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Objectives Most countries have adopted public activity intervention policies to control the coronavirus disease 2019 (COVID-19) pandemic. Nevertheless, empirical evidence of the effectiveness of different interventions on the containment of the epidemic was inconsistent. Methods We retrieved time-series intervention policy data for 145 countries from the Oxford COVID-19 Government Response Tracker from December 31, 2019, to July 1, 2020, which included 8 containment and closure policies. We investigated the association of timeliness, stringency, and duration of intervention with cumulative infections per million population on July 1, 2020. We introduced a novel counterfactual estimator to estimate the effects of these interventions on COVID-19 time-varying reproduction number (Rt). Results There is some evidence that earlier implementation, longer durations, and more strictness of intervention policies at the early but not middle stage were associated with reduced infections of COVID-19. The counterfactual model proved to have controlled for unobserved time-varying confounders and established a valid causal relationship between policy intervention and Rt reduction. The average intervention effect revealed that all interventions significantly decrease Rt after their implementation. Rt decreased by 30% (22%-41%) in 25 to 32 days after policy intervention. Among the 8 interventions, school closing, workplace closing, and public events cancellation demonstrated the strongest and most consistent evidence of associations. Conclusions Our study provides more reliable evidence of the quantitative effects of policy interventions on the COVID-19 epidemic and suggested that stricter public activity interventions should be implemented at the early stage of the epidemic for improved containment.

Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) with revealed activity against EGFR-sensitizing mutations and EGFR T790M mutation.Patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy were enrolled in this registrational phase 2 trial of aumolertinib at 110 mg orally once daily (NCT02981108). The primary end point was objective response rate (ORR) by independent central review.A total of 244 patients with EGFR T790M-positive NSCLC were enrolled. The ORR by independent central review was 68.9% (95% confidence interval [CI]: 62.6-74.6). The disease control rate was 93.4% (95% CI: 89.6-96.2). The median duration of response was 15.1 months (95% CI: 12.5-16.6). The median progression-free survival was 12.4 months (95% CI: 9.7-15.0). Among 23 patients with assessable central nervous system (CNS) metastases, the CNS-ORR and CNS-disease control rate were 60.9% (95% CI: 38.5-80.3) and 91.3% (95% CI: 72.0-98.9), respectively. The median CNS-duration of response was 12.5 months (95% CI: 5.6-not reached). Treatment-related adverse events of more than or equal to grade 3 occurred in 16.4% of the patients, with the most common being increased blood creatine phosphokinase level (7%) and increased alanine aminotransferase level (1.2%). The relative dose density of aumolertinib was 99.2% in this study.Aumolertinib is an effective and well-tolerated third-generation EGFR TKI for patients with EGFR T790M-positive advanced NSCLC after disease progression on first- and second-generation EGFR TKI therapy. On the basis of these findings, aumolertinib was approved in the People's Republic of China for patients positive for EGFR T790M NSCLC.

Background The relationship between insomnia and lung cancer is scanty. The Mendelian randomization approach provides the rationale for evaluating the potential causality between genetically-predicted insomnia and lung cancer risk. Methods We extracted 148 insomnia-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from published genome-wide association studies (GWASs). Summary data of individual-level genetic information of participants were obtained from the International Lung Cancer Consortium (ILCCO) (29,266 cases and 56,450 controls). MR analyses were performed using the inverse-variance-weighted approach, MR pleiotropy residual sum and outlier (MR-PRESSO) test, weighted median estimator, and MR-Egger regression. Sensitivity analyses were further performed using Egger intercept analysis, leave-one-out analysis, MR-PRESSO global test, and Cochran's Q test to verify the robustness of our findings. Results The results of the MR analysis indicated an increased risk of lung cancer in insomnia patients (OR = 1.1671; 95% CI 1.0754–1.2666, p = 0.0002). The subgroup analyses showed increased risks of lung adenocarcinoma (OR = 1.1878; 95% CI 1.0594–1.3317, p = 0.0032) and squamous cell lung cancer (OR = 1.1595; 95% CI 1.0248–1.3119, p = 0.0188). Conclusion Our study indicated that insomnia is a causal risk factor in the development of lung cancer. Due to the lack of evidence on both the epidemiology and the mechanism level, more studies are needed to better elucidate the results of the study.

Summary Background Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. Methods In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18–70 years, had histopathogically confirmed stage II–IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov , NCT02448797 . Findings Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6–36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4–not reached) in the icotinib group and 22·1 months (16·8–30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24–0·55]; p Interpretation Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Funding Betta Pharmaceuticals Translation For the Chinese translation of the abstract see Supplementary Materials section.

Carinal reconstruction and omental flap harvesting are traditionally performed via open approaches. We reported a case in which carinal reconstruction with bronchial flap and omental flap reinforcement was performed using minimally invasive approaches. The omental flap was harvested laparoscopically, and wrapped around the anastomosis, which reduced the risk of airway anastomosis complications. Non-circumferential resection and reconstruction used bronchial flap, which made it easier to perform under video-assisted thoracoscopic surgery conditions. Minimally invasive carinal reconstruction with bronchial flap and omental reinforcement after neoadjuvant treatment, can be safely performed.

Purpose Heart-lung transplantation (HLTx) is a life-saving treatment option for patients with advanced cardiopulmonary failure. However, posterior mediastinal bleeding and phrenic nerve damage are still intraoperative challenges for the traditional surgical method. This study reports an innovative non-in situ HLTx performed in our center, preventing posterior mediastinal bleeding and phrenic nerve damage effectively. Description Between September 2015 and September 2020, 12 patients without previous heart surgery underwent a traditional HLTx and were deemed a control group, and 3 patients underwent an innovative non-in situ HLTx. The operative time, cold ischemic time, intraoperative bleeding, intraoperative transfusion, and the intensive care unit and hospital lengths of stay were assessed between traditional HLTx and non-in situ HLTx. Evaluation The innovative non-in situ HLTx was successfully performed in the 3 patients. We found that the intensive care unit and hospital lengths of stay, total surgical time, cold ischemic time, intraoperative bleeding, and intraoperative transfusion were decreased in the 3 patients compared with the traditional surgical method. Conclusion Non-in situ HLTx may decrease posterior mediastinal bleeding and phrenic nerve damage effectively.

Vascular anastomosis is an essential step for many surgery procedures, especially for cardiovascular surgeries and lung transplantation (LTx). Although hand-sewn anastomosis is known as the standard method for vascular anastomosis,there are many limitations for hand-sewn anastomoses, such as the requirement of technical expertise, time-consuming, and a limit for developing minimally invasive surgery. In this study, we introduce a new idea to conduct the great vascular mechanical anastomosis through the arterial flap using an endo-stapler.

Immune checkpoint blockade therapies that target CTLA-4 and PD-1/PD-L1 have ushered in a new era of cancer treatment. Nevertheless, a significant proportion of patients demonstrated primary or acquired resistance. Harnessing gut microbiota has been an emerging novel therapeutic strategy to overcome resistance. Here we summarized the current research status of gut microbiota in immune checkpoint blockade therapies, clinical trials, underlying mechanisms and challenges of microbiome research in checkpoint immunotherapy. Findings from preclinical models, standardized microbiome analysis and progress of multi-omic approaches may better disclose the interaction between gut microbiota and immune checkpoint inhibitors (ICIs) and traditional Chinese medicine can be a potential microbiome modulator to sensitize the response to ICIs.

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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no effective medication. Andrographolide (Andro), extracted from Chinese herbal Andrographis paniculata, could attenuate bleomycin (BLM)-induced pulmonary fibrosis via inhibition of inflammation and oxidative stress, however, the anti-fibrotic mechanisms have not been clarified. Myofibroblasts are the primary cell types responsible for the accumulation of extracellular matrix (ECM) in fibrotic diseases, and targeting fibroblast proliferation and differentiation is an important therapeutic strategy for the treatment of IPF. Hence, this study aimed to investigate the effects of Andro on the fibroblast proliferation and differentiation in the in vivo and in vitro models. The results showed that Andro improved pulmonary function and inhibited BLM-induced fibroblast proliferation and differentiation and ECM deposition in the lungs. In vitro, Andro inhibited proliferation and induced apoptosis of TGF-β1-stimulated NIH 3T3 fibroblasts and primary lung fibroblasts (PLFs). Andro also inhibited TGF-β1-induced myofibroblast differentiation and ECM deposition in both cells. We also found that Andro suppressed TGF-β1-induced Smad2/3 and Erk1/2 activation, suggesting that Smad2/3 and Erk1/2 inactivation mediates Andro-induced effects on TGF-β1-induced fibroblast proliferation and differentiation. These results indicated that Andro has novel and potent anti-fibrotic effects in lung fibroblasts via inhibition of the proliferation and myofibroblast differentiation of fibroblasts and subsequent ECM deposition, which are modulated by TGF-β1-mediated Smad-dependent and -independent pathways.

We have reported the usefulness of the subxiphoid video-assisted thoracoscopic surgery approach in thymectomy. However, such a new method may have unknown complications that rarely occur. The brachiocephalic vein has been considered to be the vessel that is most frequently injured when performing thymectomy because of the skeletal anatomy. We herein report a case of intraoperative injury of brachiocephalic vein using tubeless subxiphoid thoracoscopic thymectomy. No additional complications have been found in the 3 months since the operation. Though subxiphoid video-assisted thoracoscopic surgery thymectomy is a safe and less invasive operation, intraoperative complications are possible, and surgeons should express caution.

It is important to evaluate the efficacy and safety of personal protective equipment (PPE) protecting healthcare workers in the coronavirus disease 2019 (COVID-19) epidemic. We conducted a survey on PPE usage among healthcare workers who completed their healthcare service for COVID-19 patients in Hubei province (the Chinese epicenter of the epidemic). Efficacy and safety information about PPE were collected from 960 participants and summarized in this study.

An article in the New England Journal of Medicine reveals a significant reduction of incidence-based mortality of non-small cell lung cancer in the U.S. and attributes this improvement to the approval of targeted therapies.

Introduction Clinical studies have shown that a combination of a tyrosine kinase inhibitor (TKI) and pemetrexed overcame acquired resistance to epidermal growth factor receptor (EGFR) TKI in NSCLC. Previously, pemetrexed+gefintib (P+G) had improved progression-free survival (PFS) compared with gefitinib. We present OS, updated PFS, biomarker analysis, and safety of P+G versus gefitinib. Methods This was a phase 2, multicenter, randomized study conducted in East Asian patients with advanced nonsquamous NSCLC with EGFR mutations. Patients were randomized (2:1) to receive P+G (500 mg/m2 intravenously 3-weekly + 250 mg/day orally) or gefitinib. Results In total, 191 patients (P+G, n=126; gefitinib, n=65) comprised the intent-to-treat and safety populations. Median OS was 43.4 months in P+G versus 36.8 months in gefitinib arm; adjusted HR 0.77 (95% CI, 0.5-1.2); one-sided P=0.105. Median PFS was significantly longer in the P+G (16.2 months) versus gefitinib arm (11.1 months); adjusted HR 0.67 (95% CI, 0.5-0.9); one-sided P=0.009. In the P+G and gefitinib arms, median PFS was 22.6 and 11.0 months, respectively, in patients with low thymidylate synthase (TS) expression, and 12.6 and 9.9 months, respectively, in patients with high TS expression. Common second-line post-discontinuation systemic therapies were EGFR-TKIs and chemotherapy. Most patients experienced at least one adverse event. Conclusions Addition of pemetrexed to EGFR TKI gefitinib resulted in significantly improved PFS and numerically longer OS compared with gefitinib in treatment-naive patients with EGFR-mutated advanced nonsquamous NSCLC. Low TS expression appeared to be a good predictor for treatment outcomes.

In this study. we compared ergonomical domains characteristics of three-dimensional (3D) versus two-dimensional (2D) video-systems in thoracoscopic lobectomy using a scoring-scale-based assessment. Seventy patients (mean age, 69 ± 6.9 years, 43 males and 27 females) with early stage lung cancer were randomized to undergo thoracoscopic lobectomy by either 3D (N = 35) or 2D (N = 35) video-systems. All operations were divided into 5 standardized surgical steps (vein, artery, bronchus, fissure, and lymph nodes), which were evaluated by 4 thoracic surgeons using a scoring scale (score range from 1, unsatisfactory to 3,excellent) entailing assessment of 3 ergonomical domains: exposure, instrumentation and maneuvering. Primary outcome was a difference ≥10% in the maneuvering domain steps. At intergroup comparisons, there was no difference in demographics. The 3D system results were better for maneuvering domain total score and particularly for the artery and bronchus steps scores (score ≥10%, P ≤ 0.006). Other significant differences included exposure of the vein, artery and bronchus (P ≤ 0.03). Results favoring the 2D system included maneuvering, exposure and instrumentation of the fissure (P = 0.001). Inter-rater concordance of ergonomics scoring was satisfactory (Cronbach's α range, 0.85-0.88). Operative time was significantly shorter in the 3D group (127 ± 19 min vs 143±18 min, P = 0.001) whereas there was no difference in hospital stay (3.4 ± 1.2 vs 4.1 ± 1.6 days, P = 0.07). In this study comparison of ergonomic domains scoring in 3D versus 2D thoracoscopic lobectomy favored the 3D system for the maneuvering total score, which proved inversely correlated with operative times possibly due to a better perception of depth and more precise surgical maneuvering.

Nonintubated spontaneous ventilation video-assisted thoracoscopic surgery (NI-VATS) has been investigated to reduce the adverse effects of tracheal intubation, mechanical ventilation, and general anesthesia in several thoracic diseases. We comparatively assess the comparison between NI-VATS vs intubated anesthesia VATS (I-VATS) on early outcomes of mediastinal lesion resection.Patients who underwent VATS resection for a mediastinal tumor between December 2015 and September 2018 were retrospectively included for analysis. Patients were divided into two groups according to anesthesia ventilation type: NI-VATS and I-VATS. Propensity score matching was applied to eliminate population bias. Intraoperative and postoperative variables were compared.A total of 198 patients was included; 75 patients underwent NI-VATS and 123 patients underwent I-VATS. After propensity score matching, both anesthesia time (173.81 vs 227.37 minutes, P.001) and operation time (82.82 vs 133.49 minutes, P.001) were shorter in the NI-VATS group. Bleeding (51.80 mL vs 56.73 mL, P = .90) and postoperative morbidity (10.9% vs 15.6%, P = .57) were similar between groups. Chest tube duration (1.11 vs 1.54 days, P = .04) was shorter in the NI-VATS group. Hospital duration after surgery (3.15 vs 5.35 days, P.001) was shorter in the NI-VATS group. D-dimer after surgery was significantly higher in both groups, but NI-VATS decreased the change (577 vs 1624 μg/L, P.001). Furthermore, a decrease in the use of postoperative opioids analgesics was seen in the NI-VATS group (31% vs 51%, P = .023).Mediastinal tumor resection is safe and feasible under NI-VATS. Better short-term outcomes suggest NI-VATS facilitates a more rapid recovery. Further multicenter prospective randomized investigation is warranted.

To investigate the incidence and distribution of lymph node metastasis in patients with different gene mutations among pathological T1 non-small-cell lung cancers (NSCLC).NSCLC cases resected in our institution between 2016 and 2018 were included. Driver mutation testing was performed in all resected tumor tissues. These patients were grouped by the type of gene mutations. On the basis of protein that mutant-genes encoded involved in the molecular pathway, the genotypes were further classified into four distinct groups: upstream receptor mutant protein (EGFR, HER2 and MET); downstream regulator mutant protein (KRAS and BRAF); fusion mutant protein (ROS1, ALK and RET) and the wild type group. The incidence of lymph node metastasis was compared among different groups.Of the 1052 patients enrolled, the frequency of positive mutations was 68.0%. The incidence of lymph node metastasis were as follows: wild type (19.3%), ROS1 (72.8%), BRAF (55.5%), ALK (44.7%), HER2 (40%), RET (23.1%), KRAS (15.3%), EGFR (15.3%) and MET mutation (0%) (P 0.001). The incidence of lymph node metastasis was significantly higher in fusion mutant protein group (45.1%) compared with others (wild type 19.3%, downstream regulator mutant protein 19.1%, upstream receptor mutant protein 15.3%, all P 0.001). Patients with fusion genes also showed higher proportion of vascular invasion and positive lymph node ratio of greater than 0.33 compared to others.Different genotypes of NSCLC have different propensity to develop lymph node metastasis. Cases of fusion gene mutations had a higher risk and burden of lymph node metastasis than other genotypes, which may indicate that more intensive treatment or surveillance strategies should be applied for these patients.

Background The optimal treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to address this important issue through a Bayesian network meta-analysis. Methods We performed a search of electronic databases for randomized controlled trials comparing the following treatments: surgery, radiotherapy, chemotherapy, and their multiple combinations before March 25, 2018. Pooled data on overall survival and treatment-related deaths were analyzed within the Bayesian framework. Results Eighteen eligible trials reporting 13 treatments were included. In terms of overall survival, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy, which tended to be consistent (hazard ratio [HR] 1.14, 95% credible interval [CrI] 0.21 to 5.93), ranked superior to other treatments. Notably, neoadjuvant chemotherapy followed by surgery and adjuvant radiotherapy was significantly more effective in prolonging survival than surgery alone (HR 0.38, 95% CrI 0.18 to 0.81), surgery plus adjuvant radiotherapy (HR 0.51, 95% CrI 0.29 to 0.92) and potentially surgery plus adjuvant chemotherapy (HR 0.49, 95% CrI 0.23 to 1.05). Overall, with 29% as the highest possibility of causing the fewest treatment-related deaths, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy was the safest treatment option. Conclusions Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy has the greatest possibility to be the optimal treatment with the best overall survival and fewest treatment-related deaths for stage IIIA-N2 NSCLC.

Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

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.

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.

Pulmonary granulomatous nodule (GN) with spiculated or lobulated appearance are indistinguishable from solid lung adenocarcinoma (SADC) based on CT morphological features, and partial false-positive findings on PET/CT. The objective of this study was to investigate the ability of quantitative CT radiomics for preoperatively differentiating solitary atypical GN from SADC.302 eligible patients (SADC = 209, GN = 93) were evaluated in this retrospective study and were divided into training (n = 211) and validation cohorts (n = 91). Radiomics features were extracted from plain and vein-phase CT images. The L1 regularized logistic regression model was used to identify the optimal radiomics features for construction of a radiomics model in differentiate solitary GN from SADC. The performance of the constructed radiomics model was evaluated using the area under curve (AUC) of receiver operating characteristic curve (ROC).16.7% (35/209) of SADC were misdiagnosed as GN and 24.7% (23/93) of GN were misdiagnosed as lung cancer before surgery. The AUCs of combined radiomics and clinical risk factors were 0.935, 0.902, and 0.923 in the training cohort of plain radiomics(PR), vein radiomics, and plain and vein radiomics, and were 0.817, 0835, and 0.841 in the validation cohort of three models, respectively. PR combined with clinical risk factors (PRC) performed better than simple radiomics models (p 0.05). The diagnostic accuracy of PRC in the total cohorts was similar to our radiologists (p ≥ 0.05).As a noninvasive method, PRC has the ability to identify SADC and GN with spiculation or lobulation.

Objectives Anlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD α/β, c-Kit and Ret. In the phase III ALTER-0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non-small-cell lung cancer (NSCLC) patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens. This study assessed quality of life (QoL) in these patients. Methods Patients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. The QoL were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the associated EORTC Quality of Life Lung Cancer Specific Module (QLQ-LC13) at baseline, end of cycle 1, end of every two cycles, and at the final visit. The analyses were conducted in the first 6 cycles. Differences in scores of 10 points or more between two arms or from baseline were considered clinically meaningful. Results A total of 437 patients were assigned to anlotinib (n = 294) and placebo (n = 143). The completion rates of the QoL questionnaires were from 69.9% to 97.0%. Mean scores of QLQ-C30 and QLQ-LC13 subscales were similar in the anlotinib and placebo arms at baseline. Compared to placebo, anlotinib improved role functioning, social functioning, dyspnea, insomnia, constipation and financial problems. Only sore mouth or tongue symptom was worse in the anlotinib arm than in the placebo arm. Conclusions Anlotinib improved quality of life versus placebo in advanced NSCLC patients who had received at least two previous chemotherapies. The QoL analyses provided evidence that anlotinib should be a choice for the third-line treatment or beyond in advanced NSCLC.

Objectives To describe and assess the techniques of spontaneous-ventilation video-assisted thoracoscopic surgery (SV-VATS) for tracheal/carinal resections and compare the outcomes with the conventional thoracoscopic intubated method. Methods From May 2015 to November 2016, some 18 consecutive patients with malignant or benign diseases invading distal trachea and carina who met the criteria for SV were treated by SV-VATS resection. To evaluate the feasibility of this novel technique, they were compared with a control group consisting of 14 consecutive patients with the same diseases who underwent VATS resection using intubated general anesthesia from October 2014 to April 2015. Data were collected with a median follow-up of 10.2 months 75 (range: 1-27). Results The SV-VATS group consisted of 4 carinal resections and 14 tracheal resections. In the control group, 2 patients underwent carinal resection and 12 underwent tracheal resection. Median operative time was shorter in the SV-VATS group compared with the intubated group (162.5 minutes vs 260 minutes), as was the median time for tracheal end-to-end anastomosis (22.5 minutes vs 45 minutes) and carinal reconstruction (40 minutes vs 86 minutes). The lowest oxygen saturation during the procedure was 94.2% ± 4.9% in SV-VATS group and 93.9% ± 4.5% in the control group. The peak carbon dioxide level at the end of expiration was greater in the SV-VATS group (47.7 ± 4.2 mm Hg vs 39.1 ± 5.7 mm Hg). No conversion to tracheal intubation was needed in the SV-VATS group. Postoperative complications occurred in 6 patients in the SV-VATS group and 9 in the control group. Patients who underwent SV-VATS had a trend toward shorter postoperative hospital stays (11.5 ± 4.3 days vs 13.2 ± 6.3 days). One recurrence (SV-VATS group) and 2 deaths (one in each group) were observed during follow-up. Conclusions SV-VATS is a feasible procedure in tracheal and carinal resection and reconstruction in highly selected patients. It can be a valid alternative to conventional intubated VATS for airway surgery.

Background: The responses of cancer patients to immune checkpoint inhibitors (ICIs) vary in success. CD8+ tumor infiltrating lymphocytes (TILs) play a key role in killing tumor cells. This study aims to evaluate the prognostic role of CD8+ TILs in cancer patients treated with ICIs. Methods: We systematically searched all publications from PubMed, EMBASE, and Cochrane Library until 12 Jul 2021 without any restriction of language or article types. Studies assessing high versus low CD8+ TILs in predicting efficacy and survival of various cancer patients were included. The outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). The study protocol is prospectively registered on PROSPERO (registration number CRD42021233654). Findings: Findings: A total of 33 studies consisting of 2559 cancer patients were included. The result showed that high CD8+ TILs were significantly associated with better OS (HR, 0.52; 95% confidence interval: 0.41–0.67; p

Currently there is no explicit guideline for the use of indocyanine green (ICG) in the localization of pulmonary nodules before surgery. How long ICG can remain in vivo is unknown. According to previous reports, ICG can be observed under infrared thoracoscope within 24 hours after injection. We unexpectedly found a case of a 54-year-old man who was injected with ICG under CT guidance, which was still clearly visible under infrared thoracoscopy after 6 days. This unexpected finding suggests that the operation time can be arranged appropriately after local injection with ICG.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are recommended first-line treatments in EGFR- mutated non-small-cell lung cancer (NSCLC). However, acquired resistance (e.g. MET amplification) is common. Savolitinib (volitinib, HMPL-504, AZD6094) is an oral, potent, and highly selective MET-TKI. Methods: In this phase 1b, open-label, multicentre study, we enrolled Chinese patients with EGFR-mutated, advanced NSCLC, whose disease progressed during or after treatment with prior EGFR-TKIs. 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 endpoints were safety and tolerability. Secondary endpoints included antitumour activity and pharmacokinetics. Findings: No dose-limiting toxicities were reported in either dose group during the safety run-in (n=13). Savolitinib 600 mg plus gefitinib 250 mg once daily was selected as the recommended phase 2 dose and evaluated in the expansion phase (n=51). The objective response rates in EGFR T790M-negative, -positive and -unknown patients were 52% (12/23), 9% (2/23), and 40% (2/5), respectively. Thirty-five patients (69%) were evaluable for longitudinal circulating tumour DNA analysis. Pharmacokinetic parameters for savolitinib plus gefitinib were consistent with previous monotherapy studies, showing no evidence of drug-drug interactions. Adverse events of grade 3 or more in the safety run-in and expansion phases (n=57) were reported in 21 (37%) patients. The most common adverse events (all grades) were: vomiting (n=26, 46%), nausea (n=23, 40%), increased aspartate aminotransferase (n=22, 39%). There were four deaths, none treatment-related. Interpretation: Savolitinib 600 mg plus gefitinib 250 mg once daily had an acceptable safety profile and demonstrated promising antitumour activity in EGFR-mutated, MET- amplified advanced NSCLC patients who had progressed on EGFR-TKIs. Trial Registration: NCT02374645. Funding Statement: The study was funded by AstraZeneca, Cambridge, UK, the manufacturer of savolitinib and gefitinib. Hutchison MediPharma authorised AstraZeneca to conduct this study. Declaration of Interests: MF, RH, GFA, CE, SM, RBV and AM are AstraZeneca employees and shareholders. RH also owns shares in Foundation medicine, and has a patent pending for Foundation Medicine. MF is also a patent holder for AstraZeneca. Y-LW has received personal fees from AstraZeneca, Roche, Boehringer Ingeiheim, Pfizer, Bristol-Myers Squibb, Merck Sharp & Dohme, and Sanofi; and grants from AstraZeneca, Roche, and Boehringer Ingelheim. J-JY, JF, Y-QS, J-HC, G-YC, J-XH, WL, X-QL, NY, CZ, J-AH and LY declare no conflicts of interest. Ethics Approval Statement: The study was approved by Institutional Review Boards/Independent Ethics Committees at each study centre, and by the Human Genetics Resources Administration of China. The trial was conducted in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines, the provisions of the Declaration of Helsinki, applicable regulatory requirements, and the AstraZeneca policy on Bioethics and Human Biological Samples. All patients provided written informed consent before study procedures.

Background: Reduction of solid organ transplant (SOT) became notable while limited data are available regarding its resumption during the novel coronavirus disease 2019 (COVID-19) pandemic. Methods: Based on the SOT and COVID-19 diagnosis data collected from open-access official organizations, we studied the trend changes of SOT in the U.S.A. since the COVID-19 outbreak, and made the validation using the U.K. dataset. Trend curves were divided into virus-free, restrictive, and/or recovery phases. Kruskal-Wallis H test was performed to assess the differences among those phases with significance set at adjusted P < 0.05 (two-sided). Findings: In a 30-week (January 5 to August 1, 2020) observing period for the U.S.A. dataset, there was an obvious association between the trends of SOT and COVID-19 diagnosis (both overall and death cases) in the 10-week restrictive phase; significant reduction of overall SOTs per day were found in the restrictive phase (median 78.0, IQR 64.6-91.4) compared with the virus-free phase (median 115.0, IQR 97.5-132.5; P < 0.001); The most affected organ transplants were kidney (35.5% reduction) and lung (35.4% reduction), and the most affected U.S. region was Northeast (62.2% reduction). Resumption occurred with no significant difference found between the comparison of recovery (median 118.5, IQR 99.3-137.8) versus virus-free phases (P = 1.000) in overall SOTs per day, as well as those stratified by donor type (deceased and living), organ, and region. The SOT reduction and resumption were validated by the U.K. dataset. Interpretation: Using the U.S.A. and U.K. datasets, our study thoroughly presented the reduction and resumption patterns of SOT during the COVID-19 pandemic. It is essential that transplant units, based on the gained experience, make adequate preparations for any further possible COVID-19 attack. Funding Statement: This study received no external funding. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Exemptions of ethics approval, institutional review board, and informed consent were granted as data used in this study were publicly available.

Background: Massive studies have examined associations between use of aspirin and lung cancer risk. However, findings from previous studies are inconsistent and it remains unclear whether there is a causality between them. Thus, we conducted a meta-analysis and further carried out Mendelian randomization (MR) analyses to elucidate the associations between aspirin use with lung cancer risk. Methods: Eligible studies were identified by searching the PubMed and several databases up to November 2019. Cohort studies, nested case-control studies, and randomized controlled trials (RCTs) investigating the impact of aspirin exposure and lung cancer were included. Relative risk (RR) were evaluated for lung cancer risk. Subgroup analyses regarding gender, pathologic subtypes and smoking status were also executed. MR analyses were conducted using statistics obtained from Neale Lab and International Lung Cancer Consortium (ILCCO) to assess the possible causal relationship of aspirin on lung cancer risk. Findings: Sixteen eligible studies involving 1,522,687 patients were included. The combined RR of aspirin use for lung cancer risk was 0.95 (95% confidence interval (CI) 0.91-0.98). In terms of pathology, a significant protective effect of aspirin on lung cancer was observed in squamous cell lung cancer (RR=0.80; 95% CI 0.65-0.98). In subgroup meta-analyses, significant association between aspirin use and reduced lung cancer risk was only observed among men (RR=0.87; 95% CI 0.77-0.97). The MR risk analysis suggested a causal effect of aspirin on lung cancer risk, with evidence of a decreased risk for overall lung cancer (OR=0.042; 95% CI 0.003-0.564) and squamous cell lung cancer (OR=0.002; 95% CI 1.21×10-5-0.301). Interpretation: Our study provided evidence for a causal protective effect of aspirin on lung cancer risk among men, particularly on the squamous cell lung cancer risk. Funding Statement: National Key RD Key Project of Guangzhou Scientific Research Project; High-level university construction project of Guangzhou Medical University Declaration of Interests: The authors declare that there is no conflict of interest. Ethics Approval Statement: No patients participated in study design, patient recruitment and research conduct. Therefore, there is no need for ethical approval.

Background: As the COVID-19 pandemic continues to spread worldwide, there is still no accurate rapid diagnostic test for COVID-19, or monitoring tool for patient’s clinical course. An artificial-intelligence system (CoviDet) was therefore developed and applied on chest computed tomography (CT), to evaluate its application for rapid diagnosis and potential monitoring of COVID-19 patients. Methods: 1,201,074 CT slices from 2527 patients were grouped into 3 main groups: COVID-19 positive group, non-COVID-19 viral pneumonia group and control group. They were used to train and validate CoviDet novel stepwise diagnostic algorithm to diagnose COVID-19, with or without clinical data. A subset of COVID-19 patients with more than 3 consecutive CT images were selected for training and validation of the auto-segmentation and monitoring algorithm. Findings: CoviDet outperforms radiologists, and can diagnose COVID-19 based on CT alone with sensitivity of 0.93, specificity of 0.95 and AUC of 0.98 (95%CI 0.97-0.99; P

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are treatments commonly used for lung cancer. The toxicity profile including toxicity incidence, severity, and spectrum (involving various specific adverse events) of each EGFR-TKI are of particular clinical interest and importance. Data from phase II and III randomized controlled trials comparing treatments among EGFR-TKIs (osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib) and chemotherapy for lung cancer were synthesized with Bayesian network meta-analysis. The primary outcome was systemic all-grade and grade ≥3 adverse events. The secondary outcome was specific all-grade adverse events including those of the skin, gastrointestinal tract, lung, etc. 40 trials randomizing 13,352 patients were included. Generally greater toxicity for dacomitinib and afatinib, and safety for icotinib were suggested. Furthermore, we found individual EGFR-TKIs had different toxicity spectrums. These findings provide a compelling safety reference for the individualized use of EGFR-TKIs for patients with lung cancer.

Objective Store operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca2 + concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. Methods We identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform. Results We found consistently significant associations of TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 with increased risk of lung cancer among the three kinds of sources of populations (additive model in combined population: adjusted OR = 1.33, 95% CI = 1.11–1.59 for rs9547991; adjusted OR = 1.21, 95% CI = 1.08–1.35 for rs978156; and adjusted OR = 1.28, 95% CI = 1.10–1.47 for rs11748198). When combining the effects of TRPC7 rs11748198, and TRPC4 rs9547991 and rs978156, subjects carrying “≥ 1” variant alleles had a 1.29-fold increased risk of lung cancer (95% CI = 1.15–1.46), compared with those carrying “0” variant allele. Lung cancer risk significantly increased with the increasing number of variant alleles of the three SNPs in a dose-dependent manner (P for trend = 7.2 × 10− 7). Conclusion These findings suggested that TRPC4 rs9547991 and rs978156, and TRPC7 rs11748198 were candidate susceptibility markers for lung cancer in Chinese population. Our study provides the epidemiological evidence supporting a connection between TRPC members and lung cancer risks., Highlights • TRPC4 and TRPC7 associated with lung cancer risk in 4866 case-control • Adverse effects of TRPCs variants estimated based on the pathway study • Subjects carrying “≥ 1” variant alleles had a 1.29-fold risk, compared with “0”. • Lung cancer risk increased with variant allele's number in a dose-response.

Background Although video-assisted thoracoscopic surgery (VATS) has been widely applied to both peripheral and central lung cancer treatment in many centers, there is great hesitation to adopt it for carinal or tracheal surgical procedures. The aims of this study were to explore the feasibility of VATS in the treatment of benign and malignant diseases involving the carina and trachea and to highlight relevant techniques. Methods Patients undergoing VATS carinal or tracheal procedures between May 2012 and July 2015 from three centers in China were included in this study. Their clinical characteristics, operative details, and postoperative course were analyzed. Results Twelve patients underwent five different types of VATS airway reconstructions with or without lobectomy: including right bronchial resection with partial carinal reconstruction (3 patients), tracheal resection and reconstruction (4 patients), tracheal or right bronchial resection with carinal reconstruction (3 patients), left bronchial resection with carinal reconstruction (1 patient), and right pneumonectomy with carinal reconstruction (1 patient). Complete resection was achieved in all patients. The mean operative time was 224 ± 78 minutes, and the median time of the first anastomosis was 41 minutes (range, 15 to 60 minutes), regardless of whether the reconstruction was a tracheal or carinal. The median estimated blood loss was 100 mL (range 10 to 1000 mL). The mean postoperative hospital stay was 12.5 ± 2.5 days. There was no perioperative mortality or major morbidity. Median duration of follow-up was 12 months (range 5 to 43 months). Conclusions VATS resection and reconstruction of the carina or trachea are feasible, and these procedures can be safely performed using the techniques described. We believe, with the accumulation of VATS experience, these procedures could be adopted as routine approaches in tracheal surgery.

Summary Background Fewer than half of the patients with completely resected non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant chemotherapy in 2004, no substantial progress has been made in adjuvant treatment. We aimed to assess the efficacy of the MAGE-A3 cancer immunotherapeutic in surgically resected NSCLC. Methods In this randomised, double-blind, placebo-controlled trial, we recruited patients aged at least 18 years with completely resected stage IB, II, and IIIA MAGE-A3-positive NSCLC who did or did not receive adjuvant chemotherapy from 443 centres in 34 countries (Europe, the Americas, and Asia Pacific). Patients were randomly assigned (2:1) to receive 13 intramuscular injections of recMAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic) or placebo during 27 months. Randomisation and treatment allocation at the investigator site was done centrally via internet with stratification for chemotherapy versus no chemotherapy. Participants, investigators, and those assessing outcomes were masked to group assignment. A minimisation algorithm accounted for the number of chemotherapy cycles received, disease stage, lymph node sampling procedure, performance status score, and lifetime smoking status. The primary endpoint was broken up into three co-primary objectives: disease-free survival in the overall population, the no-chemotherapy population, and patients with a potentially predictive gene signature. The final analyses included the total treated population (all patients who had received at least one treatment dose). This trial is registered with ClinicalTrials.gov, number NCT00480025. Findings Between Oct 18, 2007, and July 17, 2012, we screened 13 849 patients for MAGE-A3 expression; 12 820 had a valid sample and of these, 4210 (33%) had a MAGE-A3-positive tumour. 2312 of these patients met all eligibility criteria and were randomly assigned to treatment: 1515 received MAGE-A3 and 757 received placebo and 40 were randomly assigned but never started treatment. 784 patients in the MAGE-A3 group also received chemotherapy, as did 392 in the placebo group. Median follow-up was 38·1 months (IQR 27·9–48·4) in the MAGE-A3 group and 39·5 months (27·9–50·4) in the placebo group. In the overall population, median disease-free survival was 60·5 months (95% CI 57·2–not reached) for the MAGE-A3 immunotherapeutic group and 57·9 months (55·7–not reached) for the placebo group (hazard ratio [HR] 1·02, 95% CI 0·89–1·18; p=0·74). Of the patients who did not receive chemotherapy, median disease-free survival was 58·0 months (95% CI 56·6–not reached) in those in the MAGE-A3 group and 56·9 months (44·4–not reached) in the placebo group (HR 0·97, 95% CI 0·80–1·18; p=0·76). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. The frequency of grade 3 or worse adverse events was similar between treatment groups (246 [16%] of 1515 patients in the MAGE-A3 group and 122 [16%] of 757 in the placebo group). The most frequently reported grade 3 or higher adverse events were infections and infestations (37 [2%] in the MAGE-A3 group and 19 [3%] in the placebo group), vascular disorders (30 [2%] vs 17 [3%]), and neoplasm (benign, malignant, and unspecified (29 [2%] vs 16 [2%]). Interpretation Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped. Funding GlaxoSmithKline Biologicals SA.

Background It is unclear whether three-dimensional (3D) video-assisted thoracic surgery (VATS) pulmonary resections are comparable to two-dimensional (2D) VATS pulmonary resections in patients with potentially operable benign pulmonary diseases. Methods We analyzed the clinical data of patients who underwent 2D and 3D VATS pulmonary resections for benign diseases in our hospital from November 2013 to August 2014. Perioperative factors (estimated blood loss and operative time) and postoperative factors (postoperative hospital length of stay, postoperative complications, and duration of chest tube drainage) were evaluated. Results VATS was performed in 278 patients during the 10-month study period. The 2D VATS system was used in 142 patients (51.08%), and the 3D VATS system was used in 136 (48.92%). Operative time was significantly different between the two groups ( p = 0.007). However, no significant differences were found in estimated blood loss ( p = 0.75), chest drainage tube placement time ( p = 0.852), rate of postoperative complications ( p = 0.566), or postoperative hospital length of stay ( p = 0.951). Conclusions The use of 3D VATS appears to facilitate precise execution of surgical techniques in specific operative tasks and, as a result, reduces lung resection performance time in patients with benign pulmonary diseases.

Previous tracheal surgeries were performed under tracheal and cross-field intubation. However, the intubation would lead to bleeding if the tumors were large or hemorrhagic. Moreover, the tracheal intubation might interfere the surgical vision and anastomosis during the reconstruction process. Therefore, we performed a tracheal tumor resection and reconstruction via nonintubated spontaneous anesthesia. We describe the feasibility and safety of tracheal surgeries via such anesthesia.

Background Population-based cohort studies have indicated that systemic sclerosis (SSc) may be associated with an increased risk of lung cancer. However, there are few studies that comprehensively investigate their correlation and the causal effect remains unknown. Methods A systematic search of PubMed, Web of Science, Cochrane Library and Embase from the inception dates to December 1, 2019 was carried out. Meta-analysis was performed to calculate odds ratio (OR) and corresponding 95% confidence interval (CI) using random-effects models. Subgroup analyses were performed regarding gender. Two-sample Mendelian randomization (MR) was carried out with summary data from published genome-wide association studies of SSc (Neale Lab, 3871 individuals; UK Biobank, 463,315 individuals) and lung cancer (International Lung Cancer Consortium, 27,209 individuals; UK Biobank, 508,977 individuals). Study-specific estimates were summarized using inverse variance-weighted, weighted median, and MR-Egger method. Results Through meta-analysis of 10 population-based cohort studies involving 12,218 patients, we observed a significantly increased risk of lung cancer among patients with SSc (OR 2.80, 95% CI 1.55–5.03). In accordance with subgroup analysis, male patients (OR 4.11, 95% CI 1.92–8.79) had a 1.5-fold higher lung cancer risk compared with female patients (OR 2.73, 95% CI 1.41–5.27). However, using a score of 11 SSc-related single nucleotide polymorphisms (p Conclusions This study indicated an increased risk of lung cancer among patients with SSc by meta-analysis, whereas the MR study did not support a causality between the two diseases. Further studies are warranted to investigate the factors underlying the attribution of SSc to lung cancer risk.

To develop multifunctional delivery systems of targeted properties for biomedical applications, hybrid fiber-nanoparticle matrices capable of controlled and monitored nanoparticles (NPs) delivery properties were prepared. Firstly, electropinning technique was applied to produce carbon nanotubes (CNTs) incorporated biodegradable poly(ϵ-caprolactone)/gelatin (PG) polymer fibers (PGC fibers). Subsequently, the photoluminescent mesoporous silica nanoparticles (PLMSNs) were electrostatically attached on the surface of PGC fibers to form a localized delivery platform. The PGC-PLMSNs fibers can emit red light under excitation at ~395 nm, 465 nm, and ~533 nm. Additionally, under NIR (808 nm) irradiation, PGC-PLMSNs fibers revealed good photothermal effect. PLMSNs loading efficiency onto the PGC fibers and PLMSNs release kinetics were assessed by TG method. More importantly, the 808 nm NIR irradiation enabled remarkably promoted PLMSNs release rate, validating the typical NIR-triggered release properties. Meanwhile, PLMSNs released from the composite fibers could be optically monitored by decrease in the intensity of red emission. These results suggest the possibility to develop the localized therapeutic device that may inspire other means of treatment method for cancer therapy.

Summary Many COVID-19 patients infected by SARS-CoV-2 virus develop pneumonia (called novel coronavirus pneumonia, NCP) and rapidly progress to respiratory failure. However, rapid diagnosis and identification of high-risk patients for early intervention are challenging. Using a large computed Tomography (CT) database from 4,154 patients, we developed an AI system that can diagnose NCP and differentiate it from other common pneumonia and normal controls. The AI system can assist radiologists and physicians in performing a quick diagnosis especially when the health system is overloaded. Significantly, our AI system identified important clinical markers that correlated with the NCP lesion properties. Together with the clinical data, our AI system was able to provide accurate clinical prognosis that can aid clinicians to consider appropriate early clinical management and allocate resources appropriately. We have made this AI system available globally to assist the clinicians to combat COVID-19., Highlights • AI system that can diagnose COVID-19 pneumonia using CT scans • Prediction of progression to critical illness • Potential to improve performance of junior radiologists to the senior level • Can assist evaluation of drug treatment effects with CT quantification, Zhang et al. present an AI-based system, based on hundreds of thousands of human lung CT scan images, that can aid in distinguishing patients with pneumonia caused by SARS-CoV-2 versus other viral infections and can help to predict the prognosis of COVID-19 patients.