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BACKGROUND: In ALTER 1202, anlotinib prolonged the progression-free survival (PFS) and overall survival (OS) of patients with relapsed small cell lung cancer (SCLC). The aim of this study was to explore the effect of front-line thoracic radiotherapy (RT) on the benefits of anlotinib as a third-line-or-beyond treatment. METHODS: This was a subgroup analysis of a multicenter, randomized, double-blind, placebo-controlled phase 2 trial (ALTER 1202). The participants were divided into RT (previous thoracic RT) and non-RT subgroups. The outcomes included PFS, OS, objective response rate (ORR), disease control rate (DCR), and safety. RESULTS: In the ALTER 1202 trial, 68 participants (anlotinib, n=46; placebo, n=22) received RT and 51 participants (anlotinib, n=35; placebo, n=16) did not. PFS was longer for anlotinib versus placebo in both the RT (5.49 vs. 0.69 months; P

Background Chemotherapy is a common treatment for patients with resected non-small cell lung cancer (NSCLC). However, there are few models for predicting the survival outcomes of these patients. Here, we developed a clinical nomogram for predicting overall survival (OS) in this cohort. Methods A total of 16,661 patients with resected NSCLC treated with chemotherapy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified prognostic factors and integrated them into a nomogram. The model was subjected to bootstrap internal validation using the SEER database and external validation using a database in China and the National Cancer Database (NCDB). The model's predictive accuracy and discriminative ability were tested by calibration and concordance index (C-index). Results Age, sex, number of dissected lymph nodes, extent of surgery, N stage, T stage, and grade were independent factors for OS and were integrated into the model. The calibration curves for probability of 1-, 3-, and 5-year OS showed excellent agreement between the predicted and actual survivals. The C-index of the nomogram was higher than that of the Tumor-Node-Metastasis staging system for predicting OS (training cohort, 0.62 vs. 0.58; China cohort, 0.68 vs. 0.63; NCDB cohort, 0.59 vs. 0.57). Conclusions We developed a nomogram that can present individual prediction of OS for patients with resected NSCLC who are undergoing chemotherapy. This practical prognostic tool may help clinicians in treatment planning.

Lung autotransplantation is an alternative technique in treating central non-small cell lung cancer (NSCLC) for patients who are not suitable to undergo pneumonectomy. We hereby report a novel lung autotransplantation technique for treating central lung cancer. Two cases of central NSCLC involving right main bronchus underwent right basal segment and right lower lobe autotransplantation after resection. The inferior pulmonary vein of graft was anastomosed to superior pulmonary venous stump in both cases to reduce the bronchial and pulmonary arterial gap created after extensive resection. One case had anastomosis of basal segment artery to the right upper lobe anterior segment artery stump while the other case had pulmonary artery angioplasty only without segmental arterial resection. Both procedures were performed in situ without graft perfusion. The airway reconstructions were completed using parachute principle via end-to-side anastomosis of graft bronchus and lateral wall of trachea instead of end-to-end anastomosis with main bronchial stump. Both patients received ICU care postoperatively for 4 days. Chest tubes were successfully removed within 7 days. They were discharged within 11 days postoperatively. No major complication, such as severe infection, anastomotic dehiscence, anastomotic stenosis, atelectasis, or pulmonary embolism was observed. There was no evidence of recurrence at 9-month follow-up.

Background: Metastatic non-small cell lung cancer (NSCLC) has many comorbidities, such as chronic obstructive pulmonary disease, coronary heart disease, and older age-related comorbidities. A survival benefit was observed in such patients who underwent surgery for selected oligometastatic disease. However, to the best of our knowledge, there is no evidence to support whether lobectomy (compared with sub-lobar resection) would further prolong these patients' lives. Methods: Patients with metastatic NSCLC who underwent primary tumor resection were identified from the Surveillance, Epidemiology, and End Results (SEER) database and then divided into lobectomy and sub-lobar resection groups. Propensity score matching (PSM, 1:1) was performed to match the baseline characteristics of the two groups. Cancer-specific survival (CSS) was estimated. Results: In total, 24,268 patients with metastatic NSCLC were identified; 4,114 (16.95%) underwent primary tumor surgery, and of these, 2,045 (49.71%) underwent lobectomy and 1,766 (42.93%) underwent sub-lobar resection. After PSM, 644 patients in each group were included. Lobectomy was independently correlated with longer median CSS time [hazards ratio (HR): 0.70, 95% confidence interval (CI): 0.61-0.80, P

Objective We aim to report a novel surgical technique that robotic-assisted thoracoscopic surgery combined with non-intubated spontaneous ventilation to perform tracheal/airway surgery. Summary background data Our team has demonstrated video-assisted transthoracic surgery (VATS) can be used for thoracic tracheal diseases with satisfactory outcomes. Our team has also demonstrated that tracheal/ airway resection and reconstruction under spontaneous ventilation can improve the anastomosis and operating time. Recently, robotic-assisted thoracoscopic surgery (RATS) emerged as an available alternative minimally invasive approach for lung cancer, with lower perioperative mortality and conversion rate to open. Methods Five patients fulfilling the criteria for non-intubated approach underwent RATS tracheal/airway surgery. Patient 1 has a tumor in the thoracic trachea; patient 2 had involving secondary carina; patient 3 had involving trachea carina, and patient 4 had involving left main bronchus. Patient 5 had involving mid-tracheal. Results All patients had an uneventful procedure. The total operative time ranged from 5 h 5 min to 9 h 55 min. The postoperative hospital stays ranged from 4 days to 14 days. Fiber-optic bronchoscopy performed one month after the procedure showed good anastomotic healing with no stricture. Conclusion This is the first report on RATS use in tracheal/airway surgery, in combination with non-intubation spontaneous ventilation. In selected patients, this novel combined approach is feasible and safe. A patient can potentially benefit from the combined advantages of both techniques. More cases and longer-term data are required to establish its role in tracheal/airway surgery.

Background Several articles have been published about the reorganization of surgical activity during the coronavirus disease 2019 (COVID-19) pandemic but little is known about the operative volume, distribution of cases, or capacity of The Department of Thoracic Surgery to deliver surgical services in the time of COVID-19. Methods A retrospective operative logbook review was completed in department of thoracic in a designated COVID-19 hospital. We reviewed and analyzed the operative logbook and discussed our countermeasures during the outbreak. A prediction model was established to discuss the time consuming about delayed surgeries during the pandemic. Results One thousand two hundred and seventy-five operation records were collected. The thoracic surgeries of this year has decreased (43.4%) during the Wuhan lockdown. From Jan 23rd to Apr 8th in 2020, there were 461 surgeries performed in The Department of Thoracic in our hospital with 0 cases of nosocomial COVID-19 infection. Prediction model showed that it will take 6 weeks to solve the backlog if department can reach the 85% of maximum of operations per week. Conclusions An understanding of operative case volume and distribution is essential in facilitating targeted interventions to strengthen surgical capacity in the time of COVID-19. A proper guideline is imperative to ensure access to safe, timely surgical care. By developing a scientific and effective management of hospital, it is possible to ensure optimal surgical safety during this crisis. Regular updates and a further study include multicenter is required. Clinical trial registry number ChiCTR2000034346.

Background The risk factors for postoperative complications in non-intubated video-assisted thoracoscopic surgery (VATS) has not been observed before. Here to develop a simple risk score to predict the risk of postoperative complications for patients who scheduling non-intubated VATS, which is beneficial to guide the clinical interventions. Methods 1837 patients who underwent non-intubated VATS were included from January 2011 to December 2018. A development data set and a validation data set were allocated according to an approximate 3:2 ratio of total cases. The stepwise logistic regression was used to establish a risk score model, and the methods of bootstrap and split-sample were used for validation. Results Multivariable analysis revealed that the forced expiratory volume in the first second in percent of predicted, the anesthesia method, blood loss, surgical time, and preoperative neutrophil ratio were risk factors for postoperative complications. The risk score was established with these 5 factors, varied from 0–53, with the corresponding predicted probability of postoperative complications occurrence ranged from 1%-92%, and was calibrated (Hosmer-Lemeshow χ2 = 6.261; P = 0.618). Good discrimination was acquired in the development and validation data sets (C-statistic 0.705 and 0.700). A positive correlation was between the risk score and postoperative complications (P for trend 30 points] were established based on the score distribution of postoperative complications. Conclusions This simple risk score model based on risk factors of postoperative complications can validly identify the high-risk patients with postoperative complications in the non-intubated VATS, and allow for early interventions.

BACKGROUND: It has been reported that tubeless video-assisted thoracoscopic surgery (tubeless-VATS) is feasible and safe for thoracic diseases. Herein, we compared the early outcomes of mediastinal lesion resection between the tubeless and traditional VATS. METHODS: Clinical data of all patients who underwent thoracoscopic mediastinal tumor resection were retrospectively collected. The study involved two groups: tubeless and traditional VATS group. Propensity score matching (PSM) was applied to eliminate the population bias. Intraoperative and postoperative variables were compared among matched cohorts. RESULTS: In total, 43 patients in the tubeless group and 231 patients in the traditional VATS group were included. After 1:1 PSM, baseline characteristics were comparable. Anesthesia time (177.63 vs. 202.53 min; P=0.004) was shorter in tubeless group, while operation time (90.95 vs. 101.47 min; P=0.109) was similar. Overall, the total postoperative morbidity rate was similar in the two groups (15% vs. 12.5%; P=0.556). Specially, 4/43 patients in tubeless VATS group need to be re-put chest tubes postoperatively. A significant lower similar level of visual analogue scale score was observed in tubeless VATS group (1.73±0.48 vs. 3.41±0.87, P

BACKGROUND: Current clinical management of patients with pulmonary nodules involves either repeated low-dose CT (LDCT)/CT scans or invasive procedures, yet causes significant patient misclassification. An accurate noninvasive test is needed to identify malignant nodules and reduce unnecessary invasive tests. METHOD: We developed a diagnostic model based on targeted DNA methylation sequencing of 389 pulmonary nodule patients’ plasma samples and then validation in 140 plasma samples independently. We tested the model in different stages and subtypes of pulmonary nodules. RESULTS: A 100-feature model was developed and validated for pulmonary nodule diagnosis; the model achieved a receiver operating characteristic curve–AUC (ROC-AUC) of 0.843 on 140 independent validation samples, with an accuracy of 0.800. The performance was well maintained in (a) a 6 to 20 mm size subgroup (n = 100), with a sensitivity of 1.000 and adjusted negative predictive value (NPV) of 1.000 at 10% prevalence; (b) stage I malignancy (n = 90), with a sensitivity of 0.971; (c) different nodule types: solid nodules (n = 78) with a sensitivity of 1.000 and adjusted NPV of 1.000, part-solid nodules (n = 75) with a sensitivity of 0.947 and adjusted NPV of 0.983, and ground-glass nodules (n = 67) with a sensitivity of 0.964 and adjusted NPV of 0.989 at 10% prevalence. This methylation test, called PulmoSeek, outperformed PET-CT and 2 clinical prediction models (Mayo Clinic and Veterans Affairs) in discriminating malignant pulmonary nodules from benign ones. CONCLUSION: This study suggests that the blood-based DNA methylation model may provide a better test for classifying pulmonary nodules, which could help facilitate the accurate diagnosis of early stage lung cancer from pulmonary nodule patients and guide clinical decisions. FUNDING: The National Key Research and Development Program of China; Science and Technology Planning Project of Guangdong Province; The National Natural Science Foundation of China National.

BACKGROUND: An increasing number and proportion of younger lung cancer patients have been observed worldwide, raising concerns on the optimal age to begin screening. This study aimed to investigate the association between age and findings in initial CT scans. METHODS: We searched for low-dose CT screening cohorts from electronic databases. Single-arm syntheses weighted by sample size were performed to calculate the detection rates of pulmonary nodules, lung cancers (all stages and stage I), and the proportion of stage I diseases in lung cancers. In addition, we included patients who underwent chest CT in our center as a supplementary cohort. The correlation between the detection rates and age was evaluated by the Pearson Correlation Coefficient. RESULTS: A total of 37 studies involving 163,442 participants were included. We found the detection rates of pulmonary nodules and lung cancers increased with age. However, the proportion of stage I diseases in lung cancers declined with increased starting age and was significantly higher in the 40-year group than in other groups (40 vs. 45, 50, 55, P

Currently, lung transplantation is the standard of care for patients with end-stage lung disease, with interstitial lung disease (ILD) being the most common reason in the recent years In the other hand, in cases where stage II and III lung cancer have been identified following lung transplantation, long-term survival outcomes are poor when compared to lung cancer patients that have not received a lung transplant because the use of immunosuppressant and the problem of rejection and infection and the treatment of recurrence and so on. However, there is no statistical difference observed in stage I (pT1N0M0) patients. In this paper we report about a patient with ILD receiving left lung transplantation in the early time. A lesion of the right lung which was considered the normal ILD tissue and without enough attention. Post-transplant it showed progress and finally the whole right lung (native lung) was occupied by the tumor. Some ground glass changes could also be found in the transplanted lung several months later. A secondary lung transplant was performed for this patient, and there has been no postoperative recurrence thus far. For lung transplant patients with high-risk factors, effective surveillance methods are required for the early detection of lung cancer.

Immunotherapy has been proved to be a promising candidate for advanced non-small cell lung cancer (NSCLC). Despite MET mutations are regarded as an independent factor of programmed death ligand 1 (PD-L1) high expression, the efficacy of immune checkpoint inhibitors (ICIs) across NSCLC harboring Mesenchymal-epithelial transition factor exon 14 skipping alteration (METex14) is still uncleared. Moreover, when the resistance of PD-1 antibody occurs, the questions of how to interpret the resistance and how to overcome the resistance are worth exploring. We report a case of NSCLC with METex14 developed a right femoral metastasis after responding well to neoadjuvant immunotherapy, a successful lobectomy, and adjuvant immunotherapy. The subsequent attempts of MET targeted inhibitor, concurrent chemoradiotherapy, and notably programmed cell death protein 1 (PD-1) antibody plus vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) failed to prevent disease progression. However, a regimen of anti-PD-1 plus anti-cytotoxic t-lymphocyte associated protein 4 (CTLA-4) reversed the progression to a complete response. This case shows that METex14 had a significant response to immunotherapy, which would be especially beneficial for those who developed targeted therapy resistance. Importantly, this is the first case reporting that salvage CTLA-4 antibody and PD-1 antibody could reverse the progression in NSCLC harboring METex14 when the anti-PD-1 resistance occurred.

Background Subxiphoid approach for mediastinal tumor resection was reported to provide a better view and less postoperative pain. Non-intubated video-assisted thoracic surgery (NI-VATS) without muscle relaxant would decrease the possibility of postoperative airway collapse for anterior mediastinal mass operation. Herein, we sought to describe the use of NI-VATS through subxiphoid approach for anterior mediastinal tumor resection. Methods In this retrospective cohort study, patients that underwent subxiphoid VATS resection for anterior mediastinal tumor between December 2015 and September 2019 were divided into two groups: NI-VATS and intubated VATS (I-VATS). Intraoperative and postoperative variables were compared. Results A total of 40 patients were included. Among them, 21 patients received NI-VATS (52.5%) and 19 were treated with I-VATS (47.5%). In total, intraoperative (4/21 vs. 2/19; P=0.446) and postoperative complications (5/21 vs. 7/19; P=0.369) were similar between NI-VATS and I-VATS group. The anesthesia time (231.76 vs. 244.71 min; P=0.218), the operation time (152.35 vs. 143.64 min; P=0.980), chest tube duration (1.81 vs. 1.84 days; P=0.08), the total volume (351.95 vs. 348.00 mL; P=0.223), post-operative pain scores (2.79 vs. 2.93, P=0.413), and the length of stay (9.47 vs. 10.57 days; P=0.970) were all comparable between two groups. Conclusions NI-VATS for mediastinal tumor resection via subxiphoid approach is a safe and technically feasible option in selected patients, which leads to comparable perioperative clinical outcomes when compared with I-VATS via the subxiphoid approach. This technique could be used as an alteration when intubation is not available.

Background Small cell lung cancer (SCLC) is highly invasive and poorly prognostic. The effects of chemotherapy with bevacizumab are promising on other tumors but unclear in extensive-disease SCLC (ED-SCLC). A systemic review and meta-analysis were performed to investigate the efficacy and toxicity in ED-SCLC patients. Methods A review of current studies was performed on electronic databases and other sources to identify publications of ED-SCLC patients who received bevacizumab. Endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and complications. Results Nine relevant articles with six single-arm and three two-arm studies were identified. Four hundred seventy-six patients were included, of which 368 and 108 were untreated and relapse patients. Most patients were performance status 0-1 (71.6%) and male (58.1%). The comparisons showed CT/bevacizumab slightly prolonged OS (HR =0.84) but significantly improved PFS (HR =0.74). The ORRs of untreated and relapse patients were 71% and 19%, though no significant difference was observed than CT/placebo. The most grade 3-4 complication and bevacizumab-associated complications were neutropenia and hypertension, whose rates were 33% and 6%. Patients who received CT/bevacizumab had a higher hypertension rate than CT/placebo (6% vs. 2%). No different complication rate was observed between high and lose dose groups. Discussion The present study suggests that bevacizumab in the combination of standard chemotherapy provides better PFS than chemotherapy alone. Although the combined regimen is well-tolerated, no superiority in OS or response rate is observed.

BackgroundAccumulation of myofibroblasts is critical to fibrogenesis in idiopathic pulmonary fibrosis (IPF). Senescence and insufficient mitophagy in fibroblasts contribute to their differentiation into myofibroblasts, thereby promoting the development of lung fibrosis. Bone morphogenetic protein 4 (BMP4), a multifunctional growth factor, is essential for the early stage of lung development; however, the role of BMP4 in modulating lung fibrosis remains unknown.MethodsThe aim of this study was to evaluate the role of BMP4 in lung fibrosis using BMP4-haplodeleted mice, BMP4-overexpressed mice, primary lung fibroblasts and lung samples from patients with IPF.ResultsBMP4 expression was downregulated in IPF lungs and fibroblasts compared to control individuals, negatively correlated with fibrotic genes, and BMP4 decreased with transforming growth factor (TGF)-β1 stimulation in lung fibroblasts in a time- and dose-dependent manner. In mice challenged with bleomycin, BMP4 haploinsufficiency perpetuated activation of lung myofibroblasts and caused accelerated lung function decline, severe fibrosis and mortality. BMP4 overexpression using adeno-associated virus 9 vectors showed preventative and therapeutic efficacy against lung fibrosis.In vitro, BMP4 attenuated TGF-β1-induced fibroblast-to-myofibroblast differentiation and extracellular matrix (ECM) production by reducing impaired mitophagy and cellular senescence in lung fibroblasts. Pink1 silencing by short-hairpin RNA transfection abolished the ability of BMP4 to reverse the TGF-β1-induced myofibroblast differentiation and ECM production, indicating dependence on Pink1-mediated mitophagy. Moreover, the inhibitory effect of BMP4 on fibroblast activation and differentiation was accompanied with an activation of Smad1/5/9 signalling and suppression of TGF-β1-mediated Smad2/3 signallingin vivoandin vitro.ConclusionStrategies for enhancing BMP4 signalling may represent an effective treatment for pulmonary fibrosis.

Background The relationship of multiple sclerosis (MS) with lung cancer is under debate. Conventional observational studies have reported conflicting findings, but such studies are susceptible to confounding and reverse causation. With a Mendelian Randomization approach, we were able to evaluate the causality between MS and lung cancer. Methods According to published genome-wide association studies (GWASs), we obtained 35 MS-related single-nucleotide polymorphisms, which were used as instrumental variables in our study. Summary data of individual-level genetic information were obtained from the International Lung Cancer Consortium (ILCCO), with a total of 15,861 controls and 11,348 cases; the latter is composed of patients with lung adenocarcinoma and squamous cell lung cancer. The inverse variance-weighted method was applied to estimate the causation between MS and lung cancer. To further evaluate the pleiotropy, the MR-Egger and Weighted median methods were implemented. Results The results of MR analysis suggested a causal effect of MS on lung cancer incidence, with evidence of an increased risk for overall lung cancer [odds ratio (OR): 1.0648; 95% confidence interval (CI): 1.0163–1.1156; p = 0.0082]. However, subgroup analyses showed no significant causal relationships between MS and lung adenocarcinoma (OR = 1.0716; 95% CI 0.9840–1.1671, p = 0.1119) and squamous cell lung cancer (OR = 1.0284; 95% CI 0.9575–1.1045, p = 0.4424). In addition, no pleiotropy was found in our study. Conclusion Our study indicated that MS is a causal risk factor in the development of lung cancer. Further work is needed to elucidate the potential mechanisms.

BACKGROUND: A survival benefit was observed in metastatic non-small cell lung cancer (NSCLC) patients that underwent surgical resection of the primary tumor. We developed a model testing the hypothesis that only certain stage IV patients would benefit from surgery and the potential benefit would vary based on primary tumor characteristics. METHODS: Patients with stage IV NSCLC were identified in the Surveillance, Epidemiology and End Results (SEER) database and then divided into surgery and non-surgery groups. A 1:1 Propensity score matching (PSM) was performed to balance characters. We assumed that patients received primary tumor surgery that lived longer than median cancer specific survival (CSS) time of those who didn’t underwent surgery could benefit from the operation. Multivariable Cox model was used to explore the independent factors of CSS in two groups (beneficial and non-beneficial group). Logistic regression was used to build a nomogram based on the significant predictive factors. RESULTS: A total of 30,342 patients with stage IV NSCLC were identified; 8.03% (2,436) received primary tumor surgery. After PSM, surgical intervention was independently correlated with longer median CSS time (19 vs. 9 months, P

The aim of the present study was to compare the short-term outcomes between spontaneous ventilation video-assisted thoracic surgery (SV-VATS) and mechanical ventilation video-assisted thoracic surgery (MV-VATS) in the elderly. All patients included in the present study underwent lobectomy, segmentectomy, or wedge resection and lymph node dissection.A retrospective cohor.The first affiliated hospital of Guangzhou Medical University, Guangzhou, China.The present study included 799 elderly patients diagnosed with non-small-cell lung cancer undergoing SV-VATS or MV-VATS. After propensity score matching, 80 patients in the SV-VATS group and 80 patients in the MV-VATS group were analyzed.Patients in the SV-VATS group received spontaneous-ventilation anesthesia, which was administered as follows: intravenous anesthesia + laryngeal mask airway + thoracic paravertebral block + visceral pleural surface anesthesia + thoracic vagus nerve block. Patients in the MV-VATS group received general endotracheal anesthesia. SV-VATS or MV-VATS was performed according to the preference of the patients.There were no significant differences in anesthesia time (226.3 ± 79.8 v 238.5 ± 66.2 min; p = 0.44), surgery time (166.2 ± 102.6 v 170.1 ± 83.4 min; p = 0.66), and number of dissected lymph nodes (5.3 ± 7.5 v 4.4 ± 7.4; p = 0.23) between the two groups. There were significant differences in intraoperative bleeding (61.5 ± 165.1 v 82.2 ± 116.9 mL; p0.001). After surgery, the two groups were statistically comparable in terms of hospitalization (17.6 ± 7.6 v 17.2 ± 6.9 days; p = 0.95) and incidence of complications (7.5% v 13.8%; p = 0.20), while there were significant differences in chest tube duration (6.1 ± 3.3 v 4.5 ± 1.2 days; p0.001).SV-VATS is feasible and as safe as MV-VATS, and it could be considered as an alternative treatment for the elderly.

Introduction ZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage SCLC (ES-SCLC). Methods Patients with complete response (CR) or partial response (PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥ 77 kg, platelet count ≥ 150,000/μL] or 200 mg) once daily until progression or unacceptable toxicity. Primary end points were progression-free survival (PFS) (blinded independent central review) and overall survival (sample size planned: 591 patients). Secondary end points included investigator-evaluated PFS and safety. Results ZL-2306-005 was terminated early owing to ES-SCLC treatment landscape changes (data cutoff: March 20, 2020). During July 2018–February 2020, a total of 185 of 272 patients screened were randomized (niraparib: n = 125 [CR = 1, PR = 124]; placebo: n = 60 [CR = 1, PR = 59]). Median (95% confidence interval [CI]) PFS (blinded independent central review) was 1.54 months (1.41–2.69, niraparib) and 1.36 months (1.31–1.48, placebo); hazard ratio (HR) = 0.66 (95% CI: 0.46–0.95, p = 0.0242). Median overall survival was 9.92 months (9.33–13.54, niraparib) and 11.43 months (9.53–not estimable, placebo); HR = 1.03 (95% CI: 0.62–1.73, p = 0.9052). Median investigator-evaluated PFS was 1.48 months (1.41–2.56, niraparib) and 1.41 months (1.31–2.00, placebo); HR = 0.88 (95% CI: 0.61–1.26; p = 0.4653). Grade greater than or equal to 3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients. Conclusions ZL-2306-005 did not reach primary end points. Nevertheless, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal.

Background The purpose of this study was to uncover preoperative risk factors for extubation failure or re-intubation for patients undergoing lung transplant (LTx). Methods We performed a retrospective case-control study of LTx from our center between January 2017 and March 2019. Demographic and preoperative characteristics were collected for all included patients. Univariable analysis and multivariable logistic regression were used to analyze risk factors of postoperative unsuccessful extubation following LTx. Results Among 107 patients undergoing first LTx investigated, 74 (69.16%) patients who were successfully liberated from mechanical ventilation (MV), and 33 (30.84%) patients who were unsuccessful extubation, which 18 (16.82%) patients suffered from reintubation. associated preoperative factors for unsuccessful extubation following LTx included preoperative extracorporeal membrane oxygenation (ECMO) support [OR =4.631, 95% confidence interval (CI): 1.403-15.286, P=0.012], the preoperative ability of independent expectoration (OR =4.517, 95% CI: 1.498-13.625, P=0.007), the age older than 65-year-old (OR =4.039, 95% CI: 1.154-14.139, P=0.029), and receiving the double lung and heart-LTx (OR =3.390, 95% CI: 0.873-13.162, P=0.078; and OR =16.579, 95% CI: 2.586-106.287, P=0.012, respectively). Further, we investigated the preoperative predicted factors for reintubation. Only the preoperative ECMO remained a significant predictor of re-intubation (OR =4.69, 95% CI: 1.56-15.286, P=0.012). Conclusions Preoperative independent sputum clearance, preoperative ECMO, older than 65-year-old, and double lung or heart-LTx were four independent risk factors for unsuccessful extubation. Moreover, preoperative ECMO was the only independent risk factor for reintubation.

Background: The response of cancer patients to immune checkpoint inhibitors (ICIs) vary in success. CD8+ tumor infiltrating lymphocytes (TILs) play a key role in killing cancer cells. This study aimed to evaluate the prognostic role of CD8+ TILs in cancer patients treat with immune checkpoint inhibitors (ICIs).Methods: We systematically searched all publications from PubMed, EMBASE, and Cochrane Library until 31 Jan 2021 without any restriction of language or article types. Studies assessing high versus low CD8+ TILs in predicting survival of various cancer patients were included. The outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR). Findings: A total of 32 studies consisting of 2546 cancer patients were included . The result showed that high CD8+ TILs was significantly associated with better OS (HR, 0.52; 95% confidence interval: 0.41-0.67; P < 0.001), PFS (HR, 0.54; 95% confidence interval: 0.42-0.70; P < 0.001) and ORR (OR = 3.88; 95% confidence interval: 2.59-5.82;P < 0.001) in patients treated with ICIs. Subgroup analyses suggested that patients with high CD8+ TILs had better clinical benefit regardless of different treatment (ICI monotherapy, or combination therapy), cancer types (NSCLC, melanoma and other), and CD8+ T cells location (intratumor, stroma, and invasive margin). Higher baseline circulating CD8+ T cells from peripheral blood did not contribute to improved OS (HR, 0.93; 95% confidence interval: 0.67-1.29; P = 0.67) and PFS (HR, 0.89; 95% confidence interval: 0.60-1.32;P = 0.56) when compared with low baseline. Interpretation: The result showed that high intratumoral, stromal, or invasive marginal, but not circulating CD8+ TILs can predict treatment outcomes in patients with ICIs therapy across different cancer , in either single-agent ICIs or combination with other therapies. Funding: China National Science Foundation (Grant No. 82022048, 81871893), Key Project of Guangzhou Scentific Research Project (Grant No. 201804020030), High-level university construction project of Guangzhou medical university (Grant No. 20182737, 201721007, 201715907, 2017160107); National key R & D Program (Grant No. 2017YFC0907903 & 2017YFC0112704) and the Guangdong high level hospital construction "reaching peak" plan. Declaration of Interest: No potential conflicts of interest were disclosed.

Background: An effective method for monitoring the progress of patients with lung cancer has not been developed. Cell-free DNA (cfDNA) has demonstrated a useful method for diagnostic and prognostic in many cancers. Here, we application cfDNA to compare PLAC8 methylation levels between lung cancer patients and healthy control; 98 controls and 140 lung cancer samples were evaluated. Methods: Plasma samples were obtained, and cfDNA extracted used for bisulfite conversion. Droplet digital PCR (ddPCR) based detection platform was performed to calculate PLAC8 methylation level, and data were analyzed with QuantaSoft analysis software (version 1.7.4, Bio-rad). Results: PLAC8 methylaiton level significantly increased in lung cancer patients (95% CI = 21.83% - 27.57%) compared with healthy control (95% CI = 8.71% - 9.61%). 124 of 140 lung cancer (88.57%) samples were identified the methylation level over than 12.91%, and 98 control (100%) samples methylation level below in 12.91%. Conclusions: In this study, we found that PLAC8 methylation levels significantly increased in lung cancer patients than healthy control. This finding showed that PLAC8 methylation level changes might occur as a potential methylation biomarker in lung cancer diagnosis. Funding Statement: Not applicable. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was authorized by the Medical Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University.

Since little consensus has been reached on whether milder reduction in forced expiratory volume in 1 s (FEV1) increases lung cancer incidence, we conducted a meta-analysis and performed Mendelian randomization (MR) analysis to explore the association and causal relationship between FEV1 and lung cancer incidence. We conducted a comprehensive search from PubMed, Medline, EMBASE, and Cochrane Library databases as of February 2020. MR analysis was performed using summary data obtained from two large consortia [International Lung Cancer Consortium (ILCCO) and Neale Lab] to assess the possible causality between FEV1 and lung cancer risk. Eight studies involving 88,743 cases were included. The incidence of lung cancer increased with decreasing FEV1.The combined odds ratio (OR) of decreased FEV1 for lung cancer incidence was 1.91 [95% confidence interval (CI) 1.67–2.19; P 100% of predicted), the OR was 3.06 (95% CI 2.20–4.24; P

BACKGROUND: Whether non-intubated spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) is a safe procedure remains controversial for mediastinal tumor patients with impaired lung function. Herein, we assessed feasibility of SV-VATS in lung function deficiency patients underwent mediastinal tumor resection. METHODS: From December 2015 to February 2020, 32 mediastinal tumor patients with impaired lung function (preoperative forced expiratory volume in 1 second

Background Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19). Objectives We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19. Methods Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system. CRD was diagnosed based on International Classification of Diseases-10 codes. The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization. The secondary endpoint was death within 30 days after hospitalization. Results We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020. Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively. Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%). COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%). After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization. Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without. Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without. Conclusion CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19.

Background Andrographolide (Andro), a diterpenoid extracted from Andrographis paniculata, has been shown to attenuate pulmonary fibrosis in rodents; however, the potential mechanisms remain largely unclear. This study investigated whether and how Andro alleviates bleomycin (BLM)-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and epithelial-mesenchymal transition (EMT) in the lung epithelial cells. Methods The in vivo effects of Andro were evaluated in a rat model of BLM-induced pulmonary fibrosis. The roles of Andro in BLM-induced NLRP3 inflammasome activation, EMT and AKT/mTOR signaling were investigated using human alveolar epithelial A549 cells. Results We found that Andro significantly alleviated pulmonary edema and histopathological changes, decreased weight loss, and reduced collagen deposition. Andro downregulated the levels of NLRP3, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in the lungs of BLM-treated rats, suggesting the inhibitory effect of Andro on NLRP3 inflammasome activation in vivo. Additionally, the symptoms of BLM-mediated EMT phenotype in the lung were also attenuated after Andro administration. In vitro, Andro also markedly inhibited BLM-induced NLRP3 inflammasome activation and EMT in A549 cells. Moreover, Andro inhibited BLM-induced phosphorylation of AKT and mTOR in A549 cells, suggesting that AKT/mTOR inactivation mediates Andro-induced effects on BLM-induced NLRP3 inflammasome activation and EMT. Conclusions These data indicate that Andro can reduce BLM-induced pulmonary fibrosis through suppressing NLRP3 inflammasome activation and EMT in lung epithelial cells via AKT/mTOR signaling pathway.

Objectives To illustrate our workflow for lung donation and transplantation during the COVID-19 crisis and report our preliminary experience with perioperative care. Methods We retrospectively analyzed data in the China Lung Transplantation Registration from January 23rd, 2020, to March 23rd, 2020 (2020 cohort), compared to the same period in 2019 (2019 cohort). Pre- and post-lung transplantation (LTx) management strategies, including measures aiming to prevent SARS-CoV-2 infection, were applied for all recipients, including five post-COVID-19 transplants during the COVID-19 pandemic period in China. Results Twenty-eight LTx procedures were performed, including LTx for five patients with acute respiratory distress syndrome (ARDS) due to COVID-19-related pulmonary fibrosis. Compared to the 2019 cohort, more patients with urgent conditions were transplanted in 2020, with a shorter pre-LTx admission time and early mobilization post-LTx. A large proportion (60%) of lung donations were transported on high-speed trains and commercial flights or commercial flights and highways. Grafts in the preservation containers were handed over to the receiving staff at the airport for 40% (10/25) of donations, which reduced the unnecessary quarantine of transporting staff entering the city. Listed candidates were urgently transferred to other qualified centers in 17.9% (5/28) of cases, which reduced the risk of SARS-CoV-2 exposure in COVID-19 designated hospitals. The 90-day survival rate of the recipients transplanted in 2020 was 85.7%, including 3 of 5 (60%) recipients who were critically severe COVID-19 patients. Conclusion LTx and lung donation amid COVID-19 can be performed safely with coordinated efforts on medical resource sharing and medical staff protection based on stratification of the infection risk. Outcomes were not compromised during the COVID-19 outbreak. LTx can be regarded as salvage therapy for critical COVID-19 patients with a confirmed positive-turned-negative virology status., Graphical abstract

Background Lung nodules are a diagnostic challenge. Current clinical management of lung nodule patients is inefficient and therefore causes patient misclassification, which increases healthcare expenses. However, a precise and robust lung nodule classifier to minimize discomfort for patients and healthcare costs is still lacking. The aim of the present protocol is to evaluate the effectiveness of using a liquid biopsy classifier to diagnose nodules compared to physician estimates and whether the classifier can reduce the number of unnecessary biopsies in benign cases. Methods A prospective cohort of 10,560 patients enrolled at 23 clinical centers in China with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by LDCT or CT will be included. After signed consent forms, the participants' pulmonary nodules will be assessed using three evaluation tools: (I) physician cancer probability estimates (II) validated lung nodule risk models, including Mayo Clinic and Veteran's Affairs models (III) ctDNA methylation classifier previously established. Each patient will undergo LDCT/CT follow-ups for 2 to 3 years and their information and one blood sample will be collected at baseline, 3, 6, 12, 24 and 36 months. The primary study outcomes will be the diagnostic accuracy of the methylation classifier in the cohort. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) will be used to compare the diagnostic value of each testing tool in differentiating benign and malignant pulmonary nodules. Discussion We are conducting an observational study to explore the accuracy of using a ctDNA methylation classifier for incidental lung nodules diagnosis. Trial registration Clinicaltrials.gov NCT03651986.

Objective Observational studies suggest that rheumatoid arthritis (RA) may be associated with lung cancer (LC) risk, while the evidence is inconsistent. We conducted a meta-analysis and a Mendelian randomization study to investigate the association and causality between RA and the LC risk. Methods We conducted a systematic search of cohort studies and performed a meta-analysis (PROSPERO ID CRD42020159082) to calculate the relative risks (RRs) and their 95% confidence intervals (95%CIs). Subgroup analyses based on sex and initiation year of follow-up were carried out. E‐values of each study were calculated to evaluate if existing studies were sensitive to unmeasured confounding. Furthermore, we investigated the correlation between genetically predisposed RA and LC risk using summary statistics from the International Lung Cancer Consortium (11,348 cases and 15,861 controls) and 90 RA-related single nucleotide polymorphisms from European and East Asian descent as instrumental variables. A two-sample Mendelian randomization (MR) analysis was performed to detect the findings based on LC and histological subtypes. Sensitivity analyses were performed to test the robustness of our findings. Results In the meta-analysis of 11 cohort studies involving 183,888 patients, an increased risk of LC was observed among RA patients (RR = 1.44, 95%CI = 1.31–1.57). Subgroup analyses suggested that male patients have a relatively higher LC risk than female patients, and an increased incidence of LC in RA patients was found from 1950 to 2010. Conversely, in the MR analysis, we found that genetically predisposed RA was associated with a decreased risk of LC overall, while neither causally associated with the risk of lung adenocarcinoma nor squamous cell lung cancer. Nevertheless, genetically predisposed RA was associated with a decreased LC risk among the East Asian population, but not in Europeans. These results were robust against extensive sensitivity analyses. Conclusion Our meta-analysis suggested that although RA was associated with a relatively higher LC risk, the causal relationship between genetically predisposed RA and LC risk was not supported by the MR study. Further studies are warranted to elucidate the possible association between RA and the risk of LC, as well as its underlying mechanisms.

BackgroundFamily socioeconomic position (SEP) in childhood is an important factor to predict some chronic diseases. However, the association between family SEP in childhood and the risk of lung cancer is not clear. MethodsA systematic search was performed to explore their relationship. We selected education level, socioeconomic positions of parents and childhood housing conditions to represent an individual family SEP. Hazard ratios (HRs) of lung cancer specific-mortality were synthesized using a random effects model. Two-sample Mendelian randomization (MR) was carried out with summary data from published genome-wide association studies of SEP to assess the possible causal relationship of SEP and risk of lung cancer. ResultsThrough meta-analysis of 13 studies, we observed that poorer SEP was associated with increased lung cancer risk (HR: 1.25, 95% CI: 1.10, 1.43). In addition, the dose-response analysis revealed a negative correlation between SEP in childhood and lung cancer in adulthood. Same conclusion was reached in MR [(education level) OR 0.50, 95% CI: 0.39, 0.63; P: ConclusionsThis study indicates that poor family SEP in childhood is a causal risk factor for lung cancer. We believe this population may receive greater benefit from lung cancer screening programs.Systematic review registrationProspero ID: 159082

Background: Programmed cell death ligand 1 (PD-L1) expression with respect to genetic alternations has not been well established in non-small cell lung cancer (NSCLC), especially in the Asian population. Methods: We reviewed 1370 NSCLC patients from a prospectively maintained database. Immunohistochemistry was performed on tumor cells and tumor-infiltrating lymphocytes (TILs) using the VENTANA (SP142) anti-PD-L1 antibody. The tumor proportion score (TPS) cutoff values were set at ⩾1% and ⩾50%, and the immune proportion score (IPS) cutoff values were set at ⩾1% and ⩾10%. Results: In tumor cells, PD-L1 positivity was observed in 405 (29.6%), 122 (8.9%), and 27 (2.0%) patients with TPS cutoff values at ⩾1% and ⩾50%. Contrastingly, TILs of 1154 (84.2%) and 346 (25.3%) patients stained positive at IPS cutoff values of ⩾1% and ⩾50%, respectively. PD-L1 expression was more common in patients who were mutation-negative irrespective of the TPS cutoff values and tumor size. PD-L1 expression in tumor cells was less frequent in patients harboring EGFR mutations (18.8% TPS ⩾ 1% and 4.6% TPS ⩾ 50%). Conversely, PD-L1 expression was high in the presence of KRAS mutations (47.3% TPS ⩾ 1% and 22.5% TPS ⩾ 50%). Overall, KRAS, BRAF, PICK3A, MET mutations and ROS1 and RET translocations were more frequent, while EGFR and HER2 mutations and ALK translocations were less frequent compared with the overall PD-L1 expression levels. Although the difference between TILs among the PD-L1-positive cases was comparatively small, PD-L1 positivity was less prevalent in EGFR-mutated tumors and more common in those with KRAS mutations, ROS1 translocations, BRAF mutations, or MET mutations. Conclusion: Our study showed the heterogeneity in PD-L1 expression with respect to nine major oncogenic drivers in China. Future studies are warranted to further clarify the association between PD-L1 expression and driver mutations in NSCLC.

Background To evaluate the incidence, risk factors, and prognosis of acute kidney injury (AKI) after lung transplantation (LTx). Methods Records of patients who underwent LTx in a single center were retrospectively reviewed. The prevalence of post-transplant AKI, the use of continuous renal replacement therapy (CRRT), and the risk factors for AKI were investigated. The impact of AKI and CRRT on short-term outcomes and long-term survival was measured. Results 148 patients were included with 67 cases developed post-operative AKI. 31 patients underwent CRRT; the percentage of CRRT was 6.2%, 0%, 10% and 86.2% in no-AKI, and stage 1, 2 and 3 AKI, respectively. Patients with AKI had significantly higher ICU mortality and in-hospital mortality. The 1-year post-LTx survival rate of patients with AKI was 47.8%, significantly lower than those without (74.1%). There was no difference in the 1-year survival rate of those with stage 1 and stage 2 AKI, but patients with stage 3 AKI showed the worst survival. Patients who underwent CRRT had an inferior survival outcome (9.7% vs. 76.1%, P

Objective Pulmonary fibrosis is a fatal interstitial lung disease that is characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of lung. The precise mechanisms underlying pulmonary fibrosis still remain unclear. In the current study, we aimed to investigate the alteration and function of serine (or cysteine) peptidase inhibitor, clade A, member 3 N (Serpina3n) in pulmonary fibrotic models and explore the potential mechanisms. Methods We induced pulmonary fibrosis in mice by silica and bleomycin respectively and determined Serpina3n in lung tissues, and then verified the expression of Serpina3n and its correlation with pulmonary fibrosis at seven time points in a bleomycin longstanding model. Moreover, adeno-associated virus type 9 (AAV9)-mediated Serpina3n knockdown was used to treat pulmonary fibrosis in the bleomycin model, whose possible mechanisms would be preliminarily explored by detecting chymotrypsin C as an example. Results Serpina3n was up-regulated significantly in lungs of both models at mRNA and protein levels relative to control. Notably, the expression of Serpina3n peaked during the 3rd week and then decreased until nearly normal levels during the 10th week, which was closely related to fibrotic procession in bleomycin-treated mice. AAV-mediated Serpina3n knockdown in the lung tissues alleviated bleomycin-induced fibrotic symptoms at various levels and disinhibit chymotrypsin C. Conclusions Our study revealed that Serpina3n is a critical regulator in pulmonary fibrosis and suggested Serpina3n inhibition as a potential therapeutic strategy in chronic pulmonary injuries.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are recommended first-line treatments in EGFR-mutated (EGFRm) non-small-cell lung cancer (NSCLC). However, acquired resistance (e.g. MET amplification) is frequently observed. Savolitinib (volitinib, HMPL-504, AZD6094) is an oral, potent, and highly selective MET-TKI. In this phase Ib, open-label, multicenter study, we enrolled Chinese patients with EGFRm advanced NSCLC, whose disease progressed following prior EGFR-TKI treatment. In the safety run-in, patients received savolitinib 600 or 800 mg plus gefitinib 250 mg orally once daily, and dose-limiting toxicities were recorded. In the expansion phase, patients with MET amplification received savolitinib plus gefitinib. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity. Thirteen patients were enrolled in the safety phase (median age 52 years, 46% female) and 51 enrolled in the expansion phase (median age 61 years, 67% female). No dose-limiting toxicities were reported in either dose group during the safety run-in. Adverse events of grade ≥ 3 in the safety run-in and expansion phases (n = 57) were reported in 21 (37%) patients. The most frequently reported adverse events (all grades) were: vomiting (n = 26, 46%), nausea (n = 23, 40%), increased aspartate aminotransferase (n = 22, 39%). Of four deaths, none were treatment-related. The objective response rates in EGFR T790M-negative, −positive, and -unknown patients were 52% (12/23), 9% (2/23), and 40% (2/5), respectively. Savolitinib 600 mg plus gefitinib 250 mg once daily had an acceptable safety profile and demonstrated promising antitumor activity in EGFRm, MET-amplified advanced NSCLC patients who had disease progression on EGFR-TKIs. NCT02374645, Date of registration: March 2nd 2015.

BACKGROUND Early endotracheal extubation in operating room (E-OR) after lung transplantation is rarely reported worldwide. Herein, we aim to explore the feasibility and safety of E-OR after lung transplantation and demonstrate its potential benefits. METHODS This study is a single-center retrospective database analysis of 18 patients. All lung transplantation patients with E-OR attempted between June 2018 and September 2019 were included retrospectively. Perioperative variables, including ischemia time, total blood loss, blood lactic acid, the partial pressure of oxygen, partial pressure of oxygen/fraction of inspiration oxygen ratio, time of semi-open pulmonary artery occlusion clamp, extubation rate, and complications after E-OR, were analyzed. Data were compared using non-parametric tests and expressed as the median or number (percentage). RESULTS Clinical data of 18 patients with E-OR attempted were collected. Overall, 15/18 (83.33%) patients successfully underwent E-OR without reintubation. Reintubation occurred in 3/18 (16.67%) patients; one patient presented with decreased blood oxygen saturation and unconsciousness, while two patients developed hypoxemia and respiratory failure after E-OR. Extracorporeal membrane oxygenation (ECMO) was not used postoperatively. No grade 3 primary graft dysfunction was observed and all eighteen patients were alive 1 year after the transplant. No postoperative hemodialysis and tracheotomy occurred. The median length of stay in the intensive care unit (ICU) for E-OR patients was 120 hours, the median length of postoperative hospital stay was 19 days, and the median hospitalization cost was 35,577 USD. CONCLUSIONS Early endotracheal extubation in operating room was feasible and did not delay postoperative recovery in these 18 lung transplantation recipients.

Background: Since the clinical correlates, prognosis and determinants of AKI in patients with Covid-19 remain largely unclear, we perform a retrospective study to evaluate the incidence, risk factors and prognosis of AKI in severe and critically ill patients with Covid-19.Methods: We reviewed medical records of all adult patients (>18 years) with laboratory-confirmed Covid-19 who were admitted to the intensive care unit (ICU) between January 23rd 2020 and April 6th 2020 at Wuhan JinYinTan Hospital and The First Affiliated Hospital of Guangzhou Medical University. The clinical data, including patient demographics, clinical symptoms and signs, laboratory findings, treatment [including respiratory supports, use of medications and continuous renal replacement therapy (CRRT)] and clinical outcomes, were extracted from the electronic records, and we access the incidence of AKI and the use of CRRT, risk factors for AKI, the outcomes of renal diseases, and the impact of AKI on the clinical outcomes.Results: Among 210 subjects, 131 were males (62.4%). The median age was 64 years (IQR: 56-71). Of 92 (43.8%) patients who developed AKI during hospitalization, 13 (14.1%), 15 (16.3%) and 64 (69.6%) patients were classified as stage 1, 2 and 3, respectively. 54 cases (58.7%) received CRRT. Age, sepsis, Nephrotoxic drug, IMV and elevated baseline Scr were associated with AKI occurrence. The renal recover during hospitalization among 16 AKI patients (17.4%), who had a significantly shorter time from admission to AKI diagnosis, lower incidence of right heart failure and higher P/F ratio. Of 210 patients, 93 patients deceased within 28 days of ICU admission. AKI stage 3, critical disease, greater age and minimum P/F Conclusions: Among patients with Covid-19, the incidence of AKI was high. age , sepsis, nephrotoxic drug, IMV and baseline Scr were strongly associated with the development of AKI. Time from admission to AKI diagnosis, right heart failure and P/F ratio were independently associated with the potential of renal recovery. Finally, AKI KIDGO stage 3 independently predicted the risk of death within 28 days of ICU admission.

Background: Thymoma is an uncommon intrathoracic malignant tumor and has a long natural history. It is uncertain whether the survival of thymoma patient is affected by prior cancer history. Finding out the impact of a prior cancer history on thymoma survival has important implications for both decision making and research.Method: The Surveillance, Epidemiology, and End Results (SEER) database was queried for thymoma patients diagnosed between 1975 and 2015. Kaplan-Meier methods and Cox proportional hazards model were used to analyze overall survival across a variety of stages, age, and treatment methods with a prior cancer history or not.Results: A total of 3604 patients with thymoma were identified including 507 (14.1%) with a prior cancer history. The 10-year survival rate of patients with a prior cancer history (53.8%) was worse than those without a prior cancer history (40.32%, 95%CI 35.24-45.33, P < 0.0001). However,adjusted analyses showed that the impact of a prior cancer history was heterogenous across age and treatment methods. In subset analyses, prior cancer history was associated with worse survival among patients who were treated with chemoradiotherapy (HR: 2.80, 95% CI: 1.51-5.20, P = 0.001) and age ≤ 65 years (HR: 1.33, 95%CI: 1.02-1.73, P = 0.036).Conclusions: Prior cancer history provides an inferior overall survival for patients with thymoma. But it does not worsen the survival in some subgroups and these thymoma patients should not be excluded from clinical trials.

Coronavirus disease 2019 (COVID‐19) patients exhibit a spectrum of respiratory symptoms like cough and dyspnea1‐3. Airway mucus is an adhesive viscoelastic gel composed mostly of high‐molecular weight mucous glycoproteins and water, which is important in maintaining lung function and health, pathological mucus hypersecretion may cause airway obstruction and lead to respiratory distress. Mucin (MUC) glycoproteins are the major macromolecular components of mucus, which are classified into two major types: the gel‐forming, secreted mucins (i.e, MUC5AC) and the membrane‐tethered mucins (i.e. MUC1)4. Here, with an attempt to understand the lung changes, we sought to provide a delineation of the components of airway mucus from COVID‐19 patients. This article is protected by copyright. All rights reserved.

Targeted therapies against non-small-cell lung cancer (NSCLC) harboringPatients with stage IIIB or IVBetween October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with differentPyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with

• We retrospectively studied the prevalence and clinical characterization of cancer patients with asymptomatic SARS-CoV-2 infection history in the only cancer hospital in Wuhan. • Serosurvey of SARS-CoV-2 among hospital visitors from two hospitals, one at the epicenter in Wuhan, and one outside the epicenter, in Guangzhou. • Cancer patients are more likely to develop asymptomatic COVID-19 infection than persons with similar exposure history. • Transmissibility of asymptomatic cases is relatively low, even in vulnerable populations such as cancer patients.

Background The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain. Research Question The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model. Study Design and Methods A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. Results In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age ≥ 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation. Interpretation The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.