Photothermal synergistic nitric oxide controlled release injectable self-healing adhesive hydrogel for biofilm eradication and wound healing.

The development of injectable self-healing adhesive hydrogel dressings with excellent bactericidal activity and wound healing ability is urgently in demand for combating biofilm infections. Herein, a multifunctional hydrogel (QP/QT-MB) with near-infrared (NIR) light-activated mild photothermal/gaseous antimicrobial activity was developed based on the dynamic reversible borate bonds and hydrogen bonds crosslinking between quaternization chitosan (QCS) derivatives alternatively containing phenylboronic acid and catechol-like moieties in conjunction with the in situ encapsulation of BNN6-loaded mesoporous polydopamine (MPDA@BNN6 NPs). Given the dynamic reversible cross-linking feature, the versatile hybrid hydrogel exhibited injectability, flexibility, and rapid self-healing ability. The numerous phenylboronic acid and catechol-like moieties on the QCS backbone confer the hydrogel with specific bacterial affinity, desirable tissue adhesion, and antioxidant stress ability that enhance bactericidal activity and facilitate the regeneration of infection wounds. Under NIR irradiation, the QP/QT-MB hydrogels exhibited a desirable mild photothermal effect and NIR-activity controllable NO delivery, combined with the endogenous contact antimicrobial activity of hydrogel, contributing jointly to induce dispersal of biofilms and disruption of the bacterial plasma membranes, ultimately leading to bacteria inactivation and biofilm elimination. In vivo experiments demonstrated that the fabricated QP/QT-MB hydrogel platform was capable of inducing efficient eradication of the S. aureus biofilm in a severely infected wound model and accelerating infected wound repair by promoting collagen deposition, angiogenesis, and suppressing inflammatory responses. Additionally, the QP/QT-MB hydrogel demonstrated excellent biocompatibility in vitro and in vivo. Collectively, the hydrogel (QP/QT-MB) reveals great potential application prospects as a promising alternative in the field of biofilm-associated infection treatment.

Evidence of Effect of Aerobic Exercise on Cognitive Intervention in Older Adults With Mild Cognitive Impairment.

This study aimed to evaluate the effectiveness of aerobic exercise as a cognitive intervention for older adults with mild cognitive impairment (MCI). The PubMed, EMBASE (Ovid), Cochrane Library, Web of Science, and Medline databases were searched from their inception until 30 April 2021. Randomized controlled trials (RCTs) examining the effects of aerobic exercise on global cognitive function in older adults with MCI were included. Ten eligible trials with acceptable methodological quality were identified. The meta-analysis results showed that aerobic exercise significantly improved the MMSE (N = 956, MD = 0.60, 95% CI: 0.28-0.92, p = 0.0003, I 2 = 31%, fixed effects model) and MoCA scores (N = 398, MD = 1.67, 95% CI. 1.18-2.15, p < 0.0001, I 2 = 37%, fixed-effects model) and overall cognitive performance in patients with MCI. The results of this study suggest that participation in regular aerobic exercise can improve cognitive function in older adults with MCI. These findings should be used with caution considering the limitations of the study.

High-intensity focused ultrasound combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: long-term follow-up and clinical analysis.

OBJECTIVE: High-intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) has been used to treat unresectable HCC, but its long-term effects and major prognostic factors remain to be determined. The purpose of this study was to assess its long-term effects and find major prognostic factors to help us select eligible patients in the future. METHODS: 73 patients with unresectable HCC received follow-up after HIFU+TACE. The variables of sex, age, AFP level, liver function, tumor location, tumor number, tumor size, TNM staging (5th edition), TNM staging (6th edition), portal vein invasion, ultrasonic pathway of HIFU, TACE session and ablation response were evaluated by univariate analysis. Those variables with significant difference were assessed by multivariate analysis. RESULTS: The mean follow-up time was 11.7±11.1 months (range, 1-60 months). The median survival time and overall survival rates of 1, 2, 3-year were 12 months, 49.1%, 18.8%, 8.4%, respectively. 45.2% patients achieved complete ablation. At the end of follow-up, 51 patients (69.9%) died from tumor progression (27 patients), liver function failure (18 patients), hemorrhage of upper digestive tract (3 patients) and infection (3 patients). 1 with liver abscess, 2 with serious skin burns and 2 with rib fracture were observed after HIFU. On univariate analysis, age (P=0.017), tumor size (P=0.000), tumor number (P=0.039), the 5th edition of TNM staging (P=0.023), portal vein invasion (P=0.02) and ablation response (P=0.000) had significant difference. On multivariate analysis, ablation response (P=0.001) and tumor size (P=0.013) were major prognostic factors. CONCLUSION: HIFU combined with TACE is a safe method with a low rate of severe complications. As major prognostic factors, ablation response and tumor size may help us predict the survival and select eligible patients clinically.

Primary bone malignancy: effective treatment with high-intensity focused ultrasound ablation.

PURPOSE: To evaluate the long-term follow-up results of ultrasonographically (US)-guided high-intensity focused ultrasound ablation in patients with primary bone malignancy. MATERIALS AND METHODS: The study was approved by the ethics committee. Each patient or parent (if patient was younger than 18 years), signed an informed consent form before being selected and treated. From December 1997 to November 2004, 80 patients with a primary bone malignancy-60 with stage IIb disease and 20 with stage III disease (Enneking staging system)-were treated with US-guided high-intensity focused ultrasound ablation. High-intensity focused ultrasound ablation combined with chemotherapy was performed in 62 patients with osteosarcoma, one patient with periosteal osteosarcoma, and three patients with Ewing sarcoma. The remaining 14 patients had chondrosarcoma, giant cell bone cancer, periosteal sarcoma, or an unknown malignancy and were treated with high-intensity focused ultrasound ablation only. Magnetic resonance (MR) imaging or computed tomography (CT), and single photon emission computed tomography (SPECT) were used to assess tumor response. Cumulative survival rates were calculated by using the Kaplan-Meier method. Adverse effects were recorded. RESULTS: High-intensity focused ultrasound ablation guided by real-time US was performed. Follow-up images demonstrated completely ablated malignant bone tumors in 69 patients and greater than 50% tumor ablation in the remaining 11 patients. Overall survival rates at 1, 2, 3, 4, and 5 years were 89.8%, 72.3%, 60.5%, 50.5%, and 50.5%, respectively. Survival rates at 1, 2, 3, 4, and 5 years were 93.3%, 82.4%, 75.0%, 63.7%, and 63.7%, respectively, in the patients with stage IIb cancer and 79.2%, 42.2%, 21.1%, 15.8%, and 15.8%, respectively, in those with stage III disease. Among the patients with stage IIb disease, long-term survival rates were substantially improved in the 30 patients who received the full treatment-that is, complete high-intensity focused ultrasound and full cycles of chemotherapy-compared with the survival rates for the 24 patients who did not finish the chemotherapy cycles and the six patients who underwent partial ablation only. Only five (7%) of the 69 patients who underwent complete ablation had local cancer recurrence during the follow-up period. Forty adverse events were recorded, with 14 patients requiring surgical intervention. CONCLUSION: US-guided high-intensity focused ultrasound ablation of malignant bone tumors is feasible and effective and eventually may be a component of limb-sparing techniques for patients with these cancers.

High intensity focused ultrasound (HIFU) therapy for local treatment of hepatocellular carcinoma: role of partial rib resection.

OBJECTIVE: It has long been known that high intensity focused ultrasound (HIFU) can kill tissue through coagulative necrosis. However, it is only in recent years that practical clinical applications are becoming possible. Since the ribs have strong reflections to ultrasonic beams, they may affect the deposition of ultrasound energy, decreasing the efficacy of HIFU treatment and increasing the chance of adverse events when the intra-abdominal tumours concealed by ribs are treated. The aim of this study was to evaluate the influence of partial rib resection on the efficacy and safety of HIFU treatment. METHODS: This prospective study was approved by the ethics committee at Chongqing University of Medical Sciences. An informed consent form was obtained from each patient and family member. A total of 16 patients with hepatocellular carcinoma (HCC), consisting of 13 males and 3 females, were studied. All patients had the successful HIFU treatment. To create a better acoustic pathway for HIFU treatment, all of the 16 patients had the ribs that shield the tumour mass to be removed. Magnetic resonance imaging (MRI) was used to evaluate the efficacy of HIFU treatment. RESULTS: Sixteen cases had 23 nodules, including 12 cases with a single nodule, 1 case with 2 nodules, 3 cases with 3 nodules. The mean diameter of tumours was 7.0+/-2.1 cm (5-10 cm). According to TNM classification, 9 patients were diagnosed as stage II, 4 patients were stage III, and 3 patients were stage IV. Follow-up imaging showed an absence of tumour blood supply and shrinkage of all treated lesions. The survival rates at 1, 2, 3, 4, and 5 years were 100%, 83.3%, 69.4%, 55.6%, and 55.6%, respectively. No serious complications were observed in the patients treated with HIFU. CONCLUSION: Partial rib resection can create a better acoustic pathway of HIFU therapy. Even though it is an invasive treatment, this measure offers patients an improved prospect of complete tumour ablation when no other treatment is available.

High-intensity focused ultrasound (HIFU): effective and safe therapy for hepatocellular carcinoma adjacent to major hepatic veins.

Hepatocellular carcinoma (HCC) is an especially frequent malignancy in China. Radiofrequency ablation, percutaneous ethanol injection, transarterial chemoembolization, cryoablation, microwave coagulation, and laser-induced interstitial thermotherapy all offer potential local tumor control and occasionally achieve long-term disease-free survival. High-intensity focused ultrasound (HIFU), as a noninvasive therapy, can be applied to treat tumors that are difficult to treat with other techniques. The preliminary results of HIFU in clinical studies are encouraging. The aims of this investigation were to assess the efficacy of the system in obtaining necrosis of the target tissue and to determine whether HIFU ablation is hazardous to adjacent major blood vessels. Over 7 years, thirty-nine patients with HCC were enrolled in this investigation. The inferior vena cava (IVC), main hepatic vein branches, and the portal vein and its main branches were evaluated. The distance between tumor and main blood vessel was less than 1 cm in all these enrolled patients. Contrast-enhanced MRI was used to evaluate the perfusion of tumors and major blood vessels. We conducted HIFU ablation for the treatment of 39 patients with 42 tumors, with each tumor measuring 7.4+/-4.3 (1.5-22) cm in its greatest dimension. Among the 39 patients, 23 were males and 16 females. The average age was 53.2 years (range 25-77 years). Thirty-seven patients had a solitary lesion, one had two lesions, and the remaining one had three lesions. Nineteen lesions were located in the right lobe of liver, 18 in the left lobe, and 5 in both right and left lobes. Among the 42 tumors, 25 were adjacent to 1 blood vessel, 12 adjacent to 2 main vessels, 2 adjacent to 3 main vessels, and 1 adjacent to 4 main vessels. Twenty-one of the 42 tumors were completely ablated, while the rest of the tumors were ablated by more than 50% of lesion volume after one session of HIFU. No major blood vessel injury was observed in any subject after 23.8+/-17.2 months follow-up. HIFU can achieve complete tumor necrosis even when the lesion is located adjacent to the major hepatic blood vessels. Short-term and long-term follow-up results show that HIFU can be safely used to ablate the tumors adjacent to major vessels.

Feasibility of US-guided high-intensity focused ultrasound treatment in patients with advanced pancreatic cancer: initial experience.

The study was approved by the university ethics committee, and informed consent was obtained from all patients. The purpose of this study was to prospectively evaluate ultrasonographically guided high-intensity focused ultrasound in the treatment of patients with advanced-stage pancreatic cancer. Eight patients underwent high-intensity focused ultrasound ablation, and laboratory and radiologic examinations were performed after intervention. Changes in symptoms and survival time were noted at follow-up. No complications were observed, and preexisting severe back pain disappeared after intervention. Follow-up images revealed an absence of tumor blood supply and shrinkage of the ablated tumor. Four patients died, and four patients were alive at the time of this writing, with a median survival time of 11.25 months. The authors conclude that high-intensity focused ultrasound ablation is safe and feasible in the treatment of advanced pancreatic cancer.

Extracorporeal high intensity focused ultrasound treatment for patients with breast cancer.

PURPOSE: To investigate the safety, efficacy and feasibility of using high-intensity focused ultrasound (HIFU) as a non-invasive treatment for patients with breast cancer. PATIENTS AND METHODS: Twenty-two patients with breast cancer were enrolled into this non-randomized prospective trial. Disease TNM stage was classified as stage I in 4 patients, stage II(A) in 9 patients, stage II(B) in 8 patients, and stage IV in 1 patient. Tumor size ranged from 2 to 4.8 cm in diameter (mean 3.4 cm). All patients received chemotherapy, radiation and tamoxifen, following HIFU for the primary lesions. Outcome measures included radiological and pathologic assessment of the treated tumor, cosmesis, and local recurrence. A cumulative survival rate is calculated by using the Kaplan-Meier method. RESULTS: No severe complications were encountered after HIFU. Post-operative imaging demonstrated positive response and regression of all treated lesions. Follow-up biopsy revealed coagulation necrosis of target tumor and subsequent replacement by fibroblastic tissue. After a median follow-up of 54.8 months, 1 patient died, 1 was lost to follow-up, and 20 were still alive. Two of 22 patients developed local recurrence. Five-year disease-free survival and recurrence-free survival were 95% and 89%, respectively. Cosmetic result was judged as good to excellent in 94% of patients. CONCLUSIONS: HIFU treatment is safe, effective, and feasible for patients with breast cancer. But, large-scale, multiple-center clinical trials will be needed to determine the future role of this novel modality.

Advanced hepatocellular carcinoma: treatment with high-intensity focused ultrasound ablation combined with transcatheter arterial embolization.

PURPOSE: To evaluate ultrasonographically (US)-guided high-intensity focused ultrasound ablation combined with transcatheter arterial chemoembolization (TACE) in the treatment of stage IVA hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. From November 1998 to May 2000, 50 consecutive patients with stage IVA HCC (TNM classification, T4N0-1M0) were alternately enrolled in one of two treatment groups: group 1 (n = 26), in which TACE was performed alone, and group 2 (n = 24), in which transcutaneous ablation of HCC with high-intensity focused ultrasound was performed 2-4 weeks after TACE. The tumors were 4-14 cm in diameter (mean, 10.5 cm). Immediate therapeutic effects were assessed at follow-up with Doppler US and computed tomography or magnetic resonance imaging. All patients were followed up for 3-24 months (mean, 8 months) to observe long-term therapeutic effects and complications in both groups. Tumor reduction rates, median survival time, and cumulative survival rates in both groups were calculated by using the unpaired Student t test and Kaplan-Meier method. RESULTS: No severe complication was observed after focused ultrasound ablation, and no unexpected side effects were noted after TACE. Follow-up images showed absence or reduction of blood supply in the lesions after focused ultrasound ablation when compared with blood supply after TACE alone. The median survival time was 11.3 months in group 2 and 4.0 months in group 1 (P = .004). The 6-month survival rate was 80.4%-85.4% in group 2 and 13.2% in group 1 (P = .002), and the 1-year survival rate was 42.9% and 0%, respectively. Median reductions in tumor size as a percentage of initial tumor volume at 1, 3, 6, and 12 months after treatment, respectively, were 28.6%, 35.0%, 50.0%, and 50.0% in group 2 and 4.8%, 7.7%, 10.0%, and 0% in group 1 (P < .01). CONCLUSION: The combination of high-intensity focused ultrasound ablation and TACE is a promising approach in patients with advanced-stage HCC, but large-scale randomized clinical trials are necessary for confirmation.

Extracorporeal high intensity focused ultrasound ablation in the treatment of patients with large hepatocellular carcinoma.

BACKGROUND: High intensity focused ultrasound (HIFU) is a noninvasive treatment modality that induces complete coagulative necrosis of a deep tumor through the intact skin. The current study was conducted to determine the safety, efficacy, and feasibility of extracorporeal HIFU in the treatment of patients with hepatocellular carcinoma (HCC). METHODS: A total of 55 patients with HCC with cirrhosis were enrolled in this prospective, nonrandomized clinical trial. Among them, 51 patients had unresectable HCC. Tumor size ranged from 4 to 14 cm in diameter with mean diameter of 8.14 cm. According to tumor, node, metastasis (TNM) classification, 15 patients corresponded to stage II, 16 to stage IIIA, and 24 to IIIC. All patients had HIFU, and the median number of HIFU session was 1.69. Safety and efficacy of HIFU were assessed in this trial. RESULTS: No severe side effect was observed in the patients treated with HIFU. Follow-up imaging showed an absence of tumor vascular supply and the shrinkage of treated lesions. Serum alpha-fetoprotein returned to normal level in 34% of patients. The overall survival rates at 6, 12, and 18 months were 86.1%, 61.5%, and 35.3%, respectively. The survival rates were significantly higher in patients in stage II than those in stage IIIA (P = .0132) and in stage IIIC (P = .0265). CONCLUSION: As a noninvasive therapy, HIFU appears to be effective, safe, and feasible in the treatment of patients with HCC. It may play an important role in the ablation of large tumors.

Extracorporeal focused ultrasound surgery for treatment of human solid carcinomas: early Chinese clinical experience.

The objective of this article is to introduce the early Chinese clinical experience of using extracorporeal focused ultrasound (US) surgery (FUS) for the treatment of solid tumors. From December 1997 to October 2001, a total of 1038 patients with solid tumors underwent FUS ablation in 10 Chinese hospitals. The tumors included primary and metastatic liver cancer, malignant bone tumors, breast cancer, soft tissue sarcomas, kidney cancer, pancreatic cancer, abdominal and pelvic malignant tumors, uterine myoma, benign breast tumors, hepatic hemangioma and other solid tumors. In this article, pathologic changes in tumors treated with FUS, real-time diagnostic imaging for targeting, monitoring and assessment of results by follow-up images are presented. Early clinical results and complications of the technique are also reported.

Changes in biologic characteristics of breast cancer treated with high-intensity focused ultrasound.

Proliferation, invasion, immortalization and metastasis are the main malignant characteristics of cancer. Previous studies have shown that high-intensity focused ultrasound (US), or HIFU, can induce irreversible damage both to breast cancer cells and to tumor blood vessels. However, light microscopy alone may not always show this clearly. In this study, molecular biologic techniques were used to examine any changes in molecular markers associated with malignant behavior after exposure to HIFU. A total of 48 women with breast cancer were randomized to a control group (mastectomy) and a HIFU group (HIFU followed by mastectomy). Immunohistochemical staining, messenger RNA (mRNA) in situ hybridization and telomere-repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA) techniques were used to detect tumor expression of proliferating cell nuclear antigen (PCNA), cell adhesion molecule CD44v6, matrix metalloproteinase-9 (MMP-9), erbB2 mRNA, and to measure telomerase activity in both groups. The results demonstrated that there were significant alterations in expression of PCNA, CD44v6, MMP-9, erbB2 mRNA, and a dramatic decrease in telomerase activity in the HIFU group. It is concluded that malignant tumor characteristics are arrested by HIFU, and that biologic factors are potential markers for assessing HIFU efficacy.