Bone metastasis in non-small-cell lung cancer: genomic characterization and exploration of potential targets.

Background: Bone metastasis (BM) seriously affects the quality of life and reduces the survival time of patients with non-small-cell lung cancer (NSCLC). The genomic characteristics and potential targets of BMs are yet to be fully explored. Objective: To explore the genetic characteristics and potential targets of BM in NSCLC. Design: In all, 83 patients with NSCLC were retrospectively selected in this study. Genomic characterization of BMs was explored with the analysis of NGS results from primary tumors and BMs in 6 patients, then combined with NGS results of lung tumors in 16 patients with initial recurrence in bone to analyze mutations potentially associated with BMs, and finally, the correlation was further validated in 61 postoperative patients. Methods: The next generation sequencing (NGS) was performed to identify genomic differences between pulmonary primary tumors and BM. Fluorescence in situ hybridization and immunohistochemistry were performed in postoperative tumor tissues from patients who had undergone radical surgery to validate the predictive role of molecular targets for BM. The correlation between cyclin-dependent kinase 4 (CDK4) and BM was evaluated by Pearson's chi-square test. The university of alabama at birminghan cancer data analysis portal (UALCAN) was carried out for the detection of CDK4 expression in lung cancer and the relationship between CDK4 and clinicopathological parameters. The relationship between prognosis and CDK4 expression was analyzed by the Kaplan-Meier plotter. Results: The rate of gene amplification was increased (24% versus 36%) while gene substitution/indel was decreased (64% versus 52%) in BMs. The BM-specific mutations were analyzed in 16 recurrent patients which revealed the highest incidence of CDK4 amplification (18.8%). According to the Kaplan-Meier plotter database, the NSCLC patients with high CDK4 gene expression showed poor overall survival (OS) and recurrence-free survival (RFS) (p < 0.05). The incidence of CDK4 amplification tended to be higher in recurrent patients compared to the patients without BM (18.8% versus 4.7%, p = 0.118). Conclusion: Compared to the primary tumors of NSCLC, the genome of BMs showed an increased proportion of amplification and a decreased proportion of gene substitution/indel. Furthermore, the CDK4 amplification ratio seemed to be elevated in NSCLC patients with BM which may be associated with poor OS and RFS.

Genomic characterization and potential targets of bone metastasis in non-small cell lung cancer NGS was performed on the matched primary tumors and bone metastases to explore the differences in the genomes of bone metastases, and it was found that gene amplification increased in bone metastases. Combined with the results of NGS in NSCLC patients with the first postoperative recurrence site in the bone, it was found that CDK4 amplification expression increased in bone metastases. Finally, the correlation between bone metastasis and CDK4 amplification was verified by expanding the sample.

Pulmonary salivary gland tumor-hyalinizing clear cell carcinoma: a literature review.

Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a very rare lung tumor that accounts for less than 0.09% of all primary lung tumors and has no specific epidemiology. The correct diagnosis requires imaging, laboratory, pathological, immunohistochemical, and molecular examination. The most typical feature of pulmonary HCCC is the clear cell component with clear stroma. In addition, the fusion gene EWSR1::ATF1 due to t(12;22)(q13;q12) is essential for the pathological diagnosis of pulmonary HCCC. The main treatment for pulmonary HCCC is surgery. This review focus on the pathological features, immunohistochemical examination, mutation analysis and treatment of pulmonary HCCC.

Primary pulmonary myxoid sarcoma with EWSR1::CREB1 fusion: a literature review.

PURPOSE: This review primarily aims to review the epidemiology, clinical characteristics, imaging, pathology, immunohistochemistry, diagnosis, differential diagnosis, treatment, and prognosis of Primary pulmonary myxoid sarcoma (PPMS) with EWS RNA binding protein 1::cAMP response element binding protein 1 (EWSR1::CREB1) fusion. It provides reference for the diagnosis and treatment of this disease. METHODS: Retrospectively collected the literature about PPMS with EWSR1::CREB1 fusion, its clinical, radiology, histology, molecular characteristics and current treatment strategies were collated and analyzed. This review provides a detailed differential diagnosis of the disease. RESULTS: PPMS is an exceptionally rare, low-grade malignant tumor of the lung. This tumor commonly infiltrates lung tissue and develops within bronchial passages. It is identified by a genetic rearrangement involving the EWSR1 gene and a distinct chromosomal translocation t(2; 22)(q33; q12). Variants include EWSR1::CREB1 fusion and EWS RNA binding protein 1::activating transcription factors (EWSR1::ATF1) fusion. PPMS with EWSR1::CREB1 fusion is more prevalent among middle-aged individuals and affects both sexes almost equally. Clinical symptoms are relatively non-specific, primarily including cough, hemoptysis, and weight loss. Most patients undergo surgery and experience a favorable prognosis. Further research is required to validate the effectiveness of alternative treatments for PPMS with EWSR1::CREB1 fusion. CONCLUSION: EWSR1 rearrangement and EWSR1::CREB1 fusion are crucial genetic features of PPMS and serve as important diagnostic markers. Immunohistochemically, PPMS tests positive for EMA. In terms of treatment, surgery has been the primary approach in recent years. Therefore, the efficacy of other treatments still requires further investigation.

H2S-Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation.

Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first-line treatments for IBD have limited efficacy and significant side effects. An innovative H2S-releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide-loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H2S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2/HO-1, PI3K-AKT, and RAS/MAPK/AP-1, and inhibiting the p38/ERK MAPK, p65 NF-κB, and JAK-STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management.

Functionalized MoS2-nanosheets with NIR-Triggered nitric oxide delivery and photothermal activities for synergistic antibacterial and regeneration-promoting therapy.

Bacterial infection in skin and soft tissue has emerged as a critical concern. Overreliance on antibiotic therapy has led to numerous challenges, including the emergence of multidrug-resistant bacteria and adverse drug reactions. It is imperative to develop non-antibiotic treatment strategies that not only exhibit potent antibacterial properties but also promote rapid wound healing and demonstrate biocompatibility. Herein, a novel multimodal synergistic antibacterial system (SNO-CS@MoS2) was developed. This system employs easily surface-modified thin-layer MoS2 as photothermal agents and loaded with S-nitrosothiol-modified chitosan (SNO-CS) via electrostatic interactions, thus realizing the combination of NO gas therapy and photothermal therapy (PTT). Furthermore, this surface modification renders SNO-CS@MoS2 highly stable and capable of binding with bacteria. Through PTT's thermal energy, SNO-CS@MoS2 rapidly generates massive NO, collaborating with PTT to achieve antibacterial effects. This synergistic therapy can swiftly disrupt the bacterial membrane, causing protein leakage and ATP synthesis function damage, ultimately eliminating bacteria. Notably, after effectively eliminating all bacteria, the residual SNO-CS@MoS2 can create trace NO to promote fibroblast migration, proliferation, and vascular regeneration, thereby accelerating wound healing. This study concluded that SNO-CS@MoS2, a novel multifunctional nanomaterial with outstanding antibacterial characteristics and potential to promote wound healing, has promising applications in infected soft tissue wound treatment.

Urban resilience in China's eight urban agglomerations: evolution trends and driving factors.

Improving urban resilience (UR) and enhancing urban anti-risk ability are important foundations for promoting the high-quality development of new urbanization. This research employs the time-varying entropy method to evaluate the resilience level of 138 cities within China's eight urban agglomerations (UAs) between 2005 and 2019. Additionally, the Dagum Gini coefficient and the kernel density estimation method are utilized to examine the spatial disparities and distribution dynamics of UR across the eight UAs. The results of this investigation indicate that (1) the collective UR performance of the eight UAs has experienced an upward trend. However, a notable spatial disparity exits, which is primarily attributed to the differences among the UAs. (2) The overall UR development of the eight UAs has a certain gradient effect, and the UR within each UA has different degrees of polarization characteristics. (3) For the eight UAs as a whole, per capita savings deposits, capitalization of foreign capital, and per capita fiscal expenditure are the three most important driving factors. Within each UA, there was heterogeneity in the main influencing factors. The interplay between any two factors amplifies their individual driving effects on the spatial differentiation of UR.

Sintilimab plus anlotinib as second- or third-line therapy in metastatic non-small cell lung cancer with uncommon epidermal growth factor receptor mutations: A prospective, single-arm, phase II trial.

BACKGROUND: Patients with non-small-cell lung cancer (NSCLC) and uncommon EGFR alterations typically have worse treatment outcomes than patients with classically EGFR-mutated NSCLC. This study aimed to investigate the efficacy and safety of PD-1 blockade with sintilimab plus anti-angiogenic treatment with anlotinib in patients with NSCLC harboring uncommon EGFR mutations. METHODS: Patients with metastatic NSCLC harboring uncommon EGFR mutations after two previous treatments, including a platinum-based chemotherapy regimen and a targeted treatment (or chemotherapy only for patients harboring EGFR ex20ins), received sintilimab combined with anlotinib. The primary endpoint was objective response rate (ORR). RESULTS: At data cutoff (September 27, 2022), median follow-up was 22.3 months (range, 1.2-37.6). Among 21 enrolled patients, 12 had EGFR ex20ins and nine had other uncommon EGFR mutations such as L861Q, G719A, and G709X. Overall, eight patients (38.1%) achieved an objective response, and 18 (85.7%) achieved disease control. Median (95% CI) progression-free survival (PFS) was 7.0 (5.4-8.6) months, and median overall survival (OS) was 20.0 (15.6-24.4) months. The 12-month PFS rate (95% CI) was 22.2% (7.4-42.0), and the 12-month OS rate was 66.7% (42.5-82.5). Patients harboring EGFR ex20ins had similar ORR and PFS to those with other mutations. Six patients (28.6%) experienced grade 3 treatment-related adverse events (TRAEs); hand-foot syndrome was the most common grade 3 TRAE (2 patients; 9.5%). No grade ≥4 TRAEs were observed. CONCLUSIONS: The combination of sintilimab and anlotinib demonstrated durable efficacy and was generally well tolerated in patients with NSCLC and uncommon EGFR mutations who had received prior standard-of-care treatments. (ClinicalTrials.gov identifier: NCT04790409).

Electrical Synchrony Optimization for Left Bundle Branch Area Pacing in Patients With Bradycardia and Heart Failure.

Left bundle branch area pacing (LBBAP) has emerged as a promising physiological pacing modality. This study was designed to investigate the acute impact of the atrioventricular delay (AVD) on cardiac electrical characteristics and identify an optimal range of AVDs for LBBAP to achieve electrical atrioventricular and interventricular synchrony. Patients indicated for ventricular or biventricular pacing were studied during routine follow-ups at least 3 months after LBBAP implantation. Patients were excluded if they had a complete AV block or persistent atrial fibrillation. AVD was programed from 40 to 240 ms or until intrinsic conduction occurred. Optimal AVD was determined by the electrocardiography criteria, including QRS duration, reduced R-wave in lead V1, reduced notching or slurring in lateral leads, and more desirable precordial QRS transition. A total of 38 patients (age 68.7 ± 10.3 years; 16 male (42%); 18 dual-chamber pacemakers and 20 cardiac resynchronization therapy devices; average follow-up period 15.1 ± 10.2 months) were included. The fusion of LBBAP and intrinsic right ventricular conduction occurred in 21 patients with corresponding optimal AVD determined. A great proportion (∼85%) of the optimal AVDs ranged from 50% to 80% of the observed atrium-to-left bundle branch-sensing (A-LBBS) intervals. The linear correlation between the optimal AVD and corresponding A-LBBS interval (optimal AVD = 0.84 × [A-LBSs interval] - 36 ms) produced R = 0.86 and p <0.0001. In conclusion, AVD selection during LBBAP greatly impacted the ventricular electrical characteristics and the optimal AVD was linearly correlated with the corresponding A-LBBS interval.

Characterization of the substernal space with computed tomography imaging in patients with and without median sternotomy: Assessing a novel implant location for extravascular defibrillation lead placement.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) provide clinically significant therapy for the prevention of sudden cardiac death. This study aimed to characterize the substernal space using computed tomography (CT) in patients with and without prior midline sternotomy to investigate the feasibility of substernal ICD lead implantation in post-sternotomy patients. METHODS: High-quality electrocardiogram-gated CT images from 100 patients (71% male, average body mass index 23.5 ± 2.9) were retrospectively collected, including 50 patients with prior midline sternotomy (S-group) and 50 patients with no prior sternotomy (NS-group). Distances were measured from the retrosternal surface to the epicardial surface of the heart and segmented into four regions from the xiphoid tip and superiorly along the sternum. RESULTS: Results generally showed a measurable but narrower average sternum-to-heart distance in the prior sternotomy group compared to the non-sternotomy group in all four regions (p < .05). In the S-group, the sternum-to-heart distances across all regions ranged from 0 to 32.0 mm, while in the NS-group, the distances ranged from 0 to 39.9 mm. CONCLUSION: Small but measurable separations between the heart and sternum were observed in patients with prior sternotomy, particularly near the xiphoid region, indicating the potential viability of extravascular substernal ICD lead implantation in post-sternotomy patients.

Pulmonary adenoid cystic carcinoma: molecular characteristics and literature review.

BACKGROUND: Pulmonary adenoid cystic carcinoma (PACC) is an exceptionally rare salivary gland-type malignant neoplasm. Because of its clinical manifestations, imaging features are not different from other types of non-small cell lung cancer, which is a diagnostic challenge for most doctors. CONCLUSIONS: A review of the literature shows that high amounts of immunohistochemical (IHC) markers, such as CK7, CD117, P63, SMA, CK5/6, and S-100 are helpful for PACC diagnosis. Surgical resection is the main treatment of PACC, but treatment options for advanced PACC patients are limited and the research of molecular targeted drugs is ongoing in advanced cases not eligible for surgery. Currently, research on PACC targeted therapy mainly focuses on the exploration of v-myb avian myeloblastosis virus oncogene homolog (MYB) and its downstream target genes. In addition, median tumor mutation burden and PD-1/PD-L1 were lower in PACC, which may indicate poor efficacy of immunotherapy in PACC patients. This review focuses on the pathologic features, molecular characteristics, diagnosis, treatment and prognosis of PACC to establish a comprehensive understanding of PACC.

GC-MS-based untargeted metabolic profiling of malignant mesothelioma plasma.

Background: Malignant mesothelioma (MM) is a cancer caused mainly by asbestos exposure, and is aggressive and incurable. This study aimed to identify differential metabolites and metabolic pathways involved in the pathogenesis and diagnosis of malignant mesothelioma. Methods: By using gas chromatography-mass spectrometry (GC-MS), this study examined the plasma metabolic profile of human malignant mesothelioma. We performed univariate and multivariate analyses and pathway analyses to identify differential metabolites, enriched metabolism pathways, and potential metabolic targets. The area under the receiver-operating curve (AUC) criterion was used to identify possible plasma biomarkers. Results: Using samples from MM (n = 19) and healthy control (n = 22) participants, 20 metabolites were annotated. Seven metabolic pathways were disrupted, involving alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; butanoate and histidine metabolism; beta-alanine metabolism; and pentose phosphate metabolic pathway. The AUC was used to identify potential plasma biomarkers. Using a threshold of AUC = 0.9, five metabolites were identified, including xanthurenic acid, (s)-3,4-hydroxybutyric acid, D-arabinose, gluconic acid, and beta-d-glucopyranuronic acid. Conclusions: To the best of our knowledge, this is the first report of a plasma metabolomics analysis using GC-MS analyses of Asian MM patients. Our identification of these metabolic abnormalities is critical for identifying plasma biomarkers in patients with MM. However, additional research using a larger population is needed to validate our findings.

Thoracic SMARCA4-deficient undifferentiated tumor.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described smoking-related malignancy. The pathogenesis of SMARCA4-UT is the mutational inactivation and loss of expression of a subunit encoding the mammalian switch/sucrose nonfermenting ATPase-dependent chromatin remodeling complex (which can be mobilized using adenosine triphosphate hydrolysis nucleosomes and regulate other cellular processes including development, differentiation, proliferation, and apoptosis), in particular SMARCA4 and SMARCA2. The dynamic activity of this complex plays an important role in regulating the activation and repression of gene expression programs. SMARCA4-UT exhibits morphological features similar to the malignant rhabdoid tumor (MRT), small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT), and INI1-deficient tumor, but SMARCA4-UT differs from SCCOHT and MRT from a genomic perspective. SMARCA4-UT mainly involves the mediastinum and lung parenchyma, and appears as a large infiltrative mass that easily compresses surrounding tissues. At present, chemotherapy is a common treatment, but its efficacy is not clear. Moreover, the inhibitor of the enhancer of zeste homolog 2 showed promising efficacy in some patients with SMARCA4-UT. This study aimed to review the clinical characteristics, diagnosis, treatment, and prognosis of SMARCA4-UT.

Clinical use conditions of lead deployment and simulated lead fracture rate in left bundle branch area pacing.

INTRODUCTION: Left bundle branch area pacing (LBBAP) is achieved by advancing the lead tip deep in the septum. Most LBBAP implants are performed using the Medtronic SelectSecure™ MRI SecureScan™ Model 3830 featuring a unique 4 Fr fixed helix lumenless design. Details of lead use conditions and long-term reliability have not been reported. This study was designed to quantify the mechanical use conditions for the 3830 lead during and after LBBAP implant, and to evaluate reliability using bench testing and simulation. METHODS: Fifty bradycardia patients with implantation of the 3830 lead for LBBAP were enrolled. Use conditions of lead deployment at implantation were collected and computed tomography (CT) scans were performed at 3-month follow-up. Curvature amplitude along the pacing lead was determined with CT images. Fatigue bending was performed using accelerated testing in a more severe environment than routine clinical use conditions. Conductor fracture rate in a simulated patient population was estimated based on clinical use conditions and fatigue test results. RESULTS: The number of attempts to place the 3830 lead for LBBAP was 2.1 ± 1.3 (range: 1-7) with 13 ± 6 lead rotations at the final attempt. Extreme implant conditions were simulated in bench testing with 5 applications of 20 turns followed by up to 400 million bending cycles. Reliability modeling predicted a 10-year fracture rate of 0.02%. CONCLUSIONS: LBBAP implants require more lead rotations than standard pacing implants and result in unique lead bending. Application of simulated LBBAP use conditions to the 3830 lead in an accelerated in-vitro model does not produce excess conductor fractures. IMAGE-LBBP Study ID of ClinicalTrial.GOV: NCT04119323.

Nuclear protein in testis carcinoma of the lung.

Nuclear protein in testis (NUT) carcinoma is a kind of highly aggressive and fatal solid tumor characterized by a rearrangement of the NUT carcinoma family member 1 (NUTM1) gene located on chromosome 15 q l4, where the most common form of fusion is BRD4-NUT. NUT carcinoma occurred in different organs and was most commonly found in the midline organs and the lungs. NUT carcinoma can occur in patients of almost all ages, having a roughly consistent incidence in both sexes. Most of the patients were diagnosed in advanced stages with an extremely poor prognosis due to the lack of effective treatment. After years of research, the mechanism of NUT carcinoma is still not fully clear, and its therapeutic approaches need to be further studied and explored. In order to gain a more comprehensive understanding of NUT carcinoma and explore the effective treatments, this review aimed to summarize the clinical features, pathological characteristics, differential diagnosis, and treatment strategies for this disease.

Pulmonary Combined Large Cell Neuroendocrine Carcinoma.

Pulmonary combined large-cell neuroendocrine carcinoma (CLCNEC) is a rare neuroendocrine tumor pertained to lung large cell neuroendocrine carcinoma (LCNEC) with aggressive behavior and poor prognosis generally. The clinical features of CLCNEC are not specific including cough, expectoration, chest distress, chest pain, etc., which are prone to have different manifestations of the mixed components. Owing to the low incidence, there are few related small-scale retrospective studies and case reports. Currently, the treatment regimen of CLCNEC mainly refers to LCNEC that complete surgical resection is preferred in the early stage and according to previous researches, platinum-based small cell lung cancer (SCLC) standard treatment regimen showed promising results in postoperative and advanced CLCNEC as compared to that of non-small cell lung cancer (NSCLC). Adenocarcinoma-CLCNEC more likely harbor driver gene mutation, and may benefit from targeted therapy. As for immunotherapy, more clinical trial data are needed to support its benefits. This article will fill the gap and will provide new insight into the clinical characteristics, pathological diagnosis and treatment endeavors of CLCNEC.

Left Bundle Branch Area Pacing versus Biventricular Pacing for Cardiac Resynchronization Therapy on Morbidity and Mortality.

BACKGROUND: Left bundle branch area pacing (LBBAP) has emerged as an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). We aimed to compare the morbidity and mortality associated with LBBAP versus BVP in patients undergoing CRT implantation. METHODS: Consecutive patients who received CRT from two high-volume implantation centers were retrospectively recruited. The primary endpoint was a composite of all-cause death and heart failure hospitalization, and the secondary endpoint was all-cause death. RESULTS: A total of 491 patients receiving CRT (154 via LBBAP and 337 via BVP) were included, with a median follow-up of 31 months. The primary endpoint was reached by 21 (13.6%) patients in the LBBAP group, as compared with 74 (22.0%) patients in the BVP group [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.43-1.14, P = 0.15]. There were 10 (6.5%) deaths in the LBBAP group, as compared with 31 (9.2%) in the BVP group (HR 0.91, 95% CI 0.44-1.86, P = 0.79). No significant difference was observed in the risk of either the primary or secondary endpoint between LBBAP and BVP after multivariate Cox regression (HR 0.74, 95% CI 0.45-1.23, P = 0.24, and HR 0.77, 95% CI 0.36-1.67, P = 0.51, respectively) or propensity score matching (HR 0.72, 95% CI 0.41-1.29, P = 0.28, and HR 0.69, 95% CI 0.29-1.65, P = 0.40, respectively). CONCLUSION: LBBAP was associated with a comparable effect on morbidity and mortality relative to BVP in patients with indications for CRT.

Pulmonary Salivary Gland Tumor, Mucoepidermoid Carcinoma: A Literature Review.

Pulmonary mucoepidermoid carcinoma (PMEC) is the most common malignant salivary gland tumor in the lungs and accounts for 0.1-0.2% of all lung malignancies in adults. It has no specific epidemiological or clinical characteristics. Correct diagnosis requires the combined examinations of images, laboratories, pathology, and immunohistochemistry (IHC) as well as molecular characteristics. PMEC tumors are characterized by squamous, intermediate, and mucus-secreting cells. Currently, histological appearance, mitotic frequency, cellular atypia, and necrocytosis allow the classification of PMEC into low grade or high grade. Molecular changes are crucial to pathological diagnosis. The driver of PMEC seems to be the fusion protein MECT1-MAML2 that is generated from a genetic mutation in t (11; 19) (q21; p13), while other gene mutations are also reported. However, no treatment of PMEC exists so far; surgical excision is still the primary treatment, while the efficacies of chemotherapy or radiotherapy are undefined. Tyrosine kinase inhibitor (TKI) therapy and immunotherapy showed to have significant therapeutic effects but require more investigation and better understanding. This review focuses on the clinical characteristics, imaging and pathologic features, immunohistochemical examination, mutation analysis, differential diagnosis, prognosis, and treatment of PMEC.

Pulmonary Epithelial-Myoepithelial Carcinoma.

Pulmonary epithelial-myoepithelial carcinoma (P-EMC) is an exceptionally rare subtype of salivary gland lung tumor originating from tracheobronchial glands. P-EMC is a biphasic tumor consisting of an inner layer of epithelial cells and an outer layer of spindle-shaped, clear-cell-like myoepithelial cells. Bronchial obstruction symptom is the main clinical characteristic for P-EMC. Because its clinical and imaging characteristics are highly similar to other types of non-small-cell lung cancer (NSCLC), it is easy to cause missed diagnosis and misdiagnosis. The diagnosis is mainly based on the pathology and immunohistochemistry with an inner layer of epithelial cells immunoreactive for cytokeratin and an outside layer of myoepithelial cells immunoreactive for S100 protein (S-100) and smooth muscle actin (SMA). Therefore, positive for cytokeratin, S-100 and SMA can assist in the diagnosis. Although in general, P-EMC is a low-grade malignant neoplasm, it may occasionally recur and metastasize. The optimal method for P-EMC treatment has not been established, and surgical resection is still the main clinical method. Radiotherapy and chemotherapy have been shown not sensitive for P-EMC treatment, whereas targeted therapy and immunotherapy have not evaluated in clinical practice. This review focuses on the pathological characteristics, molecular characteristics, diagnosis, treatment, and prognosis of P-EMC.

Pulmonary Large Cell Neuroendocrine Carcinoma.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of malignant pulmonary tumor. The incidence rate of LCNEC was reported to be 0.3%-3% in lung cancers. Although LCNEC is classified as non-small cell lung cancer (NSCLC), it is more aggressive and malignant than other NSCLC, and its biological behavior is similar to that of small cell lung cancer (SCLC). Most of the LCNEC patients are elderly smoking male and the clinical manifestations are not specific. The imaging manifestations of the tumors are often located in the periphery and the upper lobes, and the enlargement of mediastinal or hilar lymph nodes is common. The diagnosis is mainly based on pathology by the histological features and immunohistochemistry (IHC). Specific neuroendocrine markers such as chromogranin A (CgA), synaptophysin (Syn) and CD56 are usually diffusely positive in LCNEC, and found that insulinoma-associated protein (INSM1) and high rate of Ki-67 are helpful for diagnosis. More differential diagnoses also increase the difficulty of correctly diagnosing LCNEC. The rise of LCNEC molecular typing in recent years may be helpful for diagnosis and subsequent treatment. This review focuses on the epidemiological features, imaging studies, pathology, diagnosis, treatment, and prognosis of LCNEC.

Left Bundle Branch Pacing Versus Biventricular Pacing for Acute Cardiac Resynchronization in Patients With Heart Failure.

BACKGROUND: Left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy. We sought to compare the acute improvement of electrical and mechanical synchrony, and hemodynamics between LBBP and BVP in patients with heart failure and left bundle branch block. METHODS: LBBP and BVP were performed and compared in a crossover fashion in patients with heart failure and left bundle branch block undergoing cardiac resynchronization therapy implantation. Electrical synchrony was assessed by QRS duration and area, mechanical synchrony by the SD of time to peak velocity of 12 left ventricular segments (Ts-SD) and interventricular mechanical delay, and hemodynamics by the maximum rate of left ventricular pressure rise (dP/dtmax). RESULTS: Twenty-one patient with heart failure and left bundle branch block (mean age 67±10 years, 48% male, and 90% nonischemic cause) were included. Both LBBP and BVP provided significant improvements in electrical and mechanical synchrony, and hemodynamics compared to the baseline. Compared with BVP, LBBP achieved a larger reduction in QRS duration (-11 ms [95% CI, -17 to -4 ms]; P=0.003) and QRS area (-85 µVs [95% CI, -113 to -56 µVs]; P<0.001); LBBP achieved a greater decrease in Ts-SD (-14 ms [95% CI, -21 to -7 ms]; P=0.001), with no significant difference in interventricular mechanical delay (-2 ms [95% CI, -13 to 8 ms]; P=0.63). The increase in dP/dtmax from LBBP was significantly higher than that from BVP (6% [95% CI, 2%-9%]; P=0.002). CONCLUSIONS: LBBP delivers greater acute electrical and mechanical resynchronization and hemodynamic improvement than BVP in predominantly nonischemic heart failure patients with left bundle branch block. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04505384.