Construction of Anti-hPD-L1 HCAb Nb6 and in Situ 124I Labeling for Noninvasive Detection of PD-L1 Expression in Human Bone Sarcoma.

Immunotherapy is considered the fourth major treatment mode for cancer following surgery, chemotherapy, and radiotherapy. In recent years, tumor immunotherapy has achieved breakthrough progress; therefore, it is important to screen patients to identify those who will respond to tumor immunotherapy. Here, we report the construction of a novel heavy chain-only antibody (HCAb) and its corresponding 124I-labeled probe. Using phage display technology, we generated a novel anti-hPD-L1-specific HCAb named Nb6 (selected from 95 monoclones) with high affinity for hPD-L1. The positron-emitting 124I-labeled hPD-L1-targeted HCAb probe was prepared for further evaluation, and nonradioactive natural iodine (natI)-labeled anti-hPD-L1 Nb6 was synthesized as a reference compound. 125I-anti-hPD-L1 Nb6 uptake in OS-732 cells in vitro can be blocked by the precursor. The binding affinity of 125I-anti-hPD-L1 Nb6 to OS-732 cell lines was 2.19 nM. For in vivo studies, an osteosarcoma OS-732 tumor-bearing mouse model was successfully constructed. Polymerase chain reaction (PCR) and Western blot analyses were performed to confirm the presence of the hPD-L1 gene and antigen in the tumor tissue of the OS-732 mouse model. Biodistribution showed that uptake of 124I-anti-hPD-L1 Nb6 probes at 24 h was 4.43 ± 0.33% ID/g in OS-732 tumor tissues. Tumor lesions can be clearly delineated on micro-PET (positron emission tomography)/CT (computed tomography) imaging 24 h after injection of 124I-anti-hPD-L1 Nb6, while the blocking group shows substantially decreased uptake on imaging. Pathological staining validated hPD-L1 expression on the surface of the tumor cell membrane; thus, 124I-anti-hPD-L1 Nb6 can be used for in vivo noninvasive PET imaging. When administered in tandem, Nb6 and 124I-anti-hPD-L1 Nb6 may provide a novel strategy to clinically screen patients for hPD-L1 to identify those who would benefit from immunotherapy of malignant tumors such as osteosarcoma.

The effect of anticoagulants on venous thrombosis prevention after knee arthroscopy: a systematic review.

PURPOSE: Knee arthroscopy, with its unique advantages, has become a routine surgery and is widely carried out around the world. Venous thromboembolism (VTE) after knee arthroscopy is a potentially serious complication. This article analyzes the effects of anticoagulant therapy after knee arthroscopy. METHODS: We used key words or entry terms without any limitations to search the PubMed, Embase, and Cochrane Library databases. Randomized controlled trials (RCTs) of drug prophylaxis for VTE after knee arthroscopy until November 2017 were included in our review. RESULTS: This systematic review identified nine RCTs, consisting of 4290 patients, investigating drug prophylaxis in knee arthroscopy. There are three main drugs for preventing thrombosis after arthroscopic knee surgery: low-molecular-weight heparin (LMWH), rivaroxaban, and aspirin. Our study concluded that there is no difference in symptomatic VTE (excluding symptomatic distal DVT) risk during anticoagulant prophylaxis (RR, 0.98; 95% CI, 0.44-2.19; I2 value = 0%; P = 0.97). Moreover, there was a lower incidence of symptomatic distal DVT (RR, 0.16; 95% CI, 0.06-0.45; I2 value = 0%; P = 0.0005) in the anticoagulant group than in the control group. CONCLUSIONS: In our study, anticoagulant therapy after knee arthroscopy was ineffective. We recommend that anticoagulants not be provided routinely after knee arthroscopy.

Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models.

Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herein, we constructed novel organic dopamine-melanin nanoparticles (dMNs) as a carrier and then surface-loaded them with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenograft (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specifically target the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs. 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, micro-PET/CT and PET/MRI showed that the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs as carrier (1.63 ± 0.07 vs. 0.90 ± 0.04 at 24 h, P = 0.002), a similarity found in 64Cu-labeled Her-PEG-dMNPs. Because 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the further evaluation of 124I-Her-PEG-dMNPs. Furthermore, immunohistochemistry staining confirmed the overexpression of HER2 in the animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.

Direct Anterior Approach Versus Posterolateral Approach in Total Hip Arthroplasty: A Systematic Review and Meta-analysis of Randomized Controlled Studies.

OBJECTIVE: To compare the early rehabilitation effects of total hip arthroplasty (THA) with the direct anterior approach (DAA) versus the posterior approach (PA). METHODS: We searched PubMed, Embase, Web of Science, the Cochrane Library, and Google databases from inception to June 2019 to select studies that compared the DAA and PA for THA. Only randomized controlled trials (RCT) were included. Two researchers independently screened studies for inclusion, extracted data, and assessed the methodological quality. A meta-analysis was conducted using RevMan 5.3 software provided by Cochrane Assisted Network. RESULTS: A total of 932 patients underwent THA. There were 467 cases in group DAA and 465 cases in group PA. There was a significant difference in the incidence of lateral femoral cutaneous nerve injury between DAA and PA groups (RR = 38.97, 95% CI: 7.89-192.57, P < 0.05). DAA was associated with less pain compared with PA [WMD = -0.65, 95% CI (-0.91-0.38), P < 0.05]. There was no significant difference in operation time, hospitalization stay, and intraoperative bleeding volume. Moreover, in supplementary data, the number of acetabular prostheses in Lewinnek's safety zones in DAA was more than that in the PA group (RR = 1.20, 95% CI [1.04-1.39], P < 0.05), and the time of discontinuation of walking aids in the DAA group was earlier than that in the PA group (WMD = -11.05, 95% CI [-17.79-4.31], P < 0.05). CONCLUSION: The DAA total hip arthroplasty has comparable results with PA, with earlier postoperative functional recovery, less postoperative pain scores, and higher incidence of lateral femoral cutaneous nerve injury. The results need to be validated by large-sample, high-quality RCT studies, and long-term follow-up of complications.

Short-term Follow-up of Antibiotic-loaded Articulating Cement Spacers in Two-stage Revision of Infected Total Knee Arthroplasty: A Case Series.

OBJECTIVE: Infection of total knee arthroplasty (TKA) is a rare but devastating complication. Two-stage revision is an effective treatment for late infected TKA. This study aimed to assess the short-term results of two-stage revision using articulating antibiotic-loaded spacers. METHODS: Twenty-five patients (10 men and 15 women) were diagnosed with late infections after TKA and treated with two-stage revision from April 2006 to August 2010; 19 of these patients had TKA for osteoarthritis and 6 for rheumatoid arthritis. Median age was 64.9 (range, 56-83) years. In the first-stage surgery, the prosthesis and all bone cement was removed. After thorough debridement, bone cement with vancomycin and tobramycin was put into a die cavity and made into temporary femoral and tibial spacers, respectively. In the cases of good knee range of motion, the temporary spacers were affixed to the bone surface using the same antibiotic bone cement. In the second surgery, gentamycin Refobacin Bone Cement with vancomycin was used to fix the prosthesis. After two-stage revision, patients were followed up clinically and radiologically at 1, 3, and 6 months, and then annually. Knee Society Score (KSS), knee function score, knee pain score, and knee range of motion (ROM) were assessed. RESULTS: Among the group, all spacers were easily removed, and bone defect degree showed no obvious change compared with pre-implant, 24 (96%) patients had been debrided once, and 1 patient had been debrided twice before reimplant prosthesis. Mean follow-up was 64.2 (range, 52-89) months. There was no infection recurrence at final follow-up. Compared with preoperative data, the KSS (66 [59, 71], 83 [80, 88] vs 46 [43, 57], P < 0.01), knee function score (43 [42, 49], 78 [73, 82] vs 32 [25, 37], P < 0.01), knee pain score (34 [33, 37], 42 [40, 45] vs 18 [16, 23], P < 0.01), and knee ROM (92° [86°, 96°], 94° [90°, 98°] vs 78° [67°, 86°], P < 0.01) were all improved during follow-up and at final visit. Three patients experienced complications in the interval period: one case had knee dislocation, one had knee instability, and one had a chip in the femoral component of the spacer. CONCLUSION: Using articulating antibiotic-loaded spacers showed benefits for treating infected TKA in selected patients. No infection recurrence was observed during follow-up.

Rivaroxaban versus enoxaparin for the prevention of venous thromboembolism after total knee arthroplasty: A meta-analysis.

OBJECTIVE: This article analyzed the clinical efficacy and tolerability of rivaroxaban and enoxaparin in patients undergoing total knee arthroplasty (TKA) surgery. METHODS: Five randomized, controlled clinical trials on rivaroxaban versus enoxaparin in patients who underwent TKA were identified and included in this meta-analysis. RESULTS: The meta-analysis indicated that rivaroxaban prophylaxis was associated with lower rates of symptomatic venous thromboembolism (VTE) (relative risk[RR]:0.55; 95% confidence interval [CI]: 0.35-0.86; P = .009), symptomatic deep vein thrombosis (DVT) (RR 0.44, 95% CI 0.25-0.80, P = .007), asymptomatic DVT (RR: 0.57; 95% CI: 0.37-0.89; P = .01), distal DVT (RR: 0.62; 95% CI: 0.45-0.85; P = .003) and proximal DVT (RR: 0.42; 95% CI: 0.24-0.75; P = .004). Compared with the enoxaparin group, the incidence of symptomatic pulmonary embolism (PE) (RR: 0.48; 95% CI: 0.19-1.24; P = .13) in the rivaroxaban group was not significantly different. A nonsignificant trend towards all-cause death (RR: 0.38; 95% CI: 0.03-4.92; P = .46) or major bleeding (RR: 1.59; 95% CI: 0.77-3.27; P = .21) risk between rivaroxaban and enoxaparin prophylaxis was found. CONCLUSION: Compared with the enoxaparin group, the group using rivaroxaban after TKA had a significantly lower rate of symptomatic VTE, symptomatic DVT, asymptomatic DVT, distal DVT, and proximal DVT. Our study shows that rivaroxaban after TKA is more effective than enoxaparin and did not increase major bleeding or all-cause mortality.

Efficacy and safety of low-molecular-weight heparin after knee arthroscopy: A meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is considered a potentially serious complication of knee arthroscopy and leads to conditions such as deep venous thrombosis (DVT) and pulmonary embolism (PE). Low-molecular-weight heparin (LMWH) is widely employed in knee arthroscopy to reduce perioperative thromboembolic complications. However, the efficacy and safety of LMWH in knee arthroscopy remains unclear. METHODS: Seven randomized controlled clinical trials on LMWH in knee arthroscopy were identified and included in this meta-analysis. The main outcomes of the effectiveness (prevention of DVT and PE) and complications (death, major bleeding, and minor bleeding) of LMWH in knee arthroscopic surgery were assessed using Review Manager 5.3 software. RESULTS: The meta-analysis indicated that LMWH prophylaxis comprised 79% of asymptomatic DVT. No association was found in symptomatic VTE (RR: 0.90; 95% confidence interval [CI]: 0.39-2.08; P = 0.80), symptomatic DVT (RR: 0.79; 95% CI: 0.28-2.23; P = 0.66), symptomatic PE (RR: 1.36; 95% CI: 0.37-4.97; P = 0.64) and major bleeding (RR: 0.70; 95% CI: 0.12-3.95; P = 0.68) risk during LMWH prophylaxis were identified. Death was not reported in these studies. Moreover, there was a lower incidence of minor bleeding (RR: 0.64; 95% CI: 0.49 to 0.83; P = 0.001) in the control group than in the LMWH group. CONCLUSION: Compared with the control group, the group treated with LMWH after knee arthroscopy was no association in reducing the symptomatic VTE rate, symptomatic DVT rate or symptomatic PE rate. The symptomatic VTE rate was 0.5% (11/2,166) in the LMWH group versus 0.6% (10/1,713) in the control group. Although the limitations of this meta-analysis cannot be ignored, the results of our study show that LMWH after knee arthroscopy is ineffective. We recommend that LMWH should not be routinely provided for knee arthroscopy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03164746.

Osteogenic Ability Detection of Human Bone Morphogenetic Protein-2 Gene-activated Nano Bone Putty by Reusable Double-Cavity Bone Harvest Chamber.

OBJECTIVE: To explore the feasibility of implanting a self-designed reusable double-cavity bone harvest chamber into Guizhou mini-pigs for observation of the osteogenic effect of human bone morphogenetic protein-2 (hBMP-2) gene-activated nano bone putty on bone in growth. METHODS: Eight healthy 12-month-old female Guizhou mini-pigs were used for the present experiment. In the first operation, empty double-cavity bone harvest chambers (n = 8) were implanted into the femoral metaphysis of the animals as a blank control group. In the second operation, the femoral metaphyses were implanted with the chambers filled by the nano bone putty+hBMP-2 plasmid in one cavity and nothing in the other cavity, respectively (experiment group, n = 8). The time interval between every operation was 3 months. The cavity materials were retrieved and replaced for assessment by gross observation, histological examination, and bone morphology metrology analysis to compare osteogenesis ability and alkaline phosphatase. RESULTS: Three months after surgery, the nano bone putty+hBMP-2 plasmid in one cavity of the chambers had hard gray and white tissues inside, while the cavities pre-installed with nothing were filled with soft brown tissues. Light microscopy showed new generated bone tissue around the filled material, but only fibrous tissues in the empty cavities. Osteogenesis ability and alkaline phosphatase of the nano bone putty+hBMP-2 plasmid group were significantly higher than those of the blank control group (P < 0.05). CONCLUSION: The reusable double-cavity bone harvest chamber can be used to observe the osteogenic potential of the hBMP-2 gene-activated nano bone putty.