Therapeutic Decision Making in Prevascular Mediastinal Tumors Using CT Radiomics and Clinical Features: Upfront Surgery or Pretreatment Needle Biopsy?

The study aimed to develop machine learning (ML) classification models for differentiating patients who needed direct surgery from patients who needed core needle biopsy among patients with prevascular mediastinal tumor (PMT). Patients with PMT who received a contrast-enhanced computed tomography (CECT) scan and initial management for PMT between January 2010 and December 2020 were included in this retrospective study. Fourteen ML algorithms were used to construct candidate classification models via the voting ensemble approach, based on preoperative clinical data and radiomic features extracted from the CECT. The classification accuracy of clinical diagnosis was 86.1%. The first ensemble learning model was built by randomly choosing seven ML models from a set of fourteen ML models and had a classification accuracy of 88.0% (95% CI = 85.8 to 90.3%). The second ensemble learning model was the combination of five ML models, including NeuralNetFastAI, NeuralNetTorch, RandomForest with Entropy, RandomForest with Gini, and XGBoost, and had a classification accuracy of 90.4% (95% CI = 87.9 to 93.0%), which significantly outperformed clinical diagnosis (p < 0.05). Due to the superior performance, the voting ensemble learning clinical-radiomic classification model may be used as a clinical decision support system to facilitate the selection of the initial management of PMT.

Development of a real-time RGB-D visual feedback-assisted pulmonary rehabilitation system.

Background: Following surgery, perioperative pulmonary rehabilitation (PR) is important for patients with early-stage lung cancer. However, current inpatient programs are often limited in time and space, and outpatient settings have access barriers. Therefore, we aimed to develop a background-free, zero-contact thoracoabdominal movement-tracking model that is easily set up and incorporated into a pre-existing PR program or extended to home-based rehabilitation and remote monitoring. We validated its effectiveness in providing preclinical real-time RGB-D (colour-depth camera) visual feedback. Methods: Twelve healthy volunteers performed deep breathing exercises following audio instruction for three cycles, followed by audio instruction and real-time visual feedback for another three cycles. In the visual feedback system, we used a RealSense™ D415 camera to capture RGB and depth images for human pose-estimation with Google MediaPipe. Target-tracking regions were defined based on the relative position of detected joints. The processed depth information of the tracking regions was visualised on a screen as a motion bar to provide real-time visual feedback of breathing intensity. Pulmonary function was simultaneously recorded using spirometric measurements, and changes in pulmonary volume were derived from respiratory airflow signals. Results: Our movement-tracking model showed a very strong correlation (r = 0.90 ± 0.05) between thoracic motion signals and spirometric volume, and a strong correlation (r = 0.73 ± 0.22) between abdominal signals and spirometric volume. Displacement of the chest wall was enhanced by RGB-D visual feedback (23 vs 20 mm, P = 0.034), and accompanied by an increased lung volume (2.58 vs 2.30 L, P = 0.003). Conclusion: We developed an easily implemented thoracoabdominal movement-tracking model and reported the positive impact of real-time RGB-D visual feedback on self-promoted external chest wall expansion, accompanied by increased internal lung volumes. This system can be extended to home-based PR.

Long noncoding RNA SNHG16 regulates TLR4-mediated autophagy and NETosis formation in alveolar hemorrhage associated with systemic lupus erythematosus.

BACKGROUND: Dysregulated long noncoding RNA (lncRNA) expression with increased apoptosis has been demonstrated in systemic lupus erythematosus (SLE) patients with alveolar hemorrhage (AH). SNHG16, a lncRNA, can enhance pulmonary inflammation by sponging microRNAs, and upregulate toll-like receptor 4 (TLR4) expression via stabilizing its mRNAs. TRAF6, a TLR4 downstream signal transducer, can induce autophagy and NETosis formation. In this study, we investigated whether SNHG16 could regulate TLR4-mediated autophagy and NETosis formation in SLE-associated AH. METHODS: Expression of SNHG16, TLR4 and TRAF6 and cell death processes were examined in lung tissues and peripheral blood (PB) leukocytes from AH patients associated with SLE and other autoimmune diseases, and in the lungs and spleen from a pristane-induced C57BL/6 mouse AH model. SNHG16-overexpressed or -silenced alveolar and myelocytic cells were stimulated with lipopolysaccharide (LPS), a TLR4 agonist, for analyzing autophagy and NETosis, respectively. Pristane-injected mice received the intra-pulmonary delivery of lentivirus (LV)-SNHG16 for overexpression and prophylactic/therapeutic infusion of short hairpin RNA (shRNA) targeting SNHG16 to evaluate the effects on AH. Renal SNHG16 expression was also examined in lupus nephritis (LN) patients and a pristane-induced BALB/c mouse LN model. RESULTS: Up-regulated SNHG16, TLR4 and TRAF6 expression with increased autophagy and NETosis was demonstrated in the SLE-AH lungs. In such patients, up-regulated SNHG16, TLR4 and TRAF6 expression was found in PB mononuclear cells with increased autophagy and in PB neutrophils with increased NETosis. There were up-regulated TLR4 expression and increased LPS-induced autophagy and NETosis in SNHG16-overexpressed cells, while down-regulated TLR4 expression and decreased LPS-induced autophagy and NETosis in SNHG16-silenced cells. Pristane-injected lung tissues had up-regulated SNHG16, TLR4/TRAF6 levels and increased in situ autophagy and NETosis formation. Intra-pulmonary LV-SNHG16 delivery enhanced AH through up-regulating TLR4/TRAF6 expression with increased cell death processes, while intra-pulmonary prophylactic and early therapeutic sh-SNHG16 delivery suppressed AH by down-regulating TLR4/TRAF6 expression with reduced such processes. In addition, there was decreased renal SNHG16 expression in LN patients and mice. CONCLUSIONS: Our results demonstrate that lncRNA SNHG16 regulates TLR4-mediated autophagy and NETosis formation in the human and mouse AH lungs, and provide a therapeutic potential of intra-pulmonary delivery of shRNA targeting SNHG16 in this SLE-related lethal manifestation.

Low neutrophil-to-lymphocyte ratio predicts overall survival benefit in advanced NSCLC patients with low PD-L1 expression and receiving chemoimmunotherapy.

Although combination therapy including chemotherapy and immune checkpoint inhibitors (ICIs) improves overall survival (OS) of patients with non-small-cell lung cancer (NSCLC), there is a higher incidence of adverse events and treatment discontinuation. Since programmed death-ligand 1 (PD-L1) could not serve as a predictive biomarker, we investigated the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker. In our previous research, we demonstrated that a low NLR could predict survival benefits when patients with high PD-L1 expression (> 50%) received chemoimmunotherapy as opposed to immunotherapy alone. In this current study, our objective is to evaluate this predictive capacity in patients with low PD-L1 expression (< 50%). A total of 142 patients were enrolled, 28 receiving combination therapy and 114 receiving chemotherapy alone. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Patients who received combination therapy had significantly better PFS and OS than those who received monotherapy. In the subgroup of patients with low NLR, those who received combination therapy exhibited extended PFS and OS with clinical significance, which was also confirmed by multivariate Cox regression analysis. Our study demonstrates the potential use of NLR as a biomarker for predicting survival benefits when receiving combination therapy with chemotherapy and ICIs in patients with advanced NSCLC and low PD-L1 expression.

Risk factor analysis of postoperative complications after adjunctive pulmonary resection in patients with multidrug-resistant tuberculosis: A multi-institutional study.

BACKGROUND AND OBJECTIVE: Multidrug-resistant tuberculosis (MDR-TB) requires extended treatment with regimens with multiple side effects, resulting in high treatment failure rates. Adjunctive lung resection combined with anti-tubercular agents improves outcomes. However, few studies have evaluated the potential harm from surgery and determined the optimal conditions for surgery. We aimed to analyze perioperative conditions to assess risk factors for postoperative complications in a multi-institutional setting. METHODS: This retrospective study included 44 patients with MDR-TB who underwent adjunctive lung resection at three management groups of the Taiwan MDR-TB consortium between January 2007 and December 2020. Demographic data, clinical characteristics, radiological findings, sputum culture status before surgery, primary or acquired drug resistance, surgical procedure, complications, and treatment outcomes were collected and analyzed. Multivariate logistic regression was used to identify risk factors for postoperative complications. RESULTS: Twenty-seven patients (61.4%) underwent lung resection using video-assisted thoracic surgery (VATS). The overall surgical complication rate was 20.5%, and the surgical mortality rate was 9.1%. Postsurgical hemothorax was the most common complication (11.4%). According to the univariate analysis, hilum involvement in images, positive preoperative sputum culture, and thoracotomy approach were unfavorable factors. VATS approach [adjusted OR, 0.088 (95% CI, 0.008-0.999)] was the only favorable factor identified by multivariate analysis. CONCLUSION: The minimally invasive approach is a growing trend, and lobectomies and sublobar resections were the main procedures for MDR-TB. The VATS approach significantly reduced the surgical complication rate. Postsurgical hemothorax was noteworthy, and meticulous hemostasis of the chest wall and residual lung surface is critical for successful resections.

Corrigendum: Clinical radiomics-based machine learning versus three-dimension convolutional neural network analysis for differentiation of thymic epithelial tumors from other prevascular mediastinal tumors on chest computed tomography scan.

[This corrects the article DOI: 10.3389/fonc.2023.1105100.].

Chemotherapy outcomes in EGFR-TKI resistant patients with common and uncommon EGFR mutation: An exploratory retrospective cohort study.

BACKGROUND: Some prospective studies have shown that second-generation tyrosine kinase inhibitors (TKIs) provide better control in patients with non-small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. However, studies comparing second-line chemotherapy efficacy between NSCLC patients with common and uncommon EGFR mutations remain rare. This retrospective study compared treatment outcomes in these patients. METHODS: Patients with EGFR-mutated advanced-stage NSCLC who received first-line EGFR-TKIs in a tertiary referral center were retrospectively reviewed between January 2010 and August 2022. Patients with a negative T790M test at disease progression who received second-line chemotherapy were enrolled. We compared progression-free (PFS) and overall (OS) survival between advanced NSCLC patients with common and uncommon EGFR mutations using Kaplan-Meier and log-rank tests. RESULTS: In total, 209 (54.8%) patients had a negative T790M mutation test and received second-line chemotherapy, of which 192 (91.8%) had a common EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and 17 (8.2%) had an uncommon EGFR mutation. Patients with common EGFR mutations had significantly longer PFS than those with uncommon EGFR mutations (4.57 vs. 2.57 months, p = 0.031). A Cox proportional hazard regression analysis controlling for potential confounding factors indicated that an uncommon EGFR mutation was an independent prognostic factor for PFS. CONCLUSION: This study suggests that patients with uncommon EGFR mutations have poorer chemotherapy responses and shorter survival than those with common EGFR mutations. The development of new treatment strategies for these patients remains an unmet need.

Clinical radiomics-based machine learning versus three-dimension convolutional neural network analysis for differentiation of thymic epithelial tumors from other prevascular mediastinal tumors on chest computed tomography scan.

Purpose: To compare the diagnostic performance of radiomic analysis with machine learning (ML) model with a convolutional neural network (CNN) in differentiating thymic epithelial tumors (TETs) from other prevascular mediastinal tumors (PMTs). Methods: A retrospective study was performed in patients with PMTs and undergoing surgical resection or biopsy in National Cheng Kung University Hospital, Tainan, Taiwan, E-Da Hospital, Kaohsiung, Taiwan, and Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan between January 2010 and December 2019. Clinical data including age, sex, myasthenia gravis (MG) symptoms and pathologic diagnosis were collected. The datasets were divided into UECT (unenhanced computed tomography) and CECT (enhanced computed tomography) for analysis and modelling. Radiomics model and 3D CNN model were used to differentiate TETs from non-TET PMTs (including cyst, malignant germ cell tumor, lymphoma and teratoma). The macro F1-score and receiver operating characteristic (ROC) analysis were performed to evaluate the prediction models. Result: In the UECT dataset, there were 297 patients with TETs and 79 patients with other PMTs. The performance of radiomic analysis with machine learning model using LightGBM with Extra Tree (macro F1-Score = 83.95%, ROC-AUC = 0.9117) had better performance than the 3D CNN model (macro F1-score = 75.54%, ROC-AUC = 0.9015). In the CECT dataset, there were 296 patients with TETs and 77 patients with other PMTs. The performance of radiomic analysis with machine learning model using LightGBM with Extra Tree (macro F1-Score = 85.65%, ROC-AUC = 0.9464) had better performance than the 3D CNN model (macro F1-score = 81.01%, ROC-AUC = 0.9275). Conclusion: Our study revealed that the individualized prediction model integrating clinical information and radiomic features using machine learning demonstrated better predictive performance in the differentiation of TETs from other PMTs at chest CT scan than 3D CNN model.

Is delayed fixation worthwhile in patients with long bone fracture concomitant with mild traumatic brain injury? A propensity score-matched study.

INTRODUCTION: Early definite treatment for orthopedic patients is strongly advocated. However, a consensus has not been reached on the optimal timing of long bone fracture fixation for patients with associated mild traumatic brain injury (TBI). Surgeons lack evidence on the basis on which they should decide on the operation timing. METHODS: We retrospectively reviewed the data of patients with mild TBI and lower extremity long bone fractures from 2010 to 2020. The patients receiving internal fixation within and after 24 h were defined as the early- and delayed-fixation groups. We compared the discharge Glasgow Coma Scale (GCS) scores, lengths of stay, and in-hospital complications. Propensity score matching (PSM) with multiple adjusted variables and a 1:1 matching ratio was applied to reduce selection bias. RESULTS: In total, 181 patients were enrolled; 78 (43.1%) and 103 (56.9%) patients received early and delayed fracture fixation, respectively. After matching, each group had 61 participants and were statistically identical. The delayed group did not have better discharge GCS scores (early vs. delayed: 15.0 ± 0 vs. 15.0 ± 0.1; p = 0.158). The groups did not differ in their lengths of hospital stay (15.3 ± 10.6 vs. 14.8 ± 7.9; p = 0.789), intensive care unit stay (2.7 ± 4.3 vs. 2.7 ± 3.8; p = 0.947), or incidence of complications (23.0% vs. 16.4%; p = 0.494). CONCLUSIONS: Delayed fixation for patients with lower extremity long bone fractures concurrent with mild TBI does not result in fewer complications or improved neurologic outcomes compared with early fixation. Delaying fixation may not be necessary to prevent the second hit phenomenon and has not demonstrated any clear benefits.

Impact of trauma teams on high grade liver injury care: a two-decade propensity score approach study in Taiwan.

High-grade liver laceration is a common injury with bleeding as the main cause of death. Timely resuscitation and hemostasis are keys to the successful management. The impact of in-hospital trauma system on the quality of resuscitation and management in patients with traumatic high-grade liver laceration, however, was rarely reported. We retrospectively reviewed the impact of team-based approach on the quality and outcomes of high-grade traumatic liver laceration in our hospital. Patients with traumatic liver laceration between 2002 and 2020 were enrolled in this retrospective study. Inverse probability of treatment weighting (IPTW)-adjusted analysis using the propensity score were performed. Outcomes before the trauma team establishment (PTTE) and after the trauma team establishment (TTE) were compared. A total of 270 patients with liver trauma were included. After IPTW adjustment, interval between emergency department arrival and managements was shortened in the TTE group with a median of 11 min (p < 0.001) and 28 min (p < 0.001) in blood test reports and duration to CT scan, respectively. Duration to hemostatic treatments in the TTE group was also shorter by a median of 94 min in patients receiving embolization (p = 0.012) and 50 min in those undergoing surgery (p = 0.021). The TTE group had longer ICU-free days to day 28 (0.0 vs. 19.0 days, p = 0.010). In our study, trauma team approach had a survival benefit for traumatic high-grade liver injury patients with 65% reduction of risk of death within 72 h (Odds ratio (OR) = 0.35, 95% CI = 0.14-0.86) and 55% reduction of risk of in-hospital mortality (OR = 0.45, 95% CI = 0.23-0.87). A team-based approach might contribute to the survival benefit in patients with traumatic high-grade liver laceration by facilitating patient transfer from outside the hospital, through the diagnostic examination, and to the definitive hemostatic procedures.

Effect of BIM expression on the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs.

The role of Programmed Cell Death Ligand 1 (PD-L1) expression in predicting epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) efficacy remains controversial. Recent studies have highlighted that tumor-intrinsic PD-L1 signaling can be modulated by STAT3, AKT, MET oncogenic pathway, epithelial-mesenchymal transition, or BIM expression. This study aimed to investigate whether these underlying mechanisms affect the prognostic role of PD-L1. We retrospectively enrolled patients with EGFR mutant advanced stage NSCLC who received first-line EGFR-TKI between January 2017 and June 2019, the treatment efficacy of EGFR-TKI was assessed. Kaplan-Meier analysis of progression-free survival (PFS) revealed that patients with high BIM expression had shorter PFS, regardless of PD-L1 expression. This result was also supported by the COX proportional hazard regression analysis. In vitro, we further proved that the knockdown of BIM, instead of PDL1, induced more cell apoptosis following gefitinib treatment. Our data suggest that among the pathways affecting tumor-intrinsic PD-L1 signaling, BIM is potentially the underlying mechanism that affects the role of PD-L1 expression in predicting response to EGFR TKI and mediates cell apoptosis under treatment with gefitinib in EGFR-mutant NSCLC. Further prospective studies are required to validate these results.

Pulmonary-function changes after uniportal video-assisted thoracoscopic anatomical lung resection.

OBJECTIVE: The superiority of segmentectomy over lobectomy with regard to preservation of pulmonary function is controversial. This study aimed to examine changes in pulmonary function after uniportal video-assisted thoracoscopic surgery (VATS) according to the number of resected segments. METHODS: We retrospectively reviewed 135 consecutive patients who underwent anatomical lung resection via uniportal VATS from April 2015 to December 2020. Pulmonary function loss was evaluated using forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). Patients were grouped according to number of resected segments: one-segment (n = 33), two segments (n = 22), three segments (n = 40), four segments (n = 15), and five segments (n = 25). RESULTS: Clinical characteristics did not significantly differ between groups, except for tumor size. Mean follow-up was 8.96 ± 3.16 months. FVC loss was significantly greater in five-segment resection (10.8%) than one-segment (0.97%, p = 0.008) and two-segment resections (2.44%, p = 0.040). FEV1 loss was significantly greater in five-segment resection (15.02%) than one-segment (3.83%, p < 0.001), two-segment (4.63%, p = 0.001), and three-segment resections (7.63%, p = 0.007). Mean FVC loss and FEV1 loss increased linearly from one-segment resection to five-segment resection. Mean loss in FVC and FEV1 per segment resected was 2.16% and 3.00%, respectively. CONCLUSIONS: Anatomical lung resection of fewer segments was associated with better preservation of pulmonary function in patients undergoing uniportal VATS, and function loss was approximately 2%-3% per segment resected with linear relationship.

The surgical resection of the primary tumor increases survival in patients with EGFR-mutant advanced non-small cell lung cancer: a tertiary center cohort study.

Tumor resection could increase treatment efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). This study aimed to retrospectively analyze patients with advanced EGFR-mutant NSCLC from a Taiwanese tertiary center and receiving EGFR-TKI treatment with or without tumor resection. A total of 349 patients were enrolled. After propensity score matching, 53 EGFR-TKI treated patients and 53 EGFR-TKI treated patients with tumor resection were analyzed. The tumor resection group showed improved progression-free survival (PFS) (52.0 vs. 9.8 months; hazard ratio [HR] = 0.19; p < 0.001) and overall survival (OS) (not reached vs. 30.6 months; HR = 0.14; p < 0.001) compared to the monotherapy group. In the subgroup analysis of patients with newly-diagnosed NSCLC, the tumor resection group showed longer PFS (52.0 vs. 9.9 months; HR = 0.14; p < 0.001) and OS (not reached vs. 32.6 months; HR = 0.12; p < 0.001) than the monotherapy group. In conclusion. the combination of EGFR-TKI and tumor resection provided better PFS and OS than EGFR-TKI alone, and patients who underwent tumor resection within six months had fewer co-existing genomic alterations and better PFS.

Tailored Surgical Stabilization of Rib Fractures Matters More Than the Number of Fractured Ribs.

BACKGROUND: Patients sustaining multiple rib fractures have a significant risk of developing morbidity and mortality. More evidence is emerging that the indication of surgical stabilization of rib fractures (SSRF) should expand beyond flail chest. Nevertheless, little is known about factors associated with poor outcomes after surgical fixation. We reviewed patients with rib fractures to further explore the role of SSRF; we matched two groups by propensity score (PS). METHOD: A comparison of patients with blunt thoracic trauma treated with SSRF between 2010 and 2020 was compared with those who received conservative treatment for rib fractures. Risk factors for poor outcomes were analyzed by multivariate regression analysis. RESULTS: After tailored SSRF, the number of fractured ribs was not associated with longer ventilator days (p = 0.617), ICU stay (p = 0.478), hospital stay (p = 0.706), and increased nonprocedure-related pulmonary complications (NPRCs) (p = 0.226) despite having experienced much more severe trauma. In the multivariate regression models, lower GCS, delayed surgery, thoracotomy, and flail chest requiring mechanical ventilation were factors associated with prolonged ventilator days. Lower GCS, higher ISS, delayed surgery, and flail chest requiring mechanical ventilation were factors associated with longer ICU stays. Lower GCS and older age were factors associated with increased NPRCs. In the PS model, NPRCs risk was reduced by SSRF. CONCLUSIONS: The risk of NPRCs was reduced once ribs were surgically fixed through an algorithmic approach, and poor consciousness and aging were independent risk factors for NPRCs.

Abdominal pain is a main manifestation of delayed bleeding after splenic injury in patients receiving non-operative management.

Delayed bleeding is a major issue in patients with high-grade splenic injuries who receive non-operative management (NOM). While only few studies addressed the clinical manifestations of delayed bleeding in these patients. We reviewed the patients with high-grade splenic injuries presented with delayed bleeding, defined as the need for salvage procedures following NOM. There were 138 patients received NOM in study period. Fourteen of 107 patients in the SAE group and 3 of 31 patients in the non-embolization group had delayed bleeding. Among the 17 delayed bleeding episodes, 6 and 11 patients were salvaged by splenectomy and SAE, respectively. Ten (58.9%, 10/17) patients experienced bleeding episodes in the intensive care unit (ICU), whereas seven (41.1%, 7/17) experienced those in the ward or at home. The clinical manifestations of delayed bleeding were a decline in haemoglobin levels (47.1%, 8/17), hypotension (35.3%, 6/17), tachycardia (47.1%, 8/17), new abdominal pain (29.4%, 5/17), and worsening abdominal pain (17.6%, 3/17). For the bleeding episodes detected in the ICU, a decline in haemoglobin (60%, 6/10) was the main manifestation. New abdominal pain (71.43%, 5/7) was the main presentation when the patients left the ICU. In conclusion, abdominal pain was the main early clinical presentation of delayed bleeding following discharge from the ICU or hospital.

Effectiveness of protocolized management for patients sustaining maxillofacial fracture with massive oronasal bleeding: a single-center experience.

BACKGROUND: Maxillofacial fractures can lead to massive oronasal bleeding; however, surgical hemostasis and packing procedures can be challenging owing to complex facial anatomy. Only a few studies investigated maxillofacial fractures with massive oronasal hemorrhage. However, thus far, no studies have reported a protocolized management approach for maxillofacial trauma from a single center. This study aimed to evaluate the effectiveness of protocolized management for maxillofacial fractures with oronasal bleeding. METHODS: Patients were identified from the National Cheng University Hospital trauma registry from 2010 to 2020. We included patients with a face Abbreviated Injury Scale (AIS) score of > 3 and active oronasal bleeding. Patients' characteristics were compared between the angiography and non-angiography groups and between survivors and nonsurvivors. RESULTS: Forty-nine patients were included. Among them, 34 (69%) underwent angiography, of whom 21 received arterial embolization. Forty-seven patients (96%) successfully achieved hemostasis by adhering to the treatment protocol at our institution. Compared with the non-angiography group, the angiography group had significantly more patients requiring oral intubation (97% vs. 53%, P < 0.001), Glasgow Coma Scale < 9 (GCS; 79% vs. 27%, P < 0.001), head AIS > 3 (65% vs. 13%, P = 0.001), higher Injury Severity Score (ISS; 43 [33-50] vs. 22 [18-27], P < 0.001), higher incidence of cardiopulmonary resuscitation (CPR; 41% vs. 0%, P = 0.002), higher mortality rate (35% vs. 7%, P = 0.043), and more units of packed red blood cells (PRBC) transfused within 24 h (12 [6-20] vs. 2 [0-4], P < 0.001). The nonsurvivor group had significantly more patients with hypotension (62% vs. 8%; P < 0.001), higher need for CPR (85% vs. 8%; P < 0.001), head AIS > 3 (92% vs. 33%; P < 0.001), skull base fracture (100% vs. 64%; P = 0.011), GCS score < 9 (100% vs. 50%; P = 0.003), higher ISS (50 [43-57] vs. 29 [19-48]; P < 0.001), and more units of PRBC transfused within 24 h (18 [13-22] vs. 6 [2-12]; P = 0.001) than the survivor group. More patients underwent angiography in the nonsurvivor group than in the survivor group (92% vs. 61%; P = 0.043). Among embolized vessels, the internal maxillary artery (65%) was the most common bleeding site. Hypoxic encephalopathy accounted for 92% of deaths. CONCLUSIONS: Protocol-guided management effectively optimizes outcomes in patients with maxillofacial bleeding.

Diagnostic value of apparent diffusion coefficient in predicting pathological T stage in patients with thymic epithelial tumor.

PURPOSES: This study aimed to evaluate the diagnostic capacity of apparent diffusion coefficient (ADC) in predicting pathological Masaoka and T stages in patients with thymic epithelial tumors (TETs). METHODS: Medical records of 62 patients who were diagnosed with TET and underwent diffusion-weighted imaging (DWI) prior to surgery between August 2017 and July 2021 were retrospectively analyzed. ADC values were calculated from DWI images using b values of 0, 400, and 800 s/mm2. Pathological stages were determined by histological examination of surgical specimens. Cut-off points of ADC values were calculated via receiver operating characteristic (ROC) analysis. RESULTS: Patients had a mean age of 56.3 years. Mean ADC values were negatively correlated with pathological Masaoka and T stages. Higher values of the area under the ROC curve suggested that mean ADC values more accurately predicated pathological T stages than pathological Masaoka stages. The optimal cut-off points of mean ADC were 1.62, 1.31, and 1.48 × 10-3 mm2/sec for distinguishing pathological T2-T4 from pathological T1, pathological T4 from pathological T1-T3, and pathological T3-T4 from pathological T2, respectively. CONCLUSION: ADC seems to more precisely predict pathological T stages, compared to pathological Masaoka stage. The cut-off values of ADC identified may be used to preoperatively predict pathological T stages of TETs.

Down-regulated miR-146a expression with increased neutrophil extracellular traps and apoptosis formation in autoimmune-mediated diffuse alveolar hemorrhage.

BACKGROUND: Increasing evidences have suggested an important role of microRNAs (miRNAs) in regulating cell death processes including NETosis and apoptosis. Dysregulated expression of miRNAs and increased formation of neutrophil extracellular traps (NETs) and apoptosis participate in autoimmune-mediated diffuse alveolar hemorrhage (DAH), mostly associated with pulmonary capillaritis in systemic lupus erythematosus (SLE) patients. In particular, besides the inhibition of apoptosis, miR-146a can control innate and acquired immune responses, and regulate the toll-like receptor pathway through targeting TRAF6 to reduce the expression of pro-inflammatory cytokines/chemokines like IL-8, a NETosis inducer. METHODS: Expression of miR-146a, TRAF6 and NETs were examined in peripheral blood neutrophils (PBNs) and lung tissues from SLE-associated DAH patients, and in neutrophils and pristane-induced DAH lung tissues from C57BL/6 mice. To assess NETs formation, we examined NETosis-related DNAs morphology and crucial mediators including protein arginine deiminase 4 and citrullinated Histone 3. Expression of miR-146a and its endogenous RNA SNHG16 were studied in HL-60 promyelocytic cells and MLE-12 alveolar cells during NETosis and apoptosis processes, respectively. MiR-146a-overexpressed and CRISPR-Cas13d-mediated SNHG16-silenced HL-60 cells were investigated for NETosis. MiR-146a-overexpressed MLE-12 cells were analyzed for apoptosis. Pristane-injected mice received intra-pulmonary miR-146a delivery to evaluate therapeutic efficacy in DAH. RESULTS: In DAH patients, there were down-regulated miR-146a levels with increased TRAF6 expression and PMA/LPS-induced NETosis in PBNs, and down-regulated miR-146a levels with increased TRAF6, high-mobility group box 1 (HMGB1), IL-8, NETs and apoptosis expression in lung tissues. HMGB1-stimulated mouse neutrophils had down-regulated miR-146a levels with increased TRAF6, IL-8 and NETs expression. PMA-stimulated HL-60 cells had down-regulated miR-146a levels with enhanced NETosis. MiR-146a-overexpressed or SNHG16-silenced HL-60 cells showed reduced NETosis. Apoptotic MLE-12 cells had down-regulated miR-146a expression and increased HMGB1 release, while miR-146a-overexpressed MLE-12 cells showed reduced apoptosis and HMGB1 production. There were down-regulated miR-146a levels with increased TRAF6, HMGB1, IL-8, NETs and apoptosis expression in mouse DAH lung tissues. Intra-pulmonary miR-146a delivery could suppress DAH by reducing TRAF6, IL-8, NETs and apoptosis expression. CONCLUSIONS: Our results demonstrate firstly down-regulated pulmonary miR-146a levels with increased TRAF6 and IL-8 expression and NETs and apoptosis formation in autoimmune-mediated DAH, and implicate a therapeutic potential of intra-pulmonary miR-146a delivery.

An MRI-Based Clinical-Perfusion Model Predicts Pathological Subtypes of Prevascular Mediastinal Tumors.

This study aimed to build machine learning prediction models for predicting pathological subtypes of prevascular mediastinal tumors (PMTs). The candidate predictors were clinical variables and dynamic contrast-enhanced MRI (DCE-MRI)-derived perfusion parameters. The clinical data and preoperative DCE-MRI images of 62 PMT patients, including 17 patients with lymphoma, 31 with thymoma, and 14 with thymic carcinoma, were retrospectively analyzed. Six perfusion parameters were calculated as candidate predictors. Univariate receiver-operating-characteristic curve analysis was performed to evaluate the performance of the prediction models. A predictive model was built based on multi-class classification, which detected lymphoma, thymoma, and thymic carcinoma with sensitivity of 52.9%, 74.2%, and 92.8%, respectively. In addition, two predictive models were built based on binary classification for distinguishing Hodgkin from non-Hodgkin lymphoma and for distinguishing invasive from noninvasive thymoma, with sensitivity of 75% and 71.4%, respectively. In addition to two perfusion parameters (efflux rate constant from tissue extravascular extracellular space into the blood plasma, and extravascular extracellular space volume per unit volume of tissue), age and tumor volume were also essential parameters for predicting PMT subtypes. In conclusion, our machine learning-based predictive model, constructed with clinical data and perfusion parameters, may represent a useful tool for differential diagnosis of PMT subtypes.

The impact of driver mutation on the treatment outcome of early-stage lung cancer patients receiving neoadjuvant immunotherapy and chemotherapy.

Neoadjuvant immunotherapy and chemotherapy have improved the major pathological response (MPR) in patients with early-stage operable non-small cell lung cancer (NSCLC). This study aimed to assess whether the presence of targetable driver mutations affects the efficacy of the combination of immunotherapy and chemotherapy. We enrolled patients with early-stage operable NSCLC who received preoperative neoadjuvant therapy between January 1, 2017, and December 30, 2020. Neoadjuvant therapy was delivered with platinum-doublet chemotherapy; moreover, pembrolizumab was added at the attending physician's discretion based on patient's request. Pathological responses were assessed; moreover, disease-free survival was estimated. Next-generation sequencing was performed in case sufficient preoperative biopsy specimens were obtained. We included 23 patients; among them, 11 received a combination of neoadjuvant immunotherapy and chemotherapy while 12 received neoadjuvant chemotherapy alone. The MPR and pathological complete response rates were 54.5% and 27.3%, respectively, in patients who received a combination of neoadjuvant immunotherapy and chemotherapy. These rates were significantly higher than those in patients who only received neoadjuvant chemotherapy. Three patients in the combination group experienced disease recurrence during the follow-up period even though two of them showed an MPR. These three patients had targetable driver mutations, including an EGFR exon 20 insertion, EGFR exon 21 L858R substitution, and MET exon 14 skipping. Only one patient who remained disease-free had a targetable driver mutation. Among patients with early-stage operable NSCLC requiring neoadjuvant therapy, comprehensive genomic profiling is crucial before the administration of the combination of neoadjuvant immunotherapy and chemotherapy.