Editorial

On the 23rd May the Royal College of Surgeons (England) hosted a NIHR Trauma Research Workshop that scoped the NHS priorities for research in the field of trauma care. As our military colleagues have demonstrated so effectively, particularly in the recent conflict in Afghanistan, Consultant Plastic Surgeons placed at the forefront of operative triage and first debridement have a powerful role in optimising patient outcomes and the efficiency of care pathways. Plastic Surgeons placed at the heart of definitive primary surgical care further enhance the functional restitution and cosmetic optimisation that can let patients regain the purpose and self-worth that are so necessary for holistic wellbeing and socioeconomic stability.

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Venous Thromboembolism Is an Independent Predictor of Mortality Among Patients with Gastric Cancer

Abstract

Background

Venous thromboembolism (VTE) is an independent predictor of death among patients with cancer. Patients with gastric cancer (GC) are at higher risk for VTE when compared to other solid tumors, and if one considers its prevalence, GC may be responsible for one of the highest incidences of cancer-associated thrombosis. The impact of VTE on mortality is not well defined among patients with GC.

Aim

The aim of this study is to measure the impact of VTE as independent predictor of GC mortality.

Methods

Chart review of patients with GC treated in the Department of Oncology at John Stroger Hospital between the years of 2010 and 2015. VTE events were objectively confirmed with imaging in all cases. Active GC was defined as biopsy-proven metastatic disease or on active chemotherapy. Along with cancer-specific data, we abstracted risk assessments tools, non-GC-specific, validated for VTE and mortality prediction cancer, including the Khorana score (KRS), platelet lymphocyte ratio (PLR), and neutrophil lymphocyte ratio (NLR). Continuous variables are expressed by the median as appropriate according to normality. Categorical variables are expressed as percentages. SPSS version 22 was used and chi-square, Mann-Whitney U, Kaplan-Meier curve, and Cox proportional hazard with forward modeling were applied.

Results

We included 112 patients in the analysis. The patients were predominantly men (66%), 58-year-old, with adenocarcinoma (84%) and advanced disease (59%). The median follow-up was 21.3 months (IQR 8.9–42.4). Cumulative incidence of VTE at 1 year was 9%. The median time from diagnosis to VTE occurrence was 59 days (IQR 36 to 258). Patients with VTE had worse OS when compared to the non-VTE group (medians 11.87 vs 29.97 months, p = 0.02). Patients stratified as high risk by the PLR had worse OS (medians 22.6 vs 42.77 months, p = 0.02). There was no statistical difference in OS among patients stratified as high risk by the KRS (medians 23.7 vs 42.5, p = 0.16) and NLR (medians 24.1 vs 42.7 months, p = 0.21). In multivariate analysis, the independent predictors of mortality were VTE (hazard ratio (HR), 2.9; 95% CI, 1.4 to 6.6; p < 0.01), adenocarcinoma (HR, 3.1; 95% CI, 1.1 to 9.0; p = 0.03), advanced disease (HR, 2.8; 95% CI, 1.4 to 5.8; p < 0.01), and PLR (HR, 2.2; 95% CI, 1.3 to 3.8; p < 0.01).

Conclusion

VTE is associated with worse survival among patients with GC along with adenocarcinoma, advanced disease, and PLR. Moreover, these findings were independent of other cancer- and treatment-specific variables. Although potentially predictive in other cancer types, NLR and KRS were not associated with worse survival in this cohort.

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Simple Expression Domains Are Regulated by Discrete CRMs During Drosophila Oogenesis

Eggshell patterning has been extensively studied in Drosophila melanogaster. However, the cis-regulatory modules (CRMs), which control spatiotemporal expression of these patterns, are vastly unexplored. The FlyLight collection contains over 7,000 intergenic and intronic DNA fragments that, if containing CRMs, can drive the transcription factor GAL4. We cross-listed the 84 genes known to be expressed during D. melanogaster oogenesis with the ~1200 listed genes of the FlyLight collection, and found 22 common genes that are represented by 281 FlyLight fly lines. Of these lines, 54 show expression patterns during oogenesis when crossed to an UAS-GFP reporter. Of the 54 lines, 16 recapitulate the full or partial pattern of the associated gene pattern. Interestingly, while the average DNA fragment size is ~3kb in length, the vast majority of fragments show one type of a spatiotemporal pattern in oogenesis. Mapping the distribution of all 54 lines, we found a significant enrichment of CRMs in the first intron of the associated genes' model. In addition, we demonstrate the use of different anteriorly active FlyLight lines as tools to disrupt eggshell patterning in a targeted manner. Our screen provides further evidence that complex gene-patterns are assembled combinatorially by different CRMs controlling the expression of genes in simple domains.

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Diagnostic accuracy of EUS compared with MRCP in detecting choledocholithiasis: a meta-analysis of diagnostic test accuracy of head-to-head studies

There is a wide range of reported sensitivity and specificity for endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of the choledocholithiasis with lack of a proper meta-analysis of diagnostic test accuracy (DTA) using head-to-head comparison. Here, we aimed at comparing the diagnostic accuracy of EUS and MRCP in detecting choledocholithiasis using appropriate methodology recommended by the Cochrane Collaboration.

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Fundamental Frequency and Formants Before and After Prolonged Voice Use in Teachers

This study aimed to describe and correlate the fundamental frequency behavior and the first four formants before and after exposure to usual and routinely prolonged voice use from teachers with over 4 years of experience in teaching.

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Phosphoproteomic profiling reveals ALK and MET as novel actionable targets across synovial sarcoma subtypes

Despite intensive multi‐modal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical success, urging an unbiased and comprehensive analysis of oncogenic signaling networks to reveal therapeutic targets and personalized treatment strategies. Here we applied mass spectrometry-based phosphoproteomic profiling to the largest and most heterogeneous set of sarcoma cell lines characterized to date and identified novel tyrosine phosphorylation patterns, enhanced tyrosine kinases in specific subtypes, and potential driver kinases. ALK was identified as a novel driver in the Aska-SS synovial sarcoma (SS) cell line via expression of an ALK variant with a large extracellular domain deletion (ALKΔ2-17). Functional ALK dependency was confirmed in vitro and in vivo with selective inhibitors. Importantly, ALK immunopositivity was detected in 6/43 (14%) of SS patient specimens, one of which exhibited an ALK rearrangement. High PDGFRα phosphorylation also characterized SS cell lines, which was accompanied by enhanced MET activation in Yamato-SS cells. Although Yamato-SS cells were sensitive to crizotinib (ALK/MET-inhibitor) but not pazopanib (VEGFR/PDGFR-inhibitor) monotherapy in vitro, synergistic effects were observed upon drug combination. In vivo, both drugs were individually effective, with pazopanib efficacy likely attributable to reduced angiogenesis. MET or PDGFRα expression was detected in 58% and 84% of SS patients, respectively, with co-expression in 56%. Consequently, our integrated approach has led to the identification of ALK and MET as promising therapeutic targets in SS.

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Does spinal deformity correction of non-dystrophic scoliosis in neurofibromatosis type-1 with one-stage posterior pedicle screw technique produce outcomes similar to adolescent idiopathic scoliosis?

Efficacy of one-stage posterior pedicle screw instrument used in the treatment of non-dystrophic scoliosis in neurofibromatosis type-1(NF-1) is unknown. And there is no study that has directly compared the results of spinal deformity correction between non-dystrophic scoliosis in NF-1 and adolescent idiopathic scoliosis (AIS).

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