Background: Trilaciclib, an intravenous short acting cyclin-dependent kinase 4/6 inhibitor, has been approved for the prevention of chemotherapy-induced myelosuppression (CIM) in patients with extensive stage small cell lung cancer (ES-SCLC) receiving platinum/etoposide (EP) or topotecan (TPT)-based therapy in United States (US) since February 2021. Trilaciclib use received the priority review and approval in a real-world setting in China. This study thus aimed to collect real-world data and evaluate the protective effect of trilaciclib on CIM in Chinese patients with ES-SCLC.
Methods: This single-arm, noninterventional real world study invited all patients with ES-SCLC who received trilaciclib with the platinum and etoposide ± anti-programmed cell death ligand-1 [anti-PD-(L)1] antibodies (EP group) or trilaciclib with TPT (TPT group) in Boao, Hainan China to participate in the study. The primary endpoint was the incidence of the severe (grade four) neutropenia (SN), and the secondary endpoints included other myeloprotection effects, safety and anti-tumor activity.
Results: Between August 2021 and December 2022, a total of 30 patients who received trilaciclib with chemotherapy consented to participate in this real-world study. Among the enrolled patients, 26 patients were treated with EP regimen, of these, 18 patients were combined with anti-PD-(L)1 antibodies, and 4 patients were treated with TPT. The incidence of SN was 6.7%, with one patient each in EP group and TPT group. The incidence of grade three hematological toxicities was 30% (9/30), with 19.2% (5/26) in the EP group, and 100% (4/4) in the TPT group. The incidence of grade four hematological toxicities was 5/30 (16.7%), with 3/26 (11.5%) and 2/4 (50%) in EP and TPT group, respectively. Overall, the incidence of those who received intravenous or oral antibiotics was 6/30 (20%), with 4/26 (15.4%) in the EP group, and 2/4 (50%) in the TPT group. No ≥ grade three adverse events, serious adverse events (SAEs), and adverse events of special interest associated with trilaciclib were reported.
Conclusions: Trilaciclib decreased the incidence of CIM in Chinese patients when administered prior to an EP-containing regimen [combined with or without PD-(L)1] or TPT for ES-SCLC. The effect of myeloprotection, anti-tumor and safety were all consistent with the studies conducted globally and data from the Chinese Phase three placebo-controlled study (TRACES).
Background: The standard treatment for thymomatous myasthenia gravis (TMG) patients is thymectomy, whereas its role in non-TMG (NTMG) is still under debate. The objective of this study is to assess myasthenia gravis (MG) outcomes of thymectomy using the uniportal video-assisted thoracoscopic surgery (UVATS) technique for both groups and evaluate the procedure's efficacy and safety.
Methods: We retrospectively collected data from January 2019 to December 2022 at Hospital Kuala Lumpur. The Myasthenia Gravis Activities of Daily Living (MG-ADL) scoring and the Myasthenia Gravis Foundation of America's Post Interventional Score (MGFA-PIS) measured our primary outcome. Secondary outcomes included surgery-related morbidity. All patients underwent a UVATS thymectomy, with the incision at the right anterior axillary line at the 5th intercostal space.
Results: Out of 26 patients, 22 were analysed. The MG-ADL scores indicated a significant mean score reduction post-surgery [6.9; 95% confidence interval (CI): 4.42 to 9.67; P<0.001]. NTMG patients exhibited a greater decrease in MG-ADL mean score than TMG patients {9.5 [standard deviation (SD) 4.8] vs. 6.1 (SD 5.4) P<0.001}. The MGFA-PIS showed complete stable remission (CSR) rates of 43% for TMG and 25% for NTMG patients. Surgical morbidity was observed in 13% of patients, of which were myasthenic crisis, difficult extubation due to carbon dioxide (CO2) retention and subcutaneous emphysema.
Conclusions: Thymectomy via UVATS is an effective and safe approach for improving symptoms in both TMG and NTMG patients.
Background: Thymic carcinoma is a type of rare and highly malignant tumor that originates from the thymic epithelium. Treatment and prognosis of thymic carcinoma remain controversial. We retrospectively analyzed survival data from a large sample database in a single center in China to summarize the clinicopathological features of patients with thymic carcinoma and explore the factors affecting prognosis.
Methods: The clinical data of 87 patients with thymic carcinoma who underwent surgical treatment between January 2010 and October 2023 were retrospectively analyzed. Of these, 74 patients had thymic squamous cell carcinoma, and 13 had other subtypes. The Kaplan-Meier method was used to calculate survival rate, and the log-rank test was employed for univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis to evaluate the clinical, pathological, and therapeutic information of patients with thymic carcinoma, analyze long-term survival, and identify prognostic factors associated with postoperative thymic carcinoma.
Results: The 5- and 10-year overall survival (OS) rates were 85.6% and 69.9%, respectively, and the corresponding disease-free survival (DFS) rates were 76.4% and 58.6%, respectively. Univariate analysis revealed significant associations between the Masaoka-Koga stage, resection status, postoperative radiotherapy, and OS in patients with thymic carcinoma. Furthermore, the Masaoka-Koga stage is correlated with DFS in patients who underwent postoperative treatment for thymic carcinoma. Cox multivariate analysis confirmed that the Masaoka-Koga stage [hazard ratio (HR): 2.719, 95% confidence interval (CI): 1.032-7.163, P=0.043] independently influenced DFS in surgically treated patients with thymic carcinoma, whereas the Masaoka-Koga stage (HR: 3.690, 95% CI: 1.043-13.049, P=0.043) and postoperative radiotherapy (HR: 0.319, 95% CI: 0.102-0.999, P=0.049) emerged as critical prognostic factors affecting OS.
Conclusions: Thymic squamous cell carcinoma is the most prevalent form of thymic carcinoma, and complete resection (R0 resection) is the preferred treatment modality. The Masaoka-Koga stage and postoperative radiotherapy are significant prognostic indicators for improved outcomes.
Background: 17-hydroxy-jolkinolide B (HJB) is a natural diterpenoid compound derived from plants of the Euphorbiaceae family that has anticancer properties against various types of tumors. However, its action and underlying mechanism in lung adenocarcinoma (LUAD) progression remain largely unknown. Thus, this research aimed to explore the role of HJB in LUAD pathogenesis and its clinical significance in tumor therapy.
Methods: Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and scratch wound-healing assay were utilized to evaluate the effect of HJB on proliferation, colony formation, and migration of LUAD cells in vitro. The syngeneic and xenograft tumor models were used to evaluate the anti-tumor activity of HJB in combination with cytotoxic T-lymphocyte antigen 4 antibody (CTLA4ab) on LUAD in vivo. In addition, quantitative real-time polymerase chain reaction (qPCR) and western blotting analyses were used to analyze the expression of programmed death ligand 1 (PD-L1). Lentiviral transduction and transfection were used to explore the related mechanism.
Results: Experimental data demonstrated that HJB inhibited cell viability, colony formation, and migration of murine and human LUAD cells in vitro. The syngeneic and xenograft tumor models indicated that HJB possessed a remarkable anti-tumor activity in vivo and potentiated immune checkpoint blockades (ICBs) therapy. Moreover, PD-L1 might serve as a novel target in HJB-suppressed lung cancer.
Conclusions: By targeting PD-L1, HJB inhibited tumor cell proliferation and colony formation, as well as migration ability in vitro and in vivo. Besides, HJB enhanced CTLA4ab therapy and may be a potential agent for LUAD therapy.
Sublober resection of small peripheral lung lesions using video-assisted thoracoscopic surgery may require marking and confirmation using 3D imaging in the interventional radiology suite or in the hybrid operating room (HOR) before surgery is started. We report a novel approach for intraoperative transbronchial metallic coil marking followed by thoracoscopic wedge resection in a conventional operating room under mobile 3D C-arm guidance. Under general anesthesia, an ultrathin video-bronchoscope was inserted into an objective bronchus guided with virtual bronchoscopic navigation, and a coil-feeding microcatheter was introduced through the bronchoscope's channel. After the position of the catheter tip was confirmed with cone-beam computed tomography (CT) images rendered via a mobile 3D C-arm, a metallic coil was subsequently deployed through the catheter as a marker. During surgery, the nodule with the metallic coil was grasped with pulmonary forceps and fully resected with endostaplers under fluoroscopic guidance. This method has advantages because the transbronchial approach carries a lower risk of complications such as pneumothorax and air embolism compared with a percutaneous approach, and the metallic coil provides more accurate, pinpoint localization compared with liquid dye. Mobile 3D C-arm-guided transbronchial metallic coil marking followed by thoracoscopic wedge resection under fluoroscopic guidance is a one-stop solution for intraoperative marking and resection of small peripheral pulmonary lesions in any operating room.
Background: The increasing utilization of computed tomography (CT) scans has significantly elevated the detection rate of pulmonary nodules. Pulmonary segmentectomy has become the preferred surgical technique for peripheral non-small cell lung cancer (NSCLC) measuring 2 cm or smaller. Various methods for identifying the intersegmental planes (ISPs) are currently employed. This study aims to compare the short-term clinical safety and efficacy of the watershed analysis with indocyanine green (ICG) fluorescence staining to the modified inflation-deflation method in single-port thoracoscopic complex pulmonary segmentectomy.
Methods: This retrospective study was conducted on patients who underwent single-port thoracoscopic complex pulmonary segmentectomy at The First Affiliated Hospital of Soochow University between January 2023 and December 2023. One cohort received treatment with the watershed analysis with ICG fluorescence staining, while the other cohort was treated with the modified inflation-deflation method. The study evaluated intraoperative and postoperative conditions, as well as the short-term impact on postoperative pulmonary function in both groups.
Results: The watershed analysis with ICG fluorescence staining group demonstrated less operating time (P<0.001), shorter ISPs visualization time (P<0.001), and reduced intraoperative blood loss (P<0.001). Postoperatively, 8 patients (16%) in this group experienced air leakage, compared to 20 patients (39%) in the modified inflation-deflation method group, indicating significant differences between the groups (P=0.009). Additionally, the watershed analysis with ICG fluorescence staining group had shorter postoperative drainage tube duration (P<0.001), shorter postoperative hospitalization (P<0.001), and less postoperative pleural effusion volume (P<0.001). There was no disparity observed in pulmonary function decline at three months after the surgery between the two cohorts.
Conclusions: The watershed analysis with ICG fluorescence staining is associated with less operating time, fewer postoperative complications, and a lower risk of postoperative air leakage in complex pulmonary segmentectomy. The impact on pulmonary function was comparable to the traditional method. These findings suggest that the watershed analysis with ICG fluorescence staining is a more promising, safe, and effective approach for complex pulmonary segmentectomy.
[This corrects the article DOI: 10.21037/jtd-24-591.].
Background: Recent studies have reported that diet can modulate the associations between risk factors and childhood metabolic diseases. Herein, this study aims to explore the role of dietary vitamin A (VA) in relation to asthma with hypertension in children and adolescents, and further provide some information on dietary aspect for the prevention of asthma related hypertension.
Methods: In this cross-sectional study, data of 9,448 children and adolescents were obtained from the National Health and Nutrition Examination Survey (NHANES) database for the period of 2007 to 2018. Weighted univariate logistic regression analysis was used for covariates screening, and associations of dietary VA and asthma with hypertension were explored through weighted univariate and multivariate logistic regression analyses. Odds ratios (ORs) with 95% confidence intervals (CIs) were used as evaluation indexes. Besides, subgroup analyses of age, gender, and body mass index (BMI) were also performed.
Results: There were a total of 546 participants with hypertension in the study cohort. Children and adolescents with asthma had higher odds of hypertension than non-asthma individuals after covariates adjustment (OR =1.35, 95% CI: 1.03-1.78). When there were deficient dietary VA intakes, having asthma was significantly linked to higher odds of hypertension comparing to non-asthma individuals (OR =1.46, 95% CI: 1.07-1.99). Additionally, the potential beneficial effect of sufficient dietary VA intakes on hypertension related asthma was found in aged ≥13 years old (OR =1.65, 95% CI: 1.21-2.26), male (OR =1.59, 95% CI: 1.09-2.33), and underweight/normal weight (OR =1.97, 95% CI: 1.14-3.43) subgroups.
Conclusions: Children and adolescents having asthma seemed to have higher odds of hypertension, and sufficient dietary VA intakes may help reduce the risk of asthma related hypertension. However, the causal effect of dietary VA intakes on this correlation needs further clarification.
Background: The 26S non-ATPase regulatory subunit 11 (PSMD11) is a multiprotein complex that participates in the ATP-dependent degradation of ubiquitinated proteins and is essential to the regulation of embryonic stem cell proteasome activity. PSMD11 has been demonstrated to be a factor contributing to the emergence and progression of cancer cells. However, the prognostic value and potential biological function of PMSD11 in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to comprehensively investigate the prognostic and biological value of PSMD11 in LUAD.
Methods: We primarily endeavored to comprehensively investigate the prognostic and predictive value of PSMD11 in patients with LUAD. Additionally, we aimed to further clarify the underlying mechanisms of PSMD11 in LUAD tumorigenesis and progression via rigorous bioinformatics analyses, including expression analysis, survival analysis, clinicopathological analysis, immune microenvironment analysis, somatic mutation analysis, drug analysis, and cuproptosis analysis. Subsequently, we examined effect of PSMD11 expression on immune escape in a non-small cell lung cancer (NSCLC) cell-T cell coculture model.
Results: We found that PSMD11 had a significantly higher expression in LUAD tissues than in normal lung tissues. Three clinical characteristics (age, stage, and overall survival event) exhibited significant differences between the PSMD11 high- and low-expression groups. In biological function, PSMD11 appears to exert its tumorigenic effects predominantly in pathways related to DNA replication and membrane-gated channel functions. Notably, we observed that PSMD11 exhibited the strongest positive correlation with T helper 2 cells, gamma-delta T cells, and T regulatory cells and the highest negative correlation with B cells, mast cells, and CD8+ T cells. Furthermore, we found that the expression of cuproptosis genes (DLAT, DLD, and PDHA1) was positively correlated with the expression of PSMD11 (P<0.001).
Conclusions: These results indicate that PSMD11 has the potential to be a novel therapeutic target and sensitive biomarker for patients with LUAD.
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