The clinical characteristics, novel predictive tool, and risk classification system for primary Ewing sarcoma patients that underwent chemotherapy: A large population-based retrospective cohort study.

BACKGROUND: This study aims to determine the independent prognostic predictors of cancer-specific survival (CSS) in patients with primary Ewing sarcoma (ES) that underwent chemotherapy and create a novel prognostic nomogram and risk stratification system. METHODS: Demographic and clinicopathologic characteristics related to patients with primary ES that underwent chemotherapy between 2000 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. CSS was the primary endpoint of this study. First, independent prognostic predictors of CSS identified from univariate and multivariate Cox regression analyses were used to construct a prognostic nomogram for predicting 1-, 3-, and 5-year CSS of patients with primary ES that underwent chemotherapy. Then, calibration curves and receiver operating characteristic (ROC) curves were used to evaluate the nomogram's prediction accuracy, while decision curve analysis (DCA) was used to evaluate the nomogram's clinical utility. Finally, a mortality risk stratification system was constructed for this subpopulation. RESULTS: A total of 393 patients were included in this study. Age, tumor size, bone metastasis, and surgery were independent prognostic predictors of CSS. The calibration curves, ROC, and DCA showed that the nomogram had excellent discrimination and clinical value, with the 1-, 3-, and 5-year AUCs higher than 0.700. Moreover, the mortality risk stratification system could effectively divide all patients into three risk subgroups and achieve targeted patient management. CONCLUSIONS: Based on the SEER database, a novel prognostic nomogram for predicting 1-, 3-, and 5- year CSS in patients with primary ES that underwent chemotherapy has been constructed and validated. The nomogram showed relatively good performance, which could be used in clinical practice to assist clinicians in individualized treatment strategies.

A novel nomogram model to predict the overall survival of patients with retroperitoneal leiomyosarcoma: a large cohort retrospective study.

Retroperitoneal leiomyosarcomas (RLS) are the second most common type of retroperitoneal sarcoma and one of the most aggressive tumours. The lack of early warning signs and delay in regular checkups lead to a poor prognosis. This study aims to create a nomogram to predict RLS patients' overall survival (OS). Patients diagnosed with RLS in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 were enrolled in this study. First, univariable and multivariable Cox regression analyses were used to identify independent prognostic factors, followed by constructing a nomogram to predict patients' OS at 1, 3, and 5 years. Secondly, the nomogram's distinguishability and prediction accuracy were assessed using receiver operating characteristic (ROC) and calibration curves. Finally, the decision curve analysis (DCA) investigated the nomogram's clinical utility. The study included 305 RLS patients, and they were divided into two groups at random: a training set (216) and a validation set (89). The training set's multivariable Cox regression analysis revealed that surgery, tumour size, tumour grade, and tumour stage were independent prognostic factors. ROC curves demonstrated that the nomogram had a high degree of distinguishability. In the training set, area under the curve (AUC) values for 1, 3, and 5 years were 0.800, 0.806, and 0.788, respectively, while in the validation set, AUC values for 1, 3, and 5 years were 0.738, 0.780, and 0.832, respectively. As evidenced by the calibration curve, the nomogram had high prediction accuracy. Moreover, DCA revealed that the nomogram had high clinical utility. Furthermore, the risk stratification system based on the nomogram could effectively categorise patients into three mortality risk subgroups. Therefore, the developed nomogram and risk stratification system may aid in optimising the treatment decisions of RLS patients to improve treatment prognosis and maximise their healthcare outcomes.

Adductor canal block combined with local infiltration analgesia with morphine and betamethasone show superior analgesic effect than local infiltration analgesia alone for total knee arthroplasty: a prospective randomized controlled trial.

BACKGROUND: Local infiltration analgesia (LIA) and adductor canal block (ACB) provide postoperative analgesia for total knee arthroplasty (TKA). ACB blocks the saphenous nerve and has smaller impacts on quadriceps muscle weakness. ACB theoretically does not have enough analgesic effects on posterior sensory nerves. LIA may increase its analgesic effects on the posterolateral knee. The purpose of this study was to evaluate whether ACB combined with a LIA cocktail of ropivacaine, morphine, and betamethasone has superior analgesic effect than LIA for TKA. METHODS: A total of 86 patients were assessed for eligibility from February 2019 to May 2019. 26 of those were excluded, and 60 patients were divided into 2 groups by computer-generated random number. Group A (LIA group) received LIA cocktail of ropivacaine, morphine and betamethasone. Group B (LIA+ ACB group) received ultrasound-guided ACB and LIA cocktail of ropivacaine, morphine and betamethasone. Postoperative visual analogue scale (VAS) resting or active pain scores, opioid consumption, range of motion (ROM), functional tests, complications and satisfaction rates were measured. The longest follow-up was 2 years. RESULTS: Two groups have no differences in terms of characteristics, preoperative pain or function (P > 0.05). ACB combined with LIA had significantly lower resting and active VAS pain scores, better ROM, better sleeping quality and higher satisfaction rates than LIA alone within 72 h postoperatively (P < 0.05). Complications, or adverse events and HSS score, SF-12 score were observed no significant differences within 2 years postoperatively. CONCLUSIONS: Adductor canal block combined with Local infiltration analgesia provide better early pain control. Although the small statistical benefit may not result in minimal clinically important difference, Adductor canal block combined with Local infiltration analgesia also reduce opioid requirements, improve sleeping quality, and do not increase the complication rate. Therefore, Adductor canal block combined with Local infiltration analgesia still have good application prospects as an effective pain management for total knee arthroplasty. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900021385 , 18/02/2019.

Near-Infrared Light-Controllable Multifunction Mesoporous Polydopamine Nanocomposites for Promoting Infected Wound Healing.

The successful treatment of infected wounds requires strategies with effective antimicrobial, anti-inflammatory, and healing-promoting properties. Accordingly, the use of Cu2+ and tetracycline (TC), which can promote angiogenesis, re-epithelialization, and collagen deposition, also antibacterial activity, at the wound site, has shown application prospects in promoting infected wound repair. However, realizing controllable release to prolong action time and avoid potential toxicities is critical. Moreover, near-infrared light (NIR)-activated mesoporous polydopamine nanoparticles (MPDA NPs) reportedly exert anti-inflammatory effects by eliminating the reactive oxygen species generated during inflammatory responses. In this study, we assess whether Cu2+ and TC loaded in MPDA NPs can accelerate infected wound healing in mice. In particular, Cu2+ is chelated and immobilized on the surface of MPDA NPs, while a thermosensitive phase-change material (PCM; melting point: 39-40 °C), combined with antibiotics, was loaded into the MPDA NPs as a gatekeeper (PPMD@Cu/TC). Results show that PPMD@Cu/TC exhibits significant great photothermal properties with NIR irradiation, which induces the release of Cu2+, while inducing PCM melting and, subsequent, TC release. In combination with anti-inflammatory therapy, NIR-triggered Cu2+ and TC release enables the nanocomposite to eradicate bacterial wound infections and accelerate healing. Importantly, negligible damage to primary organs and satisfactory biocompatibility were observed in the murine model. Collectively, these findings highlight the therapeutic potential of this MPDA-based platform for controlling bacterial infection and accelerating wound healing.

Long-Term Clinical Outcomes and Survivorship of Total Hip Arthroplasty for Pyogenic Arthritis: A Retrospective Cohort Study of 168 Hips.

OBJECTIVE: The aim of the present study was to evaluate the 10-year outcomes of cementless total hip arthroplasty (THA) in adult patients with the late sequelae of septic arthritis of the hip. METHODS: We followed 166 consecutive patients (168 hips) who underwent cementless THA between March 2001 and December 2011. There were 79 men and 87 women, with a mean age of 50.4 years (range 21-76 years) at the time of index THA, all of whom had hip osteoarthritis secondary to hip pyogenic infection. The average duration of follow up was 10.6 years (range 6.9-17.2 years). Preoperative and postoperative clinical ratings were evaluated, including the hip dysfunction and osteoarthritis outcome score (HOOS), the Harris hip score (HHS), range of motion, a 100-point visual analog scale for hip pain, and the severity of limp and limb length discrepancy (LLD). The anteroposterior and lateral radiographs of the hip and full-length view of the lower extremities were obtained to assess the position of the components, radiolucent lines, osteolysis, loosening of components, and heterotopic ossification. The intraoperative and postoperative complications were also recorded. RESULTS: The mean HSS and hip pain score were 44.2 points (range 29-66 points) and 42.5 points (range 32-64 points), respectively, before the index surgery and significantly improved to 88.1 points (range 78-96 points) and 15.1 points (range 10-26 points), respectively, at final follow-up examination. The HOOS and range of motion also improved significantly. The mean limb length discrepancy was reduced from 2.6 to 0.8 cm. The limp at last follow-up examination was moderate in 3 cases because of hip osteoarthritis in the other limb, slight in 26, and absent in 137. A radiolucent line was observed in 12 hips (7.1%) around the acetabular or femoral components. A progressive radiolucent line around the undersized femoral stem in all zones was seen in 1 hip, resulting in aseptic loosening and breakage of the femoral component. There were 8 cases of intraoperative fracture, 7 cases of dislocation, and 7 cases of transient nerve palsy. Recurrence of infection occurred in 2 hips. Revision surgery was conducted in 2 hips because of isolated loosening of the acetabular cup and the femoral stem, respectively. Kaplan-Meier survival was 97% at 10 years, with revision for any reason with any component as an end-point. CONCLUSION: Improved surgical techniques and development of components with various sizes provided favorable results for cementless THA conducted for late sequelae of sepsis in these young and active patients. Although the incidence of complications was relatively high, the complications were treated successfully.

Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Mitochondria-targeted phototherapy, i.e., synergistic photodynamic/photothermal therapy, has emerged as a highly promising strategy for treating drug-resistant tumors. This study proposed a new nano-drug delivery system based on near-infrared imaging and multifunctional graphene, which can target mitochondria and show synergistic phototherapy, with preferential accumulation in tumors. METHODS AND RESULTS: Based on our previous study, (4-carboxybutyl) triphenyl phosphonium bromide (TPP), a mitochondria-targeting ligand, was conjugated to indocyanine green (ICG)-loaded, polyethylenimine-modified PEGylated nanographene oxide sheets (TPP-PPG@ICG) to promote mitochondrial accumulation after cellular internalization. Thereafter, exposure to a single dose of near-infrared irradiation enabled synergistic photodynamic and photothermal therapy, which simultaneously inhibited adenosine triphosphate synthesis and mitochondrial function. Induction of intrinsic apoptosis assisted in surmounting drug resistance and caused tumor cell death. After fluorescence imaging-guided synergistic phototherapy, the mitochondria-targeting, multifunctional graphene-based, drug-delivery system showed highly selective anticancer efficiency in vitro and in vivo, resulting in marked inhibition of tumor progression without noticeable toxicity in mice bearing doxorubicin-resistant MG63 tumor cells. CONCLUSION: The mitochondria-targeting TPP-PPG@ICG nanocomposite constitutes a new class of nanomedicine for fluorescence imaging-guided synergistic phototherapy and shows promise for treating drug-resistant osteosarcoma.

Integrative analysis of the circRNA-miRNA regulatory network in atrial fibrillation.

We aimed to investigate the circRNA-miRNA regulatory network in atrial fibrillation (AF) by using Cytoscape and HMDD v3.0. Finally, 120 differentially expressed circRNAs in peripheral blood monocytes of 4 AF patients were preliminarily screened by circRNA microarray. circRNA_4648, circRNA_4631, and circRNA_2875 were the first four circRNAs with the most binding nodes in the circRNA-miRNA network. The top three most frequent miRNAs for up-regulated circRNAs were hsa-miR-328 that interacted with 5 up-regulated circRNAs, hsa-miR-4685-5p with 4 up-regulated circRNAs, hsa-miR-3150a-3p, hsa-miR-4649-5p, hsa-miR-4783-3p, and hsa-miR-8073 with 3 up-regulated circRNAs,, while the top three most frequent miRNAs for down-regulated circRNAs were hsa-miR-328 that interacted with 14 down-regulated circRNAs, hsa-miR-4685-5p with 11 down-regulated circRNAs and hsa-miR-661 with 9 down-regulated circRNAs. According to HMDD v3.0, five up-regulated and eleven down-regulated circRNAs were found to interact with AF related miRNAs. These results indicated the possible regulatory network between circRNAs and miRNAs in the pathogenesis of AF.

Genome-wide analysis of circular RNA expression profiles in patients with atrial fibrillation.

Atrial fibrillation (AF) is one of the most common clinical cardiac arrhythmias. This study was done to screen differentially expressed circular RNAs (circRNAs) in human monocytes from patients with AF and healthy controls using microarray, and preliminarily explore the role of circRNAs in the development of AF. The expression of circRNAs in peripheral blood monocytes of 4 AF patients and 4 healthy donors was detected by chip technology and validated by qRT-PCR. Differentially expressed genes were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the function of differentially expressed genes and related pathways. Potential connections between circRNAs and miRNAs were explored by using Cytoscape. 120 differentially expressed circRNAs (FC≥2, P<0.05) were preliminarily screened by circRNA microarray, of which 65 were up-regulated and 55 down-regulated. All of 4 upregulated circRNAs (circRNA_0031, circRNA_1837, circRNA_5901 and circRNA_7571) and 3 out of 4 downregulated circRNAs (circRNA_5801, circRNA_7386 and circRNA_7577) were randomly confirmed by RT-PCR. GO and KEGG analysis suggested that differentially expressed circRNA-related genes are mainly involved in inflammation, immunity, and signaling transduction. CircRNA_7571, circRNA_4648, circRNA_4631 and circRNA_2875 were the first 4 circRNAs with the most binding nodes in the co-expression network. In addition, hsa-miR-328 was the highest positively correlated miRNA in the networks. Our findings demonstrated that there were differentially expressed circRNAs in human monocytes from AF patients. circRNA_7571, circRNA_4648, circRNA_4631 and circRNA_2875 were the first 4 circRNAs with the most binding nodes in the co-expression network. hsa-miR-328 was the largest node that interacted with circRNAs in the co-expression network. circRNAs-hsa-miR-328 network may play a critical role in the pathophysiology and mechanism of AF.

Outcomes after Total Hip Arthroplasty Using a Cementless S-ROM Modular Stem for Patients with High Hip Dislocation Secondary to Hip Pyogenic Arthritis.

OBJECTIVE: To evaluate the midterm results of the cementless S-ROM modular femoral stem used with subtrochanteric transverse shortening osteotomy for the treatment of high hip dislocation secondary to hip pyogenic arthritis. METHODS: We retrospectively reviewed the data of 49 patients (49 hips) with an average infection quiescent period of 37.4 years who underwent cementless total hip arthroplasty (THA) with simultaneous subtrochanteric transverse shortening osteotomy from July 2008 to June 2012. There were 23 men and 26 women with a mean age of 44.3 years at the time of surgery. The following clinical outcomes were evaluated: the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, Harris hip score (HSS), modified Merle d'Aubigne-Postel hip (MAP) score, low back pain visual analog scale score, 12-item short-form health survey questionnaire score, limp, and Trendelenburg sign. Radiographic outcomes and complications were also evaluated. RESULTS: The mean follow-up period was 8.7 years (range, 5.5-10 years). No infection recurrence was observed after THA. The average HSS significantly improved from 45.0 to 84.8. The WOMAC score improved from 70.1 ± 3.5 (range, 65-76) to 43.1 ± 13.4 (range, 21-67). The modified MAP score improved from 5.9 ± 1.9 (range, 3-9) to 14.3 ± 2.4 (range, 11-18). The low back pain visual analog scale score, 12-item short-form health survey questionnaire score, limp, and Trendelenburg sign also improved significantly. The average limb length discrepancy decreased from 39.6 mm (range, 30-55 mm) to 7.2 mm (range, 0-22 mm). Two patients had temporary sciatic nerve paralysis but recovered within 6 months without any functional defects; one had an intraoperative fracture fixed by cerclage wires. One hip required revision surgery because of femoral stem aseptic loosening. CONCLUSIONS: The cementless S-ROM modular femoral stem used with subtrochanteric transverse shortening osteotomy is safe and effective for high hip dislocation secondary to pyogenic arthritis and provides satisfactory midterm results. Significant improvements in clinical function were observed, as were high rates of stable fixation of the cementless implant, restoration of more normal limb lengths, and a low incidence of complications.