Background: The number of deaths worldwide caused by coronavirus disease (COVID-19) is increasing rapidly. Information about the clinical characteristics of patients with COVID-19 who were not admitted to hospital is limited. Some risk factors of mortality associated with COVID-19 are controversial (eg, smoking). Moreover, the impact of city closure on mortality and admission rates is unknown. Objective: The aim of this study was to explore the risk factors of mortality associated with COVID-19 infection among a sample of patients in Wuhan whose conditions were reported on social media. Methods: We enrolled 599 patients with COVID-19 from 67 hospitals in Wuhan in the study; 117 of the participants (19.5%) were not admitted to hospital. The demographic, epidemiological, clinical, and radiological features of the patients were extracted from their social media posts and coded. Telephone follow-up was conducted 1 month later (between March 15 and 23, 2020) to check the clinical outcomes of the patients and acquire other relevant information. Results: The median age of patients with COVID-19 who died (72 years, IQR 66.5-82.0) was significantly higher than that of patients who recovered (61 years, IQR 53-69, P<.001). We found that lack of admission to hospital (odds ratio [OR] 5.82, 95% CI 3.36-10.1; P<.001), older age (OR 1.08, 95% CI 1.06-1.1; P<.001), diffuse distribution (OR 11.09, 95% CI 0.93-132.9; P=.058), and hypoxemia (odds ratio 2.94, 95% CI 1.32-6.6; P=.009) were associated with increasing odds of death. Smoking was not significantly associated with mortality risk (OR 0.9, 95% CI 0.44-1.85; P=.78). Conclusions: Older age, diffuse distribution, and hypoxemia are factors that can help clinicians identify patients with COVID-19 who have poor prognosis. Our study suggests that aggregated data from social media can also be comprehensive, immediate, and informative in disease prognosis.

Transglutaminase 2 (TGM2) is a Ca²⁺‑dependent enzyme that is closely associated with cancer progression; however, the function of TGM2 in T‑cell lymphoma remains unclear. In the present study, TGM2 was identified as an upregulated gene by bioinformatics analysis of the microarray datasets GSE132550 and GSE143382 from the Gene Expression Omnibus database. The effects and mechanisms of TGM2 on T‑cell lymphoma cells were evaluated using the Cell Counting Kit‑8, colony formation assay, 5‑ethynyl‑2'‑deoxyuridine (EdU) assay, flow cytometry, reverse transcription‑quantitative polymerase chain reaction, western blotting and gene set enrichment analysis (GSEA). TGM2 expression was shown to be elevated in formalin‑fixed paraffin‑embedded skin biopsies from patients with T‑cell lymphoma relative to skin tissue from healthy cases. TGM2 expression was also increased in T‑cell lymphoma cell lines compared with that in CD4⁺ T cells. Transfection with TGM2 small interfering RNAs (siRNAs) decreased the number of EdU‑positive cells, and the viability and colony formation of T‑cell lymphoma cells. Furthermore, TGM2 siRNAs enhanced the apoptosis of T‑cell lymphoma cells potentially via cleavage of caspase‑3 and poly ADP‑ribose polymerase. GSEA identified the IL‑6/JAK/STAT3 pathway as a potential downstream signalling pathway of TGM2. Notably, the effects of TGM2 siRNAs on T‑cell lymphoma cells were attenuated by IL‑6 and accelerated by IL‑6/JAK/STAT3 inhibitor AG490. These findings indicated that TGM2 siRNAs inhibited the proliferation of T‑cell lymphoma cells by regulating the IL‑6/JAK/STAT3 signalling pathway; therefore, TGM2 may function as a potential therapeutic target for T‑cell lymphoma.

Background Afatinib has been shown as a suitable option for the treatment of epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC) in randomized controlled trials. However, patients treated in real-world clinical practice, including elderly patients, and those with brain metastases or poor Eastern Cooperative Oncology Group (ECOG) performance statuses, are often excluded from these studies. Objective To report the final results, with a particular focus on patients enrolled in China, from a prospective phase IIIb, “near real-world” study of afatinib in tyrosine kinase inhibitor (TKI)-naïve Asian patients with EGFRm+ NSCLC. Patients and Methods NCT01953913 was conducted at 34 centers across Asia. Entry criteria were broad to reflect real-world settings. Patients received afatinib 40 mg/day until tumor progression, lack of clinical benefit, or poor tolerability. Assessments included safety, time to symptomatic progression (TTSP), and progression-free survival (PFS). Results 541 patients were treated, of whom 412 were enrolled in China. Dose reductions were implemented in 28.7% of patients overall, and 17.7% of patients from China. Safety findings were consistent with phase III studies of afatinib. Median TTSP in all patients was 14.0 months (95% CI 12.9–15.9), and median PFS was 12.1 months (95% CI 11.0–13.6). Median TTSP (13.8 months, 95% CI 12.7–16.1) and PFS (11.4 months, 95% CI 10.9–13.7) were similar in patients from China to the overall population. Among patients from China who had dose reductions, TTSP was numerically longer than in those who did not (16.4 vs. 13.8 months; P = 0.0703), while PFS was significantly longer (13.9 vs. 11.1 months; P = 0.0275). Among patients from China with brain metastases, TTSP was numerically shorter than in those without (11.0 vs. 14.4 months; P = 0.0869), whereas PFS was significantly shorter (9.2 vs. 12.9 months; P = 0.0075). Conclusions Safety data for afatinib when used in a “near real-world” setting in patients with EGFRm+ NSCLC was consistent with the known safety profile of afatinib. Supporting efficacy data of afatinib were provided in all patients, and in those enrolled in China. Tolerability-guided afatinib dose reduction allowed patients to remain on treatment and continue to experience clinical benefit. Trial Registration Number and Date of Registration NCT01953913 (1 October 2013).

The ability to differentiate between benign, suspicious, and malignant pulmonary nodules is imperative for definitive intervention in patients with early stage lung cancers. Here, we report that plasma protein functional effector sncRNAs (pfeRNAs) serve as non-invasive biomarkers for determining both the existence and the nature of pulmonary nodules in a three-stage study that included the healthy group, patients with benign pulmonary nodules, patients with suspicious nodules, and patients with malignant nodules. Following the standards required for a clinical laboratory improvement amendments (CLIA)-compliant laboratory-developed test (LDT), we identified a pfeRNA classifier containing 8 pfeRNAs in 108 biospecimens from 60 patients by sncRNA deep sequencing, deduced prediction rules using a separate training cohort of 198 plasma specimens, and then applied the prediction rules to another 230 plasma specimens in an independent validation cohort. The pfeRNA classifier could (1) differentiate patients with or without pulmonary nodules with an average sensitivity and specificity of 96.2% and 97.35% and (2) differentiate malignant versus benign pulmonary nodules with an average sensitivity and specificity of 77.1% and 74.25%. Our biomarkers are cost-effective, non-invasive, sensitive, and specific, and the qPCR-based method provides the possibility for automatic testing of robotic applications.

Background: Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC.Methods: We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs).Results: Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months).Conclusions: Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely.

Editorial: Tumor immune microenvironment topographies for prediction and evaluation: unlock the mystery of the therapeutic effects and adverse events of tumor immunotherapy