Comparative outcomes of video-assisted thoracoscopic surgery versus open surgery for bronchogenic cysts in adults: a retrospective cohort study.

Background: Open thoracotomy has been the traditional surgical approach for patients with bronchogenic cysts (BCs). This study aimed to evaluate the safety and efficacy of video-assisted thoracoscopic surgery (VATS) compared to open surgery for the treatment of BCs in adults. Methods: This single-institution, retrospective cohort study included 117 consecutive adult patients who underwent VATS (group A) or open surgery (group B) for BC resection between February 2019 and January 2023. Data regarding clinical history, operation duration, length of hospital stay, 30-day mortality, and recurrence during follow-up were collected and analyzed. Results: Of the total cohort, 103 (88.0%) patients underwent VATS, while 14 (12.0%) patients underwent open surgery. Patients' age in group B were much older than group A (P=0.014), and no significant differences in other demographic and baseline clinical characteristics were observed between the groups. The VATS group had shorter median operation duration (96 vs. 149.5 min, P<0.001) and shorter mean length of hospital stay (5.0±5.5 vs. 8.6±4.0 days, P<0.001). One death occurred in the open surgery group. During a median follow-up of 34 (interquartile range, 20.8-42.5) months, no instances of BC recurrence were observed in either group. Conclusions: Compared to open surgery, VATS is also a safe and efficacious approach for treating BCs in adults. What's more, VATS offered shorter operative times and hospital stays. Considering the minimally invasive, VATS may be a better choice in most patients with bronchial cysts.

Magnetic Silica-Coated Fluorescent Microspheres (MagSiGlow) for Simultaneous Detection of Tumor-Associated Proteins.

Multiplexed bead assays for solution-phase biosensing often encounter cross-over reactions during signal amplification steps, leading to unwanted false positive and high background signals. Current solutions involve complex custom-designed and costly equipment, limiting their application in simple laboratory setup. In this study, we introduce a straightforward protocol to adapt a multiplexed single-bead assay to standard fluorescence imaging plates, enabling the simultaneous analysis of thousands of reactions per plate. This approach focuses on the design and synthesis of bright fluorescent and magnetic microspheres (MagSiGlow) with multiple fluorescent wavelengths serving as unique detection markers. The imaging-based, single-bead assay, combined with a scripted algorithm, allows the detection, segmentation, and co-localization on average of 7500 microspheres per field of view across five imaging channels in less than one second. We demonstrate the effectiveness of this method with remarkable sensitivity at low protein detection limits (100 pg/mL). This technique showed over 85 % reduction in signal cross-over to the solution-based method after the concurrent detection of tumor-associated protein biomarkers. This approach holds the promise of substantially enhancing high throughput biosensing for multiple targets, seamlessly integrating with rapid image analysis algorithms.

Prediction of postoperative final degree and recurrence of pectus excavatum using machine learning algorithms.

Background: Chest wall re-depression after bar removal (BR) in pectus excavatum (PE) is insufficiently investigated. However, it is not easy to investigate chest wall re-depression due to its multifactorial characteristics. Herein, we investigated chest wall re-depression after BR using machine learning algorithms. To the best of my knowledge, this is the first study of chest wall re-depression after BR using machine learning algorithms. Methods: We retrospectively reviewed 199 consecutive subjects who underwent both minimally invasive repair of pectus excavatum (MIRPE) and BR at a single hospital from March 2012 to June 2020. We investigated attributes of chest wall re-depression and risk factors for recurrence after BR, predicted final degree and recurrence of PE after BR, and suggested the optimal age at the time of MIRPE based on recurrence. Data for the chest wall re-depression were analyzed to discover differences according to age group [<10 years (early repair group; EG) vs. ≥10 years (late repair group; LG)]. Results: We observed no significant difference between the Haller index and radiographical pectus index (RPI) (P=0.431) and a significant correlation between Haller index and RPI (P<0.001). RPI significantly increased for the first 6 months after BR in both age groups (both P<0.001) and was maintained at 1 year after BR. RPI value of the LG were significantly higher than those of the EG for the entire period after MIRPE (P=0.041). Recurrence of PE in the LG was significantly more frequent than in the EG (P<0.001). RPI values before and after MIRPE and age group were identified as independent risk factors for recurrence after BR (P<0.001, P=0.007, and P=0.001, respectively). The linear regression model outperformed for final RPI with performance scores of mean squared error 0.198, root mean squared error 0.445, mean absolute error 0.336, and R2 0.415. In addition, the logistic regression model outperformed for predicting recurrence with performance scores of 0.865 the area under the curve, 0.884 accuracy, 0.859 F1, 0.865 precision, and 0.884 recall. Conclusions: The present study shows that machine learning algorithms can provide good estimates for postoperative results in PE. An approach integrating machine learning models and readily available clinical data can be used to create other models in the thoracic surgery field.

Covalent-Frameworked 2D Crown Ether with Chemical Multifunctionality.

Here, we present the synthesis and characterization of a novel 2D crystalline framework, named C2O, which mainly consists of carbon and oxygen in a 2:1 molar ratio and features crown ether holes in its skeletal structure. The covalent-frameworked 2D crown ether can be synthesized on a gram-scale and exhibits fine chemical stability in various environments, including acid, base, and different organic solvents. The C2O efficiently activates KI through the strong coordination of K+ with crown ether holes in a rigid framework, which enhances the nucleophilicity of I- and significantly improves its catalytic activity for CO2 fixation with epoxides. The presence of C2O with KI results in remarkable increases in CO2 conversion from 5.7% to 99.9% and from 2.9% to 74.2% for epichlorohydrin and allyl glycidyl ether, respectively. Moreover, C2O possesses both electrophilic and nucleophilic sites at the edge of its framework, allowing for the customization of physicochemical properties by a diverse range of chemical modifications. Specifically, incorporating allyl glycidyl ether (AGE) as an electrophile or ethoxyethylamine (EEA) as a nucleophile into C2O enables the synthesis of C2O-AGE or C2O-EEA, respectively. These modified frameworks exhibit improved conversions of 97.2% and 99.9% for CO2 fixation with allyl glycidyl ether, outperforming unmodified C2O showing a conversion of 74.2%. This newly developed scalable, durable, and customizable covalent framework holds tremendous potential for the design and preparation of outstanding materials with versatile functionalities, rendering them highly attractive for a wide range of applications.

Retinal neurodegeneration in diabetic retinopathy with systemic hypertension.

PURPOSE: To identify the impact of hypertension (HTN) on inner retinal layer thickness in patients with diabetic retinopathy (DR). METHODS: In this retrospective cross-sectional study, participants were divided into three groups: type 2 diabetes patients without DR (DM group), patients with DR (DR group), and patients with both DR and HTN (DR+HTN group). The peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses, measured using optical coherence tomography, were compared among the groups. RESULTS: A total of 470 eyes were enrolled: 224 eyes in the DM group, 131 eyes in the DR group, and 115 eyes in the DR+HTN group. The mean RNFL thicknesses were 95.0 ± 7.7, 92.5 ± 10.1, and 89.2 ± 11.2 µm, and the mean GC-IPL thicknesses were 84.0 ± 5.7, 82.0 ± 7.6, and 79.2 ± 8.1 µm in each group, respectively (all P < 0.001). In the DR+HTN group, the DR stage showed a significant association with pRNFL (B = - 5.38, P = 0.014) and GC-IPL (B = - 5.18, P = 0.001) thicknesses in multivariate analyses. Subgroup analyses revealed that pRNFL (P = 0.007) and GC-IPL (P = 0.005) thicknesses decreased significantly as DR progressed only in the DR+HTN group. CONCLUSIONS: Patients with both DR and HTN exhibited much thinner pRNFL and GC-IPL, compared with patients with DR only. These results may have been related to the amplified diabetic retinal neurodegeneration and synergistic impact of ischemia in DR patients with concurrent HTN. Additionally, the progression of DR resulted in more severe inner retinal damage when combined with HTN.

Efficacy and safety of CKD-495 in acute and chronic gastritis: A Phase III superiority clinical trial.

BACKGROUND: Despite the availability of numerous treatment options, many patients with gastritis experience only partial symptom relief. CKD-495, a newly developed product with the active ingredient extracted from Cinnamomum cassia Presl., has demonstrated anti-inflammatory and antioxidant activity in vitro and an in vivo protective effect against gastric damage by stimulating mucus secretion. This study compared the efficacy and safety of CKD-495 with Artemisiae argyi folium (AAF) for the treatment of acute and chronic gastritis. AAF, a gastric mucosa protective agent that promotes gastric mucosa regeneration, has been used clinically for about 20 years. METHODS: This phase III multicenter, randomized, double-blind, parallel-group trial (ClinicalTrials.gov; NCT04255589) assigned 242 patients with endoscopically-proven gastric mucosal erosions to receive CKD-495 75 mg (n = 122) or AAF 60 mg (n = 120), respectively, with placebo (for double-blind purposes) 3 times a day for 2 weeks. The primary efficacy endpoint was the erosion improvement rate. Secondary endpoints included erosion cure rates, and improvement rates for edema, redness, hemorrhage, and gastrointestinal (GI) symptoms. Drug-related adverse events were evaluated. RESULTS: The erosion improvement rate was significantly higher in the CKD-495 group than in the AAF group for both the full analysis set (55.9% vs 39.4%, P = .0063) and per-protocol set (54.6% vs 38.2%, P = .0084). In addition, the erosion improvement rate in patients with acute or chronic gastritis showed that the CKD-495 group had better improvement of erosion than the AAF group, especially in patients with chronic gastritis. Analysis of secondary endpoints, which included erosion cure rate and the improvement rates of edema, redness, hemorrhage, and GI symptoms, showed that the CKD-495 group was more effective than the AAF group. There were no significant between-group differences in safety profiles. No serious adverse events or adverse drug reactions occurred. CONCLUSIONS: These results demonstrate that CKD-495 75 mg is superior to AAF 60 mg in terms of the endoscopic improvement rate of erosions in patients with acute or chronic gastritis. This new mucoprotective agent, CKD-495, can be considered the therapy of choice for symptomatic relief and healing of gastritis.

Neoadjuvant immunotherapy combined with chemotherapy in the treatment of stage III lung squamous cell carcinoma: a retrospective cohort study.

Background: Neoadjuvant immunochemotherapy has been proven to be a successful therapeutic strategy for patients with locally advanced non-small cell lung cancer (NSCLC). Nevertheless, there is a paucity of information regarding surgical feasibility and safety as well as tumor response. The present study aimed to investigate the therapeutic and surgical outcomes for patients with stage III lung squamous cell carcinoma (LSCC). Methods: Patients with stage III potentially resectable LSCC treated with neoadjuvant immunochemotherapy at The First Affiliated Hospital of Ningbo University between March 2020 and June 2022 were retrospectively included. Oncologic outcomes and intraoperative and postoperative variables were assessed. Results: A total of 17 locally advanced LSCC patients were included in the study. Patients in stages IIIA and IIIB were represented by 10 (58.8%) and 7 (41.2%) cases, respectively. A minimally invasive procedure was successfully completed in 12 out of 17 cases (70.6%). A total of 10 patients (58.8%) had standard lobectomies performed, 1 (5.9%) had a bilobectomy, 3 (17.6%) had pneumonectomies, and 1 (5.9%) had a wedge resection. A total of 7 patients (41.2%) experienced postoperative complications, and there were no 30- or 90-day mortalities. The 2-year disease-free survival (DFS) and overall survival (OS) rates were 76.6% and 82.5%, respectively. The rate of major pathological response (MPR) was 70.6%. Conclusions: Lung resection after immunochemotherapy for potentially resectable stage III LSCC is feasible and safe. This treatment strategy results in a significant pathologic response and promising rates of OS at 2 years.

Machine learning analysis of primary hyperhidrosis for classification of hyperhidrosis type and prediction of compensatory hyperhidrosis.

Background: Although sympathectomy is highly effective for improving symptom, compensatory hyperhidrosis (CH) is a major issue. In this study, characteristics of primary hyperhidrosis were investigated in terms of the heart rate variability (HRV) parameters. Classification of hyperhidrosis type and prediction of CH after sympathicotomy were also determined using machine learning analysis. Methods: From March 2017 to December 2021, 128 subjects who underwent HRV tests before sympathicotomy were analyzed. T2 and T3 bilateral endoscopic sympathicotomy were routinely performed in patients with craniofacial and palmar hyperhidrosis, respectively. Data collected age, sex, body mass index (BMI), hyperhidrosis type, symptom improvement after sympathicotomy, the degrees of CH after sympathicotomy, and preoperative HRV findings. The independent risk factors associated with the degree of CH after sympathicotomy were investigated. Machine learning analysis was used to determine classification of hyperhidrosis type and prediction of the degree of CH. Results: Preoperatively, patients with palmar hyperhidrosis presented with significantly larger standard deviation of normal-to-normal (SDNN), root mean square of successive differences (RMSSD), total power (TP), and low frequency (LF) than patients with craniofacial hyperhidrosis after controlling for age and sex (P=0.030, P=0.004, P=0.041, and P=0.022, respectively). More sympathetic nervous predominance was found in craniofacial type (P=0.019). Low degree of CH had significantly greater RMSSD (P=0.047), and high degree of CH showed more sympathetic nervous predominance (P=0.006). Multivariate analysis showed the type and expansion of sympathicotomy were significant factors for CH (P=0.001 and P=0.028, respectively). The neural network (NN) algorithm outperformed and showed a 0.961 accuracy, 0.961 F1 score, 0.961 precision, 0.961 recall, and 0.972 area under the curve (AUC) for classification of hyperhidrosis type. The random forest (RF) model outperformed showed a 0.852 accuracy, 0.853 F1 score, 0.856 precision, 0.852 recall, and 0.914 AUC for prediction of the degree of CH. Conclusions: The present study showed the machine learning algorithm can classify types and predict CH after sympathicotomy for primary hyperhidrosis with considerable accuracy. Further large-scale studies are needed to validate the findings and provide management guidelines for primary hyperhidrosis.

Efficient online real-time video stabilization with a novel least squares formulation and parallel AC-RANSAC.

A novel online real-time video stabilization algorithm (LSstab) that suppresses unwanted motion jitters based on cinematography principles is presented. LSstab features a parallel realization of the a-contrario RANSAC (AC-RANSAC) algorithm to estimate the inter-frame camera motion parameters. A novel least squares based smoothing cost function is then proposed to mitigate undesirable camera jitters according to cinematography principles. A recursive least square solver is derived to minimize the smoothing cost function with a linear computation complexity. LSstab is evaluated using a suite of publicly available videos against state-of-the-art video stabilization methods. Results show that LSstab achieves comparable or better performance, which attains real-time processing speed when a GPU is used.

Novel strategy of multiple-locus variable number tandem repeats analysis for genetic fingerprinting of human.

BACKGROUND: The variable number of tandem repeat (VNTR) analyses are methods based on the detection of repeated sequences within the human genome. In order to perform DNA typing at the personal laboratory, it is necessary to improve the VNTR analysis. OBJECTIVE: The VNTR markers were difficult to popularize because PCR amplification was difficult due to its GC-rich and long nucleotide sequence. The aim of this study was to select the multiple VNTR markers that could only be identified by PCR amplification and electrophoresis. METHODS: We genotyped each of the 15 VNTR markers using genomic DNA from 260 unrelated individuals by PCR amplification. Differences in the fragment length of PCR products are visualized by agarose gel electrophoresis. To confirm their usefulness as a DNA fingerprint these 15 markers were simultaneously analyzed with the DNA of 213 individuals and verified the statistical significance. In addition, to investigate the usefulness of each of the 15 VNTR markers as paternity markers, Mendelian segregation by meiotic division within a family consisting of two or three generations was confirmed. RESULTS: Fifteen VNTR loci selected in this study could be easily amplified by PCR and analyzed by electrophoresis, and were newly named DTM1 ~ 15. The number of total alleles in each VNTR showed from 4 to 16, and 100 to 1600 bp in length, and their heterozygosity ranged from 0.2341 to 0.7915. In simultaneous analysis of 15 markers from 213 DNAs, the probability of chance appearing the same genotype in different individuals was less than 4.09E-12, indicating its usefulness as a DNA fingerprint. These loci were transmitted through meiosis by Mendelian inheritance in families. CONCLUSION: Fifteen VNTR markers have been found to be useful as DNA fingerprints for personal identification and kinship analysis that can be used at the personal laboratory level.

Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis.

BACKGROUND: Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner. AIM: To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). METHODS: Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups. RESULTS: Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups. CONCLUSION: Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

Repair of pectus excavatum in a patient with an Eloesser thoracostomy window: sequential extrapleural Nuss procedure and modified Ravitch procedure.

A 28-year-old man with a history of tuberculous empyema and pectus excavatum visited our hospital for progressive dyspnea and leg edema. The patient had undergone an Eloesser window operation for repetitive pleuro-cutaneous fistula due to chronic tuberculous empyema in the left thorax one year prior. Chest computed tomography demonstrated severe compression of the right ventricle and inferior vena cava and chronic empyema with the Eloesser window in the left thorax. Because conservative treatment had failed, the patient underwent a total extrapleural Nuss procedure, resulting in marked relief of compression and complete resolution of leg edema and congestive hepatopathy. However, he required ventilation support due to carbon dioxide retention. Therefore, the patient underwent a modified Ravitch procedure and was weaned off ventilation support. Herein, we represent the first report of a sequential extrapleural Nuss procedure and a modified Ravitch procedure in a patient with chronic tuberculous empyema with an Eloesser window.

Delayed diagnosis of thoracic esophageal rupture due to blunt abdominal trauma without chest trauma: A case report.

BACKGROUND: Thoracic esophageal rupture due to blunt trauma is very rare. Moreover, there have been no reports of thoracic esophageal rupture due to blunt abdominal trauma without chest trauma. CASE PRESENTATION: We describe a rare case of esophageal rupture due to blunt abdominal trauma in a young female patient. Operation was delayed due to a misdiagnosis of chylothorax, and esophageal repair was performed six days after trauma. Postoperative esophageal leak developed and was treated with esophageal stent. She was discharged two months after surgery without sequelae. CONCLUSIONS: It is important to consider esophageal rupture as a differential diagnosis even in patients with only abdominal trauma, when in doubt.

Identification and Characterization of Cancer-Associated Fibroblast Subpopulations in Lung Adenocarcinoma.

Cancer-associated fibroblasts (CAFs) reside within the tumor microenvironment, facilitating cancer progression and metastasis via direct and indirect interactions with cancer cells and other stromal cell types. CAFs are composed of heterogeneous subpopulations of activated fibroblasts, including myofibroblastic, inflammatory, and immunosuppressive CAFs. In this study, we sought to identify subpopulations of CAFs isolated from human lung adenocarcinomas and describe their transcriptomic and functional characteristics through single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatics analyses. Cell trajectory analysis of combined total and THY1 + CAFs revealed two branching points with five distinct branches. Based on Gene Ontology analysis, we denoted Branch 1 as "immunosuppressive", Branch 2 as "neoantigen presenting", Branch 4 as "myofibroblastic", and Branch 5 as "proliferative" CAFs. We selected representative branch-specific markers and measured their expression levels in total and THY1 + CAFs. We also investigated the effects of these markers on CAF activity under coculture with lung cancer cells. This study describes novel subpopulations of CAFs in lung adenocarcinoma, highlighting their potential value as therapeutic targets.

Towards real-time 3D visualization with multiview RGB camera array.

A real-time 3D visualization (RT3DV) system using a multiview RGB camera array is presented. RT3DV can process multiple synchronized video streams to produce a stereo video of a dynamic scene from a chosen view angle. Its design objective is to facilitate 3D visualization at the video frame rate with good viewing quality. To facilitate 3D vision, RT3DV estimates and updates a surface mesh model formed directly from a set of sparse key points. The 3D coordinates of these key points are estimated from matching 2D key points across multiview video streams with the aid of epipolar geometry and trifocal tensor. To capture the scene dynamics, 2D key points in individual video streams are tracked between successive frames. We implemented a proof of concept RT3DV system tasked to process five synchronous video streams acquired by an RGB camera array. It achieves a processing speed of 44 milliseconds per frame and a peak signal to noise ratio (PSNR) of 15.9 dB from a viewpoint coinciding with a reference view. As a comparison, an image-based MVS algorithm utilizing a dense point cloud model and frame by frame feature detection and matching will require 7 seconds to render a frame and yield a reference view PSNR of 16.3 dB.

Clinical significance of tumor necrosis and viability in non-small cell lung cancer.

Background: We included tumor necrosis (TN) and tumor viability (TV) in our prognostic assessment of patients with non-small cell lung cancer (NSCLC) and investigated their clinical significance. Methods: Medical records of all consecutive subjects who underwent a lobectomy with standard mediastinal lymph node dissection for NSCLC between 2015 to 2016, were reviewed retrospectively. We analyzed the associations of TN and TV with various parameters associated with prognosis as well as survival in NSCLC patients. All analyses were performed regarding neoadjuvant therapy status [the group without neoadjuvant therapy (WON) vs. the group with neoadjuvant therapy (WN)]. Results: A consecutive 154 patients (mean age: 65.0±10.1 years) were included into the present study. Fifteen patients underwent neoadjuvant therapy. Final pathologic stages were IA1 (n=13), IA2 (n=30), IA3 (n=32), IB (n=40), IIA (n=9), IIB (n=18), and IIIA (n=12). WN significantly showed higher TN (P=0.005) and lower TV (P<0.001) than WON. Tumors with vascular, lymphatic, and perineural invasion showed significantly lower TV and higher TN than cases without these features (P=0.014, P=0.019, and P=0.012 for TV; P=0.001, P<0.001, and P<0.001 for TN, respectively). Tumors with poorer differentiation had lower TV (P<0.001) and higher TN (P<0.001) than more differentiated tumors. There was a positive correlation between TN and tumor size (P<0.001) and a negative correlation between TV and tumor size (P=0.031). TN significantly increased as pathologic stage increased (P=0.001), and TV significantly decreased as pathologic stage increased (P=0.038). The group without TN survived significantly longer than the group with TN (P=0.016) in N0 disease and presence of TN and pT stage were independent prognostic factors for survival in N0 disease (P=0.037 and P=0.021, respectively). There was a positive correlation between TN and Ki-67 level (P=0.027). In WN, TN was significantly associated with differentiation (P=0.035), tumor size (P=0.008), and pT stage (P=0.031) but not overall pathologic stage or survival. Conclusions: Presence of histological TN was associated with prognosis of NSCLC, especially in N0 disease, and its usage as a diagnostic or prognostic tool and determination of resection extent could potentially provide prognostic information that can facilitate better management of NSCLC.

Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small-cell lung cancer.

Background: Evidence of the efficacy of immune checkpoint inhibitors (ICIs) plus antiangiogenic drugs in previously treated patients with advanced non-small-cell lung cancer (NSCLC) is still insufficient, so we investigated the safety and efficacy of nivolumab plus recombinant human (rh)-endostatin in such patients. Methods: Patients without epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) targetable mutations in advanced NSCLC who did not respond to previous treatment were enrolled. Eligible patients received nivolumab (3 mg/kg, i.v. drip, day 1) every 2 weeks and rh-endostatin (210 mg, continuous i.v. infusion for 168 h) every 4 weeks until disease progression or discontinuation. The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), clinical benefit response rate (CBR), progression-free survival (PFS), overall survival (OS) and safety. Results: A total of 34 patients received a median of 4 cycles of therapy. In all, 14 patients achieved confirmed partial response (PR) with an ORR of 41.2% [14/34; 95% confidence interval (CI): 23.7-58.6%], DCR of 64.7% (22/34; 95% CI: 47.8-81.6%), CBR of 44.1% (95% CI: 26.5-61.7%), and a DOR of 6.9 (95% CI: 4.4-9.4) months. Median follow-up was 12.2 (range, 2.3-18.1) months. Median PFS (mPFS) was 6.8 (95% CI: 1.1-12.1) months, median OS (mOS) was 17.1 (95% CI: 6.6-27.6) months, and 12-month survival rate of 64.4% (95% CI: 46.2-82.6%). In all, 18 (18/34, 52.9%) patients experienced at least one treatment-related adverse event (TRAE), and Grade 3 TRAEs occurred in 4 (4/34, 11.8%) of them. Conclusions: This study is first to assess nivolumab plus rh-endostatin in previously treated patients with advanced NSCLC. In view of its favorable efficacy and safety profile, this combination represents a promising treatment regimen in this patient population.

DeepRePath: Identifying the Prognostic Features of Early-Stage Lung Adenocarcinoma Using Multi-Scale Pathology Images and Deep Convolutional Neural Networks.

The prognosis of patients with lung adenocarcinoma (LUAD), especially early-stage LUAD, is dependent on clinicopathological features. However, its predictive utility is limited. In this study, we developed and trained a DeepRePath model based on a deep convolutional neural network (CNN) using multi-scale pathology images to predict the prognosis of patients with early-stage LUAD. DeepRePath was pre-trained with 1067 hematoxylin and eosin-stained whole-slide images of LUAD from the Cancer Genome Atlas. DeepRePath was further trained and validated using two separate CNNs and multi-scale pathology images of 393 resected lung cancer specimens from patients with stage I and II LUAD. Of the 393 patients, 95 patients developed recurrence after surgical resection. The DeepRePath model showed average area under the curve (AUC) scores of 0.77 and 0.76 in cohort I and cohort II (external validation set), respectively. Owing to low performance, DeepRePath cannot be used as an automated tool in a clinical setting. When gradient-weighted class activation mapping was used, DeepRePath indicated the association between atypical nuclei, discohesive tumor cells, and tumor necrosis in pathology images showing recurrence. Despite the limitations associated with a relatively small number of patients, the DeepRePath model based on CNNs with transfer learning could predict recurrence after the curative resection of early-stage LUAD using multi-scale pathology images.

DeepCUBIT: Predicting Lymphovascular Invasion or Pathological Lymph Node Involvement of Clinical T1 Stage Non-Small Cell Lung Cancer on Chest CT Scan Using Deep Cubical Nodule Transfer Learning Algorithm.

The prediction of lymphovascular invasion (LVI) or pathological nodal involvement of tumor cells is critical for successful treatment in early stage non-small cell lung cancer (NSCLC). We developed and validated a Deep Cubical Nodule Transfer Learning Algorithm (DeepCUBIT) using transfer learning and 3D Convolutional Neural Network (CNN) to predict LVI or pathological nodal involvement on chest CT images. A total of 695 preoperative CT images of resected NSCLC with tumor size of less than or equal to 3 cm from 2008 to 2015 were used to train and validate the DeepCUBIT model using five-fold cross-validation method. We also used tumor size and consolidation to tumor ratio (C/T ratio) to build a support vector machine (SVM) classifier. Two-hundred and fifty-four out of 695 samples (36.5%) had LVI or nodal involvement. An integrated model (3D CNN + Tumor size + C/T ratio) showed sensitivity of 31.8%, specificity of 89.8%, accuracy of 76.4%, and AUC of 0.759 on external validation cohort. Three single SVM models, using 3D CNN (DeepCUBIT), tumor size or C/T ratio, showed AUCs of 0.717, 0.630 and 0.683, respectively on external validation cohort. DeepCUBIT showed the best single model compared to the models using only C/T ratio or tumor size. In addition, the DeepCUBIT model could significantly identify the prognosis of resected NSCLC patients even in stage I. DeepCUBIT using transfer learning and 3D CNN can accurately predict LVI or nodal involvement in cT1 size NSCLC on CT images. Thus, it can provide a more accurate selection of candidates who will benefit from limited surgery without increasing the risk of recurrence.