Objective: DBPR108, a novel dipeptidyl-peptidase-4 inhibitor, has shown great antihyperglycemic effect in animal models. This study was to evaluate the efficacy and safety of DBPR108 monotherapy in type 2 diabetes mellitus (T2DM).Methods: This was a 12-week, double-blind, placebo-controlled phase II clinical trial. The newly diagnosed or inadequately controlled untreated T2DM patients were randomized to receive 50, 100, 200 mg DBPR108 or placebo in a ratio of 1:1:1:1. The primary efficacy outcome was HbA1c change from baseline to week 12. Relevant secondary efficacy parameters and safety were assessed. The clinical trial registration is NCT04124484.Results: Overall, 271 of the 276 randomized patients, who received 50 mg (n = 68), 100 mg (n = 67), 200 mg (n = 69) DBPR108 or placebo (n = 67), were included in full analysis set. At week 12, HbA1c change from baseline was -0.04 ± 0.77 in placebo group, -0.51 ± 0.71, -0.75 ± 0.73, and -0.57 ± 0.78 (%, p < .001 vs. placebo) in 50, 100, and 200 mg DBPR108 groups, respectively. Since week 4, DBPR108 monotherapy resulted in significant improvements in secondary efficacy parameters. At end of 12-week treatment, the goal of HbA1c ≤7% was achieved in 29.85, 58.82, 55.22, and 47.83% of the patients in placebo, 50, 100, and 200 mg DBPR108 groups, respectively. The incidence of adverse events did not show significant difference between DBPR108 and placebo except mild hypoglycemia in DBPR108 200 mg group.Conclusions: The study results support DBPR108 100 mg once daily as the primary dosing regimen for T2DM patients in phase III development program.
Objective
To investigate the diagnostic value of pyruvate kinase M2(PKM2)gene expression in papillary thyroid carcinoma(PTC).
Methods
Quantitative real-time PCR(RT-qPCR)was used to detect the expression of PKM2 mRNA in benign thyroid nodules, PTC, and normal thyroid tissues around nodules of fine-needle aspiration(FNA)specimens. Immunohistochemistry(IHC)was used to detect the expression of PKM2 protein in thyroid tissue after thyroidectomy. The receiver operating characteristic curve was constructed to evaluate the diagnostic value of PKM2 in PTC.
Results
The expression of PKM2 mRNA was detectable in FNA specimens of thyroid nodules, higher in PTC than those in normal thyroid tissue and benign thyroid nodules(P 0.05). The expression level of PKM2 mRNA in FNA specimens of thyroid nodules was paralleled with the expression level of PKM2 protein in postoperation pathological tissues. The accuracy, sensitivity, specificity of PKM2 gene in the diagnosis of PTC were 62.8%, 46.9%, and 95.7%, respectively. The accuracy and sensitivity of PKM2 combined with BRAFV600E were increased to 87.6% and 83.7%, significantly higher than those of single detection (P<0.05) .
Conclusion
Detection of PKM2 gene in FNA specimens is highly specific in the diagnosis of PTC, making it a valuable molecular marker for preoperative diagnosis. The combination of PKM2 and BRAFV600E detection shows a higher diagnosis efficiency.
Key words:
Papillary thyroid carcinoma; Pyruvate kinase M2; Fine-needle aspiration
Abstract This study aimed to assess the severity of acute radiodermatitis (ARD) by ultrasound quantitative parameters and to try to identify the influencing factors of skin toxicity. A total of 55 patients who underwent radiotherapy after unilateral breast-conserving surgery (BCS) were included in the study. The irradiated side of the breast was used as the research object and the quantitative ultrasound parameters (skin thickness, shear wave elasticity) were evaluated before radiotherapy, every week during radiotherapy. Two weeks after radiotherapy, the patients were divided into two groups, according to the World Health Organization scoring standard: mild (0–2 grade) and severe (3–4 grade). The differences in the parameters between the groups and the changes during radiotherapy were compared, and the relationship between these parameters and the severity of ARD was analyzed. In addition, some clinical factors that may affect ARD were also included in our study. Ninety-eight percent of patients developed different degrees of ARD, and Group 2 accounted for ~31%. At the end of 5 weeks of radiotherapy, the difference in thickness between the two groups was statistically significant (P < 0.05). There was no significant change in the elastic modulus of breast skin between the two groups (P > 0.05). Body mass index >25 kg/m2, breast thickness ≥18 mm, skin basic elastic modulus <23 kPa and skin thickness increment >0.3 mm were considered to be associated with severe skin reactions (P < 0.05). Ultrasound can be a useful tool for the non-invasive and objective assessment of skin changes during radiotherapy, documenting quantitative changes in the skin of breast cancer patients following BCS undergoing radiotherapy.
Fine needle aspiration biopsy is a crucial method for preoperative diagnosis of thyroid nodules. However, thyroid nodules classified as Bethesda categories III-V cannot obtain definite cytological results. Our aim was to study the diagnostic value of thyroid imaging reporting and data system combined with BRAFV600E mutation analysis in Bethesda categories III-V thyroid nodules, so as to provide more precise direction for the follow-up treatments. A total of 174 Bethesda categories III-V thyroid nodules performed TIRADS and BRAFV600E mutation analysis were included in the study. We retrospectively analyzed the ultrasound features as well as the results of BRAFV600E mutation of the 174 thyroid nodules. In the multiple regression analysis models, ultrasound features including lobulated or irregular margin, punctate echogenic foci, and shape with taller-than-wide were statistically significant in malignant nodules (p < 0.05). The area under the curve of the combination of TIRADS and BRAFV600E increased to 0.925, which were much higher than TIRADS (0.861) and BRAFV600E (0.804) separately. Combined diagnosis was of the greatest value to identify Bethesda III-V thyroid nodules definitely, especially with higher sensitivity (93%) and accuracy (90%).
Abstract Objective : To explore the risk factors of lateral cervical lymph node metastasis(LLNM) in thyroid papillary carcinoma (PTC), establish a nomograph prediction model to predict the probability of LLNM before operation, reduce the risk of recurrence, avoid secondary surgery, and achieve the goal of accurate treatment. Methods : In this retrospective study, 242 patients were enrolled and randomly divided into two groups according to the ratio of 7:3. The preoperative clinical data of patients (including ultrasonic characteristics and selected clinical characteristics) were collected, and least absolute shrinkage and selection operator (Lasso) in the training cohort was used to screen the influencing factors. Based on the results of multivariable logistic regression, the nomograph model is established, and its performance is evaluated by its identification, calibration and clinical usefulness in training and validation cohorts. Results : This study showed that age>45 years (OR 0.340; 95%CI 0.129-0.856), abnormal serum TG (OR 3.626; 95%CI 1.397-10.187), thyroid tumer location1 (OR 0.250; 95%CI 0.083-0.702), US-reported positive central cervical lymph node (CLN) (OR 3.116; 95%CI 1.152-8.601), and US-reported positive LLN (OR 8.426; 95%CI 3.192-23.779) were independent risk factors for LLNM of PTC. The nomogram constructed based on the above factors has good resolution and calibration in predicting the LLNM of PTC. The Concordance index (C-index) of the experimental group and the validation group are 0.880 and 0.937, respectively. Conclusion : The nomogram based on ultrasound and clinical features constructed in this study has good performance in non-invasive predicting LLNM of PTC and is expected to promote clinical decision-making.
Abstract Objective This study aimed to explore whether superficial invasive lymphomas and indolent lymphomas could be identified by Ultrasonographic vascular imaging. Method A retrospectively study enrolled 82 lymphoma patients. According to proliferation rates and clinical course, the lymph nodes were classified as invasive and indolent lymphomatous lymph nodes. All patients underwent ultrasound (US) with three effective techniques: color Doppler flow imaging (CDFI), angio plus ultrasound imaging (AngioPLUS), and contrast-enhanced ultrasound (CEUS). Qualitative and quantitative parameters from the two groups were compared. Finally, the area under the receiver-operating characteristic (ROC) and regression analysis were used to compare the differences between the two groups and determine the diagnostic efficiency of the three techniques for differentiating invasive lymphoma from indolent lymphoma. Result The types of blood flow distribution between invasive and indolent lymphomatous lymph nodes were statistically different in all three Ultrasound techniques. In CDFI, invasive or indolent lymphomatous lymph nodes were determined by resistance index (RI) (p < 0.001). In CEUS, the differences between the two groups in necrosis and arrival time (ATM) (p = 0.026, 0.043) were statistically significant. Finally, CDFI combined with CEUS had the highest diagnostic sensitivity of 98.1%. Interobserver agreements for qualitative parameters were all excellent. Conclusion Ultrasonographic Vascular imaging is an aid in identifying invasive and indolent lymphomatous lymph nodes, and CDFI combined with CEUS had the highest diagnostic sensitivity, which can guide clinicians to make more accurate diagnosis and better treatment for patients.
Abstract Background The dissection of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) in papillary thyroid carcinoma (PTC) remains controversial due to the postoperative complications. Estimating the clinical probability of metastasis in LN-prRLN can facilitate the selective dissection. Objective To develop a clinical prediction model based on clinical and sonographic features for estimating the probability of metastasis of LN-prRLN in PTCs. This model was then validated. Methods A total of 601 patients with surgical-proved PTCs in the First Affiliated Hospital of Nanjing Medical University were evaluated retrospectively. Clinical data, preoperative sonographic features based on ACT TI-RADS categories, and pathological data were used to develop an US-based clinical prediction model. Performance of the model was calculated, compared and then validated by using a test set of 144 patients. Results LN-prRLN metastasis was confirmed in 133 (22.1%) patients. The US-based clinical prediction model identified age < 45 years (odds ratio [OR]:1.752), horizontal diameter > 5mm (OR:1.061), dorsal side (OR:2.185), US-suspicious RLLNM (OR:2.488), pathological size > 5mm (OR:3.697), mulifocality in the right robe (OR:2.584), other CLN metastasis (OR:2.185) and LN-arRLN metastasis ≥ 1 (OR:3.915) were independent risk factors for LN-prRLN metastasis. The AUCs of the clinical prediction model was 0.835 (95% CI: 0.803–0.864). The sensitivity, specificity, positive predictive value, and negative predictive value were 76.69%, 78.42%, 50.20%, and 92.22%, respectively. The clinical prediction model applied to the test dataset demonstrated an AUC of 0.804 (95% CI:0.722–0.886), sensitivity, specificity, positive predictive value, and negative predictive value of 78.79%, 72.07%, 43.88% and 92.46%. Conclusions The clinical prediction model based on clinical and sonographic characteristics can effectively assess LN-prRLN metastasis preoperatively and do help in selective LN-prRLN dissection of PTC.
Abstract Background: This meta-analysis was conducted in order to understand the clinical efficacy of stent insertion with high-intensity focused ultrasound (HIFU) ablation for the treatment of malignant biliary obstruction (MBO). Methods: The Pubmed, Embase, and Cochrane Library databases were searched for all relevant studies published through July 2020. The meta-analysis was conducted using RevMan v5.3, with analyzed study endpoints including the rate of stent dysfunction, time to stent dysfunction, stent patency, complication rate, and overall survival (OS). Results: In total, 35 potentially relevant studies were initially identified, of which 6 were ultimately included in the present meta-analysis. These 6 studies included 429 MBO patients that were treated either only via stenting (n = 221) or via stenting in combination with HIFU ablation (n = 208). Pooled stent dysfunction rates in the stent and stent with HIFU groups were 25.9% and 18.0%, respectively (OR: 1.59; 95% CI: 0.88, 2.84, P = .12). The average time to stent dysfunction was significantly longer in the stent with HIFU group relative to the stent group (MD: −3.15; 95% CI: −3.53, −2.77, P < .0001). Pooled complication rates in the stent and stent with HIFU groups were 17.1% and 19.6%, respectively (OR: 0.88; 95% CI: 0.49, 1.58, P = .67). Stent patency and OS were both significantly longer in the stent with HIFU group relative to the stent group ( P < .0001 and.0001, respectively). Funnel plot analyses did not reveal any significant evidence of publication bias linked to the selected study endpoints. Conclusions: This meta-analysis found that a combined stenting and HIFU ablation approach can achieve better stent patency and OS in MBO patients relative to stent insertion alone.
Objective To explore the application value of ultrasound-guided fine needle aspiration biopsy(FNAB) in diagnosing thyroid nodules of TI-RADS 4-6 categories.Methods A retrospective analysis was made on the pathologic data of 494 patients (totally 501 nodules) who underwent TI-RADS ultrasonographic stratification and ultrasound-guided FNAB.168 thyroid nodules of TI-RADS 4-6 categories were selected from 163 patients and classified into three groups:group T,TI-RADS 4A categories;group Ⅱ,TI-RADS 4B category; group Ⅲ,TI-RADS 5-6 category(the pathologically confirmed cases in category 6 had been removed).The ultimate pathologic findings were taken as golden standards to calculate the accuracy,sensitivity,specificity,positive predictive value of ultrasound-guided FNAB in the three groups.ROC curve was drawn to evaluate the diagnostic value of FNAB.Results The accuracy,sensitivity,specificity,positive predictive value of the ultrasound-guided FNAB in the three groups were listed as follows:group Ⅰ 74.4％,73.3％,75.0％,64.7％;group Ⅱ 83.9％,87.5％,71.4％,91.3％;group Ⅲ 89.3％,91.7 ％,75.0％,95.7 ％ respectively.The positive predictive values of the ultrasound-guided FNAB for group Ⅰ and group Ⅱ was higher than that of conventional TI-RADS classification criteria,so the difference was statistically significant; while the positive predictive values for group Ⅲ was close to the conventional ultrasound TI-RADS classification criteria,the difference was not statistically significant.Conclusions The combination application of TI-RADS classification criteria and FNAB can improve the accuracy of ultrasound diagnosis in group Ⅰ and group Ⅱ,and reduce the puncture rate of group Ⅲ.
Key words:
Ultrasonography; Thyroid nodules ; Biopsy, fine-needle; TI-RADS 4-6 categories
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