Effects of prophylactic antibiotic administration and antibiotic timing on culture results and clinical outcomes of paediatric musculoskeletal infection: a protocol for a randomised controlled clinical trial.

INTRODUCTION: Musculoskeletal infection (MSI) is a common cause of morbidity among the paediatric population. Some clinicians recommend withholding prophylactic antibiotics until culture collection with an aim to improve the culture sensitivity. However, a recent retrospective study reported that prophylactic antibiotic administration did not affect culture sensitivities in either disseminated or local MSI in paediatric population, which is surprising. The aim of the present study is to investigate the effects of prophylactic antibiotic administration and the timing of antibiotic administration on culture sensitivity and clinical outcomes of paediatric MSI. METHODS AND ANALYSIS: A randomised controlled clinical trial will be carried out. Individuals aged 0-18 years with a diagnosis of MSI will be screened and evaluated at the Shenzhen Children's Hospital. The participants will be randomly allocated into four groups, and they will receive the antibiotic treatment at different time points, that is, 1 week, 3 days, 1 day prior to tissue culture collection and 1 day after tissue culture collection, respectively. The primary outcome will be culture sensitivity. In addition, the disease-related markers including white blood cell count, C reactive protein, erythrocyte sedimentation rate, vital signs as well as the length of hospital stay will be measured or recorded accordingly. Using χ2 tests, the rates of positive cultures will be compared between different groups. Statistical comparisons between the different patient groups regarding the confounding and outcome variables will be conducted using independent t-tests, Mann-Whitney U tests, χ2 tests and Fisher's exact tests as appropriate with the significance level set to 5% (p<0.05). ETHICS AND DISSEMINATION: This study has received ethical approval. The findings will be disseminated both in scientific conferences and peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2100041631.

Comparison of different treatments for children with radial neck fracture and analysis of prognostic factors.

INTRODUCTION: The aim of this was to analyze the effect of different treatment options on radial neck fractures in children and to explore the factors affecting the prognosis of fractures. METHODS: The clinical data of 131 children with radial neck fractures admitted to our hospital from 2010 to 2018 were retrospectively analyzed, and the patients were divided into 6 groups according to treatment methods [manual reduction with Kirschner wires (K-wires) for internal fixation (group A); manual reduction with elastic stable intramedullary nails (ESINs) for internal fixation (group B); leverage reduction with K-wires for internal fixation (group C); leverage reduction with ESINs for internal fixation (group D); manual and leverage reduction with K-wires/ESINs for internal fixation (group E); and open reduction with K-wires/ESINs for internal fixation (group F)]. Postoperative elbow function and complications were analyzed. RESULTS: Among the 131 patients with fractures, the median age was 8 years, the median preoperative angulation was 52°, the follow-up rate was 86.3% (113/131), the average follow-up time was 58.3 months, and the postoperative complication rate was 17.7% (20/113). The comparison among the different treatment groups showed that group B had the best recovery of elbow function, postoperatively, and the lowest postoperative complication rate. Age, duration of hospitalization, and preoperative angulation were independent factors affecting postoperative complications. Older age, longer duration of hospitalization, and higher angulation increase the postoperative complications. CONCLUSION: Different treatment options have different efficacies for radial neck fractures in children, of which manipulative reduction with internal fixation using ESINs can achieve good efficacy and a low postoperative complication rate. Age, duration of hospitalization, and preoperative angulation are independent factors for postoperative complications.

Loss of correction in cubitus varus deformity after osteotomy.

ABSTRACT: We aimed to investigate the rate of loss of correction and the factors thereof in pediatric patients undergoing osteotomy for treatment of cubitus varus deformity.Between July 2008 and July 2017, we treated 30 patients who underwent osteotomy for cubital varus. We compared the preoperative and postoperative clinical and imaging findings, including the H-Cobb and Baumman angles, in all patients. Postoperative evaluation was performed by telephonic interviews.Our patients consisted of 17 males and 13 females. The mean age was 75 months. At the first follow-up, approximately 80% of patients had experienced a loss of correction of the humerus-cobb angle (H-Cobb angle); at the second follow-up, the incidence was 83%. Meanwhile, 57% and 43% of patients experienced a loss of correction of the Baumman angle at the first and second follow-ups, respectively. The average interval between the first and second follow-ups was 24 days, and the mean loss in the H-Cobb angle was 2.4°. There was a significant difference between the H-Cobb angles as measured before and after surgery (P < .05). There was no significant difference between the H-Cobb angles of the affected side and the contralateral healthy elbow at the third postoperative follow-up; however, there was a significant difference between the Baumman angle between before and after surgery (P < .05). The Baumman angles as measured at the second and third postoperative follow-ups differed significantly from those of the contralateral healthy elbow joint. According to the survival curve analysis, the median survival times of the H-Cobb and Baumman angles were 27 and 34 months, respectively.The postoperative loss of the 2 angles occurred mainly during the first and second follow-up periods. Therefore, patient follow-up is particularly important in the period directly following the operation. Additional measures may be necessary to avoid rapid angle loss.

A double-closed wedge broken-line osteotomy for cubitus varus deformity.

ABSTRACT: Various osteotomy methods have been proposed in the treatment of cubitus varus. We designed an improved stepped osteotomy to achieve improved deformity correction. We refer to this new approach as double-closed wedge broken-line osteotomy and report a series of clinical and imaging results (deformity correction, range of motion [ROM], function, osteotomy healing, and complications) of patients with cubitus varus treated with this technique.Between July 2014 and July 2019, we treated 9 cases of cubitus varus using the new technique. The study was conducted in accordance with the principles of the Declaration of Helsinki, and the study protocol was approved by the ethics committee of Shenzhen Children's Hospital. We obtained written parental consent for the minors before the study was begun. We compared preoperative and postoperative clinical and imaging parameters (humeral elbow-wrist angle, elbow ROM) in all patients. Postoperative evaluation was performed by telephone interview and outpatient review. The median follow-up was 23.2 months (range, 3-63 months).The median humeral elbow-wrist angle modified from -14.27 to 15.15. The median clinical and imaging parameters after correction of deformity were not different from that of the normal side. Using our rehabilitation program, all patients recovered preoperative elbow ROM at the last follow-up.Our double-closed wedge broken-line osteotomy has a larger cancellous bone contact surface. The deformity correction is satisfactory, the osteotomy healing is reliable, and the incidence of complications is low.Level of Evidence: Level IV.

Identification of co-expression modules and pathways correlated with osteosarcoma and its metastasis.

BACKGROUND: Osteosarcoma is the most common bone tumor that occurs in children. METHODS: To identify co-expression modules and pathways correlated with osteosarcoma and its clinical characteristics, we performed weighted gene co-expression network analysis (WGCNA) on RNA-seq data of osteosarcoma with 52 samples. Then we performed pathway enrichment analysis on genes from significant modules. RESULTS: A total of 5471 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that a module involved in microtubule bundle formation, drug metabolism-cytochrome P450, and IL-17 signaling pathway was negatively correlated with osteosarcoma and positively correlated with metastasis; a module involved in DNA replication was positively correlated with osteosarcoma; a module involved in cell junction was positively correlated with metastasis; and a module involved in heparin binding negatively correlated with osteosarcoma. Moreover, expression levels in four of the top ten differentially expressed genes were validated in another independent dataset. CONCLUSIONS: Our analysis might provide insight for molecular mechanisms of osteosarcoma.

Investigating age­induced differentially expressed genes and potential molecular mechanisms in osteosarcoma based on integrated bioinformatics analysis.

Osteosarcoma (OS) is the most common primary bone malignancy. It predominantly occurs in adolescents, but can develop at any age. The age at diagnosis is a prognostic factor of OS, but the molecular basis of this remains unknown. The current study aimed to identify age­induced differentially expressed genes (DEGs) and potential molecular mechanisms that contribute to the different outcomes of patients with OS. Microarray data (GSE39058 and GSE39040) obtained from the Gene Expression Omnibus database and used to analyze age­induced DEGs to reveal molecular mechanism of OS among different age groups (<20 and >20 years old). Differentially expressed mRNAs (DEMs) were divided into up and downregulated DEMs (according to the expression fold change), then Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Furthermore, the interactions among proteins encoded by DEMs were integrated with prediction for microRNA­mRNA interactions to construct a regulatory network. The key subnetwork was extracted and Kaplan­Meier survival analysis for a key microRNA was performed. DEMs within the subnetwork were predominantly involved in 'ubiquitin protein ligase binding', 'response to growth factor', 'regulation of type I interferon production', 'response to decreased oxygen levels', 'voltage­gated potassium channel complex', 'synapse part', 'regulation of stem cell proliferation'. In summary, integrated bioinformatics was applied to analyze the potential molecular mechanisms leading to different outcomes of patients with OS among different age groups. The hub genes within the key subnetwork may have crucial roles in the different outcomes associated with age and require further analysis.

Galectin-3 deficiency protects lipopolysaccharide-induced chondrocytes injury via regulation of TLR4 and PPAR-γ-mediated NF-κB signaling pathway.

The aim of the present study was to identify the functional role of galectin-3 (Gal-3) in lipopolysaccharide (LPS)-induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal-3 in ATDC5 cells. In addition, repression of Gal-3 obviously impeded LPS-stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)-13 and MMP-3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal-3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl-2 and a decrease in the expression of proapoptotic protein Bax and caspase-3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR-γ with the antagonist GW9662 effectively abolished Gal-3 inhibition-mediated anti-inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal-3 prevents the NF-κB signaling pathway. Taken together, these findings indicated that the absence of Gal-3 exerted chondroprotective properties dependent on TLR4 and PPAR-γ-mediated NF-κB signaling, indicating that Gal-3 functions as a protector in the development and progression of osteoarthritis.

Erythropoietin Inhibits Hypoxia-Induced Epithelial-To-Mesenchymal Transition via Upregulation of miR-200b in HK-2 Cells.

BACKGROUND/AIMS: Renal tubular epithelial-mesenchymal transition (EMT) is regarded as an important factor leading to renal interstitial fibrosis. Erythropoietin (EPO) has been reported to attenuate renal fibrosis. The mechanism underlying this protective effect of EPO remains unclear. In this study, we aim to identify possible mechanisms of the EPO renoprotective effect. METHODS: Hypoxia was induced in vitro by incubating human proximal tubular epithelial cell line HK-2 cells in 1% O2 and 5% CO2. Western blotting and reverse transcription polymerase chain reaction analyses were used to evaluate the expression of epithelial and mesenchymal markers in the cell samples. The expression of miR-200b in the HK-2 cells under hypoxia or treatment with EPO was examined. RESULTS: EPO represses hypoxia-induced EMT by upregulating miR-200b in HK-2 cells. Overexpression of miR-200b represses the effect of ETS proto-oncogene 1 (Ets-1)-induced EMT in HK-2 cells. CONCLUSION: miR-200 mediates the protective effects of EPO on EMT in hypoxic HK-2 cells. EPO attenuated hypoxia-induced EMT by increasing miR-200 expression via the repression of Ets-1.

Netrin-1 attenuates the progression of renal dysfunction by blocking endothelial-to-mesenchymal transition in the 5/6 nephrectomy rat model.

BACKGROUND: Endothelial-to-mesenchymal transition (EndoMT) is a crucial event during kidney interstitial fibrosis and it is believed to be inhibited by netrin-1. Our aim was to determine the influence of netrin-1 on renal EndoMT in chronic kidney disease by studying its effect in 5/6 nephrectomized (Nx) rats. METHODS: Male Sprague-Dawley rats were divided into three groups (10 rats/group): sham-operated rats treated with control adenovirus; 5/6 Nx rats treated with control adenovirus; and 5/6 Nx rats treated with recombinant adenovirus expressing the netrin-1 gene (Ad-netrin-1). Rats were sacrificed 13 weeks after surgery. Blood urea nitrogen (BUN) and serum creatinine (Scr) levels were measured regularly after surgery. After the rats were sacrificed, pathological changes in renal tissues were analyzed histologically. Immunofluorescence was performed to evaluate the co-expression of CD31 and α-SMA. CD31, α-SMA and Snail mRNA were detected by RT-PCR. Protein expression was detected by western blot. RESULTS: Renal function and histopathological damage were significantly improved in Ad-netrin-1-treated 5/6 Nx rats. In the sham and control-treated 5/6 Nx rats, the percentage of CD31(+)/α-SMA(+) cells increased, which indicated EndoMT. However, the percentage of CD31(+)/α-SMA(+) cells were reduced in the netrin-1-treated 5/6 Nx rats, which indicates netrin-1-induced blocking of EndoMT. CONCLUSION: From the results, it seems that netrin-1 attenuates the progression of renal dysfunction by inhibiting EndoMT in 5/6 Nx rats. Netrin-1 can therefore be considered as a potential therapeutic agent for the treatment of renal fibrosis.

Tele-ICU: the way forward in geriatric care?

Aging population is set to increase in the near future, and will need specialized care when admitted to ICUs. The elderly are beset with chronic conditions, such as cardiovascular, COPD, diabetes, renal complications and depression. Specialist opinions can now be made available through telemedicine facilities. Tele-ICU is a specialized hub consisting of highly skilled staff trained in critical care able to deliver timely, quality care service to patients admitted to ICUs in remote areas using highly advanced information technology services. These specialists in the tele-ICU hub are able to analyze and gather data arriving at timely interventional management decisions and provide this vital feedback to the nursing staff and doctors manning remote ICU locations where specialized intensivist may not be available. Known clinical benefits of such a system include better patient outcomes, reduced medical errors, mortality and reduced hospital length of stay. The main disadvantage in implementation could be the upfront high cost involved, for which low-cost models are being explored. In the face of delivering such remote care, it is up to the local health policy to make legislative changes to include associated legal and ethical issues. Considering the burgeoning aging population, tele-ICU could become the way forward in delivering geriatric critical care.