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  • Donahue Huffman posted an update 2 weeks, 1 day ago

    01). All patients were treated non-operatively; 81.8% responded to nonsteroidal anti-inflammatory drug-physical therapy program and 18.2% required an additional local steroid injection. CONCLUSION PAPS occurs after TKA; the incidence was found to be 5.6%. BMI seems to be an independent risk factor. It is a benign condition and can be effectively treated conservatively in most cases.PURPOSE Most children with intra-abdominal injuries can be managed non-operatively. However, in Europe, there are many different healthcare systems for the treatment of pediatric trauma patients. Therefore, the aim of this study was to describe the management strategies and outcomes of all pediatric patients with blunt intra-abdominal injuries in our unique dedicated pediatric trauma center with a pediatric trauma surgeon. METHODS We performed a retrospective, single-center, cohort study to investigate the management of pediatric patients with blunt abdominal trauma. From the National Trauma Registration database, we retrospectively identified pediatric (≤ 18 years) patients with blunt abdominal injuries admitted to the UMCU from January 2012 till January 2018. RESULTS A total of 121 pediatric patients were included in the study. The median [interquartile range (IQR)] age of patients was 12 (8-16) years, and the median ISS was 16 (9-25). High-grade liver injuries were found in 12 patients. Three patients had a pancreas injury grade V. Furthermore, 2 (1.6%) patients had urethra injuries and 10 (8.2%) hollow viscus injuries were found. Eighteen (14.9%) patients required a laparotomy and 4 (3.3%) patients underwent angiographic embolization. In 6 (5.0%) patients, complications were found and in 4 (3.3%) children intervention was needed for their complication. No mortality was seen in patients treated non-operatively. One patient died in the operative management group. CONCLUSIONS In conclusion, it is safe to treat most children with blunt abdominal injuries non-operatively if monitoring is adequate. These decisions should be made by the clinicians operating on these children, who should be an integral part of the entire group of treating physicians. Surgical interventions are only needed in case of hemodynamic instability or specific injuries such as bowel perforation.Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterised by an increased risk for non-Hodgkin lymphoma (NHL) development. Ectopic germinal centre (GC) in the salivary gland is associated with increased NHL risk in pSS, and the chemokine CXCL13 is implicated in B-cell migration and GC formation. Serum CXCL13 concentrations were quantified by ELISA in 48 healthy individuals, 273 pSS patients without NHL (pSS-nonL), and 38 pSS patients with NHL (pSS-NHL+) from the United Kingdom Primary Sjögren’s Syndrome Registry cohort. PSS-nonL patients were stratified into low risk (LR), moderate risk (MR) and high risk (HR) groups according to the lymphoma risk score proposed by Fragkioudaki et al. Differences in serum CXCL13 levels among groups were analysed using the Wilcoxon method. Also, changes in serum CXCL13 over a time period of at least 1 year and a median 4 years were assessed for 200 pSS-nonL and 8 pSS-NHL+ patients. In addition, associations of serum CXCL13 with B-cell and inflammatory markers were investigated by correlation analyses and logistic regression. Serum CXCL13 levels were higher in all pSS groups compared to controls (p  less then  0.0001), and in pSS-NHL+ compared to pSS-nonL patients (p = 0.0204). LR patients had lower CXCL13 levels than MR patients (p  less then  0.0001) and pSS-NHL+ patients (p = 0.0008). CXCL13 levels remained stable over the study period for all pSS groups. Zoligratinib ic50 CXCL13 was associated (p  less then  0.0005) with Immunoglobulin G (IgG), B-cell activating factor, β2 microglobulin, combined free light chains, κ and λ light chains, anti-Ro/SSA, anti-La/SSB, and erythrocyte sedimentation rate. IgG and C3 controlled for age and gender were significantly associated with NHL risk in pSS. Serum CXCL13 levels were elevated in pSS-NHL+ and MR patients compared to LR patients and remained stable over time. Further study is required to investigate the role of CXCL13 in pSS-associated NHL risk.OBJECTIVES A minority of NSCLC patients benefit from anti-PD1 immune checkpoint inhibitors. A rational combination of biomarkers is needed. The objective was to determine the predictive value of tumor mutational load (TML), CD8+ T cell infiltration, HLA class-I and PD-L1 expression in the tumor. MATERIALS AND METHODS Metastatic NSCLC patients were prospectively included in an immune-monitoring trial (NTR7015) between April 2016-August 2017, retrospectively analyzed in FFPE tissue for TML (NGS 409 cancer-related-genes) and by IHC staining to score PD-L1, CD8+ T cell infiltration, HLA class-I. PFS (RECISTv1.1) and OS were analyzed by Kaplan-Meier methodology. RESULTS 30 patients with adenocarcinoma (67%) or squamous cell carcinoma (33%) were included. High TML was associated with better PFS (p = 0.004) and OS (p = 0.025). Interaction analyses revealed that patients with both high TML and high total CD8+ T cell infiltrate (p = 0.023) or no loss of HLA class-I (p = 0.026), patients with high total CD8+ T cell infiltrate and no loss of HLA class-I (p = 0.041) or patients with both high PD-L1 and high TML (p = 0.003) or no loss of HLA class-I (p = 0.032) were significantly associated with better PFS. Unsupervised cluster analysis based on these markers revealed three sub-clusters, of which cluster-1A was overrepresented by patients with progressive disease (15 out of 16), with significant effect on PFS (p = 0.007). CONCLUSION This proof-of-concept study suggests that a combination of PD-L1 expression, TML, CD8+ T cell infiltration and HLA class-I functions as a better predictive biomarker for response to anti-PD-1 immunotherapy. Consequently, refinement of this set of biomarkers and validation in a larger set of patients is warranted.BACKGROUND Osteosarcoma (OS) is the most common malignant bone tumor and the prognosis of advanced cases is still poor. Recently, there have been several reports suggesting the relationship between innate immunity and OS, but the detailed mechanism is unknown. We demonstrate the relationship between OS and Toll-like receptor 4 (TLR4) which is one of the most important factors in innate immunity. METHODS We established a syngenic mouse tumor model using C3H/HeN, C3H/HeJ mouse and a highly metastatic OS cell line, LM8. TLR4 activation with lipopolysaccharide (LPS) was performed on both mice and its influence on the progression of OS was evaluated. We also performed CD8 + cells depletion to examine the influence on TLR4 activation effects. RESULTS Tumor volume of C3H/HeN mice was significantly smaller and overall survival of C3H/HeN mice was significantly longer than C3H/HeJ mice. We found more CD8+ cells infiltrating in lung metastases of C3H/HeN mice and depletion of CD8+ cells canceled the antitumor effects of LPS.

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