Rho GTPase-activating protein 1 promotes hepatocellular carcinoma progression via modulation by CircPIP5K1A/MiR-101-3p.

AIM: There has been an increased focus on regulating cell function with Rho family GTPases, including proliferation, migration/invasion, polarity, and adhesion. Due to the challenges involved in targeting Rho family GTPases directly, it may be more effective to target their regulators, such as Rho GTPase-activating protein 1 (ARHGAP1). This present research was performed to define the clinical significance of ARHGAP1 expression, as well as its regulatory mechanisms in hepatocellular carcinoma. METHODS: ARHGAP1 and miR-101-3p expression of liver cancer patients, and their relevance with clinicopathological characteristics and prognosis were analyzed by the Cancer Genome Atlas sequencing data, and verified using samples of hepatocellular carcinoma patients. The interactions between miR-101-3p and ARHGAP1 or circPIP5K1A were validated by bioinformatic analyses, as well as confirmed by quantitative reverse transcription polymerase chain reaction, western blotting, and dual-luciferase reporter analysis. Plate clonality assays, cell adhesion and migration experiments, and proliferation experiments were used for assessing the participation of the circPIP5K1A/miR-101-3p/ARHGAP1 pathway in cell proliferation and motility. RESULTS: Elevated ARHGAP1 and reduced miR-101-3p expression are related to poorer survival. MiR-101-3p targets ARHGAP1 to suppress hepatocellular carcinoma cell colony formation and invasion, whereas miR-101-3p inhibitor reverses liver cancer proliferation and metastasis suppression caused by ARHGAP1 knockdown. In addition, circPIP5K1A, which is mainly distributed in the cytosol, showed carcinogenic effects by sponging miR-101-3p, thus regulating ARHGAP1 expression. CONCLUSIONS: ARHGAP1 serves as an oncogenic gene in liver cancer, and the expression thereof is regulated by circPIP5K1A through sponging miR-101-3p.

A risk stratification system developed to predict contralateral incidental malignant foci in early papillary thyroid carcinoma preoperatively.

BACKGROUND: In clinical practice, contralateral incidental malignant foci (CIMFs) can be found in some early (cT1N0M0) papillary thyroid carcinomas (PTCs) on postoperative pathological examination. To screen out the patients with high risk of CIMF preoperatively would help in determining the extent of thyroid surgery. METHODS: From October 2016 to February 2021, 332 patients diagnosed with early (cT1N0M0) PTC who underwent total thyroidectomy were included and randomly allocated into a training dataset (n = 233) and a test dataset (n = 99). Demographic and clinicopathological features were recorded and analyzed using logistic regression analysis. A coefficient-based nomogram was developed and validated. RESULTS: Logistic regression analyses revealed that the predictive model including BRAF V600E mutation, multifocality and margin of the contralateral nodule achieved the best diagnostic performance. The nomogram showed good discrimination, with AUCs of 0.795 (95 % CI, 0.736-0.853) for the training set and 0.726 (95 % CI, 0.609-0.843) for the test set. The calibration curve of the nomogram presented good agreement. CONCLUSION: The risk stratification system can be used to quantify the probability of CIMF and may assist in helping the patients choose total thyroidectomy or thyroid lobectomy with early (cT1N0M0) PTC.

Preoperative prediction of macrotrabecular-massive hepatocellular carcinoma based on B-Mode US and CEUS.

OBJECTIVES: To develop a preoperative prediction model to identify macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) and evaluate the model's diagnostic performance in differentiating MTM-HCC from HCC. METHODS: We conducted a mono-center retrospective study in a grade A tertiary hospital in China. Consecutive patients with suspected HCC from February 2019 to December 2020 were eligible for inclusion. All consenting patients underwent CEUS examination and were histologically diagnosed. Based on the clinical and US features between the two groups, we developed a binary logistic regression model and a nomogram for predicting MTM-HCC. RESULTS: A total of 161 patients (median age, 57 years; interquartile range, 48-64 years; 129 men) were included in the analysis. Twenty-seven of the HCCs (16.8%) were of the MTM subtype. Binary logistic regression analysis indicated that PVP hypoenhancement (OR = 15.497; 95% CI: 1.369, 175.451; p = 0.027), AFP > 454.6 ng/mL (OR = 8.658; 95% CI: 3.030, 24.741; p < 0.001), ALB ≤ 29.9 g/L (OR = 3.937; 95% CI: 1.017, 15.234; p = 0.047), halo sign (OR = 3.868; 95% CI: 1.314, 11.391; p = 0.016), and intratumoral artery (OR = 2.928; 95% CI: 1.039, 8.255; p = 0.042) were predictors for MTM subtype. Combining any two criteria showed a high sensitivity (100.0%); combining all five criteria showed a high specificity (99.2%); and the AUC value of the logistic regression model was 0.88 (95% CI: 0.81, 0.92). CONCLUSIONS: BMUS and CEUS could be used for identifying patients suspected of having MTM-HCC. Combining clinical information, BMUS, and CEUS features could achieve a noninvasive diagnosis of MTM-HCC. KEY POINTS: • Contrast-enhanced ultrasound examination helps clinicians to identify MTM-HCCs preoperatively. • PVP hypoenhancement, high AFP levels, low ALB levels, halo signs, and intratumoral arteries could be used to predict MTM-HCCs. • A logistic regression model and nomogram were built to noninvasively diagnose MTM-HCCs with an AUC value of 0.88 (95% CI: 0.81, 0.92).

Ultrasound-based deep learning in the establishment of a breast lesion risk stratification system: a multicenter study.

OBJECTIVES: To establish a breast lesion risk stratification system using ultrasound images to predict breast malignancy and assess Breast Imaging Reporting and Data System (BI-RADS) categories simultaneously. METHODS: This multicenter study prospectively collected a dataset of ultrasound images for 5012 patients at thirty-two hospitals from December 2018 to December 2020. A deep learning (DL) model was developed to conduct binary categorization (benign and malignant) and BI-RADS categories (2, 3, 4a, 4b, 4c, and 5) simultaneously. The training set of 4212 patients and the internal test set of 416 patients were from thirty hospitals. The remaining two hospitals with 384 patients were used as an external test set. Three experienced radiologists performed a reader study on 324 patients randomly selected from the test sets. We compared the performance of the DL model with that of three radiologists and the consensus of the three radiologists. RESULTS: In the external test set, the DL model achieved areas under the receiver operating characteristic curve (AUCs) of 0.980 and 0.945 for the binary categorization and six-way categorizations, respectively. In the reader study set, the DL BI-RADS categories achieved a similar AUC (0.901 vs. 0.933, p = 0.0632), sensitivity (90.98% vs. 95.90%, p = 0.1094), and accuracy (83.33% vs. 79.01%, p = 0.0541), but higher specificity (78.71% vs. 68.81%, p = 0.0012) than those of the consensus of the three radiologists. CONCLUSIONS: The DL model performed well in distinguishing benign from malignant breast lesions and yielded outcomes similar to experienced radiologists. This indicates the potential applicability of the DL model in clinical diagnosis. KEY POINTS: • The DL model can achieve binary categorization for benign and malignant breast lesions and six-way BI-RADS categorizations for categories 2, 3, 4a, 4b, 4c, and 5, simultaneously. • The DL model showed acceptable agreement with radiologists for the classification of breast lesions. • The DL model performed well in distinguishing benign from malignant breast lesions and had promise in helping reduce unnecessary biopsies of BI-RADS 4a lesions.

HMGB1 released from dead tumor cells after insufficient radiofrequency ablation promotes progression of HCC residual tumor via ERK1/2 pathway.

BACKGROUND: Radiofrequency ablation (RFA) is a first-line treatment for early-stage hepatocellular carcinoma (HCC). However, the recurrence after RFA remains an urgent challenge. Current studies have shown that residual tumor after RFA is an important cause of recurrence. OBJECTIVE: We hypothesized that the products of dead tumor cells after RFA have direct effects on the development of residual tumors. Further, we investigated the underlying mechanisms. METHODS: The proliferation and invasion ability of HepG2 and Huh7 cells were assessed using CCK-8, colony formation, EdU, transwell invasion and migration assay. Immunofluorescence and western blotting were used to show HMGB1 released from dead tumor cells. The levels of MMP2, MMP9, CyclinE1 and pERK1/2 were determined using western blotting. Finally, in vivo validation was performed in BALB/c nude mice xenograft tumor models. RESULTS: The products of dead tumor cells after thermal treatment can promote the proliferation and invasion of residual HCC cells. Dead tumor cells could release high-mobility group box 1 (HMGB1) after thermal treatment. Similar to the products of dead tumor cells, the recombinant protein of HMGB1 can promote the proliferation and invasion of residual HCC cells. Moreover, HMGB1 could bind to receptor of advanced glycation end-products. Then, it activated the ERK1/2 pathway and significantly upregulated the expressions of MMP2, MMP9, and CyclinE1. CONCLUSION: Our study reveals that HMGB1 released by dead tumor cells after thermal treatment can promote the proliferation and invasion of residual HCC cells. Hence, the HMGB1/RAGE/ERK1/2 pathway is a potential target for improving the prognosis of HCC after radiofrequency ablation.

A Practical CEUS Thyroid Reporting System for Thyroid Nodules.

Background The role of contrast-enhanced US (CEUS) in reducing unnecessary biopsies of thyroid nodules has received little attention. Purpose To construct and externally validate a thyroid imaging reporting and data system (TI-RADS) based on nonenhanced US and CEUS to stratify the malignancy risk of thyroid nodules. Materials and Methods This retrospective study evaluated 756 patients with 801 thyroid nodules who underwent nonenhanced US, CEUS, and fine-needle aspiration and received a final diagnosis from January 2018 to December 2019. Qualitative US features of the thyroid nodules were analyzed with univariable and multivariable logistic regression to construct a CEUS TI-RADS. The CEUS TI-RADS was validated with use of internal cross-validation and external validation. Results A total of 801 thyroid nodules in 590 female (mean age, 44 years ± 13) and 166 male (mean age, 47 years ± 13 [SD]) patients were included. Independent predictive US features included nodule composition at CEUS, echogenicity, nodule shape, nodule margin, echogenic foci, extrathyroidal extension, enhancement direction, peak intensity, and ring enhancement. The CEUS TI-RADS showed a higher area under the receiver operating characteristic curve of 0.93 (95% CI: 0.92, 0.95; P < .001 in comparison with all other systems), a biopsy yield of malignancy of 66% (157 of 239 nodules), and an unnecessary biopsy rate of 34% (82 of 239 nodules). In the external validation, the area under the receiver operating characteristic curve, biopsy yield of malignancy, and unnecessary biopsy rate of CEUS TI-RADS were 0.89 (95% CI: 0.84, 0.92), 61% (65 of 106 nodules), and 39% (41 of 106 nodules) for the first external validation set and 0.90 (95% CI: 0.85, 0.94), 57% (56 of 99 nodules), and 43% (43 of 99 nodules) for the second external validation set. Conclusion A contrast-enhanced US (CEUS) thyroid imaging reporting and data system was created with thyroid nodule malignancy risk stratification according to the simplified regression coefficients of nonenhanced US and qualitative features of CEUS. Clinical trials registration no. ChiCTR2000028712 Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Superficial Femoral Artery Calcification Is a Novel Risk Factor of Microvascular Complications in T2DM Patients.

Microvascular complications are prevalent in patients with type 2 diabetes mellitus (T2DM), resulting in increased risk of cardiovascular mortality. However, it is unclear whether above-knee artery calcification relates to microvascular complications. This study was aimed to investigate the role of calcification in superficial femoral arteries (SFA), the major above-knee artery, compared with anterior tibial arteries (ATA) and posterior tibial arteries (PTA), in T2DM-related microvascular complications and explore its risk factors. A single-center and observational study involving 359 T2DM patients was conducted. Clinical and laboratory data were collected. SFA calcification was evaluated by ultrasonography. Compared with ATA and PTA calcification, operating characteristics curve analysis showed that SFA calcification was the strongest predictor (63.1% sensitivity and 69.2% specificity) for T2DM-related microvascular complications (diabetic neuropathy, diabetic nephropathy and diabetic retinopathy). With the severity of SFA calcification increased, age, duration of T2DM, and SBP were significantly elevated, but triglyceride and glucose index and estimated glomerular filtration rate (eGFR) were significantly reduced (all P < 0.05). Multivariate logistic analysis showed that eGFR (OR 0.953; 95% CI 0.931-0.976; P < 0.001) was an independent risk factor of SFA calcification, especially in young patients with HbA1c > 7.0. We identified SFA calcification as a good predictor of microvascular complications in T2DM patients. Reduced eGFR was significantly associated with increased SFA calcification prevalence, especially in young T2DM patients with bad controlled hyperglycemia.

Fine needle aspiration biopsy indications for thyroid nodules: compare a point-based risk stratification system with a pattern-based risk stratification system.

OBJECTIVES: We aim to compare the diagnostic performance to assess thyroid nodules and reliability for recommending fine needle aspiration biopsy (FNAB) between American College of Radiology thyroid image reporting and data system (ACR TI-RADS) and American Thyroid Association (ATA) guidelines. METHODS: In total, this retrospective study included 1001 consecutive thyroid nodules in 918 patients from May 2016 to December 2017. US features of the thyroid nodules, including composition, echogenicity, shape, margins, echogenic foci, and size, were reviewed and were classified according to ACR TI-RADS and ATA guidelines, respectively. The diagnostic performance to assess thyroid nodules and reliability for recommending fine needle aspiration biopsy were compared between ACR TI-RADS and ATA guidelines. RESULTS: Of the 1001 thyroid nodules, 609 (60.8%) were benign and 392 (39.2%) were malignant. The sensitivity, specificity, PPV, NPV, and accuracy were 96.7%, 77.3%, 73.3%, 97.3%, and 84.9%, respectively, for ACR TI-RADS and 99.2%, 16.1%, 43.2%, 97.0%, and 48.7%, respectively, for ATA guidelines. AUC of ACR TI-RADS was significantly greater than ATA guidelines (0.935 (0.918, 0.949) vs 0.884 (0.862, 0.903), p < 0.001). Biopsy yield of malignancy, biopsy rate of malignancy, and unnecessary FNAB rate were 59.5%, 91.3%, and 40.5%, respectively, for ACR TI-RDS and 38.5%, 97.4%, and 61.5%, respectively, for ATA guidelines. CONCLUSIONS: ACR TI-RADS was more accurate than ATA guidelines for differentiating malignant thyroid nodules from benign nodules and more reliable than ATA guidelines for recommending thyroid nodules for FNAB. KEY POINTS: • Malignant risk of thyroid nodules can be stratified by ultrasound. • American College of Radiology guidelines were more accurate for differentiating malignant thyroid nodules from benign nodules. • American College of Radiology guidelines were more reliable for recommending thyroid nodules for biopsy.

Computer-Aided Diagnosis of Solid Breast Lesions With Ultrasound: Factors Associated With False-negative and False-positive Results.

OBJECTIVES: To investigate factors that may lead to false-positive or false-negative results in a computer-aided diagnostic system (S-Detect; Samsung Medison Co, Ltd, Seoul, Korea) for ultrasound (US) examinations of solid breast lesions. METHODS: This prospective study was approved by the Institutional Review Board of Sun Yat-sen Memorial Hospital. All patients signed and provided written informed consent before biopsy or surgery. From September 2017 to May 2018, 269 consecutive women with 338 solid breast lesions were included. All lesions were examined with US and S-Detect before biopsy or surgical excision. The final US assessments made by radiologists and S-Detect were matched to the pathologic results. Patient and lesion factors in the "true" and "false" S-Detect groups were compared, and multivariate logistic regression analyses were used to identify the factors associated with false S-Detect results. RESULTS: The mean age of the patients ± SD was 42.6 ± 12.9 years (range, 18-77 years). Of the 338 lesions, 209 (61.8%) were benign, and 129 (38.2%) were malignant. Larger lesions, the presence of lesion calcifications detected by B-mode US, and grades of 2 and 3 according to Adler et al (Ultrasound Med Biol 1990; 16:553-559) were significantly associated with false-positive S-Detect results (odds ratio [OR], 1.071; P = .006; OR, 5.851; P = .001; OR, 1.726; P = .009, respectively). Smaller lesions and the absence of calcifications detected by B-mode US in malignant solid breast lesions were significantly associated with false-negative S-Detect results (OR, 1.141; P = .015; OR, 7.434; P = .016). CONCLUSIONS: Larger benign lesions, the presence of lesion calcifications, and high degrees of vascularity are likely to show false-positive S-Detect results. Smaller malignant lesions and the absence of calcifications are likely to show false-negative S-Detect results.

Radiofrequency Ablation versus Hepatic Resection for Small Hepatocellular Carcinoma: Systematic Review of Randomized Controlled Trials with Meta-Analysis and Trial Sequential Analysis.

Purpose To compare the benefits and harms of radiofrequency ablation (RFA) and hepatic resection (HR) and to test the consistency of currently available evidence. Materials and Methods PubMed, Embase, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared the effects of HR and RFA for Barcelona Clinic Liver Cancer very early or early stage hepatocellular carcinoma (HCC). The primary outcome was overall survival, and secondary outcomes were recurrence rate, complication rate, and hospitalization duration. A random- or fixed-effects model according to the level of heterogeneity was applied. The meta-analysis was performed by using software, and trial sequential analysis (TSA) was performed. Results Five trials examining 742 patients were included in this study (sizes of trials: 161, 230, 168, 120, and 63 patients). The meta-analysis showed that RFA and HR had similar overall survival at 1 year (relative risk [RR], 1.39; 95% confidence interval [CI]: 0.36, 5.33; P = .63) and 3 years (RR, 1.40; 95% CI: 0.75, 2.62; P = .29), whereas RFA resulted in decreased overall survival compared with HR at 5 years (RR: 1.91; 95% CI: 1.32, 2.79; P = .001). The TSA showed that more trials were needed to control random errors. The incidence of overall recurrence was markedly higher and the hospitalization duration was significantly shorter in the RFA group than in the HR group, which was confirmed by TSA. Complications may have been less frequent in the RFA group, but TSA showed that additional trials were necessary to confirm this conclusion. Conclusion The indication for RFA as a primary treatment for patients who are eligible for HR with early stage HCC is unclear, and additional well-designed RCTs are needed. © RSNA, 2017 Online supplemental material is available for this article.

Effect of a hypoxic microenvironment after radiofrequency ablation on residual hepatocellular cell migration and invasion.

Clinical observations have shown that the boundary of tumor ablation is often less than safe border and that the use of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) may probably accelerate its recurrence and metastasis. RFA can cause the formation of a transition zone between normal liver tissues and necrotic coagulation, where blood stagnation and thrombosis expose residual cancer cells to a hypoxic microenvironment. As the blocked vessels are slowly reperfused, the oxygen supply is gradually restored. Here, HCC cells underwent heat treatment and were cultured under hypoxic conditions to mimic the aforementioned situation, and morphological changes were observed in the surviving cells. Compared with their parental cells, hypoxic HCC cells showed changes that include enhanced invasive, metastatic, and chemoresistant abilities as well as mesenchymal characteristics. There was also a higher percentage of stem-like cells. However, either improving the hypoxic microenvironment or silencing hypoxia inducible factor (HIF)-1α signaling significantly reduced the invasive, metastatic, and chemoresistant potential and reversed the epithelial-mesenchymal transition to varying degrees. Together, these results indicated that a sustained hypoxic microenvironment after RFA may exert a negative impact on the prognosis of HCC patients, and minimizing exposure to a hypoxic microenvironment and targeting HIF-1α signaling might be effective strategies for patients who experience insufficient RFA therapy.

Diagnosis of sub-centimetre breast lesions: combining BI-RADS-US with strain elastography and contrast-enhanced ultrasound-a preliminary study in China.

OBJECTIVES: To compare the diagnostic efficacies of B-mode ultrasound (US), strain elastography (SE), contrast-enhanced ultrasound (CEUS) and the combination of these modalities for breast lesions <1 cm in size. METHODS: Between January 2013 and October 2015, 203 inpatients with 209 sub-centimetre breast lesions categorised as BI-RADS-US (Breast Imaging Reporting and Data System for Ultrasound) 3-5 were included. US, SE and CEUS were performed to evaluate each lesion. The diagnostic performances of different ultrasonic modalities were compared. The diagnostic efficacies of BI-RADS-US and our re-rating systems were also compared. The pathology findings were used as the reference standard. RESULTS: The specificities of US, SE and CEUS for tumour differentiation were 17.4 %, 56.2 % and 86.0 %, respectively (P < 0.05); and the sensitivities were 100 %, 93.2 % and 93.2 % for US, SE and CEUS, respectively (P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.867 for original BI-RADS-US, 0.882 for BI-RADS-US combined with only SE, 0.953 for BI-RADS-US combined with only CEUS and 0.924 for BI-RADS-US combined with both SE and CEUS. The best combination was BI-RADS-US combined with only CEUS. CONCLUSIONS: Evaluating sub-centimetre breast lesions with SE and CEUS could increase the diagnostic specificity while retaining high sensitivity compared with B-mode ultrasound. KEY POINTS: • Evaluating breast lesions with SE and CEUS could increase the diagnostic specificity • SE and CEUS offer alternatives to biopsy and possibly allow shorter-interval follow-ups • BI-RADS-US combined with CEUS exhibited the best diagnostic performance.

Reducing major lower extremity amputations after the introduction of a multidisciplinary team in patient with diabetes foot ulcer.

BACKGROUND: Diabetic foot ulceration is receiving more attention because of its high amputation and mortality rate. It is essential to establish the frequency of amputations in people with diabetes after any change to the management of diabetic foot care. The present study aim to compare the frequency of lower-extremity amputations in patients with diabetes foot ulcer over a ten-year period. METHODS: Six hundred forty eight patients with diabetes foot ulcer were retrospectively studied from 2004 to 2013. The clinical features, laboratory results and the lower-extremity amputations were recorded. Major amputation was defined as amputations above the ankle while minor amputation was amputations below the ankle in the present study. RESULTS: Patients with diabetic foot ulcer were old (age 66.96 ± 11.96 years), with a long duration of diabetes (10.30 ± 6.94 years), high HbA1c (9.19 ± 2.62 %), SBP (144.05 ± 24.18 mmHg), DBP (79.53 ± 11.88 mmHg), LDL-C (2.71 ± 0.93 mmol/L) and had great frequency of neuropathy (62.7 %), retinopathy (45.0 %), nephropathy (39.5 %) and PAD (33.2 %). From 2004 to 2013, the frequency of all lower-extremity amputations is 12.0 % (5.2 % major amputation, 6.8 % minor amputation). The frequency of major amputations decreased from 9.5 % in 2004 and 14.5 % in 2005 to less than 5.0 % after 2006. In particular, there was a significant decline in major amputations of diabetic foot patient with Wagner 3 to 4 wounds. The frequency rate of major amputations in diabetic foot patient with Wagner 3 to 4 wounds fell from 35.7 % in 2004 to 4.4 % after 2007. The change in frequency of minor amputations was fluctuation. CONCLUSION: This study demonstrates that the introduction of a multidisciplinary team, coordinated by an endocrinologist and a podiatrist, for managing diabetic foot disease is associated with a reduction in the frequency of major amputations in patients with diabetes.

Cilostazol Can Increase Skin Oxygen Supply Assessed by Transcutaneous Oxygen Pressure Measurement in Type 2 Diabetes With Lower Limb Ischemic Disease: A Randomized Trial.

PURPOSE: The purpose of this study was to compare the efficacy and safety of cilostazol versus acetylsalicylic acid (ASA) for amelioration of lower limb ischemia in type 2 diabetes. DESIGN: Prospective, randomized positive-controlled open clinical trial. SUBJECTS AND SETTING: Eighty-nine patients with type 2 diabetes mellitus and symptoms of lower limb ischemia (perceptions of coldness of the lower limbs, numbness, intermittent claudication, or pain at rest) present for 6 months or more that had not significantly changed within the past 3 months participated in the study. All subjects had an initial transcutaneous oxygen pressure (TcpO2) of less than 40 mm Hg in the foot when measured in the supine position. Subjects included 46 males and 43 females; their ages ranged from 35 to 80 years. METHODS: Participants were randomly allocated to 2 groups, one was treated with cilostazol 100 mg taken twice daily (n = 48), and a second group took 100 mg of ASA daily (n = 41) for 8 weeks. Clinical assessment included measurement of transcutaneous oxygenation, and symptoms associated with lower limb ischemia. Blood analyses included a full blood panel, coagulation screen, renal function tests, hepatic function tests, and lipid profiles. All tests were performed at baseline and repeated at 8 weeks. RESULTS: Age, duration of diabetes, diabetic complications, lower limb ischemic symptoms, TcpO2, and smoking status did not differ between the 2 groups. In contrast, TcpO2 significantly improved from 37.1 ± 11.9 mm Hg to 42.0 ± 9.7 mm Hg in the cilostazol-treated group (P < .05), whereas no significant change was observed in the ASA-treated group (P > .05). Ischemic symptoms such as intermittent claudication (P = .009), perception of limb coldness (P = .008), and pain at rest (P = .017) showed greater improvement in the cilostazol-treated group when compared to subjects treated with ASA. Approximately 10% of patients treated with cilostazol experienced adverse side effects (palpitations, headache, diarrhea). Cilostazol was not found to have significant detrimental effects in hematologic or biochemical indices, including renal, hepatic, and blood coagulant function tests. CONCLUSIONS: We found that 8 weeks of treatment with cilostazol 100 mg daily was safe and well tolerated for the treatment of type 2 diabetes with lower limb ischemic disease.

Thermal ablation versus liver resection for hepatocellular carcinoma in patients with cirrhosis: a systematic review and meta-analysis of propensity-score matched studies.

The outcomes of cirrhotic patients with hepatocellular carcinoma (HCC) after thermal ablation (TA) versus liver resection (LR) are debated. We aimed to compare the overall survival (OS), disease-free survival (DFS), and operative outcomes after TA and LR for HCC in patients with cirrhosis. Until November 15, 2022, we searched PubMed, Embase, and Cochrane databases by using Medical Subject Heading terms and other terms, and used the Newcastle-Ottawa literature evaluation scale to assess the quality of selected studies. OS, DFS, and operative outcomes were extracted and analyzed. The meta-analysis showed that 5 propensity-score matched (PSM) studies including 933 patients (463 TA vs. 470 LR) were included. After analysis, TA and LR had similar results at 1-year OS (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.01-2.78; P = 0.05) and 3-year OS (OR 0.76; 95% CI 0.56-1.04; P = 0.08), whereas LR increased 5-years OS (OR 0.37; 95% CI 0.18-0.74; P = 0.005). In addition to the DFS, the 1-year DFS was significantly higher in patients with LR. However, there were no obvious differences in 3-year and 5-year DFS when comparing TA and LR. The length of operative time and hospital stay were longer in the LR group. Besides, the LR group had significantly higher rate of perioperative blood transfusions and major complications. Our research proved that LR took advantage of OS and DFS for HCC patients with cirrhosis. Additional well-designed randomized controlled trials are needed.

Deep Learning Methods in Medical Image-Based Hepatocellular Carcinoma Diagnosis: A Systematic Review and Meta-Analysis.

(1) Background: The aim of our research was to systematically review papers specifically focused on the hepatocellular carcinoma (HCC) diagnostic performance of DL methods based on medical images. (2) Materials: To identify related studies, a comprehensive search was conducted in prominent databases, including Embase, IEEE, PubMed, Web of Science, and the Cochrane Library. The search was limited to studies published before 3 July 2023. The inclusion criteria consisted of studies that either developed or utilized DL methods to diagnose HCC using medical images. To extract data, binary information on diagnostic accuracy was collected to determine the outcomes of interest, namely, the sensitivity, specificity, and area under the curve (AUC). (3) Results: Among the forty-eight initially identified eligible studies, thirty studies were included in the meta-analysis. The pooled sensitivity was 89% (95% CI: 87-91), the specificity was 90% (95% CI: 87-92), and the AUC was 0.95 (95% CI: 0.93-0.97). Analyses of subgroups based on medical image methods (contrast-enhanced and non-contrast-enhanced images), imaging modalities (ultrasound, magnetic resonance imaging, and computed tomography), and comparisons between DL methods and clinicians consistently showed the acceptable diagnostic performance of DL models. The publication bias and high heterogeneity observed between studies and subgroups can potentially result in an overestimation of the diagnostic accuracy of DL methods in medical imaging. (4) Conclusions: To improve future studies, it would be advantageous to establish more rigorous reporting standards that specifically address the challenges associated with DL research in this particular field.

External Validation of Ultrasound Radiomics for Small (≤ 4 cm) Renal Mass Differentiation: A Comparison with Radiologists.

BACKGROUND: Renal cell carcinoma, especially in small renal masses (≤ 4 cm) (SRM), has increased. Pathological analysis revealed a high proportion of benign masses, highlighting the urgent need for precise SRM differentiation. OBJECTIVES: This research aimed to independently validate the performance of machine learning-based ultrasound (US) radiomics analysis in differentiating benign from malignant SRM, and to compare its performance with that of radiologists. METHODS: A total of 499 patients from two hospitals were retrospectively included in this study and divided into two cohorts. US images were used to extract radiomics features. To obtain the most robust features, inter-observer correlation coefficient, Spearman correlation coefficient, and least absolute shrinkage and selection operator methods were applied for feature selection. Three models were developed in the training data using the stochastic gradient boosting algorithm, including a clinical model, a radiomics model, and a combined model that integrated clinical factors and radiomics features. The performance of these models was evaluated in the independent external validation data, including discrimination, calibration, and clinical usefulness, and compared with pooled radiologists' assessments. RESULTS: The AUCs of the clinical, radiomics, and combined models were 0.844, 0.942, and 0.954, respectively. The radiomics and combined models significantly outperformed the clinical model (all p < 0.05), while no significant difference was observed between them (p = 0.32). The radiomics and combined models showed good discrimination and calibration. Decision curve analysis exhibited that the combined model had clinical usefulness. Compared with the pooled radiologists' assessment (AUC, 0.799), the combined model showed superior classification results (p < 0.01) and higher specificity (p < 0.01) with similar sensitivity (p = 0.62). CONCLUSION: The combined model incorporating clinical factors and radiomics features accurately distinguished benign from malignant SRM.

Fully Automatic Dual-Probe Lung Ultrasound Scanning Robot for Screening Triage.

Two-dimensional lung ultrasound (LUS) has widely emerged as a rapid and noninvasive imaging tool for the detection and diagnosis of coronavirus disease 2019 (COVID-19). However, image differences will be magnified due to changes in ultrasound (US) imaging experience, such as US probe attitude control and force control, which will directly affect the diagnosis results. In addition, the risk of virus transmission between sonographer and patients is increased due to frequent physical contact. In this study, a fully automatic dual-probe US scanning robot for the acquisition of LUS images is proposed and developed. Furthermore, the trajectory was optimized based on the velocity look-ahead strategy, the stability of contact force of the system and the scanning efficiency were improved by 24.13% and 29.46%, respectively. Also, the control ability of the contact force of robotic automatic scanning was 34.14 times higher than that of traditional manual scanning, which significantly improves the smoothness of scanning. Importantly, there was no significant difference in image quality obtained by robotic automatic scanning and manual scanning. Furthermore, the scanning time for a single person is less than 4 min, which greatly improves the efficiency of screening triage of group COVID-19 diagnosis and suspected patients and reduces the risk of virus exposure and spread.

Qualitative and quantitative features of deep endometriosis in contrast-enhanced ultrasound: An initial experience and literature review.

PURPOSE: This research aims to present the findings of contrast-enhanced ultrasound (CEUS) in a series of patients with proven deep endometriosis (DE) and provide an updated literature review. MATERIALS AND METHODS: Between January 2018 and October 2022, seven patients with DE lesions had their imaging and medical records retrospectively reviewed. Clinical data, recorded images of a standardized conventional B-mode ultrasound, and Sonovue® CEUS were interpreted by two blinded, independent, experienced radiologists in consensus. The enhanced characteristics of the DE lesion on CEUS were also assessed using VueBox® software quantitatively. RESULTS: DE lesion appeared as irregular hypoechoic or heterogeneous on conventional ultrasound with dotted blood flow signal on color Doppler. Six of seven DE lesions showed heterogeneous hypo-enhancement in arterial phases. All the lesions showed a heterogeneous washout rapidly that began in the late arterial phase. In quantified analysis, the mean relative peak enhancement compared with adjacent tissue was 0.47±0.25. CONCLUSION: Our findings and literature review suggested that CEUS could be a feasible and promising non-invasive modality for diagnosing DE.

Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.