Patient demographics, clinicopathologic features, and outcomes in wild-type gastrointestinal stromal tumor: a national cohort analysis.

Wild-type KIT and PDGFRA gastrointestinal stromal tumors (GIST) are rare tumors with limited treatment options. We sought to determine the clinicopathologic features of wild-type GIST and identify factors that influence overall survival (OS) using a large national database. Retrospective evaluation of patients with wild-type GIST in the National Cancer Database (NCDB) was performed. Demographic, clinicopathologic, and treatment data were analyzed. Features associated with OS were investigated using Kaplan-Meier analysis and Cox proportional hazards model. 244 patients with median diagnosis age of 59 years (95% CI 57-63) were identified. The stomach was the most common primary site (57%) followed by the small intestine (35%). Surgical resection was performed on 85% of patients and 53% of patients received systemic therapy. Factors associated with decreased OS on multivariable analysis included small intestine primary (HR 2.72, 95% CI 1.13-6.69, P = 0.026) and > 5 mitoses per 50 HPF (HR 4.77, 95% CI 1.86-13.2, P = 0.001). Wild-type GISTs may be identified in older patients, with most arising in the stomach and small bowel. Surgery remains the principal treatment modality. Small intestine primary site and high mitotic count were associated with abbreviated OS.

Efficiency of care and cost for common emergency general surgery conditions: Comparison by surgeon training and practice.

BACKGROUND: Our institutional emergency general surgery service is staffed by both trauma and critical care-trained surgeons and other boarded general surgeons and subspecialists. We compared efficiency of care for common emergency general surgery conditions between trauma and critical care-trained surgeons and boarded general surgeons and subspecialists. METHODS: Adults admitted between February 2014 and May 2017 with acute appendicitis, acute cholecystitis, intestinal obstruction, incarcerated hernia, or other acute abdominal diagnoses seen by emergency general surgery service were included. Demographic characteristics, consulting surgeon, operations, outcomes, and cost data were obtained. RESULTS: A total of 1,363 patients were included: 384 (28.2%) with acute appendicitis, 477 (35.0%) with acute cholecystitis, 406 (29.8%) with intestinal obstruction, 22 (1.6%) with incarcerated hernia, and 74 (5.4%) with other acute abdominal diagnoses. Trauma and critical care-trained surgeons saw 836 (61.3%) patients. There was no difference in operative management between the two groups, however, trauma and critical care-trained surgeons had significantly less time to the operative room (7.0 vs 12.9 hours; P < .001), without a difference in duration of stay or costs. The subgroups of acute appendicitis and acute cholecystitis when treated by trauma and critical care-trained surgeons had less time to the operative room (8.4 vs 17.4 hours; P < .001), shorter hospital stay (2.5 vs 2.8 days; P = .021), and less emergency department cost ($822 vs $876; P = .012). CONCLUSION: Compared with boarded general surgeons and subspecialists, trauma and critical care-trained surgeons provide more efficient care for common emergency general surgery conditions, with less time from consultation to the operative room.

Expression of miR-145-5p During Chondrogenesis of Mesenchymal Stem Cells.

Assessing the quality of tissue engineered (TE) cartilage has historically been performed by endpoint measurements including marker gene expression. Until the adoption of promoter-driven reporter constructs capable of quantitative and real time non-destructive expression analysis, temporal gene expression assessments along a timeline could not be performed on TE constructs. We further exploit this technique to utilize microRNA (miRNA or miR) through the use of firefly luciferase reporter (Luc) containing a 3' UTR perfect complementary target sequence to the mature miR-145-5p. We report the development and testing of a firefly luciferase (Luc) reporter responsive to miR-145-5p for longitudinal tracking of miR-145-5p expression throughout MSC chondrogenic differentiation. Plasmid reporter vectors containing a miR-145-5p responsive reporter (Luc reporter with a perfect complementary target sequence to the mature miR-145-5p sequence in the 3'UTR), a Luc reporter driven by a truncated Sox9 (one of the targets of miR-145-5p) promoter, or the Luc backbone (control) vector without a specific miRNA target were transfected into MSCs by electroporation. Transfected MSCs were mixed with untransfected MSC to generate chondrogenic pellets. Pellets were imaged by bioluminescent imaging (BLI) and harvested along a preset time line. The imaging signals from miR-145-5p responsive reporter and Sox9 promoter-driven reporter showed correlated time-courses (measured by BLI and normalized to Luc-control reporter; Spearman r=0.93, p=0.0002) during MSC chondrogenic differentiation. Expression analysis by qRT-PCR suggests an inverse relationship between miR-145-5p and Sox9 gene expression during MSC chondrogenic differentiation. Non-destructive cell-pellet imaging is capable of supplementing histological analyses to characterize TE cartilage. The miR-145-5p responsive reporter is relatively simple to construct and generates a consistent imaging signal responsive to miR-145-5p during MSC chondrogenesis in parallel to certain molecular and cellular events.

Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs.

Epitope content plays a critical role in determining T-cell and antibody responses to vaccines, biomaterials, and protein therapeutics, but its effects are nonlinear and difficult to isolate. Here, molecular self-assembly is used to build a vaccine with precise control over epitope content, in order to finely tune the magnitude and phenotype of T helper and antibody responses. Self-adjuvanting peptide nanofibers are formed by co-assembling a high-affinity universal CD4+ T-cell epitope (PADRE) and a B-cell epitope from Staphylococcus aureus at specifiable concentrations. Increasing the PADRE concentration from micromolar to millimolar elicited bell-shaped dose-responses that are unique to different T-cell populations. Notably, the epitope ratios that maximize T follicular helper and antibody responses differed by an order of magnitude from those that maximized Th1 or Th2 responses. Thus, modular materials assembly provides a means of controlling epitope content and efficiently skewing the adaptive immune response in the absence of exogenous adjuvant; this approach may contribute to the development of improved vaccines and immunotherapies.