Efficacy of cross-line anti-programmed death 1/programmed cell death-ligand 1 antibody in the treatment of advanced nonsmall cell lung cancer: A retrospective study.

Background and Aims: Immune checkpoint inhibitors (ICIs) across multiple treatment lines have not yet been evaluated comprehensively. The purpose of this research was to investigate whether or not continuous cross-line ICIs therapy is effective in treating non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective investigation into the medical histories of 47 patients diagnosed with advanced NSCLC and treated with ICIs at the Peking University First Hospital between January 2018 and June 2022. Results: Due to the progression of their disease, 14 patients were given the same ICIs, 5 patients were given different ICIs, and 6 patients discontinued taking ICIs altogether. The objective response rates were 7.140% in the ICIs cross-line treatment group, 0% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The disease control rates were 64.260% in the ICIs cross-line treatment group, 60% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The average overall survival durations of the three groups were 24.020 (95% confidence interval [CI]: 17.061-30.979), 31.643 (95% CI: 23.513-39.774), and 7.997 (95% CI: 3.746-12.247) months, respectively (p = 0.003). The median second progression-free survival (PFS2) durations of the three groups were 4.570 (95% CI: 3.276-5.864), 3.530 (95% CI: 0.674-6.386), and 1.570 (95% CI: 0-4.091) months, respectively (p = 0.091). Conclusions: Cross-line ICIs cannot improve the prognosis and PFS2 of patients with NSCLC, but compared to discontinuing ICIs, OS may be prolonged. A few patients may benefit from prolonged ICIs therapy.

DNA image cytometry of bronchial washing as a diagnostic adjunct to radial endobronchial ultrasound-guided sampling of peripheral lung lesions: A single center prospective study.

OBJECTIVE: The objective of this study is to study the adjunct role of combining DNA aneuploidy analysis with radial endobronchial ultrasound (R-EBUS)-guided sampling for diagnosis of peripheral lung lesions (PPLs). METHOD: A single-center prospective study was conducted in patients undergoing R-EBUS-guided sampling for PPLs. DNA image cytometry (DNA-ICM) was used to analyze DNA aneuploidy in bronchial washing from the bronchial segment of the PPL. Clinical information, R-EBUS data, pathology, DNA-ICM results, and follow-up data were analyzed. Sensitivity, specificity, and predictive values for R-EBUS-guided sampling, DNA-ICM, and the two methods combined were measured. Binary logistic regression was performed to determine influencing factors on diagnostic positivity rate. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff point for DNA-ICM. RESULTS: A total of 101 patients were enrolled. Sixty-four (63.4%) patients had confirmed malignant tumor, of whom 33 were confirmed by R-EBUS-guided sampling (biopsy and/or bronchial brush and wash cytology), and 31 by surgery or percutaneous lung biopsy. Thirty-seven patients were finally considered to have benign lesions, based on clinical information and 1-year follow-up. The sensitivity for malignant disease was 51.6% by R-EBUS, and specificity was 100%. DNA-ICM had a sensitivity of 67.2% and a specificity of 86.5%. When combining the two methods, sensitivity increased to 78.1% and specificity was 86.5%. Lesion size and whether the R-EBUS probe was located in the lesion were significantly associated with positivity rate of the combined methods. The optimal cutoff point for DNA-ICM was 5c for max DNA content, and 1 for aneuploid cell count (sensitivity 67.2%, specificity 86.5%, accuracy 63.4%). CONCLUSION: In malignant PPLs, DNA-ICM combined with R-EBUS-guided sampling can improve diagnostic positivity compared with either method alone.

Severe pigeon paramyxovirus 1 infection in a human case with probable post-COVID-19 condition.

Pigeon paramyxovirus 1 (PPMV-1) is an antigenic host variant of avian paramyxovirus 1. Sporadic outbreaks of PPMV-1 infection have occurred in pigeons in China; however, few cases of human PPMV-1 infection have been reported. The purpose of this article is to report a case of severe human PPMV-1 infection in an individual with probable post-COVID-19 syndrome (long COVID) who presented with rapidly progressing pulmonary infection. The patient was a 66-year-old man who was admitted to the intensive care unit 11 days after onset of pneumonia and recovered 64 days after onset. PPMV-1 was isolated from the patient's sputum and in cloacal smear samples from domesticated pigeons belonging to the patient's neighbour. Residual severe acute respiratory syndrome coronavirus 2 was detected in respiratory and anal swab samples from the patient. Sequencing analyses revealed that the PPMV-1 genome belonged to genotype VI.2.1.1.2.2 and had the 112RRQKRF117 motif in the cleavage site of the fusion protein, which is indicative of high virulence. This case of cross-species transmission of PPMV-1 from a pigeon to a human highlights the risk of severe PPMV-1 infection in immunocompromised patients, especially those with long COVID. Enhanced surveillance for increased risk of severe viral infection is warranted in this population.

A 71-year-old male with a life-threatening recurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury after pembrolizumab therapy: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, their use has been restricted in patients with preexisting autoimmune diseases due to concerns about increased risk of immune-related adverse events (irAEs). CASE PRESENTATION: We present a case of a patient with stage IV lung adenocarcinoma and a history of complement-mediated autoimmune hemolytic anemia in remission. After receiving a single dose of pembrolizumab, the patient experienced life-threatening recurrent hemolytic anemia, de novo thrombocytopenia, diarrhea, myocarditis, and acute kidney injury. Laboratory tests confirmed the diagnosis of Evan's syndrome, with positive PAIgG and direct antiglobulin test. Treatment with intravenous methylprednisolone at a dose of 2 mg/kg resulted in a favorable response, with resolution of symptoms and rapid recovery of kidney function. The probable cause of pre-renal hypoperfusion (evidenced by a BUN-to-creatinine ratio of 48.1) leading to acute tubular injury was attributed to pembrolizumab-induced diarrhea. CONCLUSIONS: This case illustrates a life-threatening recurrence of complement-mediated autoimmune hemolytic anemia induced by ICIs. Clinicians should carefully consider the expected efficacy and potential toxicity before initiating ICIs therapy in patients with preexisting autoimmune diseases. Additionally, the occurrence of acute kidney injury during ICIs therapy adds complexity and requires careful differential diagnosis.

Severe Hemoptysis Secondary to Actinomycosis: A Case Report.

Pulmonary actinomycosis (PA) is an uncommon, asymptomatic, and frequently misdiagnosed pulmonary infectious illness. Our patient remained undiagnosed despite extensive regular and invasive testing, significant intermittent hemoptysis, and repeated bronchial artery embolization. Ultimately, a left lower lobectomy was performed via video-assisted thoracoscopic surgery, and a histopathological examination revealed an actinomycete infection.

The value on SUV-derived parameters assessed on 18F-FDG PET/CT for predicting mediastinal lymph node metastasis in non-small cell lung cancer.

PURPOSE: To explore valuable predictors for mediastinal lymph node metastasis in non-small cell lung cancer (NSCLC) patients, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from preoperative 18F-FDG PET/CT combined with clinical characteristics. METHODS: Data from 224 NSCLC patients who underwent preoperative 18F-FDG PET/CT scans in our hospital were collected. Then, a series of clinical parameters including SUV-derived features [SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] were evaluated. The best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Predictive analyses were performed using a Logistic regression model to determine the predictive factors for mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. After multivariate model construction, data of another 100 NSCLC patients were recorded. Then, 224 patients and 100 patients were enrolled to validate the predictive model by the area under the receiver operating characteristic curve (AUC). RESULTS: The mediastinal lymph node metastasis rates in 224 patients for model construction and 100 patients for model validation were 24.1% (54/224) and 25% (25/100), respectively. It was found that SUVmax of mediastinal lymph node ≥ 2.49, primary-tumor SUVmax ≥ 4.11, primary-tumor SUVpeak ≥ 2.92, primary-tumor SUVmean ≥ 2.39, primary-tumor MTV ≥ 30.88 cm3, and primary-tumor TLG ≥ 83.53 were more prone to mediastinal lymph node metastasis through univariate logistic regression analyses. The multivariate logistic regression analyses showed that the SUVmax of mediastinal lymph nodes (≥ 2.49: OR 7.215, 95% CI 3.326-15.649), primary-tumor SUVpeak (≥ 2.92: OR 5.717, 95% CI 2.094-15.605), CEA (≥ 3.94 ng/ml: OR 2.467, 95% CI 1.182-5.149), and SCC (< 1.15 ng/ml: OR 4.795, 95% CI 2.019-11.388) were independent predictive factors for lymph node metastasis in the mediastinum. It was found that SUVmax of the mediastinal lymph node (≥ 2.49: OR 8.067, 95% CI 3.193-20.383), primary-tumor SUVpeak (≥ 2.92: OR 9.219, 95% CI 3.096-27.452), and CA19-9 (≥ 16.6 U/ml: OR 3.750, 95% CI 1.485-9.470) were significant predictive factors for mediastinal lymph node metastasis in lung adenocarcinoma patients. The AUCs for the predictive value of the NSCLC multivariate model through internal and external validation were 0.833 (95% CI 0.769- 0.896) and 0.811 (95% CI 0.712-0.911), respectively. CONCLUSION: High SUV-derived parameters (SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, MTV and TLG) might provide varying degrees of predictive value for mediastinal lymph node metastasis in NSCLC patients. In particular, the SUVmax of mediastinal lymph nodes and primary-tumor SUVpeak could be independently and significantly associated with mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. Internal and external validation confirmed that the pretherapeutic SUVmax of the mediastinal lymph node and primary-tumor SUVpeak combined with serum CEA and SCC can effectively predict mediastinal lymph node metastasis of NSCLC patients.

IgG4-related eosinophilic pleural effusion: a case report.

BACKGROUND: The diagnosis of unilateral eosinophilic pleural effusion (EPE) is difficult, especially for the elderly. IgG4-related disease (IgG4-RD) is a rare cause of EPE. CASE PRESENTATION: An 81-year-old man was admitted to the hospital for dyspnea due to right pleural effusion. Laboratory examination shows elevated IgG4 and eosinophils in both serum and pleural fluid. The patient was diagnosed with IgG4-RD by video-assisted thoracoscopy and pleural biopsy. We found no evidence of other organ involvement except for the EPE and history of prurigo. He was treated with prednisolone 40 mg daily orally and pleural effusion decreased significantly. CONCLUSION: IgG4-RD should be considered in the differential diagnosis of EPE in the elderly. High effusion IgG4 concentration may be an indication of IgG4-related pleural lesions.

DNA aneuploidy combined with radial EBUS in the diagnosis of peripheral lung lesions.

OBJECTIVE: To explore the diagnostic value of DNA aneuploidy analysis combined with radial endobronchial ultrasound (R-EBUS)-guided transbronchial biopsy in peripheral lung lesions. METHOD: We performed a retrospective analysis of patients who underwent R-EBUS examination. DNA aneuploidy analysis of bronchial washing from the target bronchial segment were performed. The clinical information, R-EBUS data, pathological results and DNA image cytometry (DNA-ICM) results were collected. For patients who did not have a clear diagnosis after bronchoscopy, follow-up data was recorded. RESULTS: A total of 42 cases were included. Thirty patients had confirmed malignant tumor of the lung, 19 of which were confirmed by pathology after bronchoscopy, and 11 cases were confirmed later by surgery or percutaneous lung puncture. Twelve patients were finally considered to have benign lesions. The sensitivity of R-EBUS is 63.3% and the specificity is 100%. DNA-ICM has a sensitivity of 76.7% and a specificity of 91.7%. When combined, they have a sensitivity of 90%, and specificity 91.7%. As for malignant lesions, we further analyzed smoking, the size and location of lesions on chest CT, the number of aneuploid cells and the maximum value of DNA content. The results indicated that increased number of aneuploid cells or increased max value of DNA content may predict higher probability of malignancy. CONCLUSION: DNA-ICM combined with R-EBUS can improve the diagnostic sensitivity of malignant peripheral lung lesions. Increased number of aneuploid cells or increased max value of DNA content may indicate that the lesions are more likely to be malignant.

Diffuse large B-cell lymphoma presenting as reversible intrapulmonary arteriovenous shunts with hypoxia, fever and progressive jaundice: a case report and literature review.

BACKGROUND: Intrapulmonary arteriovenous shunts is rare seen in a patient without lung involvement. CASE PRESENTATION: This is the first report of reversible intrapulmonary arteriovenous shunts secondary to extrapulmonary lymphoma as one initial symptom. The patient presented as fever of unknown origin and dyspnea, and examinations of infection were negative. Diagnosis of DLBCL was finally confirmed through bone marrow and splenic biopsies. Intrapulmonary arteriovenous shunts were diagnosed through 100% oxygen inhalation test and transthoracic contrast echocardiography (TTCE). After the treatment of lymphoma, his respiratory failure was relieved. We rechecked the 100% oxygen inhalation test and TTCE, which both indicated that his intrapulmonary arteriovenous shunts had resolved. CONCLUSIONS: We speculated the prominent inflammation from active DLBCL was the most possible mechanism associated with the reversible intrapulmonary shunt in this patient. These findings will assist us to better understand the mechanism of intrapulmonary shunts.

DNA image cytometric analysis of bronchial washings as an adjunct for the detection of lung cancer in a clinical setting.

BACKGROUND: DNA aneuploidy has a potential to become an adjunct to conventional cytology for diagnosis of lung cancer, but its value in bronchial washings has not been well evaluated. METHODS: We conducted a retrospective study on patients who underwent bronchoscopy and the bronchial washings were submitted for both cytology and DNA image cytometry (DNA-ICM) examination. The sensitivity and specificity of two methods and both in combination were compared. Analysis of clinical subgroups and DNA histogram were also performed. RESULTS: The study included 626 patients (326 patients with lung cancer and 300 patients with benign lung diseases). The sensitivity of cytology, DNA-ICM, and combination test for lung cancer were 53.3%, 62.3%, and 75.8%, respectively, and the sensitivity of DNA-ICM and combination test were superior to that of cytology (p < 0.05). A modest reduction of specificity was found in DNA-ICM compared with cytology (91.3% vs. 98.3%, p < 0.05). Subgroup analysis showed there was no significant difference in sensitivity of DNA-ICM between the visible tumor group and the invisible tumor group (66.5% vs. 56.9%, χ2  = 3.114, p = 0.078). Among 101 patients with invisible endobronchial tumor, the positive rates for DNA-ICM of washing, cytology of washing, brushing and biopsy were 62.4%, 41.6%, 40.6%, and 45.5%, respectively. DNA-ICM in combination with the basic bronchoscopy techniques could increase the sensitivity from 67.3% to 87.1% (p = 0.000). The DNA histogram analysis showed 25.3% washing samples of lung cancer were diploid pattern, 49.4% were scattered aneuploid cells pattern, and 25.3% were aneuploid peaks pattern. Small cell lung cancer had the highest proportion of aneuploid peaks pattern (p < 0.05). CONCLUSIONS: DNA-ICM could be used as an adjunct for the detection of lung cancer. The combination of DNA-ICM and basic bronchoscopy techniques could significantly increase the sensitivity, especially for the patients suspected of peripheral lung cancer, and contribute to select subjects for advanced bronchoscopy.

The rescue intervention strategy for asthma patients under severe air pollution: a single-center prospective randomized controlled trial.

OBJECTIVE: The aim of our study is to provide a novel strategy to administer treatment at the first signs of severe air pollution and before patients experience symptoms for preventing airway damage. METHODS: This single-center, prospective, randomized and standard treatment parallel control clinical trial recruited adult asthma patients. The patients were randomized into either the rescue intervention strategy (RIS) group or control group. The rescue intervention strategy for the RIS group included budesonide/formoterol plus the original treatment until the severe pollution ended. The control group was maintained on the original treatment. The follow-up observation period was 1 year. RESULTS: Overall, 22 participants were enrolled and 20 completed the follow-up (11 in the RIS group and 9 in the control group). Two participants dropped out of the trial for personal reasons before the first follow-up. In the intention-to-treat analysis, the frequency of asthma exacerbations per year was significantly lower in the RIS group than in the control group (RIS vs. control, 0.55 vs. 2.67; risk rate [RR] [95% confidence interval {CI}], 0.21 [0.08-0.50]; p = 0.001). The mean number of unplanned outpatient visits per person per year was also lower in the RIS group than in the control group (RIS vs. control, 0.18 vs. 1.11; RR [95% CI], 0.16 [0.04-0.75]; p = 0.019). CONCLUSION: A novel strategy to administer treatment at the first signs of severe air pollution and before patients experience symptoms may decrease the risk of asthma exacerbations and negative outcomes under severe air pollution conditions. TRIAL REGISTRATION: ChiCTR, ChiCTR1900026757. http://www.chictr.org.cn.

Early-onset interstitial pneumonitis in a patient with advanced non-small cell lung cancer treated with crizotinib and osimertinib.

Both crizotinib and osimertinib have been reported to have an adverse effect of interstitial pneumonitis in the treatment of non-small cell lung cancer (NSCLC). Here, we report the case of a 60-year-old male patient with advanced NSCLC resistant to osimertinib. Crizotinib was administered in combination with osimertinib due to elevated mesenchymal epithelial transition (MET) copy number amplification. However, early-onset interstitial pneumonitis occurred within two days.

The rescue intervention strategy for asthma patients under severe air pollution: a protocol for a single-centre prospective randomized controlled trial.

BACKGROUND: Asthma is a common chronic airway inflammatory disease. Exacerbations of asthma not only accelerate the progression of the disease but also increase the incidence of hospitalization and death. Studies have shown that air pollution is a high-risk factor for asthma exacerbations. However, few treatment strategies have been recommended to reduce the risk of severe air pollution-related asthma exacerbations. METHODS/DESIGN: This is a single-centre, prospective, randomized and standard treatment parallel control clinical trial. Seventy-two asthma patients in the nonexacerbation stage according to GINA guidelines 2017 will be recruited and randomized into the rescue intervention strategy (RIS) group and control group. Original treatments for the participants will include no use of inhaled medicine, the use of short-acting ß-agonists (SABA) on demand or the use of budesonide/formoterol (160 µg/4.5 µg/dose, 1-2 dose/time, b.i.d.). The rescue intervention strategy for the RIS group will be budesonide/formoterol plus the original treatment until the severe pollution ends (air quality index, AQI < 200). The control group will maintain the original treatment. The follow-up observation period will last 1 year. The primary outcome is the frequency of asthma exacerbations per year. Secondary outcomes include the mean number of unplanned outpatient visits, emergency visits, hospitalizations, medical costs and mortality caused by asthma exacerbations per patient per year. DISCUSSION: The results of this trial will provide a novel strategy to guide clinical practice in decreasing the risk of asthma exacerbations under severe air pollution. TRIAL REGISTRATION: ChiCTR ChiCTR1900026757 . Registered on 20 October 2019-retrospectively registered.

Living near a Major Road in Beijing: Association with Lower Lung Function, Airway Acidification, and Chronic Cough.

BACKGROUND: The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms. METHODS: We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing <100 m, 100-200 m, and >200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate (EBC) pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers. RESULTS: Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s (FEV1% -1.54, 95% confidence interval [CI]: -0.20 to -2.89). The odds ratio for chronic cough was 2.54 (95% CI: 1.57-4.10) for category 1 and 1.97 (95% CI: 1.16-3.37) for category 2, compared with category 3. EBC pH was positively correlated with road distance (rank correlation coefficient of Spearman [rs] = 0.176, P < 0.001). CONCLUSIONS: Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure.

[Analysis of factors associated with decline of FEV1 among community population in urban area of Beijing].

OBJECTIVE: To investigate risk factors correlated to the decline of FEV1among community population in the urban area of Beijing. METHOD: Subjects no younger than 40 years old were recruited from three communities in the urban area of Beijing. All of them were asked to fill in a questionnaire in regard to general health conditions, past medical history, medication usage, smoking history, etc. FEV1and FEV6 were measured by Vitalograph COPD-6 spirometer using the standard protocol. Two years after the first visit, questionnaire survey and spirometry were repeated. RESULT: Four hundred and fifty two subjects fulfilled the inclusion criteria and finished the 2nd visit, with an average age of (58.8 ± 8.6) years, 29% male and 71% female. The mean decline rate of FEV1in the cohort was (43 ± 114) ml per year. There was no significant difference of mean FEV1decline between different gender and age groups. A mean decline of FEV1by (64 ± 125) ml per year was observed in smokers (including former smokers and current smokers) whereas the decline rate in non-smokers was (36 ± 109) ml per year (P = 0.030). There was no significant statistical difference among current smokers, former smokers, passive smokers and subjects who never smoke. A higher decline rate of FEV1was observed in subjects with a history of COPD or airway hyperreactivity, chronic cough, diabetes, hypertension and coronary heart disease. The difference, however, was not statistically significant. Binary logistic regression was used to screen risk factors affected the FEV1decline rate between rapid decline (ΔFEV1 ≥ 30 ml/y) and non-rapid decline (ΔFEV1 < 30 ml/y), and found smoking was an independent risk factor of FEV1decline rate. CONCLUSION: The mean rate of FEV1 decline in 2.6 years in the surveyed community population in the urban area of Beijing was (43 ± 114) ml per year; Smoking is an independent risk factor of FEV1decline.