Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Nebulized platelet-derived extracellular vesicles attenuate chronic cigarette smoke-induced murine emphysema.

Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease usually resulting from cigarette smoking (CS). Cigarette smoking induces oxidative stress, which causes inflammation and alveolar epithelial cell apoptosis and represents a compelling therapeutic target for COPD. Purified human platelet-derived exosome product (PEP) is endowed with antioxidant enzymes and immunomodulatory molecules that mediate tissue repair. In this study, a murine model of CS-induced emphysema was used to determine whether nebulized PEP can influence the development of CS-induced emphysema through the mitigation of oxidative stress and inflammation in the lung. Nebulization of PEP effectively delivered the PEP vesicles into the alveolar region, with evidence of their uptake by type I and type II alveolar epithelial cells and macrophages. Lung function testing and morphometric assessment showed a significant attenuation of CS-induced emphysema in mice treated with nebulized PEP thrice weekly for 4 weeks. Whole lung immuno-oncology RNA sequencing analysis revealed that PEP suppressed several CS-induced cell injuries and inflammatory pathways. Validation of inflammatory cytokines and apoptotic protein expression on the lung tissue revealed that mice treated with PEP had significantly lower levels of S100A8/A9 expressing macrophages, higher levels of CD4+/FOXP3+ Treg cells, and reduced NF-κB activation, inflammatory cytokine production, and apoptotic proteins expression. Further validation using in vitro cell culture showed that pretreatment of alveolar epithelial cells with PEP significantly attenuated CS extract-induced apoptotic cell death. These data show that nebulization of exosomes like PEP can effectively deliver exosome cargo into the lung, mitigate CS-induced emphysema in mice, and suppress oxidative lung injury, inflammation, and apoptotic alveolar epithelial cell death.

Hot Air Impingement Drying Enhanced Drying Characteristics and Quality Attributes of Ophiopogonis Radix.

The effects of drying temperature and air velocity on the drying characteristics, color, bioactive compounds, rehydration ratio, and microstructure of Ophiopogonis Radix during hot air impingement drying (HAID) were explored in the current study. The experimental results showed that the drying temperature and air velocity had a significant impact on the drying characteristics and quality attributes of dried products except for the rehydration ratio. The drying time decreased from 720 to 240 min with the increase of drying temperature from 50 to 70 °C. Increasing the air velocity from 6 to 12 m/s enhanced the drying process of Ophiopogonis Radix, while the extension of air velocity to 15 m/s lowered the drying rate. The samples that were dried at a lower drying temperature obtained lower color difference. Properly increasing the drying temperature or air velocity could increase the total polysaccharide and flavonoid contents of dried products. Additionally, a back-propagation neural network (BPNN) model was developed to predict the moisture ratio of Ophiopogonis Radix during the drying process. The optimal BPNN with 3-11-1 topology were obtained to predict the moisture ratio of Ophiopogonis Radix during HAID and performed with an acceptable performance.

Noncanonical JAK1/STAT3 interactions with TGF-ß modulate myofibroblast transdifferentiation and fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited survival. Janus kinases (JAKs), tyrosine kinases that transduce cytokine-mediated signals, are known to be involved, but their specific roles in lung fibrosis are not well defined. In this study, the interactions between JAK1/signal transducers and activators of transcription (STAT)3 signaling and transforming growth factor-beta (TGF-ß)-induced fibroblast responses were investigated using both pharmacological and siRNA approaches in human normal and IPF-derived lung fibroblasts. We found that JAK1 directly interacts with the TGF-ß receptor I subunit (TßRI), and silencing JAK1 promotes myofibroblast transdifferentiation. However, the suppression of JAK1 signaling in vitro and in vivo using an inhibitor (upadacitinib) did not alter lung fibroblast activation or fibrosis development. STAT3 was constitutively active in cultured primary lung fibroblasts; this STAT3 activation required JAK1 and repressed myofibroblast transdifferentiation. Loss of phosphorylated STAT3 following transcriptional JAK1 silencing promoted myofibroblast transdifferentiation. In contrast, transcriptional silencing of unphosphorylated STAT3 suppressed TGF-ß signaling, decreased SMAD3 activation, and reduced myofibroblast transdifferentiation and ECM production. Taken together, these observations support a role for JAK1/STAT3 as a direct regulator of TGF-ß signaling in lung fibroblasts. Modulation of JAK1/STAT3 signaling in lung fibroblasts represents a noncanonical approach to regulating TGF-ß-induced fibrosis and suggests the potential for a novel approach to treat pulmonary fibrosis.

RNA Sequencing of Idiopathic Subglottic Stenosis Tissues Uncovers Putative Profibrotic Mechanisms and Identifies a Prognostic Biomarker.

Idiopathic subglottic stenosis (iSGS) is a localized airway disease that almost exclusively affects females. Understanding the molecular mechanisms involved may provide insights leading to therapeutic interventions. Next-generation sequencing was performed on tissue sections from patients with iSGS (n = 22), antineutrophil cytoplasmic antibody-associated vasculitis (AAV; n = 5), and matched controls (n = 9) to explore candidate genes and mechanisms of disease. Gene expression changes were validated, and selected markers were identified by immunofluorescence staining. Epithelial-mesenchymal transition (EMT) and leukocyte extravasation pathways were the biological mechanisms most relevant to iSGS pathogenesis. Alternatively activated macrophages (M2) were abundant in the subepithelium and perisubmucosal glands of the airway in iSGS and AAV. Increased expression of the mesenchymal marker S100A4 and decreased expression of the epithelial marker epithelial cell adhesion molecule (EPCAM) further supported a role for EMT, but to different extents, in iSGS and antineutrophil cytoplasmic antibody-associated subglottic stenosis. In patients with iSGS, high expression of prostate transmembrane protein, androgen induced 1 (PMEPA1), an EMT regulator, was associated with a shorter recurrence interval (25 versus 116 months: hazard ratio = 4.16; P = 0.041; 95% CI, 1.056-15.60). Thus, EMT is a key pathogenetic mechanism of subglottic stenosis in iSGS and AAV. M2 macrophages contribute to the pathogenesis of both diseases, suggesting a shared profibrotic mechanism, and PMEPA1 may be a biomarker for predicting disease recurrence in iSGS.

Co-option of a carotenoid cleavage dioxygenase gene (CCD4a) into the floral symmetry gene regulatory network contributes to the polymorphic floral shape-color combinations in Chrysanthemum sensu lato.

Morphological novelties, including formation of trait combinations, may result from de novo gene origination and/or co-option of existing genes into other developmental contexts. A variety of shape-color combinations of capitular florets occur in Chrysanthemum and its allies. We hypothesized that co-option of a carotenoid cleavage dioxygenase gene into the floral symmetry gene network would generate a white zygomorphic ray floret. We tested this hypothesis in an evolutionary context using species in Chrysanthemum sensu lato, a monophyletic group with diverse floral shape-color combinations, based on morphological investigation, interspecific crossing, molecular interaction and transgenic experiments. Our results showed that white color was significantly associated with floret zygomorphy. Specific expression of the carotenoid cleavage dioxygenase gene CCD4a in marginal florets resulted in white color. Crossing experiments between Chrysanthemum lavandulifolium and Ajania pacifica indicated that expression of CCD4a is trans-regulated. The floral symmetry regulator CYC2g can activate expression of CCD4a with a dependence on TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING (TCP) binding element 8 on the CCD4a promoter. Based on all experimental findings, we propose that gene co-option of carotenoid degradation into floral symmetry regulation, and the subsequent dysfunction or loss of either CYC2g or CCD4a, may have led to evolution of capitular shape-color patterning in Chrysanthemum sensu lato.

Canonical and noncanonical regulatory roles for JAK2 in the pathogenesis of rheumatoid arthritis-associated interstitial lung disease and idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are two fibrotic interstitial lung diseases that share the usual interstitial pneumonia (UIP) injury pattern. Here, we report that RNA sequencing of lung biopsies from patients with RA-ILD and IPF revealed shared and distinct disease-causing pathways. Analysis of transcriptomic data identified a JAK2 related JAK/STAT signaling pathway gene signature that distinguishes RA-UIP from idiopathic UIP. This was further confirmed by immunohistostaining, which identified JAK2 phosphorylation with two distinct forms of activation: a cytoplasmic form of JAK2 activation in most IPF cases (13/20) and a nuclear form of p-JAK2 in RA-UIP (5/5) and a minority of IPF (6/20) cases. Further immunohistostaining identified STAT5A&B as the downstream transcriptional activator for JAK2-mediated canonical signal transduction and phosphorylation of Tyr41 on histone H3 (H3Y41ph) as the downstream epigenetic regulation site for JAK2-mediated noncanonical signal transduction. Gene Set Enrichment Analysis (GSEA) of the RNA-Seq data further supported this shared pathogenic mechanism for the two diseases with the enrichment of STAT5A&B target gene sets as well as the JAK2 regulated H3Y41ph target gene set. This regulatory role of JAK2 in the pathogenesis of pulmonary fibrosis was further demonstrated by the attenuation of bleomycin-induced murine pulmonary fibrosis using a JAK2-selective pharmacological inhibitor CEP33779. In vitro studies with normal and IPF derived lung fibroblasts revealed a central role for JAK2 as an essential intermediary molecule in TGF-ß-mediated myofibroblast trans-differentiation, proliferation, and extracellular matrix protein production. These observations support a crucial role for JAK2 as an intermediary molecule in fibrotic lung disease development.

Clinical characteristics and postoperative outcomes of systemic artery-to-pulmonary vessel fistula in hemoptysis patients.

OBJECTIVES: To investigate the clinical characteristics and outcomes on the success of bronchial arterial embolization (BAE) in patients with and without systemic artery-to-pulmonary vessel fistula (SA-PF) and to evaluate the feasibility of CTA in the assessment of SA-PF. METHODS: We retrospectively enrolled 420 consecutive patients that underwent BAE for hemoptysis control in our hospital from September 2011 to May 2019. The clinical characteristics, preprocedural CTA findings, BAE procedural findings, and follow-up outcomes were collected. Patients were divided into two groups according to DSA findings: patients with SA-PF and those without. RESULTS: A total of 184 (43.7%) patients presented with SA-PF. Pneumonia was less likely to be the concomitant condition in patients with SA-PF (p < 0.001). The mean number of culprit arteries per patient was significantly higher in patients with SA-PF compared to that in patients without SA-PF (p = 0.017). The SA-PF patients saw a greater probability of recurrence (HR: 2.782, 95% CI: 1.617-4.784, p < 0.001). SA-pulmonary venous fistula (SA-PVF) favored lower hemoptysis recurrence rate (HR: 0.199, 95%CI: 0.052-0.765, p = 0.019). SA-pulmonary artery fistula (SA-PAF) can be detected by optimized CTA protocol with a detection rate of 65.3% (49/75). CONCLUSIONS: The presence of SA-PF is an independent risk factor predicting early recurrence of hemoptysis after BAE. SA-PVF seems to be a protective factor for longer hemoptysis control compared to SA-PAF. Optimized preprocedural CTA is a reliable examination to identify SA-PAF. KEY POINTS: • The appearance of SA-PF is associated with a greater probability of early recurrent hemoptysis after bronchial artery embolization. • The presence of SA-PVF seems to be a protective factor for longer hemoptysis control after BAE compared to SA-PAF. • Optimized CTA protocol seems to be a promising auxiliary examination to detect SA-PAF.

[Potential impacts of climate change on suitable habitats of Marco Polo sheep in China]. / 气候变化对中国马可波罗盘羊适宜生境的潜在影响.

Climate change may lead to biodiversity loss and species extinction. Understanding the impacts of climate change on the distribution pattern of endangered species is of great value to the identification of priority reserves and the formulation of relevant conservation strategies. Based on the distribution data of Marco Polo sheep (Ovis ammon polii) obtained from the field survey in Taxkorgan Nature Reserve (TNR) in Xinjiang during 2017-2018, the maximum entropy (MaxEnt) model was used to predict the distribution pattern of its suitable habitat under climate change. The results showed that the suitable habitat of Marco Polo sheep was mainly distributed in the northwest of the TNR, with temperature as the key factor affecting its suitable habitat distribution. Under the medium and high emission concentration (RCP4.5 and RCP8.5), the suitable habitat area of Marco Polo sheep would decrease in the next two periods (2050s and 2070s), with the loss rate of suitable habitat being as high as 40.5%. The loss of suitable habitat was mainly located in the low-altitude area, while the area of suitable habitat increased correspondingly in the high-altitude area. The area of suitable habitat from low elevation to high elevation increased with the increases of greenhouse gas emission concentration. According to the results of centroid transfer, the suitable habitat was mainly moved to the west, namely Tajikistan, the main distribution country of Marco Polo sheep.

IL-23 amplifies the epithelial-mesenchymal transition of mechanically conditioned alveolar epithelial cells in rheumatoid arthritis-associated interstitial lung disease through mTOR/S6 signaling.

Epithelial-mesenchymal transition (EMT) creates an environment facilitating fibrosis following alveolar epithelial cell injury. IL-23 has important roles in chronic autoimmune conditions like rheumatoid arthritis (RA), but its role in the interstitial lung disease that affects patients with RA is unclear. This study aimed to determine the profibrogenic role of IL-23 on somatic alveolar type I (ATI) epithelial cells. Primary ATI cells were isolated from rats and cultured on plastic dishes for 1-3 wk. After prolonged culture (≥14 days) on rigid culture dishes, primary ATI cells gradually acquired a mesenchymal phenotype, identified by decreased expression of caveolin-1, and reorganization of F-actin cytoskeleton, indicating the initiation of EMT by matrix stiffness. To determine how IL-23 promotes EMT in vitro, transitioning ATI cells, cultured on a stiff substrate for ≥14 days were stimulated with IL-23. The EMT phenotype was significantly enhanced by IL-23, which upregulated α-smooth muscle actin (α-SMA), collagen I/III protein, and decreased caveolin-1. Furthermore, IL-23 significantly promoted cell invasion, as well as apoptotic resistance on transitioning ATI cells. Mechanistically, IL-23-induced EMT was mammalian target of rapamycin/ribosomal protein S6 (mTOR/S6) signaling dependent and reversible by rapamycin. Transcriptional sequencing analysis of human lung fibrosis biopsy tissue revealed key roles for IL-23 in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This result was further validated by significantly upregulated IL-23 expression at the mRNA level in RA-ILD lung sections. Notably, transitioning ATI epithelial cells were abundantly detected in RA-ILD tissue. Taken together, these data support a role for IL-23 in the pathogenesis of RA lung fibrosis by promoting EMT in alveolar epithelial cells through mTOR/S6 signaling.

Activation of PI3K/PKB/GSK-3ß signaling by sciadopitysin protects cardiomyocytes against high glucose-induced oxidative stress and apoptosis.

Diabetic cardiomyopathy (DCM), a diabetes complication, accounts for diabetes-associated morbidity, mortality, and heart failure. Biflavonoids have been demonstrated to possess extensive pharmacological properties, such as antidiabetic and antioxidant activities. Our study aimed to explore the effects of sciadopitysin, a type of biflavonoid, on DCM and the mechanism involved. An experimental cell model was established in AC16 cardiomyocytes by exposure to high glucose (HG). Cell injury was estimated by detecting cell viability and lactate dehydrogenase (LDH) release. Oxidative stress was determined by measuring malondialdehyde (MDA) level and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). Apoptosis was assessed by flow cytometry analysis, caspase-3/7 activity assay, and Western blot analysis of cytochrome C (Cyt C) expression. Alternation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB)/glycogen synthase kinase-3ß (GSK-3ß) pathway was detected by Western blot. Results showed that HG exposure reduced viability and increased LDH release in AC16 cells, which was abolished by sciadopitysin treatment. Sciadopitysin inhibited HG-induced oxidative stress, as evidenced by the reduced MDA content, and the increased activities of SOD, CAT, and GSH-Px. Sciadopitysin suppressed HG-induced apoptosis, an increase of caspase-3/7 activity, and Cyt C expression in AC16 cells. Mechanistically, sciadopitysin activated the PI3K/PKB/GSK-3ß pathway under HG stimulation in AC16 cells. Inhibition of PI3K/PKB/GSK-3ß pathway by LY294002 blocked the effects of sciadopitysin on HG-induced injury, oxidative stress, and apoptosis in AC16 cells. Summarily, sciadopitysin alleviated HG-caused oxidative stress and apoptosis in cardiomyocytes by activating the PI3K/PKB/GSK-3ß pathway.

Clarifying Recent Adaptive Diversification of the Chrysanthemum-Group on the Basis of an Updated Multilocus Phylogeny of Subtribe Artemisiinae (Asteraceae: Anthemideae).

Understanding the roles played by geography and ecology in driving species diversification and in the maintenance of species cohesion is the central objective of evolutionary and ecological studies. The multi-phased orogenesis of Qinghai-Tibetan Plateau (QTP) and global climate changes over late-Miocene has profoundly influenced the environments and evolution of organisms in this region and the vast areas of Asia. In this study, we investigate the lineage diversification of Chrysanthemum-group in subtribe Artemisiinae (tribe Anthemideae, Asteraceae) likely under the effects of climate changes during this period. Using DNA sequences of seven low-copy nuclear loci and nrITS and the coalescent analytical methods, a time-calibrated phylogeny of subtribe Artemisiinae was reconstructed with emphasis on Chrysanthemum-group. The monophyletic Chrysanthemum-group was well resolved into two major clades corresponding to Chrysanthemum and Ajania, two genera which can be well identified by capitulum morphology but have been intermingled in previous plastid and ITS trees. Within Chrysanthemum, a later divergence between Ch. indicum-complex and Ch. zawadskii-complex can be recognized. The time frames of these sequential divergences coincide with the late Cenozoic uplift of the Northern QTP and the concomitant climatic heterogeneity between eastern and inland Asia. Reconstruction of historical biogeography suggested the origin of Chrysanthemum-group in Central Asia, followed by eastward migration of Chrysanthemum and in situ diversification of Ajania. Within Chrysanthemum, Ch. indicum-complex and Ch. zawadskii-complex exhibited contemporary distributional division, the former in more southern and the latter in more northern regions. The geographic structure of the three lineages in Chrysanthemum-group have been associated with the niche differentiation, and environmental heterogenization in Asia interior.

Dysfunction of CYC2g is responsible for the evolutionary shift from radiate to disciform flowerheads in the Chrysanthemum group (Asteraceae: Anthemideae).

Evolutionary shifts among radiate, disciform and discoid flowerheads have occurred repeatedly in a number of major lineages across the Asteraceae phylogeny; such transitions may also appear within evolutionarily young groups. Although several studies have demonstrated that CYC2 genes partake in regulating floral morphogenesis in Asteraceae, the evolution of capitulum forms within a recently diverging lineage has remained poorly understood. Here, we study the molecular regulation of the shift from a radiate to a disciform capitulum within the Chrysanthemum group. This is a recently radiating group mainly comprising two genera, Chrysanthemum and Ajania, that are phylogenetically intermingled but distinct in flowerhead morphology: Chrysanthemum spp. with radiate capitula and Ajania spp. with disciform capitula. We found that the morphogenesis of zygomorphy in the marginal floret in Ajania was disrupted soon after floral primordium emergence; CYC2g, one of the CYC2 copies that was expressed prominently in the ray floret of Chrysanthemum was not expressed in flowerheads of Ajania. Weakening the expression of ClCYC2g in Chrysanthemum lavandulifolium led to the gradual transition of a ray flower toward the disc-like form. Molecular evolutionary analyses indicated that the disciform capitulum might have evolved only once, approximately 8 Mya, arising from dysfunction of the CYC2g orthologs. A 20-nt deletion, including a putative TATA-box of the Ajania-type CYC2g promoter, appeared to inhibit the expression of the gene. Considering the divergent habitats of Chrysanthemum and Ajania, we propose that the shift from radiate to disciform capitulum must have been related to changes in pollination strategies under selective pressure.

Downregulation of reelin predicts poor prognosis for glioma.

Aim: In the present study, we studied the relationship between RELN and prognosis in glioma. Materials & methods: Expression profiles and methylation data of RELN were obtained from bioinformatic datasets. Correlations between RELN and clinicopathological features and overall survival were respectively assessed using chi-square test and Kaplan-Meier analysis. Results:RELN was downregulated in glioma, and its downregulation correlated well with glioma malignancy and overall survival. Meanwhile, hypermethylation of RELN was significantly correlated with low RELN expression. Additionally, gene set enrichment analysis demonstrated that low expression of RELN correlated with many key cancer pathways, possibly highlighting the importance of RELN in carcinogenesis of brain. Conclusion:RELN may serve as a potential prognostic marker and promising target molecule for new therapy of glioma.

Early Detection and Prediction of Anthracycline-Induced Right Ventricular Cardiotoxicity by 3-Dimensional Echocardiography.

OBJECTIVES: The purpose of this study was to assess the associations between 3-dimensional echocardiography (3DE)-derived changes in right ventricular (RV) volumes and strains with subsequent RV cardiotoxicity in patients treated with anthracyclines. BACKGROUND: Although early detection and prediction of left ventricular (LV) dysfunction has been widely studied in patients receiving anthracyclines, little is known about the early changes in RV size and function in this population. METHODS: A total of 74 patients with diffuse large B-cell lymphoma who received 6 cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline or before chemotherapy (pre-chemotherapy) (T0); after 2 cycles (T1); after 4 cycles (T2); and at the end of 6 cycles of chemotherapy (T3). Right ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV), ejection fraction (RVEF), longitudinal free wall strain (RVLFS), and longitudinal septal strain (RVLSS) were quantified by 3DE. RV cardiotoxicity was defined as a relative reduction of >10% in 3D RVEF or a relative reduction of >5% to a value of <45%. Volume status was assessed by inferior vena cava diameter (IVCD) and the estimated right atrial pressure (RAP). RESULTS: Twenty-seven patients developed cardiotoxicity after 6 cycles of chemotherapy (T3). Compared to baseline, increases in 3D RVEDV (58.5 ± 7.7 ml vs. 64.2 ± 7.0 ml; p < 0.001) and RVESV (27.8 ± 4.2 ml vs. 31.3 ± 4.2 ml; p < 0.001) were observed by the end of the fourth cycle of chemotherapy (T2). 3D RVLFS (-27.3 ± 3.1% vs. -24.2 ± 2.6%; p < 0.001) was also decreased at T2 compared to baseline. Statistically significant declines in 3D RVLSS (-26.1 ± 2.5% vs. -22.9 ± 2.7%; p < 0.001) and RVEF (54.0 ± 2.8% vs. 49.8 ± 2.4%; p < 0.001) were only observed at T3. A relative decrease in RVLFS of >12.4% (sensitivity, 78.6%; specificity, 82.6%; area under the curve (AUC), 0.80; p ＜ 0.001); and a relative increase in RVESV of >13.2% (sensitivity, 71.4%; specificity, 71.7%; AUC, 0.76; p ï¼œ0.001) from baseline to T2 predicted subsequent RV cardiotoxicity at T3. IVCD and RAP did not change significantly over time. CONCLUSIONS: 3DE-derived measurements of RV strain and volume were associated with subsequent changes in RVEF. With further study, RVLFS and RVESV could potentially be used to predict subsequent declines in RVEF with anthracyclines.

Anthracycline induced inconsistent left ventricular segmental systolic function variation in patients with lymphoma detected by three-dimensional speckle tracking imaging.

Chemotherapy contained anthracycline inevitably cause declines of cardiac function. This study evaluated the deterioration of left ventricular segmental systolic function in patients with lymphoma received anthracycline chemotherapy detected by echocardiographic three dimensional speckle tracking imaging (3D-STI). Sixty patients with newly diagnosed diffuse large B-cell lymphoma who received R-CHOP chemotherapy were enrolled. Three dimensional left ventricular global longitudinal strain (3D-GLS), three dimensional left ventricular global circumferential strain (3D-GCS) and three dimensional left ventricular longitudinal strain of different left ventricular segments (3D-LS) were measured by 3D-STI at baseline, after the completion of two cycles and four cycles of the regimen respectively. Compared with baseline, 3D-GLS reduced significantly after four cycles of anthracycline therapy (P < 0.001), while 3D-GCS showed no significant variation during the whole procedure (all P > 0.05). For individual segment, LS of apical anterior and septal walls decreased significantly after two cycles of chemotherapy (all P < 0.05). After four cycles of treatment, 3D-LS of the mid-ventricular level (all P < 0.05), apical level (all P < 0.05) and apex (P < 0.05) worsened. Serum hs-cTnT levels increased after anthracycline exposure (P < 0.05) and Serum hs-cTnT levels were correlated with 3D-GLS at the end of four cycles (r = 0.12, P = 0.03). Mean values of involved segmental 3D-LS of two and four cycles were both correlated with serum hs-cTnT levels at the end of both two and four cycles (r = 0.368, P = 0.041; r = 0.79, p < 0.001). 3D-STI evaluation of the LV provides an understanding of the segmental impairment of LV wall and the possible process of LV impairment in lymphoma patients after anthracycline chemotherapy.

Early anthracycline-induced cardiotoxicity monitored by echocardiographic Doppler parameters combined with serum hs-cTnT.

PURPOSE: As growing numbers of long-term cancer survivors faced with the cardiac side effects by anthracycline treatment, it is necessary to explore the optimal monitoring method for the early detection of cardiac toxicity. METHODS: We conducted a retrospective analysis of 82 consecutive patients with diffuse large B-cell lymphoma treated with chemotherapy. Echocardiographic Doppler imaging-derived Tei index and mitral annular peak systolic velocity (Sm) measured by tissue Doppler imaging TDI, serum high-sensitivity cardiac troponin T (hs-cTnT) levels, and left ventricular ejection fraction (LVEF) by multigated radionuclide angiography (MUGA) were obtained before, after 2-4, and after 6-8 chemotherapy cycles. Cardiotoxicity was defined as a relative reduction of LVEF ≥10% from the baseline or LVEF <50% as measured by MUGA. RESULTS: Following chemotherapy, 24 (29.3%) patients developed detectable cardiac abnormality during the treatment. Five (6.1%) patients' cardiac function changed from normal baseline LVEF to <50% after the chemotherapy. Echocardiographic pulse wave Doppler Tei index (PW Tei index) (baseline 0.347 ± 0.115 vs 2-4 cycles 0.459 ± 0.161 vs 6-8 cycles 0.424 ± 0.139, P = .000) inversely correlated with systolic (P < .001) and diastolic dysfunction (P < .001). Serum hs-cTnT levels increased significantly following chemotherapy after 2-4 cycles of chemotherapy with anthracycline. The increase in PW Tei index of 0.095 [sensitivity, 69.2%; specificity, 64.5%; area under the curve (AUC) = 0.697; P = .005] and the Sm < 13.65 cm/s (sensitivity, 66.7%; specificity, 71%; AUC = 0.682; P = .009) combined with elevation of serum hs-cTnT level of 0.0075 ng/mL (sensitivity, 69.2%; specificity, 83.9%; AUC = 0.790; P < .001) after 2-4 chemotherapy cycles from the baseline values can reliably predict cardiotoxicity. CONCLUSIONS: We demonstrated that echocardiographic PW Doppler-derived Tei index, and TDI-derived Sm, combined with serum hs-cTnT level can be obtained in outpatient settings to monitor early cardiac toxicity induced by anthracycline therapy.

Assessment of biventricular systolic strain derived from the two-dimensional and three-dimensional speckle tracking echocardiography in lymphoma patients after anthracycline therapy.

The aim of this study was to investigate the usefulness of three-dimensional (3D) speckle tracking echocardiography (STE) for assessment of both left and right ventricular systolic function in patients with lymphoma after anthracycline chemotherapy, compared with two-dimensional (2D) STE. Totally eighty-nine patients undergoing anthracycline containing chemotherapy were studied. Echocardiographic assessment included 2D and 3D left ventricular (LV) global longitudinal strain (GLS), global circumferential strain (GCS) and right ventricular (RV) GLS. All the parameters were analyzed at baseline, after the completion of four cycles and at the end of the regimen respectively. The area under the receiver operating characteristic curve was calculated to determine the capability of various echocardiographic parameters to discriminate between before and after chemotherapy. Compared with those at baseline, the 3D GLS and GCS of LV and GLS of RV decreased significantly after four cycles of the therapy (all p < 0.01). At the end of the treatment, 2D GLS and GCS of LV deteriorated markedly (both p < 0.05). The area under the curve for GLS, GCS of LV and GLS of RV derived by 3D were 0.81, 0.66 and 0.78, respectively. The cutoff value with -20.4% of LV GLS by 3D had sensitivity of 81% and specificity of 66% for differentiating patients after therapy from baselines. The cutoff value with -21.9% of RV GLS by 3D had sensitivity of 71% and specificity of 74% fordifferentiating patients after therapy from baselines. The data from this study demonstrated that both 2D and 3D STE can be conducted to evaluate the slight myocardial damage for lymphoma patients after anthracycline chemotherapy. 3D STE could examine subclinical biventricular dysfunction in earlier point than 2D STE.

The early variation of left ventricular twisting function in patients with lymphoma received anthracycline therapy assessed by three-dimensional speckle tracking echocardiography.

BACKGROUND: Anthracycline-induced cardiotoxicity remains a significant and unresolved issue in patients receiving chemotherapy. The aim of this study was to evaluate left ventricular (LV) twisting function by three-dimensional speckle tracking echocardiography (3D-STE) in patients with lymphoma after anthracycline therapy. METHODS: One hundred and one patients with newly diagnosed diffuse large B-cell lymphoma who had planned to receive anthracycline chemotherapy were enrolled. LV apical rotation, basal rotation, twist, torsion, time to peak apical rotation and time to peak basal rotation were measured by 3D-STE at baseline, after the completion of two cycles and four cycles of the regimen, respectively. Apical-basal rotation delay was calculated as the difference between time to basal and time to apical rotation. RESULTS: The results showed that LV apical rotation, basal rotation, twist and torsion declined progressively during the whole procedure (baseline vs. two and four cycles of the regimen, apical rotation: 12.5 ± ± 4.5° vs. 8.8 ± 3.6° vs. 6.0 ± 3.2°; basal rotation: -7.7 ± 3.0° vs. -5.9 ± 2.6° vs. -4.4 ± 2.5°; twist: 20.0 ± 6.4° vs. 14.5 ± 5.1° vs. 9.8 ± 4.5°; torsion: 2.9 ± 0.9°/cm vs. 2.1 ± 0.9°/cm vs. 1.4 ± 0.7°/cm; all p < 0.01). Furthermore, apical-basal rotation delay increased significantly after two cycles as well as after four cycles of the regimen (38.3 ± 67.9 ms vs. 66.7 ± 73.9 ms vs. 92.6 ± 96.9 ms; p < 0.01). CONCLUSIONS: LV twisting function deteriorated in the early stage of anthracycline therapy in patients with lymphoma, which could be detected by 3D-STE sensitively.