Indocyanine green-mediated fabrication of urchin-like hydroxyethyl starch nanocarriers for enhanced drug tumor EPR and deep penetration effects.

Effective EPR and tumor penetration are bottlenecks in current nanomedicine therapy. Comosol software was utilized to analyze the motion process of nanoparticles (NPs) with different shapes, from blood vessels to tumor tissue, to address this. By calculation, urchin-like NPs experienced higher drag forces than spherical NPs, facilitating their EPR and tumor penetration effects. Thus, urchin-like indocyanine green-loaded hydroxyethyl starch-cholesterol (ICG@HES-CH) NPs were prepared by leveraging the instability of ICG responding to near-infrared light (NIR). Upon NIR exposure, ICG degraded and partly disintegrated ICG@HES-CH NPs, and its morphology transformed from spherical to urchin-like. Vincristine (VC), as a model drug, was loaded in urchin-like ICG@HES-CH NPs for the treatment of lymphoma. A20 lymphoma cells and 3T3-A20 tumor organoids were employed to investigate the influence of shape on NPs' cellular uptake, penetration pathway, and cytotoxicity. It demonstrated that urchin-like ICG@HES-CH NPs mainly transport across the extracellular matrix through intercellular pathways, easily reaching the deep tumor sites and achieving higher cytotoxicity. In vivo VC distribution and anti-tumor results indicated that urchin-like NPs increased VC EPR and penetration ability, lowering VC neurotoxicity and superior anti-tumor effect. Therefore, urchin-like ICG@HES-CH NPs have great translational potential to be used as chemotherapeutic nanocarriers in anticancer therapy.

Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies.

BACKGROUND: Chimeric antigen receptor T (CAR-T) therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignancies, but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully understood. This study aims to explore the molecular determinants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical efficacy. METHODS: The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated killing. The in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR-T cells. In addition, the specific mechanisms influencing CAR-T cell-mediated cancer clearance were elucidated in mouse and cellular models. RESULTS: The CRISPR/Cas9-based knockout screening showed that the enrichment of autophagy-related genes (ATG3, BECN1, and RB1CC1) provided protection of cancer cells from CD19 CAR-T cell-mediated cytotoxicity. These findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of autophagy. Notably, higher expression of the three autophagy-related proteins in tumor samples was correlated with poorer responsiveness and worse survival in patients with relapsed/refractory B-cell lymphoma after CD19 CAR-T therapy. Bulk RNA sequencing analysis of bone marrow samples from B-cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR-T cell therapy. Pharmacological inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR-T cell-mediated killing in mouse models of both B-cell leukemia and lymphoma. Moreover, our study revealed that cancer-intrinsic autophagy mediates evasion of CAR-T cells via the TNF-α-TNFR1 axis-mediated apoptosis and STAT1/IRF1-induced chemokine signaling activation. CONCLUSIONS: These findings confirm that autophagy signaling in B-cell malignancies is essential for the effective cytotoxic function of CAR-T cells and thereby pave the way for the development of autophagy-targeting strategies to improve the clinical efficacy of CAR-T cell immunotherapy.

The Stress Phase Angle Measurement Using Spectral Domain Optical Coherence Tomography.

The stress phase angle (SPA), defined as the temporal phase angle between circumferential stress (CS) in the arterial wall and wall shear stress (WSS), is utilized to investigate the interactions between CS and WSS. SPA serves as an important parameter for the early diagnosis of cardiovascular disease. In this study, we proposed a novel method for measuring SPA using spectral domain optical coherence tomography (SD-OCT). The multi-M-mode scan strategy is adopted for interference spectrum acquisition. The phases of CS and WSS are extracted from the corresponding structural and flow velocity images of SD-OCT. The method is validated by measuring SPA in the outflow tract (OFT) of chick embryonic hearts and the common carotid artery of mice. To the best of our knowledge, this is the first time that OCT has been used for SPA measurement.

Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies.

Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1-2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1-2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7-14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.

Novel CD19-specific γ/δ TCR-T cells in relapsed or refractory diffuse large B-cell lymphoma.

BACKGROUND: T cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer. METHODS: We previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule. ET019003 cells were tested in preclinical studies followed by a phase 1 clinical trial. RESULTS: ET019003 cells produced less cytokines but retained comparable antitumor potency than ET190L1-CAR-T cells in vivo and in vitro. In the first-in-human trial, eight patients with relapsed or refractory DLBCL were treated. CRS of grade 1 was observed in three (37.5%) patients; ICANS of grade 3 was noted in one (12.5%) patient. Elevation of serum cytokines after ET019003 infusion was almost modest. With a median follow-up of 34 (range 6-38) months, seven (87.5%) patients attained clinical responses and six (75%) achieved complete responses (CR). OS, PFS and DOR at 3 years were 75.0%, 62.5%, and 71.4%, respectively. Notably, patient 1 with primary CNS lymphoma did not experience CRS or ICANS and got an ongoing CR for over 3 years after infusion, with detectable ET019003 cells in CSF. ET019003 showed striking in vivo expansion and persisted in 50% of patients at 12 months. Three patients received a second infusion, one for consolidation therapy after CR and two for salvage therapy after disease progression, but no response was observed. ET019003 expansion was striking in the first infusion, but poor in the second infusion. CONCLUSIONS: CD19-specific γ/δ TCR-T cells, ET019003, had a good safety profile and could induce rapid responses and durable CR in patients with relapsed or refractory DLBCL, even primary CNS lymphoma, presenting a novel and potent therapeutic option for these patients. TRIAL REGISTRATION: NCT04014894.

Elevating the potential of CAR-T cell therapy in solid tumors: exploiting biomaterials-based delivery techniques.

Chimeric antigen receptor (CAR) T cells exhibit promising progress in addressing hematologic malignancies. However, CAR-T therapy for solid tumors remains limited, with no FDA-approved CAR-T products available for clinical use at present. Primary reasons include insufficient infiltration, accumulation, tumor immunosuppression of the microenvironment, and related side effects. Single utilization of CAR-T cannot effectively overcome these unfavorable obstacles. A probable effective pathway to achieve a better CAR-T therapy effect would be to combine the benefits of biomaterials-based technology. In this article, comprehensive biomaterials strategies to break through these obstacles of CAR-T cell therapy at the tumor sites are summarized, encompassing the following aspects: 1) generating orthotopic CAR-T cells; 2) facilitating CAR-T cell trafficking; 3) stimulating CAR-T cell expansion and infiltration; 4) improving CAR-T cell activity and persistence; 5) reprogramming the immunosuppressive microenvironments. Additionally, future requirements for the development of this field, with a specific emphasis on promoting innovation and facilitating clinical translation, are thoroughly discussed.

Application of Anderson model to analyze the influencing factors of lung function test behavior in middle-aged and elderly people in China.

Introduction: Lung function tests are valuable in assessing respiratory health and disease, and the Healthy China Initiative clearly states that people over 40 years of age should have a lung function test once a year. To explore the influence of propensity factors, ability factors, and need factors on lung function detection behaviors of middle-aged and elderly Chinese, the following studies are conducted. Method: A questionnaire was designed using Anderson's model, and multi-stage sampling was used to conduct a nationwide questionnaire survey based on geographical subdivisions and population distribution. Frequency and percentages were used for descriptive statistical analysis of lung function testing among middle-aged and elderly people in China, and chi-square tests and binary logistic regression analyses were used to investigate the factors influencing lung function testing behavior among middle-aged and elderly people in China. Result: A total of 404 study participants were included in this study. Education level (relative to primary school and below, middle school and high school and secondary school OR = 2.652, P = 0.018; college and above OR = 4.566, P = 0.002), mode of health care affordability (relative to those who paid for the test, non-payers OR = 2.205, P = 0.004), dimensions of the European Five Dimensional Health Scale (mobility OR = 4.571, P = 0.006; pain or discomfort OR = 0.397, P = 0.003; anxiety or depression OR = 0.511, P = 0.028), and self-efficacy (medium group 0R = 0.294, P < 0.001; low group OR = 0.162, P = 0.003) had a significant impact on lung function testing behavior in our middle-aged and older adults. Conclusion: This study found that there is still room for improvement in the participation of middle-aged and elderly people in lung function testing. Among the propensity factors, the factor that affects the rate of lung function tests is the highest degree of education, which determines the degree of patients' attention to lung function tests. Among the need factors, the factors affecting the rate of lung function detection are the physical conditions of middle-aged and elderly people, and those with poor physical conditions need medical detection. Among the ability factors, the factor that affects the rate of lung function tests is the way of bearing medical expenses, and economic status is the key factor that determines whether patients can accept lung function tests.

Current Status and Influencing Factors of Eating Behavior in Residents at the Age of 18~60: A Cross-Sectional Study in China.

As eating behavior is important to health, this cross-sectional study was conducted to analyze the factors influencing the eating behavior related to overweight and obesity of Chinese residents aged 18~60 based on the Ecological Model of Health Behavior. The short-form of the Eating Behavior Scale (EBS-SF) was applied to evaluate eating behavior. The multivariable linear stepwise regression analysis was used to identify and analyze the influence factors, and the receiver operating characteristic curves analysis to validate the predictive capability of the EBS-SF score in differentiating overweight and obesity. A total of 8623 participants were enrolled. In the personal characteristics, male (ß = -0.03), older [36-45 years (ß = -0.06) or 46-60 years (ß = -0.07)], higher scores of Agreeableness (ß = -0.04), Conscientiousness (ß = -0.14) or Openness (ß = -0.03) contributed to healthy eating behavior. In the individual behaviors, those who smoked (ß = 0.04), drank alcohol (ß = 0.05), exercised frequently (ß = 0.07), had higher PHQ-9 scores (ß = 0.29) may have improper eating habits. As for the interpersonal networks, the residents who were married (ß = -0.04) behaved well when eating, while those who had offspring or siblings tended to have unhealthy eating behavior. At the community level, living in Western China (ß = -0.03), having a monthly household income of 6001-9000 yuan per capita (ß = -0.04), having no debt (ß = -0.02), being retired (ß = -0.03), or having lower PSSS scores (ß = -0.03) led to lower EBS-SF scores. And the EBS-SF score demonstrated a moderate-high accuracy in predicting overweight and obesity.

OCT based four-dimensional cardiac imaging of a living chick embryo using an impedance signal as a gating for post-acquisition synchronization.

Optical coherence tomography (OCT) is a non-invasive imaging modality with high spatial resolution suitable for early embryonic heart imaging. However, the most commonly used OCT systems cannot provide direct 4-D imaging due to acquisition speed limitations. We proposed a retrospective gating 4-D reconstruction method based on spectral domain OCT. A special circuit was designed to measure the impedance change of chick embryos in response to the heart beating. The impedance signal was acquired simultaneously with the OCT B-scan image sequence at several different locations along the heart. The impedance signal was used as a gating for 4-D reconstruction. The reconstruction algorithm includes cardiac period calculation, interpolation from multi-cardiac cycle image sequence into one cardiac cycle, and cardiac phase synchronization among the different locations of the heart. The synchronism of the impedance signal change with the heartbeat was verified. Using the proposed method, we reconstructed the cardiac outflow tract (OFT) of chick embryos at an early stage of development (Hamburger-Hamilton stage 18). We showed that the reconstructed 4-D images correctly captured the dynamics of the OFT wall motion.

A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma.

BACKGROUND: BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations. METHODS: We constructed a humanized bispecific BM38 CAR targeting BCMA and CD38 and tested the antimyeloma activity of BM38 CAR-Ts in vitro and in vivo. Twenty-three patients with RRMM received infusions of BM38 CAR-Ts in a phase I trial. RESULTS: BM38 CAR-Ts showed stronger in vitro cytotoxicity to heterogeneous MM cells than did T cells expressing an individual BCMA or CD38 CAR. BM38 CAR-Ts also exhibited potent antimyeloma activity in xenograft mouse models. In the phase I trial, cytokine release syndrome occurred in 20 patients (87%) and was mostly grade 1-2 (65%). Neurotoxicity was not observed. Hematologic toxicities were common, including neutropenia in 96% of the patients, leukopenia in 87%, anemia in 43% and thrombocytopenia in 61%. At a median follow-up of 9.0 months (range 0.5 to 18.5), 20 patients (87%) attained a clinical response and minimal residual disease-negativity (≤ 10-4 nucleated cells), with 12 (52%) achieving a stringent complete response. Extramedullary plasmacytoma was eliminated completely in 56% and partially in 33% and of 9 patients. The median progression-free survival was 17.2 months. Two relapsed patients maintained BCMA and CD38 expression on MM cells. Notably, BM38 CAR-Ts cells were detectable in 77.8% of evaluable patients at 9 months and 62.2% at 12 months. CONCLUSION: Bispecific BM38 CAR-Ts were feasible, safe and significantly effective in patient with RRMM. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1800018143.

An Smp43-Derived Short-Chain α-Helical Peptide Displays a Unique Sequence and Possesses Antimicrobial Activity against Both Gram-Positive and Gram-Negative Bacteria.

Scorpion venoms are rich resources of antimicrobial peptides (AMPs). While the short-chain noncysteine-containing AMPs have attracted much attention as templates for drug development, the antimicrobial potential of long-chain noncysteine-containing AMPs has been largely overlooked. Here, by using the online HeliQuest server, we designed and analyzed a series of 14-residue fragments of Smp43, a 43-residue long-chain noncysteine-containing AMP identified from the venom of Scorpio maurus palmatus. We found that Smp43(1-14) shows high antimicrobial activity against both Gram-positive and Gram-negative bacteria and is nontoxic to mammalian cells at the antimicrobial dosage. Sequence alignments showed that the designed Smp43(1-14) displays a unique primary structure that is different from other natural short-chain noncysteine-containing AMPs from scorpions, such as Uy17, Uy192 and IsCT. Moreover, the peptide Smp43(1-14) caused concentration-dependent fluorescence increases in the bacteria for all of the tested dyes, propidium iodide, SYTOXTM Green and DiSC3-5, suggesting that the peptide may kill the bacteria through the formation of pore structures in the plasma membrane. Taken together, our work sheds light on a new avenue for the design of novel short-chain noncysteine-containing AMPs and provides a good peptide template with a unique sequence for the development of novel drugs for use against bacterial infectious diseases.

PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report.

MYC/BCL2/BCL6 triple-hit lymphoma (THL) is an uncommon subset of high-grade B-cell lymphoma with aggressive clinical behavior and poor prognosis. TP53 mutation is an independently poor progonistic indicator in patients with THL, hence novel therapeutic strategies are needed for these patients. CD19-directed chimeric antigen receptor(CAR19)-T cell therapy has shown promising efficacy for relapsed/refractory diffuse large B cell lymphoma (RR DLBCL), but the majority of CAR19-T cell products to date have been manufactured using viral vectors. PiggyBac transposon system, with an inclination to memory T cells, offers a more convenient and economical alternative for transgene delivery. We herein report the first case of triple-hit RR DLBCL with TP53 mutation who was treated with piggyBac-generated CAR19-T cells and accompanied by grade 2 cytokine release syndrome. The patient obtained a complete remission (CR) in the 2nd month post-infusion and demanded maintenance therapy. Whether maintenance therapy is favorable and how to administrate it after CAR-T cell infusion remain controversial. Preclinical studies demonstrated that lenalidomide could enhance antitumor activity of CAR19-T cells. Therefore, we pioneered oral lenalidomide after CAR19-T therapy in the patient from the 4th month, and he discontinued after one cycle due to side effects. The patient has still kept sustained CR for over 24 months. Our case have firstly demonstrated the feasibility, preliminary safety and efficacy of piggyBac-produced CAR19-T cell therapy in triple-hit lymphoma. The innovative combination with lenalidomide warrants further investigation. Our findings shed new light on the possible solutions to improve short-term relapse after CAR19-T cell therapy in RR DLBCL. ChiCTR, number ChiCTR1800018111.

Effects of air discharge on surface charges and cell walls of Fusarium oxysporum.

Air discharge showed significant inhibition on mycelial growth and spore germination of Fusarium oxysporum, one of the main spoilage fungi in post-harvest lotus roots which is an important economic aquatic vegetable in China. However, the antimicrobial mechanism of air discharge is not clear yet. In the present study, the effects of air discharge on F. oxysporum separated from post-harvest rotten lotus roots were characterized by analyzing surface charges, cell wall permeability, and changes in chitin and chitosan including surface morphology, functional groups, degree of deacetylation, crystallinity, and C/N ratio. After air discharge treatments, alkaline phosphatase leak assay revealed that cell wall permeability of F. oxysporum was magnified. What's more, zeta potentials of F. oxysporum increased and negative charges on cell surfaces decreased. The ordered and compact molecular arrangements of chitin and chitosan in cell walls of F. oxysporum were reduced. The deacetylation degree of chitin and chitosan increased, and the C/N ratios of chitin and chitosan decreased. It was concluded from these results that air discharge caused the transformation in structures of chitin and chitosan, resulting in the exposure of positively charged amino groups and decrease of negative charges on cell surfaces which brought damage to the structure and function of F. oxysporum's cell walls.

Two new cationic α-helical peptides identified from the venom gland of Liocheles australasiae possess antimicrobial activity against methicillin-resistant staphylococci.

Methicillin-resistant staphylococci have become growing threats to human health, and novel antimicrobials are urgently needed. Natural antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics. Here, two novel cationic α-helical antimicrobial peptides, Lausporin-1 and Lausporin-2, were identified from the venom gland of the scorpion L. australasiae through a cDNA library screening strategy. Biochemical analyses demonstrated that Lausporin-1 and Lausporin-2 are cationic α-helical amphipathic molecules. Antimicrobial assays demonstrated that the two peptides possess antibacterial activities against several species of antibiotic-resistant staphylococci. Importantly, they are active against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus capitis, with the minimum inhibitory concentrations ranging from 2.5 to 10 µg/ml. Moreover, both peptides can induce dose-dependent plasma membrane disruptions of the bacteria. In short, our work expands the knowledge of the scorpion L. australasiae venom-derived AMPs and sheds light on the potential of Lausporin-1 and Lausporin-2 in the development of novel drugs against methicillin-resistant staphylococci.

Effects of treprostinil on pulmonary arterial hypertension during surgery for congenital heart disease complicated with severe pulmonary arterial hypertension.

BACKGROUND: The aim of this study is to evaluate the effects of treprostinil injection on the control of pulmonary blood pressure in children with congenital heart disease (CHD) complicated by severe pulmonary arterial hypertension (PAH). METHODS: Eighty children with CHD complicated by severe pulmonary arterial hypertension admitted to our hospital from January 2015 to June 2018 were selected and randomly divided into a control group (N.=40) and a treatment group (N.=40). Based on standard treatment, the treatment group was intravenously infused with 8-12 ng/kg·min treprostinil, while the control group received the same dose of normal saline. Hemodynamic parameters such as BP, AP, P and SpO2% were monitored before anesthesia induction (T0), before cardiopulmonary bypass (T1), 1 h after cardiopulmonary bypass (T2) and at the end of cardiopulmonary bypass (T3). Pulmonary arterial pressure parameters (PASP, PADP and PAMP) were measured at T1, T2 and T3 by transesophageal echocardiography. RESULTS: For the treatment group, the HR values at T2 and T3 were lower than that at T0 (P<0.05). For the control group, HR at T3 was lower than that at T0 (P<0.05). HR at T3 of the treatment group was lower than that of the control group (P<0.05). SpO2 of the treatment group was higher than that of the control group at T3 (P<0.05). At T2 and T3, PASP, PADP and PAMP of both groups were lower than those before surgery (P<0.05), and the values of the treatment group were lower than those of the control group (P<0.05). CONCLUSIONS: Treprostinil can improve cardiac function and reduce pulmonary circulation resistance in PAH children.

Consolidative allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: who? When? Why?

Although anti-CD19 chimeric antigen receptor (CAR) T-cell therapy shows good efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), it fails to improve long-term leukemia-free survival (LFS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR T-cell therapy has emerged as a promising strategy to prolong LFS. Nevertheless, which patients are likely to benefit from consolidative allo-HSCT, as well as the optimal therapeutic window, remain to be explored. Recent clinical data indicate that patients with complex karyotypes, adverse genes, and high pre-infusion minimal residual disease (MRD) by flow cytometry in the bone marrow, were at high risk of relapse after CAR T-cell therapy. High pre-lymphodepletion lactate dehydrogenase, low pre-lymphodepletion platelet count, absence of fludarabine in lymphodepletion, persistent leukemic sequence by high throughput sequencing in bone marrow after CAR T-cell infusion, and early loss of CAR T cells have also been linked to relapse after CAR T-cell therapy. In patients having these risk factors, consolidative allo-HSCT after CAR T-cell therapy may prolong LFS. Allo-HSCT provides optimal clinical benefit in patients with MRD-negative complete remission, typically within three months after CAR T-cell therapy. Herein, we summarize the clinical data on consolidative allo-HSCT after anti-CD19 CAR T-cell therapy, as well as the potential factors associated with allo-HSCT benefit. We also discuss the optimal therapeutic window and regimen of consolidative allo-HSCT. Finally, and most importantly, we provide recommendations for the assessment and management of r/r B-ALL patients undergoing anti-CD19 CAR T-cell therapy.

Diagnostic values of shear wave elastography and strain elastography for breast lesions

ABSTRACT Background: Strain elastography (SE) and shear wave elastography (SWE) have high diagnostic yield for breast lesions, but the optimal parameters remain elusive. Aim: To evaluate the diagnostic yield of SWE and SE for breast lesions by multivariate logistic regression analysis. Material and Methods: A total of 132 patients with 164 breast tumors were enrolled. Breast lesions were classified with the breast imaging reporting and data system (BI-RADS). Maximum (Emax), mean (Emean) and standard deviation (Esd) of elastic modulus, lesion/fat elasticity ratio and elastographic classification were obtained by SWE. Strain ratio (SR) and elastographic score were obtained by SE. A multivariate logistic regression analysis was performed. The diagnostic efficiencies of BI-RADS classification, SWE, SE and their combination were compared plotting ROC curves. Results: There were 110 benign and 54 malignant lesions which had significantly different SWE and SE parameters. The parameters included in the logistic regression were Esd and elastographic classification obtained by SWE and the elastographic score obtained by SE. When combining SWE with SE, Esd, SR and SWE classification were included in the equation. The areas under ROC curves for BI-RADS classification, SWE, SE and their combination were 0.75, 0.88, 0.79 and 0.89, respectively. Conclusions: The diagnostic value of SWE in combination with SE for breast lesions exceeded that of SE or SWE alone. Esd showed a good diagnostic yield when SWE was used alone or combined with SE.

Antecedentes: La elastografía de deformación (SE) y de onda cortante (SWE) son útiles para el diagnóstico de lesiones mamarias, pero falta definir los parámetros óptimos. Objetivo: Evaluar el valor diagnóstico de SE y SWE en lesiones mamarias usando una regresión logística multivariable. Material y Métodos: Ciento treinta y dos pacientes con 164 tumores mamarios fueron evaluados, los que se clasificaron usando el sistema BI-RADS (breast imaging reporting and data system). El módulo elástico máximo, promedio y su desviación estándar (Esd), la razón entre la elasticidad de la lesión y de la grasa y la clasificación elastográfica se obtuvieron con SWE. La razón de deformación (SR) y el puntaje elastográfico se obtuvieron con SE. Se efectuó una regresión logística y las eficiencias diagnósticas de la clasificación BI-RADS, SWE and SE y su combinación se compararon usando curvas ROC (receiver operating characteristic curves). Resultados: Ciento diez lesiones fueron benignas y 54 malignas. Estas tenían parámetros SWE y SE significativamente diferentes. En la ecuación de regresión logística, se incluyeron la clasificación elastográfica y el Esd obtenidos por SWE y el puntaje elastográfico obtenido por SE. Cuando se combinó SWE y SE, se incluyeron en la ecuación el Esd, SR y la clasificación por SWE. Las áreas bajo la curva ROC para la clasificación BI-RADS, SWE y SE y la combinación de ambas fueron 0.75, 0.88, 079 y 0.89 respectivamente. Conclusiones: La combinación de SWE y SE tuvo un mejor rendimiento diagnóstico para lesiones mamarias que cada parámetro por separado. Esd tuvo un buen rendimiento diagnóstico cuando se utilizó SWE sola o combinada con SE.

Characterization of Immune Dysfunction and Identification of Prognostic Immune-Related Risk Factors in Acute Myeloid Leukemia.

PURPOSE: This study aims to provide comprehensive insights into longitudinal immune landscape in acute myeloid leukemia (AML) development and treatment, which may contribute to predict prognosis and guide clinical decisions. EXPERIMENTAL DESIGN: Periphery blood samples from 79 patients with AML (at diagnosis or/and after chemotherapy or at relapse) and 24 healthy controls were prospectively collected. We performed phenotypic and functional analysis of various lymphocytes through multiparametric flow cytometry and investigated prognostic immune-related risk factors. RESULTS: Immune defects in AML were reflected in T and natural killer (NK) cells, whereas B-cell function remained unaffected. Both CD8+ T and CD4+ T cells exhibited features of senescence and exhaustion at diagnosis. NK dysfunction was supported by excessive maturation and downregulation of NKG2D and NKP30. Diseased γδ T cells demonstrated a highly activated or even exhausted state through PD-1 upregulation and NKG2D downregulation. Effective therapeutic response following chemotherapy correlated with T and NK function restoration. Refractory and relapsed patients demonstrated even worse immune impairments, and selective immune signatures apparently correlated clinical outcomes and survival. PD-1 expression in CD8+ T cells was independently predictive of poor overall survival and event-free survival. CONCLUSIONS: T-cell senescence and exhaustion, together with impaired NK and γδ T-cell function, are dominant aspects involved in immune dysfunction in AML. Noninvasive immune testing of blood samples could be applied to predict therapeutic reactivity, high risk for relapse, and unfavorable prognosis.

Diagnostic values of shear wave elastography and strain elastography for breast lesions.

BACKGROUND: Strain elastography (SE) and shear wave elastography (SWE) have high diagnostic yield for breast lesions, but the optimal parameters remain elusive. AIM: To evaluate the diagnostic yield of SWE and SE for breast lesions by multivariate logistic regression analysis. MATERIAL AND METHODS: A total of 132 patients with 164 breast tumors were enrolled. Breast lesions were classified with the breast imaging reporting and data system (BI-RADS). Maximum (Emax), mean (Emean) and standard deviation (Esd) of elastic modulus, lesion/fat elasticity ratio and elastographic classification were obtained by SWE. Strain ratio (SR) and elastographic score were obtained by SE. A multivariate logistic regression analysis was performed. The diagnostic efficiencies of BI-RADS classification, SWE, SE and their combination were compared plotting ROC curves. RESULTS: There were 110 benign and 54 malignant lesions which had significantly different SWE and SE parameters. The parameters included in the logistic regression were Esd and elastographic classification obtained by SWE and the elastographic score obtained by SE. When combining SWE with SE, Esd, SR and SWE classification were included in the equation. The areas under ROC curves for BI-RADS classification, SWE, SE and their combination were 0.75, 0.88, 0.79 and 0.89, respectively. CONCLUSIONS: The diagnostic value of SWE in combination with SE for breast lesions exceeded that of SE or SWE alone. Esd showed a good diagnostic yield when SWE was used alone or combined with SE.