Genome-wide DNase I-hypersensitive site assay reveals distinct genomic distributions and functional features of open chromatin in autopolyploid sugarcane.

The characterization of cis-regulatory DNA elements (CREs) is essential for deciphering the regulation of gene expression in eukaryotes. Although there have been endeavors to identify CREs in plants, the properties of CREs in polyploid genomes are still largely unknown. Here, we conducted the genome-wide identification of DNase I-hypersensitive sites (DHSs) in leaf and stem tissues of the auto-octoploid species Saccharum officinarum. We revealed that DHSs showed highly similar distributions in the genomes of these two S. officinarum tissues. Notably, we observed that approximately 74% of DHSs were located in distal intergenic regions, suggesting considerable differences in the abundance of distal CREs between S. officinarum and other plants. Leaf- and stem-dependent transcriptional regulatory networks were also developed by mining the binding motifs of transcription factors (TFs) from tissue-specific DHSs. Four TEOSINTE BRANCHED 1, CYCLOIDEA, and PCF1 (TCP) TFs (TCP2, TCP4, TCP7, and TCP14) and two ethylene-responsive factors (ERFs) (ERF109 and ERF03) showed strong causal connections with short binding distances from each other, pointing to their possible roles in the regulatory networks of leaf and stem development. Through functional validation in transiently transgenic protoplasts, we isolate a set of tissue-specific promoters. Overall, the DHS maps presented here offer a global view of the potential transcriptional regulatory elements in polyploid sugarcane and can be expected to serve as a valuable resource for both transcriptional network elucidation and genome editing in sugarcane breeding.

Adult head and neck rhabdomyosarcoma: radiotherapy- based treatment, outcomes, and predictors of survival.

BACKGROUND: Adult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS. METHODS: We retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan-Meier method. The chi-square and Fisher's exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan-Meier method. Prognostic variables were assessed through univariate Cox analyses. RESULTS: The median patient age was 28 years (range, 16-82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis (n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival. CONCLUSIONS: The main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.

Haplotype variations of sucrose phosphate synthase B gene among sugarcane accessions with different sucrose content.

BACKGROUND: Sucrose phosphate synthase B (SPSB) gene encoding an important rate-limiting enzyme for sucrose synthesis in sugarcane is mainly expressed on leaves, where its alleles control sucrose synthesis. In this study, genetic variation of SPSB gene represented by different haplotypes in sugarcane was investigated in hybrid clones with high and low sugar content and various accessory species. RESULTS: A total of 39 haplotypes of SPSB gene with 2, 824 bp in size were identified from 18 sugarcane accessions. These haplotypes mainly distributed on Chr3B, Chr3C, and Chr3D according to the AP85-441 reference genome. Single nucleotide polymorphisms (SNPs) and insertion/deletion (InDels) were very dense (42 bp/sequence variation) including 44 transitional and 23 transversional SNPs among the 39 haplotypes. The sequence diversity related Hd, Eta, and Pi values were all lower in clones of high sucrose content (HS) than those in clones of low sucrose content (LS). The evolutionary network analysis showed that about half SPSB haplotypes (19 out of 39) were clustered into one group, including 6 (HAP4, HAP6, HAP7, HAP9, HAP17 and HAP20) haplotypes under positive selection in comparison to HAP26 identified in Badila (S. officinarum), an ancestry noble cane species and under purification selection (except HAP19 under neutral selection) in comparison to HAP18 identified from India1 (S. spontaneum), an ancestry species with low sugar content but high stress tolerance. The average number of haplotypes under positive selection in HS clones was twice as that in LS. Most of the SNPs and InDels sequence variation sites were positively correlated with sucrose and fiber content and negatively correlated with reducing sugar. CONCLUSIONS: A total of 39 haplotypes of SPSB gene were identified in this study. Haplotypes potentially associated with high sucrose synthesis efficiency were identified. The mutations of SPSB haplotypes in HS were favorable and tended to be selected and fixed. The results of this study are informative and beneficial to the molecular assisted breeding of sucrose synthesis in sugarcane in the future.

A comprehensive molecular cytogenetic analysis of the genome architecture in modern sugarcane cultivars.

Modern sugarcane cultivars are derived from the hybridization of Saccharum officinarum (2n = 80) and S. spontaneum (2n = 40-128), leading to a variety of complex genomes with highly polyploid and varied chromosome structures. These complex genomes have hindered deciphering the genome structure and marker-assisted selection in sugarcane breeding. Ten cultivars were analyzed by fluorescence in situ hybridization adopting chromosome painting and S. spontaneum-specific probes. The results showed six types of chromosomes in the studied cultivars, including S. spontaneum or S. officinarum chromosomes, interspecific recombinations from homoeologous or nonhomoeologous chromosomes, and translocations of S. spontaneum or S. officinarum chromosomes. The results showed unexpectedly high proportions of interspecific recombinations in these cultivars (11.9-40.9%), which renew our knowledge that less than 13% of chromosomes result from interspecific exchanges. Also, the results showed a high frequency of translocations (an average of 2.15 translocations per chromosome) between S. officinarum chromosomes. The diverse types of chromosomes in cultivars imply that hybrid gametes of S. spontaneum and S. officinarum may form unusual chromosome pairs, including homoeologous or nonhomoeologous chromosomes either between or within S. spontaneum and S. officinarum. Moreover, we consistently observed 11 or 12 copies for the four studied chromosomes, i.e., chromosomes 1, 2, 7, and 8, suggesting steady transmission during the breeding program. By comparison, we found a relatively fewer copies of S. spontaneum chromosome 1 than those of S. spontaneum chromosomes 2, 7, and 8. These results provide deep insights into the structure of cultivars and may facilitate chromosome-assisted selection in sugarcane breeding.

Butein Inhibits the Glycation of α-Crystallin: An Approach in Prevention of Retinopathy.

The aggregation of lens proteins induced by glycation is one of the key drivers of diabetic retinopathy and development of diabetic cataracts. Moreover, glycation also causes numerous alterations not only to the tertiary structure of lens proteins but also to serum proteins. There are also evidences of covalent crosslinking among lens crystallins resulting in development of cataract. In this article, the inhibitory potential of butein was tested against the glucose induced glycation and the aggregation α-crystallin (α-cry). The results showed that there was inhibition of advanced glycation products (78.28%) and early glycation products (86.30%) following the treatment of butein. Additionally, the presence of butein caused a significant improvement in the tested biochemical markers of glycation. The treatment with butein reduced the free lysine modification to 23.67%. The secondary and tertiary structural distortions of α-cry were also protected. The mechanism of inhibition further investigated at the molecular level using biophysical and computational techniques. The interaction data showed the butein exhibited strong affinity towards the α-cry. The binding event was entropically driven and energetically favourable. The Gibb's free energy of the interaction was found to be -5.99 to -7.17 kcal mol-1. The binding site of butein in α-cry was deciphered by molecular docking and the dynamics was studied using molecular dynamics (MD) simulations. The simulation data showed that butein formed stable complex with α-cry under physiological conditions. Most of the tested parameters from molecular simulations, such as secondary structure, was found to be stable. The data clearly show the potential of butein in inhibiting the glycation induced aggregation of α-cry and hence can be developed as useful inhibitor in the management of diabetic cataract and retinopathy.

SNHG9/miR-214-5p/SOX4 feedback loop regulates osteosarcoma progression.

Osteosarcoma (OS) is a high-grade, aggressive bone sarcoma. LncRNAs play a key regulatory role in controlling biological and pathological processes. The expression of lncRNA SNHG9 varies among different cancer tissues, and the role of SNHG9 in OS progression is unclear. In this study, we found SNHG9 overexpression in OS tissues and cells. In addition, downregulated SNHG9 expression impaired the proliferation, migration, and invasion abilities of OS cells. SNHG9 expression was positively regulated by the transcription factor SOX4. SNHG9 interacted with miR-214-5p as a molecular sponge and SOX4 was identified as the target of miR-214-5p. The interaction affected the expression of SNHG9, miR-214-5p, and SOX4, and regulated OS cell proliferation, migration, and invasion. Therefore, the SNHG9/miR-214-5p/SOX4 feedback loop performs an important role in OS progression and might be used as a new potential therapeutic target for the treatment of OS.

Ofloxacin-Loaded Niosome-Laden Contact Lens: Improved Properties of Biomaterial for Ocular Drug Delivery.

Currently, bacterial conjunctivitis is managed by multiple antibiotic eye-drop solution, which is highly inefficient due to low ocular bioavailability and frequent dosing. Therapeutic soft contact lenses can be used to sustain the release of ocular drugs. However, the conventional soaking method (economic and widely used) showed low drug uptake and high burst release, and the optophysical properties of the contact lens were altered for clinical application. In this paper, novel ofloxacin-loaded niosomes were developed to increase the drug loading capacity of contact lenses while also sustaining ocular drug delivery. Ofloxacin-loaded niosomes were prepared by the thin film hydration technique with three levels of cholesterol. The niosome-laden contact lenses (OFL-Nio-L) led to improved optophysical properties (swelling, transmittance, oxygen permeability) and lysozyme adherence compared to the conventional soaked contact lens (CV-OFL-L). The in vitro drug release data of CV-OFL-L showed high burst release, while OFL-Nio-L lenses showed sustained release up to 48-96 h. In a rabbit tear fluid model, the OFL-Nio-100-L lens showed a high drug concentration at all-time points compared to the CV-OFL-L and eye-drop solution. The efficacy study in the rabbit model showed improved healing effect with OFL-Nio-100-L lens compared to frequent eye-drop therapy. In conclusion, the paper demonstrated the successful application of niosomes to deliver ofloxacin using contact lens without affecting the critical lens properties to substitute eye-drop therapy.

Biomechanical comparison of suture-button, bioabsorbable screw, and metal screw for ankle syndesmotic repair: A meta-analysis.

BACKGROUND: To compare biomechanically metal screw fixation to suture-button or bioabsorbable screw fixation for ankle syndesmotic injuries. METHODS: A literature search of the comparison studies in Pubmed and Google Scholar was conducted. The biomechanical outcomes of interest were syndesmotic stability in the coronal, sagittal, and axial planes as well as torque and rotation at failure. RESULTS: A total of 11 cadaveric studies were included. In the suture-button group, coronal displacement (MD 1.72mm, p = 0.02) and sagittal displacement (MD 2.65mm, p = 0.0003) were increased relative to the metal screw group. In contrast, no difference was found with axial rotation (MD 0.35 degrees, p = 0.57). Bioabsorbable screws exhibited equivalent failure torque (MD -3.04Nm, p = 0.53) and rotation at failure (MD 3.77 degrees, p = 0.48) in comparison to metal screws. CONCLUSIONS: Suture-button provide less rigidity when compared to metal screw fixation. They afford flexible syndesmotic micromotion which may more closely resemble a physiological state and be helpful for ligament healing. Bioabsorbable screws demonstrate similar mechanical strength properties to metal screws.

Loss of Stag2 cooperates with EWS-FLI1 to transform murine Mesenchymal stem cells.

BACKGROUND: Ewing sarcoma is a malignancy of primitive cells, possibly of mesenchymal origin. It is probable that genetic perturbations other than EWS-FLI1 cooperate with it to produce the tumor. Sequencing studies identified STAG2 mutations in approximately 15% of cases in humans. In the present study, we hypothesize that loss of Stag2 cooperates with EWS-FLI1 in generating sarcomas derived from murine mesenchymal stem cells (MSCs). METHODS: Mice bearing an inducible EWS-FLI1 transgene were crossed to p53-/- mice in pure C57/Bl6 background. MSCs were derived from the bone marrow of the mice. EWS-FLI1 induction and Stag2 knockdown were achieved in vitro by adenovirus-Cre and shRNA-bearing pGIPZ lentiviral infection, respectively. The cells were then treated with ionizing radiation to 10 Gy. Anchorage independent growth in vitro was assessed by soft agar assays. Cellular migration and invasion were evaluated by transwell assays. Cells were injected with Matrigel intramuscularly into C57/Bl6 mice to test for tumor formation. RESULTS: Primary murine MSCs with the genotype EWS-FLI1 p53-/- were resistant to transformation and did not form tumors in syngeneic mice without irradiation. Stag2 inhibition increased the efficiency and speed of sarcoma formation significantly in irradiated EWS-FLI1 p53-/- MSCs. The efficiency of tumor formation was 91% for cells in mice injected with Stag2-repressed cells and 22% for mice receiving cells without Stag2 inhibition (p < .001). Stag2 knockdown reduced survival of mice in Kaplan-Meier analysis (p < .001). It also increased MSC migration and invasion in vitro but did not affect proliferation rate or aneuploidy. CONCLUSION: Loss of Stag2 has a synergistic effect with EWS-FLI1 in the production of sarcomas from murine MSCs, but the mechanism may not relate to increased proliferation or chromosomal instability. Primary murine MSCs are resistant to transformation, and the combination of p53 null mutation, EWS-FLI1, and Stag2 inhibition does not confer immediate conversion of MSCs to sarcomas. Irradiation is necessary in this model, suggesting that perturbations of other genes beside Stag2 and p53 are likely to be essential in the development of EWS-FLI1-driven sarcomas from MSCs.

The efficacy and safety of Apatinib mesylate in the treatment of metastatic osteosarcoma patients who progressed after standard therapy and the VEGFR2 gene polymorphism analysis.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of Apatinib mesylate in the treatment of metastatic osteosarcoma patients who progressed after standard therapy and the VEGFR2 gene polymorphism analysis. METHODS: Designed as a retrospective study, a total of 105 metastatic osteosarcoma patients who progressed after standard therapy were included in this study. The metastatic osteosarcoma patients received 500-750 mg Apatinib mesylate according to body surface area until disease progression or unacceptable toxicity with 28 days one cycle. Overall response was evaluated after two cycles Apatinib treatment, then progression-free survival (PFS) and overall survival (OS) were evaluated, and safety data were recorded. Additionally. peripheral blood and peripheral blood mononuclear cell (PBMC) specimens in the osteosarcoma patients were collected for the genotyping of VEGFR2 genetic variation and mRNA expression, respectively. Analysis on the association between genotype and baseline characteristics and VEGFR2 gene mRNA expression was analyzed. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis was adjusted by Cox regression analysis. RESULTS: The objective response rate (ORR) of the 105 metastatic osteosarcoma patients was 37.14%, disease control rate (DCR) was 77.14%, median PFS was 4.1 months, and median OS was 9.0 months. Regarding the VEGFR2 gene polymorphisms analysis, only - 906 T > C was of clinical significance. The prevalence of - 906 T > C in VEGFR2 among the study population was as follows: TT genotype 62 cases (59.05%), TC genotype 36 cases (34.29%) and CC genotype 7 cases (6.66%), minor allele frequency of - 906 T > C was 0.24. Compared with patients with TC/CC genotype, patients with TT genotype showed longer median PFS (5.0 versus 3.1 months, P = 0.011) and median OS (9.8 versus 7.6 months, P = 0.032). There was no correlation between the polymorphism and adverse reactions. Additionally, the mRNA expression in 69 randomly selected sample indicated that the mRNA expression of VEGFR2 of the patients with CC/TC genotypes were significantly higher than those of the TT genotype patients (P < 0.001). CONCLUSION: Apatinib was safe and effective in the treatment of metastatic osteosarcoma patients who progressed after standard therapy. The clinical outcomes of Apatinib may be influenced by the polymorphism - 906 T > C of VEGFR2 through mediating the mRNA expression of VEGFR2.

Do Early Results of Proximal Humeral Allograft-Prosthetic Composite Reconstructions Persist at 5-year Followup?

BACKGROUND: Insufficiency of the rotator cuff is a major problem after resections of proximal humeral tumors and can limit shoulder motion despite preservation of the deltoid muscle and axillary nerve. Allograft-prosthetic composite reconstruction offers one method to reattach the rotator cuff tendons and has been successful in small studies with short followup. However, data are lacking with regard to implant durability, changes in Musculoskeletal Tumor Society (MSTS) scores over time, and delayed complications with extended followup. QUESTIONS/PURPOSES: (1) What is the cumulative incidence of allograft-prosthetic composite revision surgery 5 years after the procedure? (2) What are the early- and intermediate-term MSTS scores of allograft-prosthetic composite reconstruction of the shoulder? (3) What are the complications of allograft-prosthetic composite reconstruction? METHODS: Twenty-one patients underwent allograft-prosthetic composite reconstruction after tumor resection of the proximal humerus between 2000 and 2015. Six patients who were lost to followup were not included. All patients had malignant or aggressive benign tumors that could be treated with a wide intraarticular approach preserving the deltoid muscle, axillary nerve, and glenoid. Cumulative incidence of implant revision was calculated with death of the patient as a competing risk. Minimum followup was 24 months (with the exception of one patient who died at 22 months), and median followup was 97 months (range, 20-198 months). The upper extremity MSTS score was used to assess function. Various complications were identified from radiographs and charts. RESULTS: The cumulative risk of implant revision was 10.1% at 5 years (95% confidence interval [CI], 1.6%-28.0%). Mean MSTS scores were 86% (± SD 9%) at 1 year and 78% (± SD 13%) at 5 years (mean difference ± SD 9% ± 14%, p = 0.015). Mean active forward elevation was 101° (± SD 33°) at 1 year and 92° (± SD 34°) at 5 years (mean difference ± SD 8° ± 36°, p = 0.41). Notable adverse events included progressive radiographic superior subluxation > 1 cm after 12 months followup (12 of 21 patients), delayed union > 12 months (10 of 21 patients), resorption of the greater tuberosity (nine of 21 patients), and aseptic loosening (three of 21 patients). CONCLUSIONS: At intermediate 5-year followup, allograft-prosthetic composite reconstruction of the proximal humerus has an acceptable overall MSTS score and a low incidence of implant revision, but loss of patients to followup and exclusion from the study likely make the results seem better than they actually are. The MSTS score deteriorates between 1 and 5 years. Decreased active forward elevation is not likely to be the sole reason for worsening MSTS scores. A variety of delayed complications including delayed union, resorption of the greater tuberosity, and superior subluxation occurs frequently and may contribute to overall scores. Future studies that compare allograft-prosthetic composites against other forms of reconstruction should attempt to control for possible selection bias and have sufficiently long followup to detect the deterioration of MSTS scores that occur with time. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Distal Tibiofibular Syndesmosis Dysfunction: A Systematic Literature Review of Dynamic Versus Static Fixation Over the Last 10 Years.

The goal of the present work was to perform a systematic review of the literature of the past 10 years regarding dynamic and static fixation of the distal tibiofibular syndesmosis to determine any clinical differences between the 2 procedures. A literature search of the PubMed MEDLINE database was conducted to identify relevant studies related to distal tibiofibular syndesmosis. Studies before January 1, 2007, were excluded to limit the project to the recent literature. Clinical outcomes, device removal rates, time to weightbearing after the initial procedure, and the cost effectiveness of each device were explored. In these 26 studies, 350 patients were treated using a dynamic technique and 845 were treated using a static technique. The weighted American Orthopedic Foot and Ankle Score was 91.70 (standard error [SE] 1.87) for dynamic fixation patients and the weighted average was 86.48 (SE 2.17) for static fixation patients (p = .068). A secondary procedure to remove the fixation device was performed in 7.7% of dynamic fixation patients and in 39.4% of static fixation patients when studies with 100% device removal were excluded (p < .0001). The mean time to weightbearing was 5.96 (SE 0.72) weeks for patients who underwent dynamic fixation and 10.45 (SE 0.99) weeks for those who had static fixation (p = .0002). The cost for dynamic fixation was found to be less than that for static fixation when secondary procedures for device removal were considered. Based on similar clinical functional scores, lower secondary procedure rates, faster time to full weightbearing, and lower costs to patients, dynamic fixation of the distal tibiofibular syndesmosis may be a superior option compared with static fixation.

ONZIN Upregulation by Mutant p53 Contributes to Osteosarcoma Metastasis Through the CXCL5-MAPK Signaling Pathway.

BACKGROUND/AIMS: Gain-of-function of mutant p53 is associated with a high rate of lung metastasis in osteosarcoma. To investigate the mechanism of mutant p53-induced osteosarcoma metastasis, expression array analysis was performed, comparing non-metastatic osteosarcomas from p53+/- mice with metastatic osteosarcomas from p53R172H/+ mice. Onzin (Plac8) was identified as one of the genes upregulated in p53R172H/+ mouse metastatic osteosarcomas. Accordingly, we investigated the role of ONZIN in human osteosarcoma metastasis. METHODS: ONZIN function and its downstream targets were examined in osteosarcoma cell lines. Assays related to tumorigenesis and metastasis, including cell migration, invasion, clonogenic survival, and soft agar colony formation, were performed in osteosarcoma cells. Additionally, mouse xenograft models were used to examine the role of ONZIN overpression in tumorigenesis in vivo. Lastly, 87 osteosarcoma patients were recruited to investigate the clinical relevance of ONZIN overexpression in metastasis and prognosis. RESULTS: ONZIN overexpression enhanced osteosarcoma cell proliferation, clonogenic survival, migration, and invasion independent of p53 status. Furthermore, ONZIN overexpression induced CXCL5 upregulation and resulted in increased ERK phosphorylation, which contributed to more aggressive osteosarcoma metastatic phenotypes. More importantly, overexpression of ONZIN in human osteosarcoma patients was closely associated with lung metastasis, poor prognoses, and survival. CONCLUSIONS: Overexpression of ONZIN promotes osteosarcoma progression and metastasis, and can serve as a clinical biomarker for osteosarcoma metastasis and prognosis.

AZGP1 inhibits soft tissue sarcoma cells invasion and migration.

BACKGROUND: One of the major challenges in soft tissue sarcomas is to identify factors that predict metastasis. AZGP1 is a potential biomarker of cancer progression, but its value in soft tissue sarcomas remains unknown. The aim of this study is to determine the expression level of AZGP1 in soft tissue sarcomas, and to analyze its influence on tumor progression. METHODS: AZGP1 immunohistochemistry (IHC) and RT-PCR were performed in 86 patients with soft tissue sarcomas. The relationships between AZGP1 levels and clinicopathologic features were analyzed. In vitro experiments were performed using fibrosarcoma (HT1080), rhabdomyosarcoma (RD) and synovial sarcoma (SW982) cell lines to corroborate our findings. We used lentiviral over-expression and knockdown assays to examine how changes of AZGP1 expressions might affect cellular migration and invasion. RESULTS: The quantitative RT-PCR results showed that AZGP1 expression was negatively correlated with metastasis and overall survival in soft tissue sarcomas (p < 0.05). Immunohistochemical staining showed lower expression of AZGP1 in patients with metastasis than in those without. Kaplan-Meier survival analysis showed that patients with low expression of AZGP1 had shorter overall (p = 0.056) and metastasis-free survivals (p = 0.038). These findings were corroborated by our in vitro experiments. Over-expression of AZGP1 significantly decreased RD cellular migration and invasion by 64% and 78%, respectively. HT1080 cells migration was inhibited by 2-fold, whereas their invasion was repressed by 7-fold after AZGP1 knockdown. CONCLUSIONS: Our study reveals that reduced AZGP1 expression correlates with in vitro cellular migration and invasion. In vivo, it is associated with higher metastatic risk and shorter survival in patients with soft tissue sarcomas.

Comparison of intramedullary nail, plate, and external fixation in the treatment of distal tibia nonunions.

PURPOSE: The purpose of this study was to examine time to union of extra-articular distal tibia nonunions based on fracture type and fixation methods: intramedullary nail (IMN), plate osteosynthesis (PO), and external fixation (EF). METHODS: This retrospective chart review included all patients who presented at a Level I trauma center with AO/OTA 43A & distal third 42A-C fracture nonunions between 2008 and 2014. Fixation methods were recorded and patient course was followed until nonunion had healed clinically. RESULTS: Thirty-three distal tibia nonunions were included, and 29 reached eventual union (88%). Five AO/OTA fracture types were present. Mean times to union from nonunion diagnosis between original fracture types were compared (p = 0.203). Comminuted fracture types had longer times to union from nonunion diagnosis compared to simple fracture types (78 vs. 46 weeks, p = 0.051) and more revision fixations (1.5 vs. 0.5, p = 0.037). Mean time to union from nonunion diagnosis was shorter when no revision fixation was done compared to revisions (15 vs. 42 weeks, p = 0.102). Times to union from nonunion diagnosis without revision fixation were: IMN (12 weeks), PO (27 weeks), and EF (13 weeks) (p = 0.202). Times to union from definitive revision fixation were: IMN (17 weeks), PO (21 weeks), and EF (66 weeks) (p = 0.009), with EF taking significantly longer than both other methods. 21 patients (64%) underwent revision fixation. Revision fail rates were: IMN (0/6, 0%), PO (2/8, 25%), and EF (15/21, 71%). Time to union was longer in revisions that changed fixation method compared to revisions that used the same method (51 vs. 18 weeks, p = 0.030). Deep infections were also associated with longer union times (81 vs. 47 weeks, p = 0.040). CONCLUSIONS: In this nonunion population, comminuted fracture types needed more time and revisions to reach union. Time to union was only clinically shorter when revision fixation was not performed, but IMN and PO were both successful fixation options with significantly shorter times to union than EF. Mean time to union increased even more when revision of fixation method was performed vs. exchange revision, as did nonunions with deep infections.

Complications of Talar Neck Fractures by Hawkins Classification: A Systematic Review.

The goal of the present study was to perform a systematic review of the published data on talar neck fractures for a better understanding of the postoperative clinical outcomes using open reduction and internal fixation stratified by Hawkins type. A PubMed search was performed using the keywords "talar," "neck," and "fracture." This search identified 209 potential studies, which were reviewed to yield 16 studies that met the criteria. The surgical outcomes of talar neck fractures stratified by the Hawkins classification analyzed in the present study were as follows: American Orthopaedic Foot and Ankle Society scale score was 77.00 for type I, 86.10 for type II, 68.30 for type III, 68.30 for type IV, and 76.50 for all talar neck fractures. Avascular necrosis presented in 0.00% of type I fractures, 15.91% of type II fractures, 38.89% of type III fractures, 55.00% of type IV fractures, and 26.47% of all fractures. Osteoarthritis presented in 25.00% of type I fractures, 41.33% of type II fractures, 54.23% of type III fractures, 72.73% of type IV fractures, and 51.69% of all fractures. Subtalar arthritis presented in 0.00% of type I fractures, 54.29% of type II fractures, 46.43% of type III fractures, 45.45% of type IV fractures, and 44.97% of all fractures. The malunion prevalence was 13.29% and the nonunion prevalence was 3.97% for all fractures. Type II fractures were the most common (50.88%) fracture type reported in the reports reviewed in the present study.

Efficacy of vinorelbine combined with low-dose methotrexate for treatment of inoperable desmoid tumor and prognostic factor analysis.

OBJECTIVE: To assess the efficacy of conservative chemotherapy for inoperable desmoid tumor (DT) and analyze the prognostic factors. METHODS: From November 2008 to April 2016, 71 patients of inoperable DT were treated with vinorelbine and low-dose methotrexate in the Department of Bone and Soft Tissue Tumors, Peking University Cancer Hospital & Institute, and enrolled in this retrospective study. The chemotherapy duration is one year. The efficacy of chemotherapy and the prognosis were observed. RESULTS: Of the 71 patients, 55% were female. Age of onset varied from 1 to 47 years, and the median age was 14 years. Only 11 (15.5%) cases suffered primary tumor. The distribution of the site of tumors was: 31 (43.7%) in the trunk, 36 (50.7%) in the limbs, and 4 (5.6%) in the peritoneal and pelvic cavity. The size of tumor (the maximum diameter) differed from 2 to 37 cm with a mean of 9.3 cm. The median follow-up duration was 28 (range, 6-87) months. Common side effects included: nausea and vomiting, liver injury, bone marrow suppression and oral ulcers. When the chemotherapy finished, 1 (1.4%) case achieved complete response, 24 (33.8%) achieved partial response, 37 (52.1%) achieved stable disease and 9 (12.7%) had progressive disease. The overall response rate was 87.3%. The progression-free survival (PFS) of the participants were from 6 to 87 months, and the 2-, 3- and 5-year PFS was 79.9%, 68.4% and 36.3%, respectively. No significant difference was identified in PFS in subgroups of gender, age of onset, age of chemotherapy, tumor site and tumor size. CONCLUSIONS: For recurrent, inoperable and progressive DT, enough course of chemotherapy with vinorelbine combined with low-dose methotrexate was an optional choice for local control.