Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To explore the value of the Nomogram model established by CT radiomics combined with clinical indicators for prediction of the severity of early acute pancreatitis (AP).Methods:From January 2016 to March 2023, the AP patients in the Second Affiliated Hospital of Soochow University were retrospectively collected. According to the revised Atlanta classification and definition of acute pancreatitis in 2012, all patients were divided into the severe group and the non-severe group. All patients were first diagnosed, and abdominal CT plain scan and enhanced scan were completed within 1 week. Patients were randomly (random number) divided into training and validation groups at a ratio of 7:3. The pancreatic parenchyma was delineated as the region of interest on each phase CT images, and the radiomics features were extracted by python software. LASSO regression and 10-fold cross-validation were used to reduce the dimension and select the optimal features to establish the radiomics signature. Multivariate Logistic regression was used to select the independent predictors of severe acute pancreatitis (SAP), and a clinical model was established. A Nomogram model was established by combining CT radiomics signature and clinical independent predictors. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the predictive efficacy of each model.Results:Total of 205 AP patients were included (59 cases in severe group, 146 cases in non-severe group). 3, 5, 5 and 5 optimal radiomics features were selected from the plain CT scan, arterial phase, venous phase and delayed phase images of all patients, and the radiomics models were established. Among them, the arterial phase radiomics model had relatively better performance in predicting SAP, with an area under curve (AUC) of 0.937 in the training group and 0.913 in the validation group. Multivariate Logistic regression showed that C-reactive protein (CRP) and lactate dehydrogenase (LDH) were independent predictors of SAP, and they were used to establish a clinical model. The AUC in the training and validation groups were 0.879 and 0.889, respectively. The Nomogram model based on arterial phase CT radiomics signature, CRP and LDH was established, and the AUC was 0.956 and 0.947 in the training group and validation group, respectively. DCA showed that the net benefit of Nomogram model was higher than that of clinical model or radiomics model alone.Conclusions:The Nomogram model established by CT radiomics combined with clinical indicators has high application value for early prediction of the severity of AP, which is conducive to the formulation of clinical treatment plans and prognosis evaluation.

Objective:To investigate the value of dual-detector spectral CTA in distinguishing infarct core from penumbra in patients with acute ischemic stroke(AIS), and to further explore the risk factors associated with infarct core and their predictive value.Methods:The imaging and clinical data of 163 patients with AIS who met the inclusion criteria admitted to the Second Affiliated Hospital of Soochow University from March 2022 to May 2023 were retrospectively analyzed. Patients from March 2022 to December 2022 were used as the training group, and patients from January 2023 to May 2023 were used as the validation group for internal validation. The head and neck spectral CTA and brain CT perfusion imaging with dual-layer detector spectral CT were all carried out on all patients. Using CTP as reference, the patients were divided into infarct core group and non-infarct core group according to whether an infarct core occurred in the hypoperfusion regions of brain tissue. Multivariate logistic regression analysis was used to screen predictors related to the infarct core. The receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy.Results:A total of 163 patients were included in the study, including 112 in the training group and 51 in the validation group. There were significant differences in iodine density, effective atomic number, hypertension, triglyceride and neutrophils between the two groups ( P< 0.05). The cutoff values for iodine density values and effective atomic number values were 0.215 mg/mL and 7.405, respectively. Multivariate logistic regression analysis showed that iodine density and hypertension were independent risk factors for infarct core in AIS, and triglyceride was an independent protective factor. The area under the ROC curve (AUC) of iodine density value was the largest (0.859), with a sensitivity of 70.27%, and a specificity of 90.67%, which had a good predictive value. The ROC curve analysis results for the validation group were consistent with the training group. Conclusions:Spectral CT parameters iodine density values and effective atomic number values have the potential to distinguish the infarct core area from the penumbra area in patients with AIS. Iodine density and hypertension were independent risk factors of infarct core in AIS, triglyceride was an independent protective factor, and iodine density values obtained by dual-layer spectral detector CT had a high predictive value.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To establish and validate a nomogram model for early prediction of the risk of acute pancreatitis (AP) progressing to severe acute pancreatitis (SAP).Methods:CT signs and clinical laboratory parameters of 361 AP patients admitted to our Hospital from January 2016 to July 2022 were retrospectively collected. There were 221 males (61.2%) and 140 females (38.8%). According to the Atlantic score, all patients were divided into the SAP group (64 cases) and the non-SAP (NSAP) group (297 cases). Univariate analysis was used to screen out variables with statistically significant differences. Multivariate Logistic regression analysis was used to screen out the independent risk factors of SAP, and finally a nomogram prediction model was established. Receiver operating characteristic (ROC) curve, calibration curve and decision curve (DCA) were used to evaluate the predictive efficacy, accuracy and clinical practicability of the model, and Bootstrap method was used to verify the model internally.Results:Univariate analysis and multivariate Logistic regression analysis showed that pleural effusion ( OR=7.353, 95% CI: 3.344-16.170), posterior pararenal space (PPS) involvement ( OR=3.149, 95% CI: 1.314-7.527), serum creatinine concentration (Cr) ( OR=1.027, 95% CI: 1.017-1.038) and serum calcium concentration (Ca 2+) ( OR=0.038, 95% CI: 0.009-0.166) were independent risk factors for SAP ( P<0.05). A Nomogram model was established based on these four factors. The area under the ROC curve (AUC) of this model was 0.905 (95% CI: 0.869-0.933), indicating high predictive efficiency. Internal verification showed that the model had good accuracy in predicting SAP, and C-index was 0.90. DCA analysis showed that the model had high clinical practicability. Conclusions:The Nomogram model combining pleural effusion, PPS involvement, Cr and Ca 2+ had a good effect on early prediction of SAP, which could provide a new reference tool for clinical diagnosis and treatment.

Objective:To investigate the efficacy of osteochondral fragment fixation using bioabsorbable pins for Hepple Ⅱ osteochondral lesions of the talus (OLT) in adolescents.Methods:Retrospective case analysis was used. The clinical data and follow-up results of 13 adolescent patients (13 feet) with Hepple Ⅱ OLT were all treated with osteochondral fragment fixation using bioabsorbable pins admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were retrospectively analyzed. There were 7 males and 6 females, with 13 right feet. The age was (14.85±2.23) years old, ranged from 12 to 18 years old. According to the American orthopedic foot and ankle society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS) and SF-36 score before operation and at the last follow-up were used to evaluate the efficacy and function of the patients. Measurement data with normal distribution were represented as mean ± standard deviation( ± s), and the comparison between groups was conducted using the t-test; The mearsurement data with skewness distribution were expressed by M( Q1, Q3), and rank-sum test was used for inter-group comparison. Results:Thirteen adolescent patients (13 feet) with Hepple Ⅱ OLT underwent surgery successfully and were followed up for (25.54±9.95) months. All wounds healed by first intention, and no complications such as wound infection and delayed healing occurred. Preoperative AOFAS ankle-posterior foot score, VAS and SF-36 score were 58.62±3.55, 7.00 (6.50, 8.00) and 68.38±4.81, respectively. At the last follow-up, the scores were 97.38±2.73, 1.00 (0.00, 1.00), 91.15±4.28, respectively, and the results were significantly improved at the last follow-up, with the difference between the two groups statistically significant( P<0.05). Conclusion:Osteochondral fragment fixation using bioabsorbable pins which can promote cartilage repair, significantly improve symptoms, and achieve better clinical satisfaction with fewer complications, is a safe and effective surgical treatment option for Hepple Ⅱ OLT in adolescents with satisfactory short-term clinical outcomes.

Ankle Injuries ; Fractures, Compression ; Humans ; Knee Injuries

Objective:To evaluate the short-term outcome of arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy for the treatment of chronic lateral ankle instability combined with subtle cavus foot.Methods:A retrospective cohort study was conducted to analyze the clinical data of 12 patients suffering chronic lateral ankle instability combined with subtle cavus foot admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from November 2016 to November 2020, including 5 males and 7 females, aged 16-62 years [(40.3±15.1)years]. All patients were treated with arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy. The calcaneal pitch angle, Meary′s angle and medial cuneiform height on the foot weight-bearing lateral view plus calcaneus valgus angle on the hindfoot long axial view were compared to evaluate the improvement of bony structure and foot alignment preoperatively and at 3 months and 1 year postoperatively. At the same time, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) were used to evaluate the improvement of ankle function and pain. Postoperative complications were also observed and recorded.Results:All patients were followed up for 1-3 years [(1.6±0.6)years]. The calcaneal pitch angle was decreased from (24.6±5.3)° preoperatively to (22.5±4.9)° at postoperative 3 months and (22.3±5.0)° at postoperative 1 year; the Meary′s angle was decreased from 6.6°(5.2°,7.6°) preoperatively to 2.5°(0.5°,3.8°) at postoperative 3 months and 2.1°(0.5°,3.2°) at postoperative 1 year; the medial cuneiform height was decreased from (24.3±5.3)mm preoperatively to (22.3±4.8)mm at postoperative 3 months and (22.3±4.6)mm at postoperative 1 year; the calcaneus valgus angle was increased from -7.1°(-10.3°,-5.9°) preoperatively to 2.3°(-2.5°,4.5°) at postoperative 3 months and 2.4°(-1.6°,3.8°) at postoperative 1 year (all P<0.01). However, there were no significant differences in the calcaneal pitch angle, Meary′s angle, medial cuneiform height, and calcaneus valgus angle at postoperative 3 months and 1 year (all P>0.05). AOFAS ankle-hindfoot score was increased from (66.8±8.7)points preoperatively to (81.0±5.9)points at postoperative 3 months and (88.6±3.6)points at postoperative 1 year (all P<0.01). According to AOFAS ankle-hindfoot score, the results were excellent in four patients and good in eight patients at postoperative 1 year, with the excellent and good rate of 100%. VAS was decreased from 2.5(2.0,4.0)points preoperatively to 2.0(1.3,2.8)points at postoperative 3 months and 1.0(0,2.0)points at postoperative 1 year (all P<0.01). There were significant differences in the AOFAS ankle-hindfoot score and VAS at postoperative 3 months and 1 year (all P<0.05). Wound malunion was seen in one patient, and healed with a dress changing. All patients had no complications such as vascular or nerve injury. There was no recurrence of malformation or joint instability during 1-year follow-up. Conclusion:For chronic lateral ankle instability combined with subtle cavus foot, arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy can stabilize ankle joint, correct hindfoot alignment, improve function and relieve pain.

Objective:To investigate the efficacy of posterior ankle arthroscopic microfracture with platelet-rich plasma (PRP) injection for the treatment of posterior osteochondral lesions of the talus (OLT).Methods:A retrospective case series study was conducted on clinical data of 13 patients with posterior OLT admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from September 2019 to October 2020. There were 10 males and 3 females, aged 10-65 years [(38.2±15.9)years]. According to Hepple′s classification, four patients were with type II, three with type IV, and six with type V. According to Elias′ grid scheme, nine patients were in zone 7 and four patients in zone 9. The disease duration was 13-51 months [(26.2±11.4)months]. All patients underwent posterior ankle arthroscopic microfracture with PRP injection. The operation time was recorded. The visual analogue scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and ankle range of motion (ROM) were compared before operation and at 3 months and 1 year after operation. The magnetic resonance observation of cartilage repair tissue (MOCART) score was used to evaluate the repair of cartilage injury at 1 year after operation. Complications were recorded.Results:All patients were followed up for 12-25 months [(15.7±3.7)months]. The operation time ranged from 50 to 90 minutes [(63.8±13.3)minutes]. The VAS improved from 3.0(3.0, 4.0)points before operation to 1.0(0, 2.0)points at 3 months after operation and 1.0(0,1.5)points at 1 year after operation; the AOFAS ankle-hindfoot score was improved from (66.1±11.8)points before operation to (84.8±9.5)points at 3 months after operation and (92.9±8.6)points at 1 year after operation; the ankle ROM was improved from (48.5±7.5)° before operation to (61.9±10.3)° at 3 months after operation and (65.4±11.8)° at 1 year after operation (all P<0.05). There was no significant difference in VAS at 3 months and 1 year after operation ( P>0.05). There were significant differences in AOFAS ankle-hindfoot score and ankle ROM at 3 months and 1 year after operation (all P<0.05). According to AOFAS ankle-hindfoot score, the results were excellent in 11 patients, good in one, and fair in one, with the excellent and good rate of 92%. The MOCART score was 40-85 points [(70.4±14.2)points] at 1 year after operation. There was no postoperative necrosis, infection or neurovascular injury. Two patients had slight transient pain during rehabilitation training and were improved after non-surgical treatment. Conclusion:For posterior OLT, posterior ankle arthroscopic microfracture with PRP injection can effectively alleviate pain, improve ankle function and repair cartilage damage, with satisfactory short-term efficacy.

Objective:To evaluate the mid-term efficacy of surgery for sub-acute injury to distal tibiofibular syndesmosis associated with ankle fracture.Methods:From July 2014 to October 2019, 14 patients were treated at Foot & Ankle Section, Department of Orthopaedics, Shanghai Sixth People’s Hospital for sub-acute injury to distal tibiofibular syndesmosis associated with ankle fracture.There were 11 males and 3 females, aged from 17 to 61 years (mean, 35.9 years).According to Danis-Weber classification, 6 cases were type B and 8 type C; according to Lauge-Hansen classification, 7 cases belonged to supination-external rotation, one to pronation-abduction, and 6 to pronation-external rotation (Maisonneuve fracture in 4).The syndesmosis injury was treated by fixation with distal tibiofibular screws in 11 cases, by Tightrope elastic fixation in one, by hybrid fixation with distal tibiofibular screws and Tightrope in one, and by distal tibiofibular fusion in one.Postoperative complications were recorded.Their visual analogue scale (VAS) and American Orthopaedic Foot and Ankle Society ankle-hindfoot scores (AOFAS-AH) were compared between preoperation and the last follow-up.Results:The 14 patients were followed up for 24 to 85 months (mean, 46.8 months). Of the 9 patients whose distal tibiofibular screws had been removed (including one with hybrid fixation), wound infection occurred in one after removal of all the internal fixation, distal tibiofibular widening in 2, ankle degeneration in 5 and fibular nonunion in one. Of the other 3 patients whose distal tibiofibular screws had not been removed, screw breakage happened in 2, screw loosening in one and distal tibiofibular widening in one. The VAS scores were significantly improved from preoperative 6.8±0.9 to 1.4±1.3 at the last follow-up; the AOFAS-AH scores were increased significantly from preoperative 35.3±6.3 to 86.8±11.7 at the last follow-up (both P<0.001). According to AOFAS-AH scores, 8 cases were excellent, 4 good and 2 moderate. Conclusion:Surgery for sub-acute injury to distal tibiofibular syndesmosis associated with ankle fracture can restabilize the distal tibiofibular syndesmosis and ankle joint, reduce pain and improve ankle function, leading to fine mid-term efficacy.