较低的特异性（13.34%）和 NNT（9.88）。然而，当 DD 临界值调整为正常值上限（ULN）的 2 倍时，灵敏度增加到 93.19%，特异性仍为 29.55%，AUC 为 0.610，NNT 为 4.76。最佳 DD 临界值为 3010 μg/L（约 5 × ULN），灵敏度为 75.22%，特异度为 61.72%，AUC 为 0.727，NNT 为 2.7。结论使用免疫比浊法测量 DD，门诊疑似 PE 患者应考虑年龄调整后的 DD 临界值（年龄×10 μg/L，如果年龄为 50 岁）。对于住院患者，将 DD 临界值提高到至少 2 × ULN 可获得最佳检测效果。

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引用次数: 0

EGFR amplification indicated poor prognosis in EGFR-mutated lung cancer with leptomeningeal metastases 表皮生长因子受体扩增表明表皮生长因子受体突变肺癌伴有脑膜转移者预后不良

IF 1.7 4区医学 Q3 Medicine

Clinical Respiratory Journal

Pub Date : 2024-02-01 DOI: 10.1111/crj.13733

Di Geng, Ruina Niu, Jinghong Li, Sanxing Guo, Qianqian Guo, Siyuan Huang, Yurong Wang

Background

Leptomeningeal metastasis (LM) is a lethal complication of advanced lung cancer, and due to limited access to the leptomeningeal lesion, we explored the potential role of cerebrospinal fluid (CSF) as a source for liquid biopsy in LM patients of lung cancer with EGFR mutation.

Materials and Methods

From August 2018 to June 2021, we collected CSF samples of lung cancer patients at First Affiliated Hospital of Zhengzhou University. Next-generation sequencing was performed to detect the mutations in EGFR genes, and 38 patients detected with EGFR mutations were finally enrolled in further clinical analyses.

Results

TP53 missense mutation (50%) was the most frequently detected concurrent gene in CSF. In those 10 patients whose CSF was obtained upon resistance to first TKI, TP53 missense mutation (40%, n = 4) and EGFR copy number amplification (40%, n = 4) was detected with high frequency; meanwhile, T790M mutation was found only in two patients. Known mechanisms of acquired resistance to third EGFR-TKIs were found in 31.8% of cases. C797S or C797G mutation was identified in three patients. Possible EGFR-independent resistant mechanism included MET amplification (4.5%), RET gene fusion (4.5%), PIK3CA missense mutation (4.5%) and CDK4 amplification (4.5%). The median OS was 55 months, the median OS_LM was 38 months. EGFR amplification was associated with shortened OS in these EGFR-mutated lung cancer with leptomeningeal metastases.

Conclusion

EGFR amplification indicated poor prognosis in EGFR-mutated lung cancer with leptomeningeal metastases, providing a novel pathogenesis and treatment direction of these patients.

背景脑膜转移（LM）是晚期肺癌的一种致命并发症，由于脑膜病变的可及性有限，我们探索了脑脊液（CSF）作为EGFR突变的肺癌LM患者液体活检来源的潜在作用。材料与方法 2018年8月至2021年6月，我们在郑州大学第一附属医院采集了肺癌患者的脑脊液样本。通过新一代测序检测EGFR基因突变，最终将检测到EGFR基因突变的38例患者纳入进一步临床分析。结果 TP53错义突变（50%）是脑脊液中最常检测到的并发基因。在对第一种TKI耐药后获得CSF的10例患者中，TP53错义突变（40%，4例）和表皮生长因子受体拷贝数扩增（40%，4例）被高频率检测到；而T790M突变仅在2例患者中发现。31.8%的病例发现了对第三种表皮生长因子受体-TKIs的已知获得性耐药机制。3例患者发现了C797S或C797G突变。与表皮生长因子受体无关的可能耐药机制包括MET扩增（4.5%）、RET基因融合（4.5%）、PIK3CA错义突变（4.5%）和CDK4扩增（4.5%）。中位OS为55个月，中位OSLM为38个月。表皮生长因子受体扩增与这些表皮生长因子受体突变并伴有脑膜转移的肺癌患者的OS缩短有关。结论表皮生长因子受体扩增预示着表皮生长因子受体突变肺癌伴隐窝转移的不良预后，为这些患者提供了新的发病机制和治疗方向。

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引用次数: 0

Translation regulatory long non-coding RNA 1 negatively regulates cell radiosensitivity via the miR-22-3p/SP1 axis in non-small cell lung cancer 翻译调控长非编码 RNA 1 通过 miR-22-3p/SP1 轴负向调节非小细胞肺癌细胞的放射敏感性。

IF 1.7 4区医学 Q3 Medicine

Clinical Respiratory Journal

Pub Date : 2024-01-29 DOI: 10.1111/crj.13734

Ming Zhong, Zheng Fang, Weixi Guo, Xiuyi Yu

Objective

Non-small cell lung cancer (NSCLC) occupies 85% of lung cancer. Long non-coding RNAs (LncRNAs) can regulate the radiosensitivity of cancers. This study explored the mechanism of lncRNA TRERNA1 in the radiosensitivity of NSCLC cells.

Methods

LncRNA TRERNA1 level in NSCLC cell lines was determined. NSCLC cell radiation tolerance was measured. TRERNA1 expression was silenced or overexpressed in A549/HCC827 cells with the highest/lowest radiation tolerance, respectively. The contents of γ-H2AX and SA-β-gal in NSCLC cells after radiation induction were detected. The targeted binding of TRERNA1 to miR-22-3p and miR-22-3p to SP1 were verified by dual-luciferase assay. SP1 expression were detected. Functional rescue experiments were implemented to confirm the roles of miR-22-3p and SP1 in the regulatory mechanism of TRERNA1.

Results

TRERNA1 was upregulated in NSCLC cells. TRERNA1 silencing enhanced radiosensitivity of NSCLC cells. TRERNA1 silencing elevated the contents of γ-H2AX and SA-β-gal in A549 cells after radiation induction, while TRERNA1 overexpression showed an opposite trend in HCC827 cells. There were targeting relationships between TRERNA1 and miR-22-3p, and miR-22-3p and SP1. miR-22-3p repression or SP1 overexpression abolished the effects of TRERNA1 silencing.

Conclusion

TRERNA1 silencing enhanced radiosensitivity of NSCLC cells via the miR-22-3p/SP1 axis. This study may offer new targets for NSCLC treatment.

目标：非小细胞肺癌（NSCLC）占肺癌的 85%：非小细胞肺癌（NSCLC）占肺癌的 85%。长非编码 RNA（LncRNA）可调控癌症的放射敏感性。本研究探讨了lncRNA TRERNA1在NSCLC细胞放射敏感性中的作用机制：方法：测定NSCLC细胞系中LncRNA TRERNA1的水平。方法：测定 NSCLC 细胞系中 LncRNA TRERNA1 的水平，测量 NSCLC 细胞的辐射耐受性。分别在辐射耐受性最高/最低的 A549/HCC827 细胞中沉默或过表达 TRERNA1。检测了辐射诱导后 NSCLC 细胞中 γ-H2AX 和 SA-β-gal 的含量。通过双荧光素酶试验验证了 TRERNA1 与 miR-22-3p 的靶向结合以及 miR-22-3p 与 SP1 的靶向结合。检测到了 SP1 的表达。通过功能拯救实验证实了 miR-22-3p 和 SP1 在 TRERNA1 调控机制中的作用：结果：TRERNA1在NSCLC细胞中上调。沉默 TRERNA1 可增强 NSCLC 细胞的放射敏感性。沉默TRERNA1可提高辐射诱导后A549细胞中γ-H2AX和SA-β-gal的含量，而TRERNA1在HCC827细胞中的过表达则表现出相反的趋势。TRERNA1与miR-22-3p、miR-22-3p与SP1之间存在靶向关系，miR-22-3p抑制或SP1过表达可消除TRERNA1沉默的影响：结论：TRERNA1沉默通过miR-22-3p/SP1轴增强了NSCLC细胞的放射敏感性。这项研究可能为治疗 NSCLC 提供新的靶点。

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