Background New combination regimens with third generation of EGFR-TKIs plus antibody-drug conjugate exhibited superior clinical efficacy over EGFR-TKI monotherapy. However, the frequency of adverse events, inconvenience of medication and drug cost increased. Thus, we initiated a national, multi-center survey to assess multi-dimensional acceptance of this novel combination therapies among physicians and advanced NSCLC patients. Methods This survey questionnaire included 4 dimensions and 5 questions to ask people's intentions for accepting this new treatment, which included 1-year survival benefits, i.v. every 2 weeks, increased side effects, increased drug costs, and simultaneous occurrence of the above 4 situations. 1,260 valid questionnaires were systematically collected within 15 days. Results The results indicated generally consistent, but gradually decreased acceptance between physician and patient groups across four dimensions—survival benefit (physicians 91% vs patients 85%), i.v. frequency (69% vs 69%), toxicity risk (40% vs 37%), financial burden (24% vs 24%) and overall acceptance (21% vs 24%). Stratified analysis revealed observed differences: senior physicians showed lower acceptance than junior physicians regarding i.v. frequency (11% vs 8%), increased toxicity (26% vs 24%), and higher costs (33% vs 30%). Within the patient group, patients themselves paid more attention to toxicity risks (31% vs 25%) and economic burdens (39% vs 34%) than their family members, leading to lower acceptance. Treatment-naive patients also demonstrated lower acceptance compared to previously treated patients in terms of frequent hospital visits (21% vs 9%), increased toxicity (32% vs 26%), and higher costs (41% vs 33%). Conclusions This study provides critical evidence for implementing novel combination therapies in advanced NSCLC with EGFR sensitizing mutations, while revealing core barriers to their clinical application.

The mortality rate associated with invasive pulmonary fungal infection (IPFI) is substantial, whereas epidemiological data pertaining to non-neutropenic patient cohorts is deficient. This study aims to analyze the epidemiology and identify risk factors associated with mortality from invasive pulmonary fungal infection in non-neutropenic populations. A retrospective study was conducted encompassing adult patients diagnosed with IPFI at the First Affiliated Hospital of Sun Yat-sen University between January 1, 2013, and December 31, 2022. A total of 513 patients were included in the study, and their survival information was retrospectively collected. A comparison of IPFI patient demographics between 2013-2017 and 2018-2022 revealed a marked elevation in the median age and a significant increase in the prevalence of comorbidities, including hypertension, hematological malignancies, and bronchiectasis. There was a notable shift in the prevalence of fungal pathogens, marked by an elevation in the proportion of individuals afflicted with Pneumocystis jirovecii. The 30-day mortality rate for IPFI patients remained relatively stable compared with the previous 5 years (11.71% versus 16.02%, P = 0.275). The Cox multivariate regression analysis revealed that intensive care unit admission (P <0.001), repeated blood transfusions (P = 0.042), and Aspergillus infection (P = 0.001) may be independent risk factors for all-cause mortality, respectively. A nomogram predicting 30-day all-cause mortality among patients with IPFI demonstrated satisfactory performance in terms of classification ability and calibration ability. These findings will contribute to better management of patients with IPFI by preventing the identified risk factors.

This study investigates pulmonary immune-related adverse events (pirAEs) in patients undergoing immune checkpoint inhibitors (ICIs), including anti-PD-1 antibodies, anti-PD-L1 antibodies, and anti-CTLA-4 antibodies. Reports for pirAEs from the Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization Global Database on Case Safety Reporting (VigiBase) between the first quarter of 2015 and the second quarter of 2020 were analyzed.16,372 and 7,943 individual case safety reports (ICSRs)were collected using FAERS database and VigiBase database, respectively. More than 50 % of pirAEs occurred within 60 days after treatment with ICIs, and their mortality was higher than that after 60 days. In each period after the use of ICIs, pirAEs with the highest incidence were interstitial lung disease, dyspnoea, and pneumonitis. The all-cause mortality of respiratory failure, pulmonary hemorrhage, acute interstitial pneumonitis, and stridor was over 25 %. The mortality of respiratory failure remained stable at a high level in each period after initiation of immunotherapy, of which the mortality was still 40 % after one year of initiation of immunotherapy. This study can better help physicians understand the types and mortality rate of pirAEs at each period after using such drugs, particularly during the initial 60 days of ICI therapy, so as to achieve early identification and treatment.

BackgroundTargeted next-generation sequencing (tNGS) has become a trending tool in the field of infection diagnosis, but concerns are also raising about its performance compared with metagenomic next-generation sequencing (mNGS). This study aims to explore the clinical feasibility of a tNGS panel for respiratory tract infection diagnosis and compare it with mNGS in the same cohort of inpatients.Methods180 bronchoalveolar lavage fluid samples were collected and sent to two centers for mNGS and tNGS blinded tests, respectively. The concordance between pathogen reports of both methods and the clinical significance among samples with/without known etiology was further evaluated.ResultsOverall, both methods displayed high agreement on pathogen reports, as the average percent agreement reached 95.29%. But tNGS presented a slightly higher detection rate per species than mNGS (PWilcoxon=1.212e-05; standard mean difference = 0.2887091), as detection rates for 32 out of 48 species were higher than those of mNGS. Due to limitations of panel coverage, tNGS identified 28 fewer species than mNGS, among which only 3 were considered clinically relevant. In reference to composite reference standard, accuracy, sensitivity, and specificity combining both tNGS and mNGS reached 95.61%, 96.71%, and 95.68%, respectively, while positive prediction value (PPV) was low at 48.13%, which was caused by low agreement regarding opportunistic pathogens. tNGS and mNGS improved the etiology identification in 30.6% (55/180) and 33.9% (61/180) cases, respectively.ConclusionCollectively, tNGS presented a similar overall performance in pathogen identification compared to mNGS, but outperformed in some pathogens. This study also demonstrated that deployment of tNGS significantly improves etiology identification in routine practice and provides hints for clinical decisions. The low agreement between clinical diagnosis and NGS reports towards opportunistic pathogens implies that adjudication is essential for report interpretation. Finally, We proposed tNGS as a diagnosis option in clinical practice due to its cost-efficiency.

A 16-year-old boy presented to the emergency room complaining of right-sided chest discomfort and dyspnoea persisting for the past 10 days. Despite his previous good health, he had been hospitalized 3 months prior for fever and productive cough with yellowish phlegm. Diminished vocal fremitus and breath sounds were noted over the right chest. Chest computed tomography demonstrated right pneumothorax with blebs near the apex and diffuse pleural thickening (Fig. S1). Air and a small amount of purulent fluid were evacuated through closed thoracic drainage. The pleural effusion analysis revealed markedly elevated leukocyte count (white blood cell count, 1566 × 106/L), lactate dehydrogenase (5094 U/L), and adenosine deaminase (56.3 U/L), along with extremely low glucose levels (0.1 mmol/L), indicating a diagnosis of empyema. A single sequence of Aspergillus fumigatus was detected in the effusion through metagenomic next-generation sequencing, but was considered contaminated as β-D-glucan and galactomannan were both negative. Medical thoracoscopy was performed to investigate the underlying cause. Yellow, cheese-like lesions were visualized on the apical visceral pleura and the parietal pleura near the right diaphragm, accompanied by diffuse pleural thickening (Fig. 1). Tissue biopsy specimen histology revealed chronic granulomatous inflammation with hyphae resembling Aspergillus (Fig. 2). Tissue culture confirmed A fumigatus infection. Although recurrent pneumothorax had been reported as a potential aetiology [ 1 Abreu I. Guedes M. Duro R. Lopes S. Maciel J. Santos L. Pleural aspergillosis in a patient with recurrent spontaneous pneumothorax: the challenge of an optimal therapeutic approach. Med Mycol Case Rep. 2020; 28: 4-7https://doi.org/10.1016/j.mmcr.2020.02.004 Crossref PubMed Scopus (6) Google Scholar ], pleural aspergillosis is so uncommon in immunocompetent individuals that the initial diagnosis suggested by metagenomic next-generation sequencing was overlooked. The application of medical thoracoscopy and subsequent histological investigation played a pivotal role in establishing the diagnosis. Thoracoscopy has previously been considered as a viable therapeutic option [ 2 Ichikawa H. Doi R. Matsumoto K. Tomoshige K. Hirabaru M. Machino R. et al. Spontaneous pleural aspergillosis in an immunocompetent young adult treated with minimally invasive surgery. Respir Med Case Rep. 2023; 44101869https://doi.org/10.1016/j.rmcr.2023.101869 Crossref PubMed Scopus (1) Google Scholar ]. However, the patient was cured with administration of oral voriconazole and intrapleural amphotericin B. Fig. 2A tissue biopsy specimen revealed the presence of Aspergillus-like hyphae, stained with hematoxylin–eosin, the bar stands for (a) 625 μm or (b–d) 50μm. View Large Image Figure Viewer Download Hi-res image

Negative conversion of nucleic acid was a key factor in deciding discharge or the end of isolation of asymptomatic or mild COVID-19 patients. We aimed to explore the effect of vaccination on the time to negative conversion after Omicron infection. This retrospective cohort study included asymptomatic or mild patients with COVID-19 admitted to Fangcang shelter Hospital from November 10, 2022 to December 2, 2022. The relationship between vaccination status and the time to negative conversion was analyzed by multiple linear regression. A total of 2,104 asymptomatic or mild COVID-19 patients were included in the analysis, of whom 1,963 were vaccinated. The mean time to negative conversion of no vaccination, one dose, two doses, and three doses were 12.57 (5.05), 12.18 (3.46), 11.67 (4.86) and 11.22 (4.02) days, respectively (p = 0.002). Compared with no vaccination, two doses (β=-0.88, 95

Bioluminogenic probes emerged as powerful tools for imaging and analysis of various bioanalyses, but traditional approaches would be limited to the low sensitivity during determine the low activity of protease in clinical specimens. Herein, we proposed a caged luciferase inhibitor-based bioluminescence-switching strategy (CLIBS) by using a cleavable luciferase inhibitor to modulate the activity of luciferase reporter to amplify the detective signals, which led to the enhancement of detection sensitivity, and enabled the determination of circulating Aminopeptidase N (APN) activity in thousands of times diluted serum. By applying the CLIBS to serum samples in non-small cell lung cancer (NSCLC) patients from two clinical cohorts, we revealed that, for the first time, higher circulating APN activities but not its concentration, were associated with more NSCLC metastasis or higher metastasis stages by subsequent clinical analysis, and can serve as an independent factor for forecasting NSCLC patients' risk of metastasis.

Stage III non-small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Importance: Checkpoint inhibitor pneumonitis (CIP) is a rare but serious adverse event that may impact treatment decisions. However, there is limited information comparing CIP risks between immune checkpoint inhibitor (ICI) monotherapy and combination with chemotherapy due to a lack of direct cross-comparison in clinical trials.Objective: To determine whether ICI combination with chemotherapy is superior to ICI in other drug regimens (including monotherapy) in terms of CIP risk.Study Design and Methods: This observational, cross-sectional and worldwide pharmacovigilance cohort study included patients who developed CIP from the World Health Organization database (WHO) VigiBase and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Individual case safety reports (ICSR) were extracted from 2015 to 2020 in FAERS and from 1967 to 2020 in VigiBase. Timing and reporting odds ratio (ROR) of CIP in different treatment strategies were used to detect time-to-onset and the risk of pneumonitis after different immunotherapy regimens.Results: A total of 93,623 and 114,704 ICI-associated ICSRs were included in this study from VigiBase and FAERS databases respectively. 3450 (3.69%) and 3278 (2.86%) CIPs occurred after therapy initiation with a median of 62 days (VigiBase) and 40 days (FAERS). Among all the CIPs, 274 (7.9%) and 537 (16.4%) CIPs were associated with combination therapies. ICIs plus chemotherapy combination was associated with pneumonitis in both VigiBase [ROR 1.35, 95% CI 1.18-1.52] and FAERS [ROR 1.39, 95% CI 1.27–1.53]. The combination of anti-PD-1 antibodies and anti-CTLA-4 antibodies with chemotherapy demonstrated an association with pneumonitis in both VigiBase [PD-1+chemotherapy: 1.76, 95% CI 1.52-2.05; CTLA-4+chemotherapy: 2.36, 95% CI 1.67-3.35] and FAERS [PD-1+chemotherapy: 1.70, 95% CI 1.52-1.91; CTLA-4+chemotherapy: 1.70, 95% CI 1.31-2.20]. Anti-PD-L1 antibodies plus chemotherapy combinations did not show the association.Conclusion: Compared to ICI in other drug regimens (including monotherapy), the combination of ICI plus chemotherapy is significantly associated with higher pneumonitis toxicity. Anti-PD-1/CTLA4 medications in combination with chemotherapy should be obviated in patients with potential risk factors for CIP.Trial Registration: clinicaltrials.gov, ChiCTR2200059067

Abstract Background: FAM83A (Family with sequence similarity 83, member A) has been found to promote tumor cell proliferation and accelerate the progression of several cancer types. However, integrated studies on the prognostic value of FAM83A and its function as an immunotherapy target in pan-cancers remain limited.Methods: Multiple online databases, including ONCOMINE, PrognoScan, Kaplan-Meier plotter, GEPIA, Lung Cancer Explorer, and TIMER, were accessed to evaluate the clinical prognostic value of FAM83A and its association with tumor-infiltrating immune cells across different cancer types.Results: Compared with normal tissues, the expression of FAM83A was higher in breast, colorectal, gastric, head and neck, and lung cancers. High FAM83A expression significantly correlated with inferior overall survival (OS) in lung cancer including lung adenocarcinoma (LUAD). In patients with LUAD, overexpressed FAM83A was negatively associated with infiltration levels of B cells and dendritic cells. In addition, the FAM83A expression level was positively associated with PD-L1, STAT1, STAT3, and JAK1 in LUAD.Conclusions: The high expression level of FAM83A was significantly correlated with a worse prognosis, which was also associated with a decreased level of infiltration of B cells and dendritic cells. FAM83A might increase the expression of PD-L1 through JAK / STAT pathway in the tumor microenvironment of lung adenocarcinoma.

e14587 Background: Pneumonitis is one of the most common fatal pulmonary adverse events that stem from immune checkpoint inhibitors (ICIs). Although the combination of ICI plus chemotherapy has become the standard first-line treatment regiments for various tumors, how the risk of pneumonitis changes during the combination treatments remains unclear. We used the World Health Organization pharmacovigilance database (VigiBase) to compare the risk of pneumonitis from the combinations of ICI plus chemotherapy with ICI in other regimens, including monotherapy. Methods: This observational, retrospective, pharmacovigilance study is a disproportionality analysis based on the individual case safety reports (ICSRs) extracted from the VigiBase from 1997 to 2020. The disproportionality analysis (known as case-non-case analysis) was conducted to compare the reporting of pneumonitis from the combination of ICI plus chemotherapy with ICI in other drug regimens, including monotherapy. The reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated. Results: From 1994 to 2020, A total of 93,623 ICI-associated ICSRs were reported in Vigibase, including 3,453 reports of pneumonitis (3.7%), among which 274 were associated with the combinations of ICI plus chemotherapy. The median time to event onset occurred about 2 months after therapy either in ICI without chemotherapy group or in the combination with chemotherapy group (61.5 days vs 74 days, respectively, p > 0.05). The ICI plus chemotherapy combination demonstrated a significant association with pneumonitis (ROR 1.35, 95% Cl 1.18-1.52). Among all the ICIs, anti-PD-1 antibodies combinations and anti-CTLA-4 antibodies combinations demonstrated a significant association with pneumonitis (PD-1+chemotherapy: 1.76, 95 % CI 1.52-2.05; CTLA-4+chemotherapy: 2.36, 95% Cl 1.67-3.35), while anti-PD-L1 antibodies plus chemotherapy combinations did not show similar association (ROR 0.37, 95% Cl 0.28-0.47). Conclusions: The combination of ICI plus chemotherapy is associated with higher risk of pneumonitis toxicity compared to other ICI-containing regimens (including ICI monotherapy) based on real-world data. The anti-PD-L1 plus chemotherapy combination has different pneumonitis profiles compared to anti-PD-1/CTLA-4 combinations. It suggests that a close monitoring for pneumonitis may be needed when using ICI plus chemotherapy combinations.[Table: see text]

e21124 Background: The addition of bevacizumab to first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) has shown promising efficacy in delaying TKI resistance and prolonging PFS in treating EGFR-mutated advanced lung cancer. However, data on the afatinib-bevacizumab combination therapy are limited. Methods: A total of 47 patients with EGFR-mutated advanced lung cancer were retrospectively analyzed, including 21 patients treated with afatinib combined with bevacizumab and 26 patients treated with afatinib monotherapy. Clinical data, survival outcomes and toxic effects were evaluated. Results: There was no significant difference in basic clinical features between the combination and monotherapy groups. The overall response rate (ORR), median progression-free survival (PFS) and overall survival (OS) in the combination group (afatinib 40 mg/day combined with bevacizumab 7.5 mg/kg every 3 weeks) were 42.9%, 16.5 months and 35.2 months, respectively, while the ORR, PFS and OS in the afatinib group was 53.8%, 13.8 months and 33.8 months, respectively. No significant difference was noted in ORR, PFS or OS between the two groups ( p＞0.05). However, among the subgroup with concurrent genetic mutations, combination therapy provided a significant PFS benefit (18.2 months, [95% CI 7.1-29.3] vs. 11.0 months [95%CI 7.5-14.5], p= 0.036). Although there was a longer trend in OS, no statistical difference was presented (35.2 months [95% CI 29.8-40.6] vs. 27.5 months [95% CI 13.1-41.9], p= 0.138). The safety of the combination therapy was acceptable and manageable. Conclusions: Afatinib-bevacizumab combination therapy could provide superior PFS benefit over afatinib alone in the subset of patients with concomitant genetic mutations in EGFR-mutated advanced NSCLC, and the safety of the combination therapy is acceptable.[Table: see text]

2655 Background: Clinical trials lack direct cross-comparison in safety between immune checkpoint inhibitor (ICI) as monotherapy and in combination with chemotherapy. The adverse event of checkpoint inhibitor pneumonitis (CIP) is an important factor influencing the treatment decision making. We performed a real-world pharmacovigilance study in the US Food and Drug Administration Adverse Event Reporting System (FAERS) to determine if ICI combination therapy is superior to monotherapy for lung cancer patients in terms of CIP incidence. Methods: The database of lung cancer patients receiving ICI between 2015 and 2020 was extracted for this study. The strategy-specific durations of the pneumonitis event were compared using the Kaplan-Meier method. Reporting odds ratio (ROR), a surrogate measure in disproportionality analysis, was used to assess the signal of CIP between ICI treatment strategies. Results: A total of 27,882 lung cancer patients with reported adverse events were involved. Among them, 1763 (6.3%) CIP after ICIs therapy were identified. In general, ICI usage was associated with over-reporting frequencies of CIP, but this association was no longer significant after adjustment (ROR: 1.14, 95%CI 0.86-1.49). The median times to CIP occurred early after therapy onset, either in ICI monotherapy or in combination with chemotherapy (41 days and 37 days, log-rank p>0.05). Different reporting frequencies emerged when we further compared different ICI strategies. Combination therapy with anti-PD-1 and chemotherapy was associated with a higher CIP incidence compared with anti-PD-1 monotherapy (ROR: 1.86, 95%CI 1.37-2.51), whereas anti-PD-L1/ CTLA-4 medications had lower risks in combination with chemotherapy (ROR: 0.31, 95%CI 0.16-0.56 and ROR: 0.41, 95%CI 0.09-1.22). Subgroup analyses on those with recorded therapy duration also indicated that reports of CIP were significantly lower with combination therapy of PD-L1 and CTLA-4 (ROR: 0.52, 95%CI 0.36-0.74 and ROR: 0.22, 95%CI 0.09-0.51 respectively). Conclusions: Compared with ICI monotherapy, the combination with chemotherapy might have an acceptable risk of CIP. Anti-PD-1 medications with additional chemotherapy could increase the risk of pneumonitis, whereas the risk was lower in the combination strategy with anti-PD-L1/CTLA-4. The combination might be a better therapeutic strategy than ICI monotherapy in treating lung cancer, regarding the CIP incidence. [Table: see text]

BACKGROUND:Kodamaea ohmeri is a rare pathogen with high mortality and is found among blood samples in a considerable proportion; however, gastrointestinal infection of K. ohmeri is extremely rare. Invasive pulmonary aspergillosis is also an uncommon fungal; these two fungal infections reported concomitantly are unprecedented.CASE PRESENTATION:We described a case of a 37-year-old male who got infected with K. ohmeri and invasive pulmonary aspergillosis. We used the mass spectrometry and histopathology to identify these two fungal infections separately. For the treatment of K. ohmeri, we chose caspofungin. As for invasive pulmonary aspergillosis, we used voriconazole, amphotericin B, and then surgery. The patient was treated successfully through the collaboration of multiple disciplines.CONCLUSIONS:We speculate that the destruction of the intestinal mucosa barrier can make the intestine one of the ways for certain fungi to infect the human body.

由中国抗癌协会肺癌专业委员会和广东省临床试验协会/中国胸部肿瘤研究协作组主办的“第19届中国肺癌高峰论坛”于2022年3月5日在广州顺利召开。此次论坛中，来自肺癌临床研究、转化性研究、基础研究的专家们围绕可切除/不可切除Ⅲ期非小细胞肺癌（non-small cell lung cancer,NSCLC）的多学科综合治疗和生物标志物进行了深入交流和讨论，并最终达成了专家共识。

Abstract Background: Precisely detecting anaplastic lymphoma kinase (ALK) rearrangement ensures ideal efficacy of ALK targeted tyrosine kinase inhibitors (ALK-TKIs). Next generation sequencing (NGS) has been widely used in clinics, while, numbers of studies indicated NGS would yield false negative outcome, especially for fusion analysis. Instead, more fusions can be detected by RT-PCR at transcription level. This study aims to compare the capacity of RT-PCR and NGS approach to detect ALK rearrangement in Chinese non-small-cell lung cancer (NSCLC) patients. Methods: Formalin-fixed paraffin-embedded (FFPE) tissues from 153 patients pathologically diagnosed as NSCLC with eligible ALK status given by previous NGS testing (29 patients were ALK positive and 124 patients were ALK negative) were collected from November 2017 to October 2019. RT-PCR were applied to detect ALK rearrangements in both groups. For samples with discordant result of ALK status, fluorescence in situ hybridization (FISH) or Sanger's sequencing were used for validation. Results: One hundred and twenty-four samples (26 of 30 ALK positive samples; 98 of 124 ALK negative samples) were successfully subjected to RT-PCR. Five of 98 ALK negative samples given by NGS test were re-defined as ALK positive by RT-PCR. Meanwhile, in 26 ALK positive samples, RT- PCR yielded acceptable result with 96.15% of concordance rate. Only one NGS-defined ALK positive sample was uncovered by RT-PCR due to a rare ALK rearrangement. Four of 6 RT-PCR defined ALK positive cases (3 RT-PCR positive and 1 NGS positive) were validated by either FISH or sanger's sequencing, which resulted positive result. Conclusions: RT-PCR displays reliable and superior capacity to detect ALK fusion in NSCLC patients. Citation Format: Yukun Kuang, Peihang Xu, Jiyu Wang, Yifan Zheng, Xue Sun, Zimu Li, RunJing Gan, Huixia Li, Yubiao Guo, Guanshan Zhu, Changbin Zhu, Zunfu Ke, Kejing Tang. Detecting ALK rearrangement by RT-PCR: A superior approach to next generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 467.

目的 提高免疫检查点抑制剂相关性肺炎(CIP)的早期诊断与治疗.方法 对1例接受程序性死亡蛋白-1单抗治疗的晚期肺腺癌患者继发免疫相关性肺炎的临床表现、影像学、微生物学、支气管镜检查、病理诊断及治疗过程进行回顾分析.结果 该例患者经过支气管镜冷冻肺活检病理显示为机化性肺炎,早期诊断CIP,临床分级2级,予停用免疫检查点抑制剂,同时给予口服强的松(按1 mg·kg-1·d-1)治疗2周后症状好转,复查胸部CT见肺部病灶较前大部分吸收.结论 CIP临床表现多样化,早期诊断困难;支气管镜检查尤其是经支气管镜冷冻肺活检有助早期CIP明确诊断,CIP使用糖皮质激素治疗效果好.

目的 探讨经支气管冷冻肺活检(TBCB)对弥漫性实质性肺疾病(DPLD)的诊断价值.方法 回顾性分析2017年10月-2019年12月中山大学附属第一医院30例经支气管镜肺活检(TBLB)联合TBCB患者的临床资料,胸部CT主要表现为DPLD.其中,男16例,女14例;年龄25～71岁,平均(57.1±9.4)岁.结果 TBCB组标本(19.9±5.4)mm2,明显较TBLB组的(2.2±0.6)mm2大,两组比较,差异有统计学意义(t=-39.31,P=0.000);TBCB组提供有价值的病理结果为80.0％(24/30),明显高于TBLB组的36.7％(11/30),两组比较,差异有统计学意义(x2=115.88,P=0.000);TBCB对26例DPLD患者的诊断率为76.9％(20/26);16例经硬镜下TBCB和14例经非硬镜下TBCB的诊断率分别为75.0％和85.7％,两组比较,差异无统计学意义(P>0.05);术中使用预置球囊及无预置球囊的平均出血量分别为6.1和10.2 mL,中度出血情况分别为20.0％(2/10)和37.5％(6/16),两组比较,差异均无统计学意义(P>0.05).结论 经硬质支气管镜与非硬质支气管镜下进行TBCB均能达到检查目的,TBCB对DPLD有良好的诊断阳性率,且安全性较高.术中使用预置球囊止血可减少术中出血量及中度出血的病例数,虽然与非预置球囊组比较差异无统计学意义,但仍建议术中使用预置球囊止血,以提高对大出血风险的干预能力,提高病理科诊断水平可提高DPLD诊断率.

Osimertinib has efficacy superior to that of standard epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for the first-line treatment of patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, patients treated with osimertinib eventually acquire drug resistance. MET missense mutations have been demonstrated to mediate resistance to MET-TKIs, such as crizotinib. But the role of MET missense mutations in mediating EGFR TKI resistance is undefined. With the increasing use of next-generation sequencing (NGS) at diagnosis, many mechanisms of acquired resistance have been discovered in patients with activated tyrosine kinase receptors. Herein, we report the first case of MET D1228N mutation mediating acquired resistance to osimertinib in a MET TKI-naïve NSCLC. The patient with advanced lung adenocarcinoma harboring EGFR exon 19 deletion initially responded to osimertinib with progression-free survival (PFS) lasting 11 months and then developed resistance with an acquired mutation of MET D1228N. Subsequently, combination therapy of cabozantinib and osimertinib was administrated to the patient, and her clinical symptoms were rapidly relieved within one week with good tolerance. She remained on the combined treatment for 10 months. Finally, she achieved an overall survival (OS) of 25 months. Based on our findings, patient with MET D1228N mutant lung adenocarcinoma clinically benefited from combinatorial therapy of cabozantinib and osimertinib after osimertinib resistance.

Background Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern characterized by the intra-alveolar fibrin deposition and organizing pneumonia. Its clinical characteristics are still not well known and there is no consensus on treatment yet. Case presentation We report two female cases in their fifties diagnosed with AFOP confirmed by a second lung biopsy. Case 1 was idiopathic AFOP with manifestation of 6-week fever, dyspnea, and cough, while case 2 was secondary to systemic lupus erythematosus and fever was the major symptom. Their chest CT scans revealed bilateral multiple consolidations, predominantly in the lower lobes. Both cases were initially diagnosed with pneumonia, but did not improve after treatment with broad-spectrum antibiotics. In both cases, transbronchial biopsy and bronchoalveolar lavage fluid examination were inconclusive and the pathological diagnosis was confirmed by percutaneous lung biopsy. Both patients had a good clinical response to prednisone. Conclusions We report two rare AFOP cases to highlight the importance of awareness of this disease. We further perform the most comprehensive review to date in AFOP, including 150 patients since 2002. Consolidation was the most common imaging pattern, followed by ground-glass opacity and nodules. A lung biopsy is required for a definitive diagnosis. Corticosteroids is recommended as the most effective therapy, but treatment options should depend on the etiology and disease severity.