Precise Identification of Glioblastoma Micro-Infiltration at Cellular Resolution by Raman Spectroscopy.

Precise identification of glioblastoma (GBM) microinfiltration, which is essential for achieving complete resection, remains an enormous challenge in clinical practice. Here, the study demonstrates that Raman spectroscopy effectively identifies GBM microinfiltration with cellular resolution in clinical specimens. The spectral differences between infiltrative lesions and normal brain tissues are attributed to phospholipids, nucleic acids, amino acids, and unsaturated fatty acids. These biochemical metabolites identified by Raman spectroscopy are further confirmed by spatial metabolomics. Based on differential spectra, Raman imaging resolves important morphological information relevant to GBM lesions in a label-free manner. The area under the receiver operating characteristic curve (AUC) for Raman spectroscopy combined with machine learning in detecting infiltrative lesions exceeds 95%. Most importantly, the cancer cell threshold identified by Raman spectroscopy is as low as 3 human GBM cells per 0.01 mm2. Raman spectroscopy enables the detection of previously undetectable diffusely infiltrative cancer cells, which holds potential value in guiding complete tumor resection in GBM patients.

Tannic acid-poloxamer self-assembled nanoparticles for advanced atherosclerosis therapy by regulation of macrophage polarization.

Atherosclerosis (AS) is a significant contributor to cardiovascular events. Advanced AS is particularly concerning, as it leads to the formation of high-risk vulnerable plaques. Current treatments for AS focus on antithrombotic and lipid-lowering interventions, which are effective in treating early-stage AS. Recent studies have shown that macrophage polarization plays a crucial role in the development of AS. This study presents a new biomedical application of natural tannic acid as an anti-inflammatory nanoplatform for advanced AS. Tannic acid-poloxamer nanoparticles (TPNP) are fabricated through self-assembly of tannic acid (TA) and poloxamer. TPNP has the potential to provide effective treatment for advanced AS. According to in vitro studies, TPNP has been found to suppress the inflammatory response in lipopolysaccharide-stimulated macrophages by scavenging reactive oxygen species (ROS), downregulating the expression levels of inflammatory cytokines (such as interleukin-10 and tumor necrosis factor-α) and regulating polarization of macrophages. In vivo studies further reveal that TPNP can retard the development of advanced atherosclerotic plaques by reducing ROS production and promoting M2 macrophage polarization in the aorta of ApoE-/- mice. Overall, these findings suggest that TPNP could be used to develop natural multifunctional nanoplatforms for molecular therapy of AS and other inflammation-related diseases.

Protein-assisted synthesis of chitosan-coated minicells enhance dendritic cell recruitment for therapeutic immunomodulation within pulmonary tumors.

The efficacy of cancer therapies is significantly compromised by the immunosuppressive tumor milieu. Herein, we introduce a previously unidentified therapeutic strategy that harnesses the synergistic potential of chitosan-coated bacterial vesicles and a targeted chemotherapeutic agent to activate dendritic cells, thereby reshaping the immunosuppressive milieu for enhanced cancer therapy. Our study focuses on the protein-mediated modification of bacterium-derived minicells with chitosan molecules, facilitating the precise delivery of Doxorubicin to tumor sites guided by folate-mediated homing cues. These engineered minicells demonstrate remarkable specificity in targeting lung carcinomas, triggering immunogenic cell death and releasing tumor antigens and damage-associated molecular patterns, including calreticulin and high mobility group box 1. Additionally, the chitosan coating, coupled with bacterial DNA from the minicells, initiates the generation of reactive oxygen species and mitochondrial DNA release. These orchestrated events culminate in dendritic cell maturation via activation of the stimulator of interferon genes signaling pathway, resulting in the recruitment of CD4+ and CD8+ cytotoxic T cells and the secretion of interferon-ß, interferon-γ, and interleukin-12. Consequently, this integrated approach disrupts the immunosuppressive tumor microenvironment, impeding tumor progression. By leveraging bacterial vesicles as potent dendritic cell activators, our strategy presents a promising paradigm for synergistic cancer treatment, seamlessly integrating chemotherapy and immunotherapy.

Sex Differences in Coronary Inflammation and Atherosclerosis Phenotypes in Response to Imaging Marker of Stress-Related Neural Activity.

BACKGROUND: Sex-specific differences in coronary phenotypes in response to stress have not been elucidated. This study investigated the sex-specific differences in the coronary computed tomography angiography-assessed coronary response to mental stress. METHODS: This retrospective study included patients with coronary artery disease and without cancer who underwent resting 18F-fluorodexoyglucose positron emission tomography/computed tomography and coronary computed tomography angiography within 3 months. 18F-flourodeoxyglucose resting amygdalar uptake, an imaging biomarker of stress-related neural activity, coronary inflammation (fat attenuation index), and high-risk plaque characteristics were assessed by coronary computed tomography angiography. Their correlation and prognostic values were assessed according to sex. RESULTS: A total of 364 participants (27.7% women and 72.3% men) were enrolled. Among those with heightened stress-related neural activity, women were more likely to have a higher fat attenuation index (43.0% versus 24.0%; P=0.004), while men had a higher frequency of high-risk plaques (53.7% versus 39.3%; P=0.036). High amygdalar 18F-flourodeoxyglucose uptake (B-coefficient [SE], 3.62 [0.21]; P<0.001) was selected as the strongest predictor of fat attenuation index in a fully adjusted linear regression model in women, and the first-order interaction term consisting of sex and stress-related neural activity was significant (P<0.001). Those with enhanced imaging biomarkers of stress-related neural activity showed increased risk of major adverse cardiovascular event both in women (24.5% versus 5.1%; adjusted hazard ratio, 3.62 [95% CI, 1.14-17.14]; P=0.039) and men (17.2% versus 6.9%; adjusted hazard ratio, 2.72 [95% CI, 1.10-6.69]; P=0.030). CONCLUSIONS: Imaging-assessed stress-related neural activity carried prognostic values irrespective of sex; however, a sex-specific mechanism linking psychological stress to coronary plaque phenotypes existed in the current hypothesis-generating study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05545618.

Significance of Arterial Spin Labeling for Reducing Biopsies in Patients With Kidney Allograft Dysfunction.

BACKGROUND: Although biopsy is often entailed for managing patients with kidney allograft dysfunction, it is associated with potential complications of severe hemorrhage. Arterial spin labeling (ASL) is a non-invasive technique that assesses tissue perfusion. PURPOSE: To assess the utility of ASL for the discrimination of patients with post-transplant allograft dysfunction who do not need biopsy from those who need. STUDY TYPE: Prospective. SUBJECTS: Forty-six patients (34 males/12 females, aged 38.8 ± 9.5 years) with kidney allograft dysfunction, including 31 in which biopsy directly lead to changes in management (NECESSARY group) and 15 in which clinical management did not alter after biopsy (UNNECESSARY group). FIELD STRENGTH/SEQUENCE: 3.0 T and 3D fast-spin echo sequence. ASSESSMENT: All patients underwent both ASL scan and biopsies. The serum creatinine, proteinuria, pathologic results, and cortical ASL readings were obtained and compared between the two groups. STATISTICAL ANALYSES: Chi-square test, independent student t-test, Mann-Whitney U test, receiver-operating characteristic curve. A two-tailed P < 0.05 denoted statistical significance. RESULTS: The NECESSARY group presented with significantly elevated serum creatinine as compared with the UNNECESSARY group (1.87 ± 0.56 mg/dL vs. 1.31 ± 0.37 mg/dL). The acute composite score was significantly higher in the NECESSARY group than that in the UNNECESSARY group (7 [4-8] vs. 1 [0-2]). Cortical ASL in the NECESSARY group was significantly decreased as compared with the UNNECESSARY group (108.06 [69.96-134.92] mL/min/100 g vs. 153.48 [113.19-160.37] mL/min/100 g). Serum creatinine differentiated UNNCESSARY group from the NECESSARY group with an area under the curve (AUC) and specificity of 0.79 and 54.84%, respectively. By comparison, the cortical ASL yielded an AUC of 0.75 and a specificity of 70.97%. Notably, the specificity was increased to 90.30% by combined use of serum creatinine and cortical ASL. DATA CONCLUSION: The combined use of ASL and serum creatinine yielded a high specificity for selecting patients who may not need allograft biopsy. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Rapid visualization of PD-L1 expression level in glioblastoma immune microenvironment via machine learning cascade-based Raman histopathology.

INTRODUCTION: Combination immunotherapy holds promise for improving survival in responsive glioblastoma (GBM) patients. Programmed death-ligand 1 (PD-L1) expression in immune microenvironment (IME) is the most important predictive biomarker for immunotherapy. Due to the heterogeneous distribution of PD-L1, post-operative histopathology fails to accurately capture its expression in residual tumors, making intra-operative diagnosis crucial for GBM treatment strategies. However, the current methods for evaluating the expression of PD-L1 are still time-consuming. OBJECTIVE: To overcome the PD-L1 heterogeneity and enable rapid, accurate, and label-free imaging of PD-L1 expression level in GBM IME at the tissue level. METHODS: We proposed a novel intra-operative diagnostic method, Machine Learning Cascade (MLC)-based Raman histopathology, which uses a coordinate localization system (CLS), hierarchical clustering analysis (HCA), support vector machine (SVM), and similarity analysis (SA). This method enables visualization of PD-L1 expression in glioma cells, CD8+ T cells, macrophages, and normal cells in addition to the tumor/normal boundary. The study quantified PD-L1 expression levels using the tumor proportion, combined positive, and cellular composition scores (TPS, CPS, and CCS, respectively) based on Raman data. Furthermore, the association between Raman spectral features and biomolecules was examined biochemically. RESULTS: The entire process from signal collection to visualization could be completed within 30 min. In an orthotopic glioma mouse model, the MLC-based Raman histopathology demonstrated a high average accuracy (0.990) for identifying different cells and exhibited strong concordance with multiplex immunofluorescence (84.31 %) and traditional pathologists' scoring (R2 ≥ 0.9). Moreover, the peak intensities at 837 and 874 cm-1 showed a positive linear correlation with PD-L1 expression level. CONCLUSIONS: This study introduced a new and extendable diagnostic method to achieve rapid and accurate visualization of PD-L1 expression in GBM IMB at the tissular level, leading to great potential in GBM intraoperative diagnosis for guiding surgery and post-operative immunotherapy.

Burden and distribution of monosodium urate deposition in patients with hyperuricemia and gout: a cross-sectional Chinese population-based dual-energy CT study.

Background: To investigate the distribution and burden of monosodium urate (MSU) deposition in hyperuricemia and gout patients with dual-energy computed tomography (DECT). Methods: A total of 1,936 consecutive patients from January 1, 2009, to September 15, 2017, underwent DECT examinations in Jinling Hospital. Of these, 1,294 patients were excluded due to other clinical diagnoses (n=1,041), inappropriate locations (n=82), poor-quality images (n=105), training cases (n=30) and duplicated data (n=36). Finally, 642 patients were included in this study. We retrospectively analyzed 1,127 DECT examinations in 642 consecutive patients (hyperuricemia group, n=121; gout group, n=521) and recorded the volume and number of MSU deposits. For each anatomical location, we recorded MSU deposition in the soft tissue and joint cavity. MSU deposition was analyzed and compared between groups. For normally distributed data, independent sample t-tests were used for comparison between the two groups. The independent samples nonparametric test was used to analyze nonnormally distributed data. Results: (I) The burden of MSU deposition in the gout group {volume [0.14 (0.04-1.36)] and numbers [10.00 (5.00-19.00)]} was significantly higher than that {volume [0.08 (0.02-0.47), P=0.003] and numbers [9.50 (2.00-16.00), P=0.01]} in the hyperuricemia group. (II) The burden of MSU deposition in the knees {volume [0.24 (0.01-1.79), P=0.002] and quantity [6.00 (2.00-12.00), P=0.04]} and feet {volume [0.10 (0.04-0.66)] and number [9.00 (5.00-15.00)]} was significantly higher in the gout group than those {knees: the volume [0.03 (0.00-0.27), P=0.002] and the quantity [4.00 (0.00-9.00), P=0.04]; feet: the volume [0.07 (0.02-0.19), P=0.003)] and number [8.00 (2.25-12.00), P=0.04]} in the hyperuricemia group, respectively. (III) In the hyperuricemia group, the volume of MSU deposition was significantly higher in the soft tissues of the knee (0.022±0.042) and ankle (0.062±0.305) than in those (knee: 0.001±0.005, P=0.02; ankle: 0.027±0.234, P=0.02) in the joint cavity. Conclusions: Although subclinical urate deposition can occur in patients with asymptomatic hyperuricemia, the burden of urate deposition is greater in patients with symptomatic gout, and the distribution is more pronounced in the foot/knee. Thus, more effective patient management and monitoring can be achieved by measuring the burden of MSU deposits in the patient's feet/knees. These data suggest that a threshold for urate crystal volume at typical sites may be required before symptomatic disease develops.

Stress-Related Neural Activity Associates With Coronary Plaque Vulnerability and Subsequent Cardiovascular Events.

BACKGROUND: Stress-related neural activity (SNA) assessed by amygdalar activity can predict cardiovascular events. However, its mechanistic linkage with plaque vulnerability is not fully elucidated. OBJECTIVES: The authors aimed to investigate the association of SNA with coronary plaque morphologic and inflammatory features as well as their ability in predicting major adverse cardiovascular events (MACE). METHODS: A total of 299 patients with coronary artery disease (CAD) and without cancer underwent 18F-fluorodexoyglucose positron emission tomography/computed tomography (PET/CT) and available coronary computed tomographic angiography (CCTA) between January 1, 2013, and December 31, 2020. SNA and bone-marrow activity (BMA) were assessed with validated methods. Coronary inflammation (fat attenuation index [FAI]) and high-risk plaque (HRP) characteristics were assessed by CCTA. Relations between these features were analyzed. Relations between SNA and MACE were assessed with Cox models, log-rank tests, and mediation (path) analyses. RESULTS: SNA was significant correlated with BMA (r = 0.39; P < 0.001) and FAI (r = 0.49; P < 0.001). Patients with heightened SNA are more likely to have HRP (40.7% vs 23.5%; P = 0.002) and increase risk of MACE (17.2% vs 5.1%, adjusted HR 3.22; 95% CI: 1.31-7.93; P = 0.011). Mediation analysis suggested that higher SNA associates with MACE via a serial mechanism involving BMA, FAI, and HRP. CONCLUSIONS: SNA is significantly correlated with FAI and HRP in patients with CAD. Furthermore, such neural activity was associated with MACE, which was mediated in part by leukopoietic activity in the bone marrow, coronary inflammation, and plaque vulnerability.

The prognostic value of multiparametric cardiac magnetic resonance in patients with systemic light chain amyloidosis.

Background: Late gadolinium enhancement (LGE) is a classic imaging modality derived from cardiac magnetic resonance (CMR), which is commonly used to describe cardiac tissue characterization. T1 mapping with extracellular volume (ECV) and native T1 are novel quantitative parameters. The prognostic value of multiparametric CMR in patients with light chain (AL) amyloidosis remains to be thoroughly investigated. Methods: A total of 89 subjects with AL amyloidosis were enrolled from April 2016 to January 2021, and all of them underwent CMR on a 3.0 T scanner. The clinical outcome and therapeutic effect were observed. Cox regression was used to investigate the effect of multiple CMR parameters on outcomes in this population. Results: LGE extent, native T1 and ECV correlated well with cardiac biomarkers. During a median follow-up of 40 months, 21 patients died. ECV (hazard ratio [HR]: 2.087 for per 10% increase, 95% confidence interval [CI]: 1.379-3.157, P < 0.001) and native T1 (HR: 2.443 for per 100 ms increase, 95% CI: 1.381-4.321, P=0.002) were independently predictive of mortality. A novel prognostic staging system based on median native T1 (1344 ms) and ECV (40%) was similar to Mayo 2004 Stage, and the 5-year estimated overall survival rates in Stage I, II, and III were 95%, 80%, and 53%, respectively. In patients with ECV > 40%, receiving autologous stem cell transplantation had higher cardiac and renal response rates than conventional chemotherapy. Conclusion: Both native T1 and ECV independently predict mortality in patients with AL amyloidosis. Receiving autologous stem cell transplantation is effective and significantly improves the clinical outcomes in patients with ECV > 40%.

Development and validation of a CT-based radiomics model for differentiating pneumonia-like primary pulmonary lymphoma from infectious pneumonia: A multicenter study.

BACKGROUND: Pneumonia-like primary pulmonary lymphoma (PPL) was commonly misdiagnosed as infectious pneumonia, leading to delayed treatment. The purpose of this study was to establish a computed tomography (CT)-based radiomics model to differentiate pneumonia-like PPL from infectious pneumonia. METHODS: In this retrospective study, 79 patients with pneumonia-like PPL and 176 patients with infectious pneumonia from 12 medical centers were enrolled. Patients from center 1 to center 7 were assigned to the training or validation cohort, and the remaining patients from other centers were used as the external test cohort. Radiomics features were extracted from CT images. A three-step procedure was applied for radiomics feature selection and radiomics signature building, including the inter- and intra-class correlation coefficients (ICCs), a one-way analysis of variance (ANOVA), and least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor model. Two radiologists reviewed the CT images for the external test set. Performance of the radiomics model, clinical factor model, and each radiologist were assessed by receiver operating characteristic, and area under the curve (AUC) was compared. RESULTS: A total of 144 patients (44 with pneumonia-like PPL and 100 infectious pneumonia) were in the training cohort, 38 patients (12 with pneumonia-like PPL and 26 infectious pneumonia) were in the validation cohort, and 73 patients (23 with pneumonia-like PPL and 50 infectious pneumonia) were in the external test cohort. Twenty-three radiomics features were selected to build the radiomics model, which yielded AUCs of 0.95 (95% confidence interval [CI]: 0.94-0.99), 0.93 (95% CI: 0.85-0.98), and 0.94 (95% CI: 0.87-0.99) in the training, validation, and external test cohort, respectively. The AUCs for the two readers and clinical factor model were 0.74 (95% CI: 0.63-0.83), 0.72 (95% CI: 0.62-0.82), and 0.73 (95% CI: 0.62-0.84) in the external test cohort, respectively. The radiomics model outperformed both the readers' interpretation and clinical factor model ( P <0.05). CONCLUSIONS: The CT-based radiomics model may provide an effective and non-invasive tool to differentiate pneumonia-like PPL from infectious pneumonia, which might provide assistance for clinicians in tailoring precise therapy.

Engineered Toll-like Receptor Nanoagonist Binding to Extracellular Matrix Elicits Safe and Robust Antitumor Immunity.

Cancer immunotherapy, such as the Toll-like receptor (TLR) agonist including CpG oligodeoxynucleotide, has shown potency in clinical settings. However, it is still confronted with multiple challenges, which include the limited efficacy and severe adverse events caused by the rapid clearance and systemic diffusion of CpG. Here we report an improved CpG-based immunotherapy approach composed of a synthetic extracellular matrix (ECM)-anchored DNA/peptide hybrid nanoagonist (EaCpG) via (1) a tailor designed DNA template that encodes tetramer CpG and additional short DNA moieties, (2) generation of elongated multimeric CpG through rolling circle amplification (RCA), (3) self-assembly of densely packaged CpG particles composed of tandem CpG building blocks and magnesium pyrophosphate, and (4) incorporation of multiple copies of ECM binding peptide through hybridization to short DNA moieties. The structurally well-defined EaCpG shows dramatically increased intratumoral retention and marginal systemic dissemination through peritumoral administration, leading to potent antitumor immune response and subsequent tumor elimination, with minimal treatment-related toxicity. Combined with conventional standard-of-care therapies, peritumor administration of EaCpG generates systemic immune responses that lead to a curative abscopal effect on distant untreated tumors in multiple cancer models, which is superior to the unmodified CpG. Taken together, EaCpG provides a facile and generalizable strategy to simultaneously potentiate the potency and safety of CpG for combinational cancer immunotherapies.

Reversing Immune Suppression and Potentiating Photothermal Immunotherapy via Bispecific Immune Checkpoint Inhibitor Loaded Hollow Polydopamine Nanospheres.

Despite the great achievements of immune checkpoint blockade (ICB) therapy on programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis, ICB monotherapy still faces obstacles in eradicating solid tumors due to the lack of tumor-associated antigens or tumor-specific cytotoxicity. Photothermal therapy (PTT) is a potential therapeutic modality because it can noninvasively kill tumor cells by thermal ablation and generate both tumor-specific cytotoxicity and immunogenicity, which holds great feasibility to improve the efficiency of ICB by providing complementary immunomodulation. Except for the PD-1/PD-L1 axis, the cluster of differentiation 47 (CD47)/signal regulatory protein alpha (SIRPα) pathway has been considered as a novel strategy of tumor cells to evade the surveillance of macrophages and inactivate the immune response of PD-L1 blockade therapy. Therefore, it is necessary to synergize the antitumor effect of dual-targeting PD-L1 and CD47. Although promising, the application of PD-L1/CD47 bispecific antibodies, especially in combination with PTT, remains a formidable problem, due to the low objective response, activity loss at relatively high temperature, or nonvisualization. Herein, instead of using antibodies, we use MK-8628 (MK) to down-regulate both PD-L1 and CD47 simultaneously through halting the active transcription of oncogene c-MYC, leading to elicitation of the immune response. The hollow polydopamine (HPDA) nanospheres are introduced as a biocompatible nanoplatform with high loading capacity and magnetic resonance imaging (MRI) ability to deliver MK and induce PTT (HPDA@MK). Compared to preinjection, HPDA@MK exhibits the strongest MRI signal at 6 h postintravenous injection to guide the precise combined treatment time. However, due to the local delivery and controlled release of inhibitors, HPDA@MK down-regulates c-MYC/PD-L1/CD47, promotes the activation and recruitment of cytotoxic T cells, regulates the M2 macrophages polarization in tumor sites, and especially boosts the combined therapeutic efficacy. Collectively, our work presents a simple but distinctive approach for c-MYC/PD-L1/CD47-targeted immunotherapy combined with PTT that may provide a desirable and feasible strategy for the treatment of other clinical solid tumors.

Precision Delivery of Dual Immune Inhibitors Loaded Nanomodulator to Reverse Immune Suppression for Combinational Photothermal-Immunotherapy.

Although photothermal therapy (PTT) can noninvasively kill tumor cells and exert synergistic immunological effects, the immune responses are usually harmed due to the lack of cytotoxic T cells (CTLs) pre-infiltration and co-existing of intricate immunosuppressive tumor microenvironment (TME), including the programmed cell death ligand 1 (PD-L1)/cluster of differentiation 47 (CD47)/regulatory T cells (Tregs)/M2-macrophages overexpression. Indoleamine 2, 3-dioxygenase inhibitor (NLG919) or bromodomain extra-terminal inhibitor (OTX015) holds great promise to reprogram suppressive TME through different pathways, but their collaborative application remains a formidable challenge because of the poor water solubility and low tumor targeting. To address this challenge, a desirable nanomodulator based on dual immune inhibitors loaded mesoporous polydopamine nanoparticles is designed. This nanomodulator exhibits excellent biocompatibility and water solubility, PTT, and bimodal magnetic resonance/photoacoustic imaging abilities. Owing to enhanced permeability and retention effect and tumor acidic pH-responsiveness, both inhibitors are precisely delivered and locally released at tumor sites. Such a nanomodulator significantly reverses the immune suppression of PD-L1/CD47/Tregs, promotes the activation of CTLs, regulates M2-macrophages polarization, and further boosts combined therapeutic efficacy, inducing a strong immunological memory. Taken together, the nanomodulator provides a practical approach for combinational photothermal-immunotherapy, which may be further broadened to other "immune cold" tumors.

Exploration of thoracoabdominal aortic mixed reality optimisation and its clinical application value in type A aortic dissection.

OBJECTIVES: This study aimed to explore the feasibility of low-dose computed tomography (CT)-based mixed reality and its clinical role in type A aortic dissection (TAAD) operations. METHODS: Eighty-seven patients diagnosed with TAAD were prospectively enrolled and underwent thoracoabdominal aorta mixed reality. They were randomly divided into a low-dose mixed reality group, a conventional mixed reality group and a conventional thoracoabdominal aorta computed tomography angiography (CTA) group. Three-dimensional modelling, mixed reality and CT reconstruction technology were selected. The radiation dose and image quality were compared using Student's t test. Doctors with different seniorities evaluated the clinical application value of thoracoabdominal aorta mixed reality using a Likert scale. The consistency was assessed using the Cohen kappa coefficient (k). The Pearson chi-square test was used to test the correlation of perioperative index results in TAAD operations. RESULTS: Low-dose CT technology can be effectively applied to thoracoabdominal aorta mixed reality and reduces the radiation dose by approximately 59% and the operation time and auxiliary cardiopulmonary bypass time by approximately 22% and 29%, respectively. The subjective scores of doctors with different seniorities on the clinical application value of thoracoabdominal aorta mixed reality were higher than those of thoracoabdominal aorta CTA (all p > 0.05). CONCLUSIONS: Low-dose CT can be effectively used in thoracoabdominal aortic mixed reality to reduce the radiation dose while ensuring quality. Low-dose thoracoabdominal aortic mixed reality has clinical application value and can effectively reduce the operation time and auxiliary cardiopulmonary bypass time in TAAD operations. KEY POINTS: • Low-dose CT technology can ensure the mixed reality quality of the thoracoabdominal aorta with a radiation dose reduction of approximately 59%. • Compared with thoracoabdominal aorta CTA, low-dose thoracoabdominal aorta mixed reality can reduce the operation time and auxiliary cardiopulmonary bypass time by approximately 20% and 29%, respectively, in TAAD operations. • The application value of low-dose thoracoabdominal aorta mixed reality in operation scheme formulation, operation risk assessment, operation navigation and diagnosis and treatment under safe distance was greater than that of thoracoabdominal aorta CTA in TAAD.

Perfusion and oxygenation in allografts with transplant renal artery stenosis: Evaluation with functional magnetic resonance imaging.

BACKGROUND: Transplant renal artery stenosis (TRAS) has been shown to reduce kidney perfusion leading to post-operative hypertension. We aimed to measure the perfusion and oxygenation changes in TRAS with arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) imaging, respectively. METHODS: In this single-center prospective study, a total of seven patients with TRAS and seven age- and sex-matched normal kidney transplant recipients underwent both ASL and BOLD imaging. Moreover, measurements of ASL and BOLD were also performed in five patients after successful angioplasty for TRAS. RESULTS: Allograft cortical perfusion as measured by ASL in the TRAS group was significantly decreased as compared with normal control group (129.9 ± 46.6 ml/100 g vs. 202.4 ± 47.7 ml/100 g, P = .01). Interestingly, allograft oxygenation as indicated by R2* derived from BOLD in both the cortex (16.42 ± 1.90 Hz vs. 18.25 ± 4.34 Hz, P = .33) and the medulla (30.34 ± 2.35 Hz vs. 30.43 ± 6.85 Hz, P = .97) showed no statistical difference between the TRAS and normal control group. In addition, both cortical and medullary oxygenation remained unchanged despite significantly improved cortical perfusion in those undergone successful angioplasty. CONCLUSION: Cortical and medullary oxygenation were preserved in the presence of reduced allograft perfusion in clinically significant TRAS. Prospective larger studies are needed to conclusively establish perfusion and oxygenation changes in TRAS.

Development and Validation of a DeepSurv Nomogram to Predict Survival Outcomes and Guide Personalized Adjuvant Chemotherapy in Non-Small Cell Lung Cancer.

Objective: To develop and validate a DeepSurv nomogram based on radiomic features extracted from computed tomography images and clinicopathological factors, to predict the overall survival and guide individualized adjuvant chemotherapy in patients with non-small cell lung cancer (NSCLC). Patients and Methods: This retrospective study involved 976 consecutive patients with NSCLC (training cohort, n=683; validation cohort, n=293). DeepSurv was constructed based on 1,227 radiomic features, and the risk score was calculated for each patient as the output. A clinical multivariate Cox regression model was built with clinicopathological factors to determine the independent risk factors. Finally, a DeepSurv nomogram was constructed by integrating the risk score and independent clinicopathological factors. The discrimination capability, calibration, and clinical usefulness of the nomogram performance were assessed using concordance index evaluation, the Greenwood-Nam-D'Agostino test, and decision curve analysis, respectively. The treatment strategy was analyzed using a Kaplan-Meier curve and log-rank test for the high- and low-risk groups. Results: The DeepSurv nomogram yielded a significantly better concordance index (training cohort, 0.821; validation cohort 0.768) with goodness-of-fit (P<0.05). The risk score, age, thyroid transcription factor-1, Ki-67, and disease stage were the independent risk factors for NSCLC.The Greenwood-Nam-D'Agostino test showed good calibration performance (P=0.39). Both high- and low-risk patients did not benefit from adjuvant chemotherapy, and chemotherapy in low-risk groups may lead to a poorer prognosis. Conclusions: The DeepSurv nomogram, which is based on the risk score and independent risk factors, had good predictive performance for survival outcome. Further, it could be used to guide personalized adjuvant chemotherapy in patients with NSCLC.

The correlation study on chest CT features and kidney injury in severe COVID-19 pneumonia from a multicenter cohort study.

Background: Among confirmed severe COVID-19 patients, although the serum creatinine level is normal, they also have developed kidney injury. Early detection of kidney injury can guide doctors to choose drugs reasonably. Study found that COVID-19 have some special chest CT features. The study aimed to explore which chest CT features are more likely appear in severe COVID-19 and the relationship between related (special) chest CT features and kidney injury or clinical prognosis. Methods: In this retrospective study, 162 patients of severe COVID-19 from 13 medical centers in China were enrolled and divided into three groups according to the estimated glomerular filtration rate (eGFR) level: Group A (eGFR < 60 ml/min/1.73 m2), Group B (60 ml/min/1.73 m2 ≤ eGFR < 90 ml/min/1.73 m2), and Group C (eGFR ≥ 90 ml/min/1.73 m2). The demographics, clinical features, auxiliary examination, and clinical prognosis were collected and compared. The chest CT features and eGFR were assessed using univariate and multivariate Cox regression. The influence of chest CT features on eGFR and clinical prognosis were calculated using the Cox proportional hazards regression model. Results: Demographic and clinical features showed significant differences in age, hypertension, and fatigue among the Group A, Group B, and Group C (all P < 0.05). Auxiliary examination results revealed that leukocyte count, platelet count, C-reactive protein, aspartate aminotransferase, creatine kinase, respiratory rate ≥ 30 breaths/min, and CT images rapid progression (>50%) within 24-48 h among the three groups were significantly different (all P < 0.05). Compared to Group C (all P < 0.017), Groups A and B were more likely to show crazy-paving pattern. Logistic regression analysis indicated that eGFR was an independent risk factor of the appearance of crazy-paving pattern. The eGFR and crazy-paving pattern have a mutually reinforcing relationship, and eGFR (HR = 0.549, 95% CI = 0.331-0.909, P = 0.020) and crazy-paving pattern (HR = 2.996, 95% CI = 1.010-8.714, P = 0.048) were independent risk factors of mortality. The mortality of severe COVID-19 with the appearance of crazy-paving pattern on chest CT was significantly higher than that of the patients without its appearance (all P < 0.05). Conclusions: The crazy-paving pattern is more likely to appear in the chest CT of patients with severe COVID-19. In severe COVID-19, the appearance of the crazy-paving pattern on chest CT indicates the occurrence of kidney injury and proneness to death. The crazy-paving pattern can be used by doctors as an early warning indicator and a guidance of reasonable drug selection.

The Genus Parabacteroides Is a Potential Contributor to the Beneficial Effects of Truncal Vagotomy-Related Bariatric Surgery.

PURPOSE: Evidences about the gut microbiota role in weight loss after bariatric surgery (BS) are growing. The objective of this study was to observe the changes of gut microbiota after sleeve gastrectomy (SG) and SG plus truncal vagotomy (SG-TV) and identify specific microbes that may contribute to the improvement of obesity after surgeries. MATERIALS AND METHODS: Forty high-fat diet-induced obesity (DIO) mice were randomized to SG, SG-TV, or sham operation (SH) groups. Body weight (BW) and fast blood glucose (FBG) were measured before and 1, 2, 4, 8, and 12 weeks post-operatively. Fecal samples were collected before and at post-operative week 12 and profiled using 16S rRNA relative and absolute quantitative sequencing. RESULTS: After the surgery, the SG and SG-TV surgeries significantly reduce BW and FBG levels compared with SH, and the SG-TV achieved better effects than SG. A decreasing trend in alpha diversity of gut microbiota and significant changes in taxonomic composition were observed after surgeries. Then, we identified a set of microbes and pathways significantly different in abundance after BS. The genus Parabacteroides and one pathway (polyketide sugar unit biosynthesis) increased in SG-TV group specially, which was also negatively correlated with BW and FBG. CONCLUSION: SG and SG-TV indeed achieve effects of weight loss, but TV could enhance the efficacy of SG. The identified different microbes and pathways, like Parabacteroides, polyketide sugar unit biosynthesis, may partly mediate the beneficial effects of BS, and thus possibly contribute to the development of novel bacteria-based therapeutic approaches.

Incidence Trends and Survival Prediction of Malignant Skin Cancer: A SEER-Based Study.

Purpose: This study aimed to analyze the incidence trend and further explore the risk factors influencing the survival among patients of malignant skin cancer in America. Methods: Age-adjusted incidence rates, annual percentage change (APC) of different sex and ethnicity in 1973-2015 and patient records were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate analysis and multivariate Cox regression were used to analyze risk factors influencing the survival in skin cancer patients. Survival curves and nomograms were constructed to evaluate the survival prediction by R. Results: The overall age-adjusted incidence of skin cancer increased in America from 1973 to 2005 (APC = 2.8%, 95% CI: 2.6-2.9%, P < 0.05), particularly in white patients, 66-year-old people, and males. The 3- and 5-year overall survival (OS) rates were 51.4% and 33.8%, respectively. Independent predictors for short OS include age over 65, white ethnicity, other marital status and no surgery (P < 0.05). Stage was not an independent factor of survival (P > 0.05). The nomogram with a C-index of 0.72 (95% CI: 0.71-0.73) matched an appropriate calibration curve. Conclusion: Incidence of skin cancer in America was on the rise during 1973-2015 based on SEER database. Age, ethnicity, marital status and surgical history were related with survival of malignant skin cancer. Nomograms were effective tools for predicting the survival prognosis.

Long-term prognostic value of the serial changes of CT-derived fractional flow reserve and perivascular fat attenuation index.

BACKGROUND: To investigate the serial changes of computed tomography (CT) fractional flow reserve (CT-FFR) and fat attenuation index (FAI), and explore their relationships with long-term clinical outcomes. METHODS: Consecutive symptomatic patients with an intermediate pretest probability of coronary artery disease 1-4 were prospectively enrolled if coronary CT angiography (CCTA) revealed at least 1 lesion with 30-70% stenosis on major epicardial arteries. Follow-up CCTA was performed at 1 to 1.5-year intervals. All patients were further followed up after the second CCTA until September 2019. The Coronary Artery Disease - Reporting and Data System (CAD-RADS) grade, high-risk plaque features, lesion-specific CT-FFR, and FAI were measured for prognosis analysis. RESULTS: A total of 263 patients were included in the analysis, and 38 major adverse cardiac events (MACEs) occurred. In the MACE group, the lesion-specific CT-FFR decreased significantly at the follow-up CCTA [0.80 (0.74-0.90) versus 0.85 (0.76-0.93); P=0.01], whereas the FAI did not notably increase (-70.4±8.9 versus -71.3±7.1 HU; P=0.436). In the non-MACE group, lesion-specific CT-FFR increased markedly [0.91 (0.84-0.95) versus 0.90 (0.82-0.94); P<0.001], while the FAI decreased substantially (-74.0±10.8 versus -72.4±11.5 HU; P=0.004). Decreased CT-FFR (adjusted overall hazard ratio =2.455; P=0.023) and increased FAI (adjusted hazard ratio =2.956; P=0.002) were the strongest independent predictors of MACEs. Serial changes of CT-FFR and FAI provided incremental prognostic value (Concordance statistic =0.716; P=0.003; over conventional clinical and imaging parameters (Concordance statistic =0.762; P=0.004). CONCLUSIONS: Decreased CT-FFR and increased FAI at follow-up CCTA were the 2 strongest predictors of MACEs. Serial changes of CT-FFR and FAI provided incremental prognostic value over conventional clinical and imaging parameters for risk stratification. In addition, decreased CT-FFR provided incremental predictive value for MACEs from 15 months after second CCTA, while increased FAI added prognostic value from the second CCTA onwards.