Clinical and radiomics integrated nomogram for preoperative prediction of tumor-infiltrating lymphocytes in patients with triple-negative breast cancer.

Objectives: The present study aimed to develop a radiomics nomogram based on conventional ultrasound (CUS) to preoperatively distinguish high tumor-infiltrating lymphocytes (TILs) and low TILs in triple-negative breast cancer (TNBC) patients. Methods: In the present study, 145 TNBC patients were retrospectively included. Pathological evaluation of TILs in the hematoxylin and eosin sections was set as the gold standard. The patients were randomly allocated into training dataset and validation dataset with a ratio of 7:3. Clinical features (age and CUS features) and radiomics features were collected. Then, the Rad-score model was constructed after the radiomics feature selection. The clinical features model and clinical features plus Rad-score (Clin+RS) model were built using logistic regression analysis. Furthermore, the performance of the models was evaluated by analyzing the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Univariate analysis and LASSO regression were employed to identify a subset of 25 radiomics features from a pool of 837 radiomics features, followed by the calculation of Rad-score. The Clin+RS integrated model, which combined posterior echo and Rad-score, demonstrated better predictive performance compared to both the Rad-score model and clinical model, achieving AUC values of 0.848 in the training dataset and 0.847 in the validation dataset. Conclusion: The Clin+RS integrated model, incorporating posterior echo and Rad-score, demonstrated an acceptable preoperative evaluation of the TIL level. The Clin+RS integrated nomogram holds tremendous potential for preoperative individualized prediction of the TIL level in TNBC.

Radiofrequency ablation for papillary thyroid microcarcinoma close to the thyroid capsule versus far from the thyroid capsule: a retrospective study.

INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) for the management of papillary thyroid microcarcinoma (PTMC) close to the thyroid capsule. MATERIAL AND METHODS: This was a retrospective study of 202 patients with PTMC who underwent RFA close to the thyroid capsule and 80 patients with PTMC who underwent RFA far from the thyroid capsule between June 2015 and December 2022. The follow-up time after RFA, change in size of tumour, location, thyroid function, the rates of PTMC disappearance, and complications were evaluated. RESULTS: A total of 202 patients with PTMC close to the thyroid capsule and 80 patients with PTMC far from the thyroid capsule successfully treated with RFA were studied. The thyroid function including free triiodothyronine (fT3), free thyroxine (fT4), triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) showed no changes after RFA for one months in both groups. The tumour size was increased at 1, 3, and 6 months after RFA compared with pre-operative RFA in both groups. The tumour size was decreased at 12 and 24 months after RFA compared with pre-operative RFA both in both group. Seventy-nine PTMC close to the thyroid capsule and 30 PTMC far from the thyroid capsule completely disappeared as assessed by ultrasound examination. Eighty-four PTMC patients close to the thyroid capsule and 34 PTMC patients far from the thyroid capsule had minor complications after RFA treatment. The complication rates between the 2 groups were similar. CONCLUSION: Ultrasound-guided RFA seems to be an effective and safe method for patients with PTMC close to the thyroid capsule.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

Enhanced macromolecular substance extravasation through the blood-brain barrier via acoustic bubble-cell interactions.

The blood-brain barrier (BBB) maintains brain homeostasis, regulates influx and efflux transport, and provides protection to the brain tissue. Ultrasound (US) and microbubble (MB)-mediated blood-brain barrier opening is an effective and safe technique for drug delivery in-vitro and in-vivo. However, the exact mechanism underlying this technique is still not fully elucidated. The aim of the study is to explore the contribution of transcytosis in the BBB transient opening using an in-vitro model of BBB. Utilizing a diverse set of techniques, including Ca2+ imaging, electron microscopy, and electrophysiological recordings, our results showed that the combined use of US and MBs triggers membrane deformation within the endothelial cell membrane, a phenomenon primarily observed in the US + MBs group. This deformation facilitates the vesicles transportation of 500 kDa fluorescent Dextran via dynamin-/caveolae-/clathrin- mediated transcytosis pathway. Simultaneously, we observed increase of cytosolic Ca2+ concentration, which is related with increased permeability of the 500 kDa fluorescent Dextran in-vitro. This was found to be associated with the Ca2+-protein kinase C (PKC) signaling pathway. The insights provided by the acoustically-mediated interaction between the microbubbles and the cells delineate potential mechanisms for macromolecular substance permeability.

Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects.

BACKGROUND: Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers. RESULTS: To address these problems, a radically different strategy is proposed that can leave the off-targeted drugs inactive but activate the tumor-distributed drugs for cancer-targeting therapy in a tumor microenvironment-independent manner. The feasibility and effectiveness of this strategy is demonstrated by developing an ultrasound (US)-activated prodrug-loaded liposome (CPBSN38L) comprising the sonosensitizer chlorin e6 (Ce6)-modified lipids and the prodrug of pinacol boronic ester-conjugated SN38 (PBSN38). Once CPBSN38L is accumulated in the tumor and internalized into the cancer cells, under US irradiation, the sonosensitizer Ce6 rapidly induces extensive production of intracellular reactive oxygen species (ROS), thereby initiating a cascade amplified ROS-responsive activation of PBSN38 to release the active SN38 for inducing cell apoptosis. If some of the injected CPBSN38L is distributed into normal tissues, the inactive PBSN38 exerts no pharmacological activity on normal cells. CPBSN38L exhibited strong anticancer activity in multiple murine tumor models of colon adenocarcinoma and hepatocellular carcinoma with no chemotherapy-induced side effects, compared with the standard first-line anticancer drugs irinotecan and topotecan. CONCLUSIONS: This study established a side-effect-evitable, universal, and feasible strategy for cancer-targeting therapy.

Radiomics-based Machine Learning to Predict the Recurrence of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: Recurrence of hepatocellular carcinoma (HCC) is a major concern in its management. Accurately predicting the risk of recurrence is crucial for determining appropriate treatment strategies and improving patient outcomes. A certain amount of radiomics models for HCC recurrence prediction have been proposed. This study aimed to assess the role of radiomics models in the prediction of HCC recurrence and to evaluate their methodological quality. MATERIALS AND METHODS: Databases Cochrane Library, Web of Science, PubMed, and Embase were searched until July 11, 2023 for studies eligible for the meta-analysis. Their methodological quality was evaluated using the Radiomics Quality Score (RQS). The predictive ability of the radiomics model, clinical model, and the combined model integrating the clinical characteristics with radiomics signatures was measured using the concordance index (C-index), sensitivity, and specificity. Radiomics models in included studies were compared based on different imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound/sonography (US), contrast-enhanced ultrasound (CEUS). RESULTS: A total of 49 studies were included. On the validation cohort, radiomics model performed better (CT: C-index = 0.747, 95% CI: 0.70-0.79; MRI: C-index = 0.788, 95% CI: 0.75-0.83; CEUS: C-index = 0.763, 95% CI: 0.60-0.93) compared to the clinical model (C-index = 0.671, 95% CI: 0.65-0.70), except for ultrasound-based models (C-index = 0.560, 95% CI: 0.53-0.59). The combined model outperformed other models (CT: C-index = 0.790, 95% CI: 0.76-0.82; MRI: C-index = 0.826, 95% CI: 0.79-0.86; US: C-index = 0.760, 95% CI: 0.65-0.87), except for CEUS-based combined models (C-index = 0.707, 95% CI: 0.44-0.97). CONCLUSION: Radiomics holds the potential to predict HCC recurrence and demonstrates enhanced predictive value across various imaging modalities when integrated with clinical features. Nevertheless, further studies are needed to optimize the radiomics approach and validate the results in larger, multi-center cohorts.

Combination of HIFU with sulfur hexafluoride microbubbles in the treatment of solitary uterine fibroids: a systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy and safety of sulfur hexafluoride microbubbles on ultrasound-guided high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. METHODS: Studies that compared HIFU-microbubble combination with HIFU-only in patients with uterine fibroids were searched from inception to April 2022. The standardized mean difference (SMD) or relative risk (RR) with 95% confidence interval (CI) for different outcome parameters was calculated. RESULTS: Seven studies were included, with a total of 901 patients (519 in the combination group and 382 in the HIFU-only group). The energy consumption for treating 1 cm3 of the lesion in the combination group was less than that in the HIFU-only group [SMD = - 2.19, 95%CI (- 3.81, - 0.57), p = 0.008]. The use of microbubbles was associated with shortening the duration of the treatment and sonication [SMD = - 2.60, 95%CI (- 4.09, - 1.10), p = 0.0007; SMD = - 2.11, 95%CI (- 3.30, - 0.92), p = 0.0005]. The rates of significant greyscale changes during HIFU were greater in the combination group, as well as the increase of non-perfused volume ratio [RR = 1.26, 95%CI (1.04, 1.54), p = 0.02; SMD = 0.32, 95%CI (0.03, 0.61), p = 0.03]. The average sonication durations to reach significant greyscale changes and for ablating 1 cm3 of the fibroid lesion were shorter in the combination group [SMD = - 1.24, 95%CI (- 2.02, - 0.45), p = 0.002; SMD = - 0.22, 95%CI (- 0.42, - 0.02), p = 0.03]. The two groups had similar post-HIFU adverse effects, while the combination group had fewer intraprocedural adverse events like abdominal pain, sacrum pain, and leg pain. CONCLUSIONS: Sulfur hexafluoride microbubbles can be safely used to enhance and accelerate the ablation effects of HIFU in the treatment of uterine fibroids. CLINICAL RELEVANCE STATEMENT: The combination of HIFU with sulfur hexafluoride microbubbles offers a promising non-invasive treatment option for patients with uterine fibroids. KEY POINTS: • Sulfur hexafluoride microbubbles combined with ultrasound-guided high-intensity focused ultrasound (USgHIFU) has potential advantages in the treatment of uterine fibroids. • Sulfur hexafluoride microbubbles not only enhance the effects of USgHIFU treatment for uterine fibroids but also shorten its duration. • Sulfur hexafluoride microbubbles do not increase the incidence of USgHIFU-related adverse events in the treatment of uterine fibroids.

Important parameters should be paid attention in PTMC radiofrequency ablation.

In order to provide clinical references for the RFA procedure and to study the pivotal factors affecting the recovery time of radiofrequency ablation (RFA) in patients with papillary thyroid microcarcinoma (PTMC), 176 patients with low-risk intrathyroidal PTMC were included in this research. We randomly divided the whole cohort into training and test groups at a ratio of 7:3. The two-sample t-test was used to detect differences between the two groups. Least absolute shrinkage and selection operator (LASSO) regression was used to select the best predictor variables for predicting the status of RFA zone. Multiple test methods were used to ensure the scientific nature and accuracy of the Cox proportional hazards model. We tested the performance for the parameters and revealed the best cut-off value of each variable by the ROC curve and log-rank tests. The results showed patients aged above 49 years old, with RFA energy above 2800 J, the average diameter of the original tumour above 0.6 cm, or the average diameter of ablation zone at 1 month after RFA above 1.1 cm are risk factors for RFA zone delayed healing.

Technical Acoustic Measurements Combined with Clinical Parameters for the Differential Diagnosis of Nonalcoholic Steatohepatitis.

Background and aim: Diagnosing nonalcoholic steatohepatitis (NASH) is challenging. This study intended to explore the diagnostic value of multiple technical acoustic measurements in the diagnosis of NASH, and to establish a diagnostic model combining technical acoustic measurements with clinical parameters to improve the diagnostic efficacy of NASH. Methods: We consecutively enrolled 75 patients with clinically suspected nonalcoholic fatty liver disease (NAFLD) who underwent percutaneous liver biopsy in our hospital from June 2020 to December 2021. All cases underwent multiple advanced acoustic measurements for liver such as shear wave dispersion (SWD), shear wave speed (SWS), attenuation imaging (ATI), normalized local variance (NLV), and liver-kidney intensity ratio (Ratio) examination before liver biopsies. A nomogram prediction model combining the technical acoustic measurements and clinical parameters was established and the model is proposed to improve the diagnostic performance of NASH. Results: A total of 75 cases were included in this study. The classification of pathological grade for NASH was as follows: normal liver, (n = 15, 20%), nonalcoholic fatty liver (NAFL), (n = 44, 58.7%), and NASH, (n = 16, 21.3%). There were statistically significant differences in SWS (p = 0.002), acoustic coefficient (AC) (p = 0.018), NLV (p = 0.033), age (p = 0.013) and fasting blood glucose (Glu) (p = 0.049) between NASH and non-NASH. A nomogram model which includes SWS, AC, NLV, age and Glu was built to predict NASH, and the calibration curves showed good calibrations in both training and validation sets. The AUCs of the combined nomogram model for the training set and validation set were 0.8597 and 0.7794, respectively. Conclusion: There were statistically significant differences in SWS, AC, NLV, age and Glu between NASH and non-NASH. A nomogram model which includes SWS, AC, NLV, age and Glu was built to predict NASH. The predictive model has a higher diagnostic performance than a single factor model in the diagnosis of NASH and has good clinical application prospects.

New Technologies in the Assessment of Carotid Stenosis: Beyond the Color-Doppler Ultrasound-High Frame Rate Vector-Flow and 3D Arterial Analysis Ultrasound.

Atherosclerotic plaque in the carotid artery is the main cause of ischemic stroke, with a high incidence rate among people over 65 years. A timely and precise diagnosis can help to prevent the ischemic event and decide patient management, such as follow up, medical, or surgical treatment. Presently, diagnostic imaging techniques available include color-Doppler ultrasound, as a first evaluation technique, computed tomography angiography, which, however, uses ionizing radiation, magnetic resonance angiography, still not in widespread use, and cerebral angiography, which is an invasively procedure reserved for therapeutically purposes. Contrast-enhanced ultrasound is carving out an important and emerging role which can significantly improve the diagnostic accuracy of an ultrasound. Modern ultrasound technologies, still not universally utilized, are opening new horizons in the arterial pathologies research field. In this paper, the technical development of various carotid artery stenosis diagnostic imaging modalities and their impact on clinical efficacy is thoroughly reviewed.

Extraoral type of intraductal papilloma in sublingual gland: A case report.

INTRODUCTION: It is rare for intraductal papilloma (IDP), a benign papillary tumor, to occur in the sublingual gland (SLG). CASE SUMMARY: A 55-year-old man incidentally found a painless mass in his left submandibular region (SMR). He had a history of two surgeries for bilateral SLG cyst. Contrast enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) were performed. The patient received trans-cervical excision of left residual SLG in combination with excision of left submandibular gland (SMG). The postoperative course was uneventful and no signs of recurrence during 5 months of follow-up. DISCUSSION: For a SMR mass, extraoral type of IDP in SLG should be considered in the differential diagnosis.

A Diagnostic Model for Breast Lesions With Enlarged Enhancement Extent on Contrast-Enhanced Ultrasound Improves Malignancy Prediction.

OBJECTIVE: The aim of the work described here was to develop a diagnostic model based on contrast-enhanced ultrasound (CEUS) features to improve performance in predicting the probability of malignancy for breast lesions with an enlarged enhancement extent on CEUS. METHODS: In total, 299 consecutive patients who underwent CEUS examination and had confirmed pathological results were retrospectively enrolled. Among the 299 patients, an enlarged enhancement extent on CEUS was found in 142 patients. In this special cohort, we analyzed the association of malignant pathologic results with perfusion patterns emphatically by reclassifying the patterns. RESULTS: A diagnostic model was developed and presented as a nomogram, assessed with discrimination and calibration. Receiver operating characteristic (ROC) curve analysis revealed that the areas under the curves of the conventional perfusion and modified perfusion patterns were 0.58 and 0.76 (p < 0.001), respectively. A diagnostic model was built and exhibited good discrimination with a C-index of 0.95 (95% confidence interval: 0.91-0.98), which was confirmed to be 0.93 via internal bootstrapping validation. CONCLUSION: The nomogram based on CEUS features provides radiologists with a quantitative tool to predict the probability of malignancy in this special cohort of breast lesions.

Comments and illustrations of the WFUMB CEUS liver guidelines: Rare focal liver lesions - infectious (bacterial).

In this series of papers on comments and illustrations of the World Federation for Medicine and Biology (WFUMB) guidelines on contrast enhanced ultrasound (CEUS) the topics of bacterial infections are discussed. Improved detection and characterization of common focal liver lesions (FLL) are the main topics of these guidelines but detailed and illustrating information is missing. The focus in this paper on infectious (bacterial) focal liver lesions is on their appearance on B-mode and Doppler ultrasound and CEUS features. Knowledge of these data should help to raise awareness of these rarer findings, to think of these clinical pictures in the corresponding clinical situation, to interpret the ultrasound images correctly and thus to initiate the appropriate diagnostic and therapeutic steps in time.

Clinical features combined with ultrasound-based radiomics nomogram for discrimination between benign and malignant lesions in ultrasound suspected supraclavicular lymphadenectasis.

Background: Conventional ultrasound (CUS) is the first choice for discrimination benign and malignant lymphadenectasis in supraclavicular lymph nodes (SCLNs), which is important for the further treatment. Radiomics provide more comprehensive and richer information than radiographic images, which are imperceptible to human eyes. Objective: This study aimed to explore the clinical value of CUS-based radiomics analysis in preoperative differentiation of malignant from benign lymphadenectasis in CUS suspected SCLNs. Methods: The characteristics of CUS images of 189 SCLNs were retrospectively analyzed, including 139 pathologically confirmed benign SCLNs and 50 malignant SCLNs. The data were randomly divided (7:3) into a training set (n=131) and a validation set (n=58). A total of 744 radiomics features were extracted from CUS images, radiomics score (Rad-score) built were using least absolute shrinkage and selection operator (LASSO) logistic regression. Rad-score model, CUS model, radiomics-CUS (Rad-score + CUS) model, clinic-radiomics (Clin + Rad-score) model, and combined CUS-clinic-radiomics (Clin + CUS + Rad-score) model were built using logistic regression. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) curve analysis. Results: A total of 20 radiomics features were selected from 744 radiomics features and calculated to construct Rad-score. The AUCs of Rad-score model, CUS model, Clin + Rad-score model, Rad-score + CUS model, and Clin + CUS + Rad-score model were 0.80, 0.72, 0.85, 0.83, 0.86 in the training set and 0.77, 0.80, 0.82, 0.81, 0.85 in the validation set. There was no statistical significance among the AUC of all models in the training and validation set. The calibration curve also indicated the good predictive performance of the proposed nomogram. Conclusions: The Rad-score model, derived from supraclavicular ultrasound images, showed good predictive effect in differentiating benign from malignant lesions in patients with suspected supraclavicular lymphadenectasis.

Contrast-Enhanced Ultrasound and Strain Elastography for Differentiating Benign and Malignant Parotid Tumors.

OBJECTIVES: Preoperative differentiation between benign parotid tumors (BPT) and malignant parotid tumors (MPT) is crucial for treatment decisions. The purpose of this study was to investigate the benefits of combining contrast-enhanced ultrasound (CEUS) and strain elastography (SE) for preoperative differentiation between BPT and MPT. METHODS: A total of 115 patients with BPT (n=72) or MPT (n=43) who underwent ultrasound (US), SE, and CEUS were enrolled. US and CEUS features and the elasticity score were evaluated. Receiver operating characteristic curve (ROC) analysis was used to assess the diagnostic performance of SE, CEUS, and SE + CEUS with respect to identifying MPT from BPT. RESULTS: Solitary presentation, larger diameter, irregular shape, ill-defined margin, heterogeneous echogenicity, and calcification on US and higher elasticity score on SE had a significant association with malignancy. MPT also presented an unclear margin, larger size after enhancement, and "fast-in and fast-out" pattern on CEUS. The combination of SE and CEUS was effective for differentiating MPT from BPT (AUC: 0.88, 0.80-0.95), with a sensitivity of 86.0%, specificity of 88.9%, and accuracy of 87.8%, which were significantly higher than the values for SE (AUC: 0.75, 0.66-0.85) and CEUS (AUC: 0.82, 0.73-0.91) alone. CONCLUSION: The combination of CEUS and SE is valuable for distinguishing MPT from BPT.

A nomogram based on combining clinical features and contrast enhanced ultrasound is not able to identify Her-2 over-expressing cancer from other breast cancers.

Objective: The aim of this study was to evaluate whether a predictive model based on a contrast enhanced ultrasound (CEUS)-based nomogram and clinical features (Clin) could differentiate Her-2-overexpressing breast cancers from other breast cancers. Methods: A total of 152 pathology-proven breast cancers including 55 Her-2-overexpressing cancers and 97 other cancers from two units that underwent preoperative CEUS examination, were included and divided into training (n = 102) and validation cohorts (n = 50). Multivariate regression analysis was utilized to identify independent indicators for developing predictive nomogram models. The area under the receiver operating characteristic (AUC) curve was also calculated to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff nomogram value were compared. Results: In the training cohort, 7 clinical features (menstruation, larger tumor size, higher CA153 level, BMI, diastolic pressure, heart rate and outer upper quarter (OUQ)) + enlargement in CEUS with P < 0.2 according to the univariate analysis were submitted to the multivariate analysis. By incorporating clinical information and enlargement on the CEUS pattern, independently significant indicators for Her-2-overexpression were used for further predictive modeling as follows: Model I, nomogram model based on clinical features (Clin); Model II, nomogram model combining enlargement (Clin + Enlargement); Model III, nomogram model based on typical clinical features combining enlargement (MC + BMI + diastolic pressure (DP) + outer upper quarter (OUQ) + Enlargement). Model II achieved an AUC value of 0.776 at nomogram cutoff score value of 190, which was higher than that of the other models in the training cohort without significant differences (all P>0.05). In the test cohort, the diagnostic efficiency of predictive model was poor (all AUC<0.6). In addition, the sensitivity and specificity were not significantly different between Models I and II (all P>0.05), in either the training or the test cohort. In addition, Clin exhibited an AUC similar to that of model III (P=0.12). Moreover, model III exhibited a higher sensitivity (70.0%) than the other models with similar AUC and specificity, only in the test cohort. Conclusion: The main finding of the study was that the predictive model based on a CEUS-based nomogram and clinical features could not differentiate Her-2-overexpressing breast cancers from other breast cancers.

Correlation between ultrasonographic scores and American college of rheumatology recommended rheumatoid arthritis disease activity measures: a systematic review and network meta-analysis.

BACKGROUND: To validate and facilitate ultrasound examinations on rheumatoid arthritis (RA) disease activity measurements in routine clinical practice. METHODS: A systematic review and network meta-analysis (NMA) of ultrasound examinations on joints and its correlation with clinical RA disease activity was performed. PubMed, Embase and Cochrane library were searched for literatures published up to May 01st 2021. Bayesian random-effect NMA was conducted to pool the correlations of ultrasonographic assessment scores with composite RA disease activity measurements. RESULTS: Fifteen studies evaluating twelve different existing ultrasonographic measurements on joints evaluation for RA disease activity scoring were included in this NMA. For comparisons with clinical disease activity index and simplified disease activity index, synovitis gray scale ultrasound 7 joints (GSUS7) demonstrated modest correlation of 0.30[- 0.74, 1.23] and 0.46[- 0.45, 1.15] respectively, followed by synovitis power Doppler ultrasound 7 joints (PDUS7) (0.25[- 0.57, 1.14], 0.31[- 0.46, 1.24]) and power Doppler ultrasound 12 joints (PDUS12) (0.23[- 1.36, 0.83], 0.25[- 1.18, 0.88]). As for disease activity score using 28 joint counts, PDUS12 showed the biggest correlation of 0.53[- 0.09, 1.11], followed by ultrasound 7 joints (US7) (0.50[0.06, 0.93]), PDUS7 (0.49[- 0.24, 1.12]), power Doppler ultrasound 6 joints (PDUS6) (0.42[- 0.29, 1.21]), synovitis PDUS7 (0.47[- 0.09, 1.27]) and synovitis GSUS7 (0.40[0.01, 0.86]). CONCLUSION: Comparative validity was observed on fewer joints ultrasonic evaluation for RA disease activity measurements, such as synovitis GSUS7 and synovitis PDUS7. Ultrasonographic measurements can be complementary for clinical RA disease activity measures with clinical efficiency, and technical guidelines were in need for clinical routine practice.

Catalytically Active Metal-Organic Frameworks Elicit Robust Immune Response to Combination Chemodynamic and Checkpoint Blockade Immunotherapy.

Chemodynamic therapy (CDT) strategies rely on the generation of reactive oxygen species (ROS) to kill tumor cells, with hydroxyl radicals (•OH) serving as the key mediators of cytotoxicity in this setting. However, the efficacy of CDT approaches is often hampered by the properties of the tumor microenvironment (TME) and associated limitations to the Fenton reaction that constrains ROS generation. As such, there is a pressing need for the design of new nanoplatforms capable of improving CDT outcomes. In this study, an Fc-based metal-organic framework (MOF) vitamin k3 (Vk3)-loaded cascade catalytic nanoplatform (Vk3@Co-Fc) was developed. This platform was capable of undergoing TME-responsive degradation without impacting normal cells. After its release, Vk3 was processed by nicotinamide adenine dinucleotide hydrogen phosphate (NAD(P)H) quinone oxidoreductase-1 (NQO1), which is highly expressed in tumor cells, thereby yielding large quantities of H2O2 that in turn interact with Fe ions via the Fenton reaction to facilitate in situ cytotoxic •OH production. This process leads to immunogenic cell death (ICD) of the tumor, which then promotes dendritic cell maturation and ultimately increases T cell infiltration into the tumor site. When this nanoplatform was combined with programmed death 1 (PD-1) checkpoint blockade approaches, it was sufficient to enhance tumor-associated immune responses in breast cancer as evidenced by increases in the frequencies of CD45+ leukocytes and CD8+ cytotoxic T lymphocytes, thereby inhibiting tumor metastasis to the lungs and improving murine survival outcomes. Together, this Vk3@Co-Fc cascading catalytic nanoplatform enables potent cancer immunotherapy for breast cancer regression and metastasis prevention.

Unraveling the Plasma Protein Corona by Ultrasonic Cavitation Augments Active-Transporting of Liposome in Solid Tumor.

Ligand/receptor-mediated targeted drug delivery has been widely recognized as a promising strategy for improving the clinical efficacy of nanomedicines but is attenuated by the binding of plasma protein on the surface of nanoparticles to form a protein corona. Here, it is shown that ultrasonic cavitation can be used to unravel surface plasma coronas on liposomal nanoparticles through ultrasound (US)-induced liposomal reassembly. To demonstrate the feasibility and effectiveness of the method, transcytosis-targeting-peptide-decorated reconfigurable liposomes (LPGLs) loaded with gemcitabine (GEM) and perfluoropentane (PFP) are developed for cancer-targeted therapy. In the blood circulation, the targeting peptides are deactivated by the plasma corona and lose their targeting capability. Once they reach tumor blood vessels, US irradiation induces transformation of the LPGLs from nanodrops into microbubbles via liquid-gas phase transition and decorticate the surface corona by reassembly of the lipid membrane. The activated liposomes regain the capability to recognize the receptors on tumor neovascularization, initiate ligand/receptor-mediated transcytosis, achieve efficient tumor accumulation and penetration, and lead to potent antitumor activity in multiple tumor models of patient-derived tumor xenografts. This study presents an effective strategy to tackle the fluid biological barriers of the protein corona and develop transcytosis-targeting liposomes for active tumor transport and efficient cancer therapy.