Non­diagnostic electromagnetic navigation bronchoscopy biopsy: Predictive factors and final diagnoses.

The present study aimed to explore the final diagnosis of pulmonary nodules with an initial non-diagnostic result on electromagnetic navigation bronchoscopy (ENB) biopsy and the predictive factors for a non-diagnostic result. A total of 198 nodules from 194 patients that were suspected to be malignant tumors were included in the present study. The initial biopsy pathology results were divided into two groups: The diagnostic group and the non-diagnostic group. The diagnostic group was defined as a successful initial biopsy to obtain a diagnosis, including malignant and benign diagnoses. The non-diagnostic group was defined as a non-specific benign diagnosis, normal lung tissue or an unsuccessful biopsy. Among the 198 nodules, 139 (70.2%) were in the diagnostic group and 59 (29.8%) were in the non-diagnostic group. Predictive factors for a non-diagnostic biopsy included nodule size ≤1.5 cm [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.03-4.09], non-solid nodules (OR, 2.71; 95% CI, 1.33-5.64) and nodules in the left lung (OR, 2.50; 95% CI, 1.27-4.92). Of the 59 non-diagnostic biopsies, 46 were finally confirmed to be malignant by surgery. Notably, non-diagnostic biopsies with non-solid nodules (OR, 7.64; 95% CI, 3.11-18.76) were more likely to be malignant. In conclusion, the predictive factors for a non-diagnostic biopsy were nodule size ≤1.5 cm and non-solid nodules. It was not rare for patients to finally be diagnosed with a malignancy in the non-diagnostic group. Therefore, care should be taken when the results of an ENB are non-diagnostic to prevent misdiagnosis.

The combination of a seven-autoantibody panel with computed tomography scanning can enhance the diagnostic efficiency of non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) is still of concern in differentiating it from benign disease. This study aims to validate the diagnostic efficacy of a novel seven-autoantibody (7-AAB) panel for the diagnosis of NSCLC. Methods: We retrospectively enrolled 2650 patients who underwent both the 7-AAB panel test and CT scanning. We compared the sensitivity, specificity, and PPV of 7-AAB, CT, and PET-CT in the diagnosis of NSCLC in different subgroups. Then, we established a nomogram based on CT image features and the 7-AAB panel to further improve diagnostic efficiency. Moreover, we compared the pathological and molecular results of NSCLC patients in the 7-AABs positive group and the negative group to verify the prognostic value of the 7-AAB panel. Results: The strategy of a "both-positive rule" combination of 7-AABs and CT had a specificity of 95.4% and a positive predictive value (PPV) of 95.8%, significantly higher than those of CT or PET-CT used alone (P<0.05). The nomogram we established has passed the calibration test (P=0.987>0.05) with an AUC of 0.791. Interestingly, it was found that the 7-AABs positive group was associated with higher proportion of EGFR mutations (P<0.001), lower pathological differentiation degrees (P=0.018), more advanced pathological stages (P=0.040) and higher Ki-67 indexes (P=0.011) in patients with adenocarcinoma. Conclusion: This study shows that combination of a 7-AAB panel with CT has can significantly enhance the diagnostic efficiency of lung cancer. Moreover, the 7-AAB panel also has potential prognostic value and has reference significance for the formulation of the treatment plan.

The pattern of lymph node metastasis in peripheral pulmonary nodules patients and risk prediction models.

Background: For peripheral pulmonary nodules, the regularity of lymph node (LN) metastasis has not been studied. This study aimed to evaluate the metastasis pattern of intrapulmonary and relevant mediastinal lymph nodes in early-stage lung cancer, and further selected patients who were of low risk of LN metastasis as potential population to receive sub-lobectomy. Methods: This study prospectively included consecutive patients with peripheral clinical T1N0M0 disease who underwent complete resection with LN dissection or sampling from August 2014 to July 2015. The patients were followed up to 15, May 2021. Univariable or multivariable Logistic analysis was used to identify the risk factors. Models predicting LN metastasis risk were conducted. The area under the curve for the receiver operating characteristic curves was used to evaluate the diagnostic value. Disease-free survival and overall survival were compared between groups. Results: Finally, 201 patients were included in this study. For patients with negative tumor-bearing (TB) 13 and 14 station LNs, the positive rate of other lymph node stations was extremely low. Maximum CT value, pleural indentation and CEA level were risk factors for N1 station LNs metastasis. Besides, the factors above and lobulation sign were risk factors for skip metastasis beyond TB 13 and 14 station LNs. We constructed two scoring tables to predict N1 station metastasis and skip metastasis beyond TB 13 and 14 station. The AUC were 0·837 and 0·823, respectively. Based on the first table, 40·9% of patients suffered N1 station LNs metastasis and 27·3% had N2 disease in "high risk group" while the proportion was only 5·7% and 4·5% in "low risk group". For patients with negative TB13 and TB14 station LNs, based on the latter table, 11·1% of patients had N1 stations LNs metastasis and 16·7% had pN2 disease in "high risk group" while only 2·3% patients in "low risk group" suffered this kind of metastasis. Conclusion: For peripheral pulmonary nodules patients, stations 13 and 14 LNs may be the sentinel nodes. For patients with low risk of N1 metastasis and skip metastasis, sub-lobar resection might be sufficient for those who were of negative TB 13 and 14 station LNs.

Evaluation of the safety and effectiveness of neoadjuvant combined chemoimmunotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective single-arm cohort study.

Background: Transforming potentially resectable advanced esophageal squamous cell carcinoma (ESCC) into resectable ESCC through preoperative induction therapy is an important component of ESCC comprehensive treatment. Immune checkpoint inhibitor (ICI) therapy has been shown to have significant effects in the treatment of advanced ESCC, but its role in the neoadjuvant treatment of potentially resectable ESCC is unclear. This study aims to investigate the safety and effectiveness of camrelizumab combined with chemotherapy in the neoadjuvant treatment of ESCC. Methods: We recruited consecutive patients with potentially resectable ESCC who received preoperative camrelizumab in combination with chemotherapy. Data including demographic data, clinicopathological characteristics, neoadjuvant treatment regimens, lesion changes observed by imaging, and surgical details were retrospectively collected through specially designed forms. Toxic effects of neoadjuvant therapy on hematology, gastrointestinal tract, liver, kidney, skin, and thyroid were also collected. Imaging assessments were performed every 1-2 treatment cycles. Follow-up is based on the patient's regular admission to the hospital for examination and treatment, at least 3 months after surgery. Results: A total of 66 patients with locally advanced ESCC were included in this study, including 8 patients with stage II, 29 patients with stage III, and 29 patients with stage IVA. The objective response rate (ORR) of the neoadjuvant immunotherapy combined with chemotherapy was 75.76% (50/66), and no one developed disease progression. A total of 60 patients underwent surgery, and the R0 resection rate was 98.3% (59/60). The pathological complete remission (pCR) rate and the major pathological response (MPR) rate was 6.7% (4/60) and 20% (12/60), respectively. There were 14 cases of treatment-related adverse reactions >3, but no perioperative deaths occurred. Conclusions: Neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection may be an available treatment for patients with locally advanced ESCC.

A five-m6A regulatory gene signature is a prognostic biomarker in lung adenocarcinoma patients.

We analyzed the prognostic value of N6-methyladenosine (m6A) regulatory genes in lung adenocarcinoma (LADC) and their association with tumor immunity and immunotherapy response. Seventeen of 20 m6A regulatory genes were differentially expressed in LDAC tissue samples from the TCGA and GEO databases. We developed a five-m6A regulatory gene prognostic signature based on univariate and Lasso Cox regression analysis. Western blot analysis confirmed that the five prognostic m6A regulatory proteins were highly expressed in LADC tissues. We constructed a nomogram with five-m6A regulatory gene prognostic risk signature and AJCC stages. ROC curves and calibration curves showed that the nomogram was well calibrated and accurately distinguished high-risk and low-risk LADC patients. Weighted gene co-expression analysis showed significant correlation between prognostic risk signature genes and the turquoise module enriched with cell cycle genes. The high-risk LADC patients showed significantly higher PD-L1 levels, increased tumor mutational burden, and a lower proportion of CD8+ T cells in the tumor tissues and improved response to immune checkpoint blockade therapy. These findings show that this five-m6A regulatory gene signature is a prognostic biomarker in LADC and that immune checkpoint blockade is a potential therapeutic option for high-risk LADC patients.

A Novel Tubeless Urinary Catheter Protocol Enhanced Recovery After Minimally Invasive Lung Surgery.

Objectives: Although previous studies have shown the feasibility of non-intubated techniques, it is unknown whether avoiding urinary catheters can enhance recovery. This study aimed to determine whether the tubeless urinary catheter protocol is feasible and beneficial for minimally invasive lung surgery. Methods: Patients were randomized to the control group, completely tubeless group, and partially tubeless group. A propensity score-matched (PSM) analysis was performed to balance the non-random baseline characteristics. Complications and postoperative recovery were compared. Regression analysis was performed to identify the independent predictors of complications. A nomogram for predicting the risk of non-automatic micturition was constructed and internally validated. Results: One hundred fifty-nine patients were enrolled. The incidence rates of urinary irritation and urinary tract infection (UTI) were significantly lower in the tubeless groups (74.4 vs. 39.5%, p < 0.001; 28.2 vs. 8.6%, p = 0.001, respectively). The tubeless group had a higher proportion of 0-degree discomfort (81.5 vs. 30.8%, p = 0.001) and shorter duration of postoperative hospital stay than the control group (4.59 vs. 5.53 days, p < 0.001). No difference was observed in terms of urination retention and urinary incontinence between the tubeless group and the control group. After PSM, the advantages of the tubeless group still existed, and comparing to the partially tubeless group, the completely tubeless group was of even less UTI and more 0-degree discomfort (18.5 vs. 0.0%, p = 0.019; 96.3 vs. 59.3%, p = 0.002). The tubeless protocol was the only independent protective factor of urinary complications. A nomogram was constructed and showed good predictive ability. Conclusions: The tubeless catheterization protocol led to fewer complications, better compliance, and shorter hospital length of stay. The advantages were more significant with the completely tubeless protocol. The utility of our nomogram can assist clinicians in avoiding risks in performing the tubeless protocol.

H3K27ac-activated LINC00519 promotes lung squamous cell carcinoma progression by targeting miR-450b-5p/miR-515-5p/YAP1 axis.

OBJECTIVES: Long non-coding RNAs (lncRNAs) are extensively reported as participants in the biological process of diverse malignancies, including lung squamous cell carcinoma (LUSC). Long intergenic non-protein coding RNA 519 (LINC00519) is identified as a novel lncRNA which has not yet been studied in cancers. MATERIALS AND METHODS: LINC00519 expression was detected by qRT-PCR. The effect of LINC00519 on LUSC cellular activities was determined by in vitro and in vivo assays. Subcellular fractionation and FISH assays were conducted to identify the localization of LINC00519. The interaction between miR-450b-5p/miR-515-5p and LINC00519/YAP1 was verified by RIP, RNA pull-down and luciferase reporter assays. RESULTS: Elevated level of LINC00519 was identified in LUSC tissues and cell lines. High LINC00519 level predicted unsatisfactory prognosis. Then, loss-of-function assays suggested the inhibitive role of silenced LINC00519 in cell proliferation, migration, invasion and tumour growth and promoting effect on cell apoptosis in LUSC. Mechanically, LINC00519 was activated by H3K27 acetylation (H3K27ac). Moreover, LINC00519 sponged miR-450b-5p and miR-515-5p to up-regulate Yes1 associated transcriptional regulator (YAP1). Additionally, miR-450b-5p and miR-515-5p elicited anti-carcinogenic effects in LUSC. Finally, rescue assays validated the effect of LINC00519-miR-450b-5p-miR-515-5p-YAP1 axis in LUSC. CONCLUSIONS: H3K27ac-activated LINC00519 acts as a competing endogenous RNA (ceRNA) to promote LUSC progression by targeting miR-450b-5p/miR-515-5p/YAP1 axis.

Effects of divalent copper on microbial community, enzymatic activity and functional genes associated with nitrification and denitrification at tetracycline stress.

The effects of divalent copper (Cu(II)) on microbial community, enzymatic activity and functional genes in a sequencing batch reactor (SBR) at tetracycline (TC) stress were investigated. The enzymatic activity and functional genes abundance associated with nitrification and denitrification at a 20 mg L-1 TC stress were higher than those at a mixtures stress of 20 mg L-1 TC and 10 mg L-1 Cu(II), while they were lower than those at a mixtures stress of 20 mg L-1 TC and 40 mg L-1 Cu(II). Compared to lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production at a 20 mg L-1 TC stress, they were lower at the TC stress with 10 mg L-1 Cu(II), while they were higher at the TC stress with 40 mg L-1 Cu(II). The incremental Cu(II) concentration at a 20 mg L-1 TC stress could not change the result that the sensitivity of denitrifying enzymatic activity to TC was higher than nitrifying enzymatic activity. Compared to the relative abundance of nitrifers and denitrifers at a 20 mg L-1 TC stress, the 10 mg L-1 Cu(II) addition resulted in their increase, while they decreased as the 40 mg L-1 Cu(II) addition. The relative abundance of genera Pseudomonas, Rivibacter and Nitrobacter at the stress of Cu(II) and TC were higher than those at TC stress, suggested they had an ability to resist the stress of Cu(II) and TC.

Combination therapy of apatinib with icotinib for primary acquired icotinib resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.

Multi-targeted agents represent the next generation of targeted therapies for solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third-generation targeted drugs, such as osimertinib, are very expensive, thus a more economical solution is required. The aim of this study was to explore the use of apatinib combined with icotinib therapy for primary acquired resistance to icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR mutations. We achieved favorable oncologic outcomes in all three patients, with progression-free survival of four to six months. Unfortunately, the patients ultimately had to cease combination therapy because of intolerable adverse effects of hand and foot syndrome and oral ulcers. Combination therapy of apatinib with icotinib for primary acquired resistance to icotinib may be an option for patients with advanced pulmonary adenocarcinoma with EGFR mutations, but physicians must also be aware of the side effects caused by such therapy.

Semi-quantitative Analysis of EBUS Elastography as a Feasible Approach in Diagnosing Mediastinal and Hilar Lymph Nodes of Lung Cancer Patients.

This study aimed to semi-quantitatively evaluate the elastographic imaging color distribution of mediastinal and hilar lymph nodes (LNs), and explored its utility in helping define malignant and benign LNs for lung cancer patients. We prospectively collected patients who underwent preoperative mediastinal staging of suspected lung cancer by EBUS-TBNA. We analyzed the elastography color distribution of each LN and calculated the blue color proportion (BCP). The LN elastographic patterns were compared with the final EBUS-TBNA pathological results. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of BCP. We sampled and analyzed 79 LNs from 60 patients. The average BCP in malignant LNs was remarkably higher than that in benign LNs (57.1% versus 30.8%, P < 0.001). The area under the ROC curve (AUC) for the BCP was 0.86 (95% CI: 0.78-0.94). The best cutoff BCP for differentiating between benign and malignant LNs was determined as 36.7%. All the 16 LNs (20.3%) with a BCP lower than 27.9% were diagnosed as benign tissues. Our study suggests that elastography is a feasible technique that may safely help to predict LN metastasis during EBUS-TBNA. We found a clear BCP cutoff value to help define positive and negative LNs.

Long-term effects of combined divalent copper and tetracycline on the performance, microbial activity and community in a sequencing batch reactor.

The long-term effects of combined divalent copper (Cu(II)) and tetracycline (TC) on the performance, microbial activity and community in a sequencing batch reactor (SBR) were investigated. The addition of Cu(II), TC or mixed Cu(II)/TC caused the decrease of the organics and nitrogen removal efficiencies, and their decreased degrees were the lowest at the addition of mixed Cu(II)/TC. The increase of mixed Cu(II)/TC concentrations in the influent did not change the antagonistic effects between Cu(II) and TC on nitrifying and denitrifying activities. Nitrifiers had higher tolerances to Cu(II), TC and mixed Cu(II)/TC than denitrifiers. Compared to the addition of Cu(II) or TC alone, the microbial community richness was higher at the addition of mixed Cu(II)/TC, while the microbial community diversity was lower. The increased protein (PN) in extracellular polymeric substances (EPS) was a protective response of bacteria to Cu(II), TC and mixed Cu(II)/TC.