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To investigate the predictive value of CT-derived fractional flow reserve (FFRPatients undergoing CABG with both pre- and post-operative coronary computed tomographic angiography (CCTA) were retrospectively included. Preoperative CCTA studies were used to evaluate anatomical and FFRA total of 270 anastomoses were identified in 88 enrolled patients. Forty-one anastomoses from 30 patients exhibited occlusion during a follow-up of 15.3 months after CABG. The occluded group had significantly increased prevalence of non-severe DS (58.5% vs. 40.2%; p = 0.023) and non-significant FFRFFR• FFR

To investigate the optimal measurement site of coronary-computed tomography angiography-derived fractional flow reserve (FFRCT) for the assessment of coronary artery disease (CAD) in the whole clinical routine practice.This retrospective multicenter study included 396 CAD patients who underwent coronary-computed tomography angiography, FFRCT, and invasive FFR. FFRCT was measured at 1 cm (FFRCT-1 cm), 2 cm (FFRCT-2 cm), 3 cm (FFRCT-3 cm), and 4 cm (FFRCT-4 cm) distal to coronary stenosis, respectively. FFRCT and invasive FFR ≤0.80 were defined as lesion-specific ischemia. The diagnostic performance of FFRCT to detect ischemia was obtained using invasive FFR as the reference standard. Reduced invasive coronary angiography rate and revascularization efficiency were calculated. After a median follow-up of 35 months in 267 patients for major adverse cardiovascular events (MACE), Cox hazard proportional models were performed with FFRCT values at each measurement site.For discriminating lesion-specific ischemia, the areas under the curve of FFRCT-1 cm (0.91) as well as FFRCT-2 cm (0.91) were higher than those of FFRCT-3 cm (0.89) and FFRCT-4 cm (0.88), respectively (all P0.05). The higher reduced invasive coronary angiography rate (81.6%) was found at FFRCT-1 cm than FFRCT-2 cm (81.6% vs. 62.6%, P0.05). Revascularization efficiency did not differ between FFRCT-1 cm and FFRCT-2 cm (80.8% vs. 65.5%, P=0.019). In 12.4% (33/267) MACE occurred and only values of FFRCT-2 cm were independently predictive of MACE (hazard ratio: 0.957 [95% CI: 0.925-0.989]; P=0.010).This study indicates FFRCT-2 cm is the optimal measurement site with superior diagnostic performance and independent prognostic role.

Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma (DLBCL). Using whole exome/genome sequencing, RNA-sequencing, and fluorescence in situ hybridization in 337 newly diagnosed DLBCL patients, we established a simplified 38-gene algorithm (termed ‘LymphPlex’) based on the information on mutations of 35 genes and rearrangements of three genes (BCL2, BCL6, and MYC), identifying seven distinct genetic subtypes: TP53Mut (TP53 mutations), MCD-like (MYD88, CD79B, PIM1, MPEG1, BTG1, TBL1XR1, PRDM1, IRF4 mutations), BN2-like (BCL6 fusion, NOTCH2, CD70, DTX1, BTG2, TNFAIP3, CCND3 mutations), N1-like (NOTCH1 mutations), EZB-like (BCL2 fusion, EZH2, TNFRSF14, KMT2D, B2M, FAS, CREBBP, ARID1A, EP300, CIITA, STAT6, GNA13 mutations, with or without MYC rearrangement), and ST2-like (SGK1, TET2, SOCS1, DDX3X, ZFP36L1, DUSP2, STAT3, IRF8 mutations). Extended validation of 1001 DLBCL patients revealed clinical relevance and biological signature of each genetic subtype. TP53Mut subtype showed poor prognosis, characterized by p53 signaling dysregulation, immune deficiency, and PI3K activation. MCD-like subtype was associated with poor prognosis, activated B-cell (ABC) origin, BCL2/MYC double-expression, and NF-κB activation. BN2-like subtype showed favorable outcome within ABC-DLBCL and featured with NF-κB activation. N1-like and EZB-like subtypes were predominated by ABC-DLBCL and germinal center B-cell (GCB)-DLBCL, respectively. EZB-like-MYC+ subtype was characterized by an immunosuppressive tumor microenvironment, while EZB-like-MYC- subtype by NOTCH activation. ST2-like subtype showed favorable outcome within GCB-DLBCL and featured with stromal-1 modulation. Genetic subtype-guided targeted agents achieved encouraging clinical response when combined with immunochemotherapy. Collectively, LymphPlex provided high efficacy and feasibility, representing a step forward to the mechanism-based targeted therapy in DLBCL.

Objective Logistic regression model combined with receiver operating characteristic curve(ROC) was used to construct a clinical differential score model between spotted fever (SF) and severe fever with thrombocytopenia syndrome (SFTS). To provide a reference for clinical preliminary identification. Methods Patients with SF and SFTS from May 2017 to may 2021 in Lu'an secondary hospitals and above were selected, and all patients were confirmed by laboratory. The basic data, epidemic history, clinical data and laboratory data of patients with the two diseases were collected for comparative analysis, logistic regression analysis was conducted to find out the independent influencing factors, and Logistic regression model and scoring system were established. At the same time, the Roc curve was drawn to determine the optimal cut-off value and the area under the ROC curve. Results Multifactorial logistic regression analysis showed that the presence of rash (OR=153.294,,95%CI:7.800-3012.492), elevated C-reactive protein (>10 mg/L) (OR=47.095,95%CI: 3.161-701.735), and normal platelets (>100×109/L ) (OR=37.727, 95% CI: 2.492-571.185) were risk factors for the development of spotted fever, and a score of 1 was assigned to each of these three factors, resulting in a total score of 3 for this scoring system. When the cutoff value was 1, the area under the ROC curve (AUC) of the modeling group was 0.985, the sensitivity was 90.7%, the specificity was 98.8%, the P value in the Hosmer-Lemeshow test was 0.881, and the Kappa value in the consistency test was 0.910. The AUC of validation group was 0.985, the sensitivity was 94.7%, the specificity was 97.1%, the P value of Hosmer-Lemeshow test was 0.977, and the Kappa value of consistency test was 0.918. Conclusion The differential scoring system constructed based on the presence of rash, elevated C-reactive protein, and normal platelets can provide a reference basis for the differentiation of SF from SFTS and has some application value.

Supplementary Table S1: The sequences of PCR primers

Supplementary Figure S3. Relative mRNA expression of activating and inhibitory markers. (A) Relative mRNA expression (mean {plus minus} SD) of activating markers in the complete remission (CR) and partial remission (PR) group. (B) Relative mRNA expression (mean {plus minus} SD) of inhibitory markers in the CR and PR group. Student's t-test, one-way ANOVA, Wilcoxon signed-rank test or Friedman test was used, as appropriate. SD: Standard Deviation, IQR: interquartile range.

Supplementary Table S2: Amount and potency of CAR T cells

Purpose:Anti-CD19 chimeric antigen receptor (CAR) T cells represent a novel immunotherapy and are highly effective in treating relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL). How tumor microenvironment influences clinical response to CAR T therapy remains of great interest.Patients and Methods:A phase I, first-in-human, dose-escalation study of anti-CD19 JWCAR029 was conducted in refractory B-NHL (NCT03355859) and 10 patients received CAR T cells at an escalating dose of 2.5 × 107(n = 3), 5 × 107(n = 4), and 1 × 108(n = 3) cells. Core needle biopsy was performed on tumor samples collected from diffuse large B-cell lymphoma patients on Day −6 (1 day before lymphodepletion) and on Day 11 after CAR T-cell infusion when adequate CAR T-cell expansion was detected.Results:The overall response rate was 100%, with 6 of 9 (66.7%) evaluable patients achieving complete remission. The most common adverse events of grade 3 or higher were neutropenia (10/10, 100%), anemia (3/10, 30%), thrombocytopenia (3/10, 30%), and hypofibrinogenemia (2/10, 20%). Grade 1 cytokine release syndrome occurred in all patients and grade 3 neurotoxicity in 1 patient. The average peak levels of peripheral blood CAR T cells and cytokines were similar in 3 different dose levels, but CAR T cells were significantly higher in patients achieved complete remission on Day 29. Meanwhile, RNA sequencing identified gene expression signatures differentially enriched in complete and partial remission patients. Increased tumor-associated macrophage infiltration was negatively associated with remission status.Conclusions:JWCAR029 was effective and safe in treating refractory B-NHL. The composition of the tumor microenvironment has a potential impact in CAR T therapy response.

Supplementary Figure S1. PET-CT and CT evaluation of the partial remission patients before CAR T treatment and on Day 29 after treatment.

Supplementary Figure S4. EGFR+ and Ki67+ expression in the complete remission and partial remission patients after CAR T treatment. Immunohistochemistry of CAR T cells (EGFR+, red) and Ki67+ (brown) in tumor samples of the complete remission (CR) and partial remission (PR) patients after CAR T treatment. The cells were counted from five randomly selected visions. Bar plots showing the comparison of absolute quantification of double EGFR+Ki67+ cells.

Supplementary Figure S2. Kinetics of peripheral blood CAR-T cells and serum biomarkers. (A) Bar plots showing the comparison of the peak value (mean {plus minus} SD) and the peak day (median {plus minus} IQR) of CAR T cells in DL1 (purple), DL2 (blue) and DL3 (red). (B) CAR-T cell count (mean {plus minus} SD) change over time from peripheral blood in the CR (green) and PR group (blue). (C) The concentration of serum biomarkers (mean {plus minus} SD) change over time in DL1 (purple), DL2 (blue) and DL3 (red). Student's t-test, one-way ANOVA, Wilcoxon signed-rank test or Friedman test was used, as appropriate. SD: Standard Deviation, IQR: interquartile range.

Supplementary Table S3: Adverse Events

BACKGROUND Although rectal prolapse is not a life-threatening condition, it can cause defecation disorders, anal incontinence, sensory abnormalities, and other problems that can seriously affect quality of life. AIM To study the efficacy of the modified Gant procedure for elderly women with internal rectal prolapse. METHODS Sixty-three elderly female patients with internal rectal prolapse underwent the modified Gant procedure. The preoperative and postoperative anal symptoms, Patient Assessment of Constipation Quality of Life (PAC-QOL), Wexner incontinence score, incontinence quality of life score, and complications (massive hemorrhage, infection, anorectal stenosis, and anorectal fistula) were compared. RESULTS The improvement rates of postoperative symptoms were defecation disorders (84.5%), anal distention (69.6%), defecation sensation (81.4%), frequent defecation (88.7%), and anal incontinence (42.9%) (P < 0.05). All dimensions and total scores of the PAC-QOL after the procedure were lower than those before the operation (P < 0.05). The postoperative anal incontinence score and Wexner score were significantly lower than those before the procedure (P < 0.05). The quality of life and total scores of postoperative anal incontinence were significantly higher than those before the procedure (P < 0.05). There were no serious complications and no deaths. CONCLUSION The modified Gant procedure has significant advantages in the treatment of elderly women with internal rectal prolapse.

Background Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear. Objective To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19. Methods This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan–Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes. Results The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years, P

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with variable clinical outcomes and prediction of prognosis remains important for long-term remission. We performed serial serum soluble interleukin-2 receptor (sIL-2R) measurement pretreatment and before each cycle of the treatment in 599 patients with de novo DLBCL. Genomic and transcriptomic features were analyzed by 223 DNA- and 227 RNA-sequencing, respectively. Applying the cut-off value to sIL-2R pretreatment and cycle 2 (C2) level, patients were classified into FINE subtype (pretreatment low level) with good prognosis, RES subtype (pretreatment high level and C2 low level) with intermediate prognosis, and RET subtype (pretreatment high level and C2 high level) with poor prognosis, independent of International Prognostic Index. In “others” genetic subtype, dynamic change of sIL-2R showed prognostic significance and genetic features. Compared with FINE subtype, RES subtype had increased ARID1A and MYD88 mutations, and RET subtype had increased KMT2D, LYN and SOCS1 mutations. RES and RET subtypes showed significant enrichment in oncogenic pathways, such as ERK, NF-κB, JAK-STAT, and immune-associated pathways. As for tumor microenvironment, RES subtype exhibited increased recruiting activity of CD8 + T, T helper 1, and natural killer cells, and RET subtype with increased recruiting activity of CD4 + T and regulatory T cells in silico. There was a positive correlation between transcripts of IL-2R and immune checkpoint expressions including PD-1 and CTLA-4. Our findings identified that dynamic change of sIL-2R, with this simple and easy detection method in peripheral blood, had long-term prognostic effect and specific relation to microenvironment alterations in DLBCL.

To investigate the utility of coronary CT angiography–derived fractional flow reserve (FFRCT) and plaque progression in patients undergoing serial coronary CT angiography for predicting major adverse cardiovascular events (MACE). This retrospective study evaluated patients suspected or known coronary artery disease who underwent serial coronary CT angiography examinations between January 2006 and December 2017 and followed up until June 2019. The primary endpoint was MACE, defined as acute coronary syndrome, rehospitalization due to progressive angina, percutaneous coronary intervention, or cardiac death. FFRCT and plaque parameters were analyzed on a per-vessel and per-patient basis. Univariable and multivariable COX regression analysis determined predictors of MACE. The prognostic value of FFRCT and plaque progression were assessed in nested models. Two hundred eighty-four patients (median age, 61 years (interquartile range, 54–70); 202 males) were evaluated. MACE was observed in 45 patients (15.8%, 45/284). By Cox multivariable regression modeling, vessel-specific FFRCT ≤ 0.80 was associated with a 2.4-fold increased risk of MACE (HR (95% CI): 2.4 (1.3–4.4); p = 0.005) and plaque progression was associated with a 9-fold increased risk of MACE (HR (95% CI): 9 (3.5–23); p < 0.001) after adjusting for clinical and imaging risk factors. FFRCT and plaque progression improved the prediction of events over coronary artery calcium (CAC) score and high-risk plaques (HRP) in the receiver operating characteristics analysis (area under the curve: 0.70 to 0.86; p = 0.002). Fractional flow reserve and plaque progression assessed by serial coronary CT angiography predicted the risk of future MACE. • Vessel-specific CT angiography–derived fractional flow reserve (FFR CT ) ≤ 0.80 and plaque progression improved the prediction of events over current risk factors. • Major adverse cardiovascular events (MACE) significantly increased with the presence of plaque progression at follow-up stratified by the FFR CT change group.

In December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in Wuhan, Hubei Province, China and spread across China and beyond. On February 12, 2020, WHO officially named the disease caused by the novel coronavirus as Coronavirus Disease 2019 (COVID-19). Since most COVID-19 infected patients were diagnosed with pneumonia and characteristic CT imaging patterns, radiological examinations have become vital in early diagnosis and assessment of disease course. To date, CT findings have been recommended as major evidence for clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the etiology, epidemiology, and clinical symptoms of COVID-19, while highlighting the role of chest CT in prevention and disease control. A full translation of this article in Chinese is available in the supplement. - 请见䃼充资料阅读文章中文版∘

Coronary computed tomographic angiography (CCTA) is an effective examination with high sensitivity to rule out obstructive coronary artery disease (CAD). It can provide anatomical information of coronary artery disease, such as the degree of stenosis, plaque characteristics, but has poor discriminatory power for hemodynamically significant lesions, which may lead to unnecessary referrals for invasive coronary angiography (ICA). Invasive fractional flow reserve (FFR) is generally considered as the gold standard for the functional evaluation of CAD. However, high cost and invasive characteristics of FFR limit its wide clinical application. Recently, non-invasive CT-derived fractional flow reserve (CT-FFR), a novel image post-processing technique combining the advantages of CCTA and FFR, allows us to obtain both anatomic and functional information of a coronary lesion. CT-FFR has been used in diagnosing and guiding clinical management of CAD patients. This review introduces the basic principles, key points of CT-FFR analysis, and current research progress of CT-FFR.

Background Histone methyltransferase KMT2D is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL) and has been identified as an important pathogenic factor and prognostic marker. However, the biological relevance of KMT2D mutations on tumor microenvironment remains to be determined.Methods KMT2D mutations were assessed by whole-genome/exome sequencing (WGS/WES) in 334 patients and by targeted sequencing in 427 patients with newly diagnosed DLBCL. Their correlation with clinical outcomes and immune cell characteristics were evaluated. Underlying molecular mechanisms on tumor microenvironment were investigated both in vitro and in vivo.Results Among all 761 DLBCL patients, somatic mutations in KMT2D were observed in 143 (18.79%) patients and significantly associated with advanced Ann Arbor stage and MYC expression ≥ 40%, as well as inferior progression-free survival and overall survival. In B-lymphoma cells, the mutation or knockdown of KMT2D inhibited methylation of lysine 4 on histone H3 (H3K4), downregulated FBXW7 expression, activated NOTCH signaling pathway and downstream MYC/TGF-β1, resulting in alterations of tumor-induced regulatory T cell trafficking. In B-lymphoma murine models established with subcutaneous injection of SU-DHL-4 cells, xenografted tumors bearing KMT2D mutation presented lower H3K4 methylation, higher regulatory T cell recruitment, thereby provoking rapid tumor growth compared with wild-type KMT2D via FBXW7-NOTCH-MYC/TGF-β1 axis. Conclusions Our work thus contributed to the better understanding of aberrant histone methylation on tumor microenvironment as an alternative mechanism of tumor progression in DLBCL.

Two recent reports in the New England Journal of Medicine highlight the successful application of novel targeted therapies to improve the clinical outcomes of diffuse large B-cell lymphoma (DLBCL). These findings encourage us to pursue further mechanism-based therapeutic uses to make DLBCL curable in the era of precision medicine.

The optimal treatment for older adults with diffuse large B-cell lymphoma (DLBCL) needs to be further explored due to patient comorbidities, standard immunochemotherapy intolerance, and unfavourable genetic features. We did a phase 2 trial of ibrutinib, rituximab, and lenalidomide (iR2) to evaluate the efficacy and safety in older adult patients with de novo DLBCL.In this phase 2, single-arm study, unfit or frail patients with de novo DLBCL aged 75 years or older were enrolled at Shanghai Ruijin Hospital, Shanghai, China. During the induction phase from cycle 1 to 6, 560 mg ibrutinib was given orally daily throughout each 21-day treatment cycle, 375 mg/mBetween May 15, 2019, and May 8, 2020, a total of 30 patients were enrolled. The end of induction complete response rate was 56·7% (95% CI 37·4-74·5), and overall response rate was 66·7% (95% CI 47·2-82·7). With a median follow-up of 27·6 months (IQR 23·9-29·6), the 2-year progression-free survival rate was 53·3% (95% CI 34·3-69·1) and the 2-year overall survival rate was 66·7% (95% CI 46·9-80·5). The main grade 3-4 haematological adverse events were neutropenia (seven patients [23%]), thrombocytopenia (three patients [10%]), and anaemia (two patients [7%]). The most common grade 3-4 non-haematological adverse event was pulmonary infection (seven patients [23%]). Atrial fibrillation was observed in three (10%) patients, including one grade 2 and two grade 3.A chemotherapy-free iR2 regimen is clinically effective and safe and warrants further investigation in phase 3 trials as first-line treatment in older adult patients with DLBCL.National Natural Science Foundation of China, Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support, Clinical Research Plan of Shanghai Hospital Development Center, and Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine.

Purpose: The purpose of the study was to investigate the diagnostic performance of instantaneous wave-free ratio (iFR) based on coronary computed tomography (CT) angiography (CCTA) (iFRCT) for a myocardial bridge (MB). Materials and Methods: One hundred and fourteen patients with 115 MBs from 9 Chinese medical centers were prospectively included in this study. All patients underwent CCTA and subsequent invasive coronary angiography with fractional flow reserve (FFR). iFRCTs were measured at 2–4 cm distal to the lesions. Diagnostic performance of iFRCT was assessed using Bland–Altman analysis with invasive FFR as the reference in the entire sample, as well as in subgroups based on MB depth and length. Results: iFRCT has 0.90 sensitivity (95% confidence interval: 0.75–0.97), 0.73 specificity (0.62–0.83), and 0.79 accuracy (0.70–0.86) in the overall analysis. None of the three measures (sensitivity, specificity, and accuracy) differed significantly between superficial (≤2 mm) and deep MB, short (≤30 mm) and long MB, or low ( 0.05 for all). However, positive predictive value was lower in the low stenosis (

MicroRNAs (miRNAs) are involved in lymphoma progression by regulating the tumor microenvironment. Serum miR130b is overexpressed in diffuse large B-cell lymphoma (DLBCL), inducing Th17 cell alterations. To further illustrate its biological significance and therapeutic rationale, miR130b was detected by quantitative real-time PCR in the serum samples of 532 newly diagnosed DLBCL patients. The mechanism of miR130b on lymphoma progression and the tumor microenvironment was investigated both in vitro and in vivo. Therapeutic targeting miR130b was also evaluated, including OX40 agonistic antibody and lipid nanoparticles (LNPs)-miR130b antagomir. The results showed that serum miR130b significantly correlated with tumor miR130b and serum interleukin-17, indicating lymphoma relapse and inferior survival of DLBCL patients. MiR130b overexpression altered tumor microenvironment signaling pathways and increased Th17 cell activity. As mechanism of action, miR130b downregulated tumor OX40L expression by directly targeting IFNAR1/p-STAT1 axis, recruiting Th17 cells via OX40/OX40L interaction, thereby promoting immunosuppressive function of Th17 cells. In co-culture systems of B-lymphoma cells with immune cells, miR130b inhibited lymphoma cell autophagy, which could be counteracted by OX40 agonistic antibody and LNPs-miR130b antagomir. In murine xenograft model established with subcutaneous injection of A20 cells, both OX40 agonistic antibody and LNPs-miR130b antagomir remarkably inhibited Th17 cells and retarded miR130b-overexpressing tumor growth. In conclusion, as an oncogenic biomarker of DLBCL, miR130b was related to lymphoma progression through modulating OX40/OX40L-mediated lymphoma cell interaction with Th17 cells, attributing to B-cell lymphoma sensitivity towards OX40 agonistic antibody. Targeting miR130b using LNPs-miR130b antagomir could also be a potential immunotherapeutic strategy in treating OX40-altered lymphoid malignancies.

To investigate the utility of coronary CT angiography-derived fractional flow reserve (FFRThis retrospective study evaluated patients suspected or known coronary artery disease who underwent serial coronary CT angiography examinations between January 2006 and December 2017 and followed up until June 2019. The primary endpoint was MACE, defined as acute coronary syndrome, rehospitalization due to progressive angina, percutaneous coronary intervention, or cardiac death. FFRTwo hundred eighty-four patients (median age, 61 years (interquartile range, 54-70); 202 males) were evaluated. MACE was observed in 45 patients (15.8%, 45/284). By Cox multivariable regression modeling, vessel-specific FFRFractional flow reserve and plaque progression assessed by serial coronary CT angiography predicted the risk of future MACE.• Vessel-specific CT angiography-derived fractional flow reserve (FFR

Background: The risk factors for adverse events of Coronavirus Disease-19 (COVID-19) have not been well described. We aimed to explore the predictive value of clinical, laboratory and CT imaging characteristics on admission for short-term outcomes of COVID-19 patients. Methods: This multicenter, retrospective, observation study enrolled 703 laboratory-confirmed COVID-19 patients admitted to 16 tertiary hospitals from 8 provinces in China between January 10, 2020 and March 13, 2020. Demographic, clinical, laboratory data, CT imaging findings on admission and clinical outcomes were collected and compared. The primary endpoint was in-hospital death, the secondary endpoints were composite clinical adverse outcomes including in-hospital death, admission to intensive care unit (ICU) and requiring invasive mechanical ventilation support (IMV). Multivariable Cox regression, Kaplan-Meier plots and log-rank test were used to explore risk factors related to in-hospital death and in-hospital adverse outcomes. Results: Of 703 patients, 55 (8%) developed adverse outcomes (including 33 deceased), 648 (92%) discharged without any adverse outcome. Multivariable regression analysis showed risk factors associated with in-hospital death included ≥ 2 comorbidities (hazard ratio [HR], 6.734; 95% CI; 3.239-14.003, p < 0.001), leukocytosis (HR, 9.639; 95% CI, 4.572-20.321, p < 0.001), lymphopenia (HR, 4.579; 95% CI, 1.334-15.715, p = 0.016) and CT severity score > 14 (HR, 2.915; 95% CI, 1.376-6.177, p = 0.005) on admission, while older age (HR, 2.231; 95% CI, 1.124-4.427, p = 0.022), ≥ 2 comorbidities (HR, 4.778; 95% CI; 2.451-9.315, p < 0.001), leukocytosis (HR, 6.349; 95% CI; 3.330-12.108, p < 0.001), lymphopenia (HR, 3.014; 95% CI; 1.356-6.697, p = 0.007) and CT severity score > 14 (HR, 1.946; 95% CI; 1.095-3.459, p = 0.023) were associated with increased odds of composite adverse outcomes. Conclusion: The risk factors of older age, multiple comorbidities, leukocytosis, lymphopenia and higher CT severity score could help clinicians identify patients with potential adverse events.

e19556 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Recently, based on in-depth genomic analysis, new taxonomies for DLBCL have been proposed. Genetic subtype MCD is predominantly enriched with B-cell receptor-dependent NF-κB activation and well responded to Bruton’s tyrosine kinase (BTK) inhibitors. Ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) proved the efficacy in patients with MCD DLBCL in PHOENIX study. Orelabrutinib is a novel BTK inhibitor with excellent target selectivity. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing regimens for the treatment of patients with MCD DLBCL in a real-world setting. Methods: Eligible patients with pathologically confirmed MCD DLBCL, regardless previous treatment, were included from 6 centers between January and December 2021. All patients received orelabrutinib-containing regimens and underwent at least one treatment response evaluation. Patients with known CNS lymphoma and primary mediastinal lymphoma were excluded. The primary endpoint was complete response rate (CRR) assessed by investigator using PET-CT per the 2014 Lugano Response Criteria for Non-Hodgkin Lymphoma. Safety was assessed by adverse events (AEs) referring to Common Terminology Criteria for AEs version 5.0. Results: Fourteen patients (10 males) were included. The median age was 66 (range 45-77) years, and 35.71% (5/14) documented ≥2 extranodal involved sites. Most patients had an Eastern Cooperative Oncology Group score of 0-1 (9/14, 64.29%), Ann Arbor Stage III-IV disease (11/14, 78.57%), elevated lactate dehydrogenase (9/14, 64.29%), and International Prognostic Index score ≥3 (8/14, 57.14%). All patients received orelabrutinib 150 mg once daily. Among them, 8 (57.14%) were treated with R-CHOP or rituximab plus etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) as first-line therapy, and 6 (42.86%) with rituximab plus ifosfamide, carboplatin and etoposide (R-ICE), R-CHOP or rituximab with lenalidomide as second-line therapy. The CRR for the first-line and second-line therapy were 75.00% and 66.67%, respectively. The most common AEs were hematologic (platelet count decrease, white blood count decrease or lymphocyte count decrease), and non-hematologic AE was infection (urinary or respiratory). Reported AEs were generally manageable and resolved soon after supportive treatment. AEs associated with off-target activities such as atrial fibrillation, diarrhea, and major hemorrhage were not reported. Conclusions: Orelabrutinib-containing regimens demonstrated encouraging efficacy and well-tolerated safety profile among patients with MCD DLBCL. A large-scale prospective clinical study is on registration, which would offer a new potential therapeutic option for patients with MCD DLBCL.

To investigate the effect of coronary calcification morphology and severity on the diagnostic performance of machine learning (ML)–based coronary CT angiography (CCTA)–derived fractional flow reserve (CT-FFR) with FFR as a reference standard. A total of 442 patients (61.2 ± 9.1 years, 70% men) with 544 vessels who underwent CCTA, ML-based CT-FFR, and invasive FFR from China multicenter CT-FFR study were enrolled. The effect of calcification arc, calcification remodeling index (CRI), and Agatston score (AS) on the diagnostic performance of CT-FFR was investigated. CT-FFR ≤ 0.80 and lumen reduction ≥ 50% determined by CCTA were identified as vessel-specific ischemia with invasive FFR as a reference standard. Compared with invasive FFR, ML-based CT-FFR yielded an overall sensitivity of 0.84, specificity of 0.94, and accuracy of 0.90 in a total of 344 calcification lesions. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of CT-FFR across different calcification arc, CRI, or AS levels. CT-FFR exhibited improved discrimination of ischemia compared with CCTA alone in lesions with mild-to-moderate calcification (AUC, 0.89 vs. 0.69, p < 0.001) and lesions with CRI ≥ 1 (AUC, 0.89 vs. 0.71, p < 0.001). The diagnostic accuracy and specificity of CT-FFR were higher than CCTA alone in patients and vessels with mid (100 to 299) or high (≥ 300) AS. Coronary calcification morphology and severity did not influence diagnostic performance of CT-FFR in ischemia detection, and CT-FFR showed marked improved discrimination of ischemia compared with CCTA alone in the setting of calcification. • CT-FFR provides superior diagnostic performance than CCTA alone regardless of coronary calcification. • No significant differences in the diagnostic performance of CT-FFR were observed in coronary arteries with different coronary calcification arcs and calcified remodeling indexes. • No significant differences in the diagnostic accuracy of CT-FFR were observed in coronary arteries with different coronary calcification score levels.

To investigate the effect of image quality of coronary CT angiography (CCTA) on the diagnostic performance of a machine learning–based CT-derived fractional flow reserve (FFRCT). This nationwide retrospective study enrolled participants from 10 individual centers across China. FFRCT analysis was performed in 570 vessels in 437 patients. Invasive FFR and FFRCT values ≤ 0.80 were considered ischemia-specific. Four-score subjective assessment based on image quality and objective measurement of vessel enhancement was performed on a per-vessel basis. The effects of body mass index (BMI), sex, heart rate, and coronary calcium score on the diagnostic performance of FFRCT were studied. Among 570 vessels, 216 were considered ischemia-specific by invasive FFR and 198 by FFRCT. Sensitivity and specificity of FFRCT for detecting lesion-specific ischemia were 0.82 and 0.93, respectively. Area under the curve (AUC) of high-quality images (0.93, n = 159) was found to be superior to low-quality images (0.80, n = 92, p = 0.02). Objective image quality and heart rate were also associated with diagnostic performance of FFRCT, whereas there was no statistical difference in diagnostic performance among different BMI, sex, and calcium score groups (all p > 0.05, Bonferroni correction). This retrospective multicenter study supported the FFRCT as a noninvasive test in evaluating lesion-specific ischemia. Subjective image quality, vessel enhancement, and heart rate affect the diagnostic performance of FFRCT. • FFR CT can be used to evaluate lesion-specific ischemia. • Poor image quality negatively affects the diagnostic performance of FFR CT . • CCTA with ≥ score 3, intracoronary enhancement degree of 300–400 HU, and heart rate below 70 bpm at scanning could be of great benefit to more accurate FFR CT analysis.

To investigate the effect of reader experience, calcification and image quality on the performance of deep learning (DL) powered coronary CT angiography (CCTA) in automatically detecting obstructive coronary artery disease (CAD) with invasive coronary angiography (ICA) as reference standard.A total of 165 patients (680 vessels and 1505 segments) were included in this study. Three sessions were performed in order: (1) The artificial intelligence (AI) software automatically processed CCTA images, stenosis degree and processing time were recorded for each case; (2) Six cardiovascular radiologists with different experiences (low/ intermediate/ high experience) independently performed image post-processing and interpretation of CCTA, (3) AI + human reading was performed. Luminal stenosis ≥50% was defined as obstructive CAD in ICA and CCTA. Diagnostic performances of AI, human reading and AI + human reading were evaluated and compared on a per-patient, per-vessel and per-segment basis with ICA as reference standard. The effects of calcification and image quality on the diagnostic performance were also studied.The average post-processing and interpretation times of AI was 2.3 ± 0.6 min per case, reduced by 76%, 72%, 69% compared with low/ intermediate/ high experience readers (all P 0.001), respectively. On a per-patient, per-vessel and per-segment basis, with ICA as reference method, the AI overall diagnostic sensitivity for detecting obstructive CAD were 90.5%, 81.4%, 72.9%, the specificity was 82.3%, 93.9%, 95.0%, with the corresponding areas under the curve (AUCs) of 0.90, 0.90, 0.87, respectively. Compared to human readers, the diagnostic performance of AI was higher than that of low experience readers (all P 0.001). The diagnostic performance of AI + human reading was higher than human reading alone, and AI + human readers' ability to correctly reclassify obstructive CAD was also improved, especially for low experience readers (Per-patient, the net reclassification improvement (NRI) = 0.085; per-vessel, NRI = 0.070; and per-segment, NRI = 0.068, all P 0.001). The diagnostic performance of AI was not significantly affected by calcification and image quality (all P 0.05).AI can substantially shorten the post-processing time, while AI + human reading model can significantly improve the diagnostic performance compared with human readers, especially for inexperienced readers, regardless of calcification severity and image quality.

Feature-based algorithms are widely used in automatic matching of multi-source images (e.g., LiDAR, optical, infrared, map, and SAR images). However, it remains a challenging task to find sufficient correct correspondences for image pairs in the presence of significant noise and nonlinear intensity differences. To solve this problem, this paper proposes a novel feature descriptor named the histogram of maximum phase congruency (HMPC), which is based on the structural properties of images. Then, a novel distance formula is designed by normalizing the phase orientation and histogram value to calculate the similarity. Furthermore, the precise bilateral matching principle and consistency-checking algorithm based on the phase orientation are used to perform matching between the corresponding point sets. Benefiting from combinatorial features, the proposed method can effectively capture the structural information of images and present robust matching performance for complex texture structures and noise images compared to that of the sole feature, and it has been tested with a variety of SAR, LiDAR, optical,and map datas. The results demonstrate that the proposed HMPC achieves a more robust and accurate matching performance than many state-of-the-art methods.

To investigate the prognostic significance of Follicular Lymphoma International Prognostic Index 2 (FLIPI2) in FL patients treated with rituximab maintenance.A tatol of 140 newly diagnosed FL patients who received Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy in our department were retrospectively analyzed from December 2002 to December 2014. Among 140 patients with FL 122 patients achieved response, from them 56 patients received R maintenance (RM) every 2 months for median 8 times (RM group) while the rest 66 patients did not receive further anti-lymphoma treatment (non-RM group).There was no statistical difference in age, sex, pathologic grading, staging, FLIPI or FLIPI2 between RM and non-RM groups. The 2-year progression-free survival (PFS) of RM and non-RM groups were 89.7% and 77.6% (P=0.043) while the 2-year overall survival were 100% and 98.6% (P=0.131). FLIPI2 is a significant prognostic model either in the total cohort, RM or non-RM groups (P0.001 all). In subgroup analysis, RM was able to decrease disease progression in low and intermediate-risk group of FLIPI2, while the 2-year PFS of RM and non-RM groups in high-risk group were similar (55.6% vs 46.9%)(P=0.920).FLIPI2 presents robust prognostic significance either in RM or OBS patients, the patients in FLIPI2 low and intermediate-risk group may benefite from RM, but the role of RM in high-risk patients should be further to investigate.

Modified by silane coupling agents APTES and MPTES, PAN fiber was provided with multi-chelating-group on it. Through the chelating effect, it can be directly used to eletroless silver plating without roughening, sensitization and activation. The molecule structure, morphology and thermal stability were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and therm-gravimetric (TG) analysis. In addition, electrical conductivity, and washing performance were also tested respectively. The results indicated that silver-coated PAN fiber based on APTES/MPTES modification had high conductivity with a compact and homogeneous silver layer, as well as good washing fastness performance.

A novel nitrate- and selenite reducing bacterium strain ZYKT was isolated from a rice paddy soil in Dehong, Yunnan, China. Strain ZYKT is a facultative anaerobe and grows in up to 150, 000 ppm O2. The comparative genomics analysis of strain ZYKT implies that it shares more orthologues with B. subtilis subsp. subtilis NCIB 3610T (ANIm values, 85.4–86.7%) than with B. azotoformans NBRC 15712T (ANIm values, 84.4–84.7%), although B. azotoformans NBRC 15712T (96.3% 16S rRNA gene sequence similarity) is the closest Bacillus species according to 16S rRNA gene comparison. The major cellular fatty acids of strain ZYKT were iso-C14:0 (17.8%), iso-C15:0 (17.8%), and C16:0 (32.0%). The polar lipid profile consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and an unidentified aminophospholipid. Based on physiological, biochemical and genotypic properties, the strain was considered to represent a novel species of the genus Bacillus, for which the name Bacillus oryziterrae sp. nov. is proposed. The type strain is ZYKT (=DSM 26460T =CGMCC 1.5179T). Strain ZYKT can reduce nitrate to nitrite and ammonium and possesses metabolic genes for nitrate reduction including nar, nap and nrf. Biogenic selenium nanoparticles of strain ZYKT show a narrow size distribution and agree with the gaussian distribution. These selenium nanoparticles show significant dose-dependent inhibition of the lung cancer cell line H157, which suggests potential for application in cancer therapy.

PurposeBuilding energy efficiency retrofit (BEER) not only provides excellent opportunities to reduce overall energy consumption of buildings in a city but also encourages environmental protection, the rational use of resources, and occupants' healthcare, which all contribute towards the sustainability of existing buildings. However, there is a lack of effective performance indicators to measure the sustainability of BEER projects. The aim of this paper is to formulate a list of key performance indicators (KPI) for the sustainability assessment of BEER in hotel buildings.Design/methodology/approachFirst, a literature review and in‐depth interviews with industry experts and academic researchers were conducted, which filtered the performance indicators for assessing sustainability. Second, a questionnaire survey was conducted to collect data from various groups of experts to analyze the significance of the selected performance indicators. Finally, a model based on fuzzy set theory was designed to identify the key performance indicators (KPIs) for the sustainability of BEER.FindingsEight KPIs were identified based on fuzzy set theory in this study. They are: quality performance, hotel energy management, cost performance, project profitability, energy consumption and resources saving, health and safety, stakeholder satisfaction, and innovation and improvement.Practical implicationsThe KPIs of sustainability of BEER identified for hotel buildings in China in this study can be useful reference for other similar research. However, with the different requirements for building types and building ownerships, the KPIs of sustainability of BEER for different buildings may be variable. The findings in this study may not be directly relevant to other types of building.Originality/valueKey performance indicators for the sustainability assessment of BEER in hotel buildings in China are identified and analyzed in this study. The KPIs can help decision‐makers to identify an optimal solution between alternatives, which presents the maximum sustainability performance.

To analyze the prognostic related factors of elderly patients with T/NK cell lymphoma.The clinical data of 62 T/NK cell lymphoma patients with age over 60 years and treated in Shanghai Jiaotong University Medical School affiliated Ruijin Hospital from 1999 to 2011 were collected and analyzed. Multivariate and univariate analysis of clinical data were performed using a COX regression model, including stage, performance status, extranodal infiltration, bone marrow involvement and LDH level. According to IPI or PIT systems, survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test.Using the IPI system, the CR rate of the low risk (IPI = 1, n = 7), intermediate-low risk (IPI = 2, n = 22), intermediate-high risk (IPI = 3, n = 13) and high risk (IPI = 4-5, n = 20) groups were 85.7%, 59.1%, 0% and 5.0%, with the median overall survival (OS) of 90.0, 63.9, 10.1 and 5.0 months, respectively. The patients with IPI = 1-2 had significant longer OS than those with IPI = 3-5 (P0.01), but no significant difference of OS was observed between IPI = 1 and IPI = 2 (P = 0.3647). As for the PIT system, CR rate of patients with PIT = 1 (n = 18), PIT = 2 (n = 18) and PIT = 3-4 (n = 26) were 61.1%, 44.4% and 3.8%, with the median survival of 90.0, 46.9 and 5.0 months, respectively. Significant difference of OS was found among groups of PIT = 1, PIT = 2 and PIT = 3-4 (P0.01). Therefore, PIT index was more effective than IPI in predicting prognosis of elderly T/NK cell lymphoma patients. The significant parameters of the univariate analysis were B symptom (P = 0.025), increased LDH level (P = 0.004), bone marrow infiltration (P = 0.023) and extranodal involvements (P = 0.033). Multivariate analysis showed that only increased LDH level (P = 0.007) and bone marrow involvement (P = 0.016) were the two independent prognostic factors of survival. These two factors were included in PIT index.PIT is more effective than IPI to predict outcomes of elderly T/NK lymphoma patients.

To analyze the prognostic factors in elderly patients with acute myeloid leukemia (AML).The clinical data of 211 AML patients with age 55 years or over and treated in Shanghai Jiaotong University Medical School affiliated Ruijin Hospital from 2007 to 2011 were collected and analyzed. Multivariate and univariate analysis of clinical data were performed using a Cox regression model and log-rank test, including age, subtype, performance status, white blood cell count, serum LDH and albumin level, and treatment strategy.Acute promyelocytic leukemia (APL) patients had longer survival than other subtypes. To rule out the impact of APL on the prognostic analysis, we conducted multivariate and univariate analysis excluding APL patients. The significant parameters of the univariate analysis were age (P = 0.003), achieving remission (P0.01), performance status (P0.01), organ dysfunction (P0.01), increased WBC counts (P = 0.022), increased LDH level (P = 0.006) and low albumin level (P0.01). Multivariate analysis showed that only failure of achieving remission (P0.01), poor performance status (ECOG 3-4) (P0.01) and increased WBC counts (P0.01) were independent prognostic factors. The patients aged 70 years or over had poor overall survival, and no significant difference of OS was observed among patients with age between 55 and 69 years. For patients aged 55 - 69 years received either DA/IA or CAG treatments had longer survival than those with palliative treatments. For those aged 70 years or over, only patients with CAG treatment had significantly longer survival than palliative treatment. For the patients with age less than 70 years and achieving complete remission after induction, intermediate-dose cytarabine consolidation might not improve survival.Elderly AML patients should be treated individually. The intermediate-dose cytarabine consolidation might not improve survival of elderly AML patients.