Gastrointestinal Stromal Tumors: Molecular Mechanisms and Targeted Therapies

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are diverse not only in their clinical behavior but also in their histologic appearance. GISTs are insensitive to conventional sarcoma chemotherapy and radiation. However GISTs are sensitive to small-molecule tyrosine kinase inhibitors as 85–90% of GISTs have KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations, which drive tumorigenesis. This review will briefly touch on the clinicopathological features of GIST, while the majority of the review will focus on the clinical and treatment ramifications of KIT and PDGFRA mutations found in GIST

Assessing the impact of a cattle risk-based trading scheme on the movement of bovine tuberculosis infected animals in England and Wales

The adoption of bovine tuberculosis (bTB) risk-based trading (RBT) schemes has the potential to reduce the risk of bTB spread. However, any scheme will have cost implications that need to be balanced against its likely success in reducing bTB. This paper describes the first stochastic quantitative model assessing the impact of the implementation of a cattle risk-based trading scheme to inform policy makers and contribute to cost–benefit analyses. A risk assessment for England and Wales was developed to estimate the number of infected cattle traded using historic movement data recorded between July 2010 and June 2011. Three scenarios were implemented: cattle traded with no RBT scheme in place, voluntary provision of the score and a compulsory, statutory scheme applying a bTB risk score to each farm. For each scenario, changes in trade were estimated due to provision of the risk score to potential purchasers. An estimated mean of 3981 bTB infected animals were sold to purchasers with no RBT scheme in place in one year, with 90% confidence the true value was between 2775 and 5288. This result is dependent on the estimated between herd prevalence used in the risk assessment which is uncertain. With the voluntary provision of the risk score by farmers, on average, 17% of movements was affected (purchaser did not wish to buy once the risk score was available), with a reduction of 23% in infected animals being purchased initially. The compulsory provision of the risk score in a statutory scheme resulted in an estimated mean change to 26% of movements, with a reduction of 37% in infected animals being purchased initially, increasing to a 53% reduction in infected movements from higher risk sellers (score 4 and 5). The estimated mean reduction in infected animals being purchased could be improved to 45% given a 10% reduction in risky purchase behaviour by farmers which may be achieved through education programmes, or to an estimated mean of 49% if a rule was implemented preventing farmers from the purchase of animals of higher risk than their own herd. Given voluntary trials currently taking place of a trading scheme, recommendations for future work include the monitoring of initial uptake and changes in the purchase patterns of farmers. Such data could be used to update the risk assessment to reduce uncertainty associated with model estimates

Interobserver Variation in the Diagnosis of Gastric Epithelial Dysplasia and Carcinoma between Two Pathologists in Japan and Korea

Although the biological potential of gastric epithelial dysplasia (GED) as a precursor of gastric cancer has never been in doubt, the classification of these lesions has been controversial and fraught with marked variations in approach to diagnosis across the world. The complexity of cyto-architectural features has been considered to be of paramount importance for the diagnosis of carcinoma in Japan, while breach of the basement membrane and invasion into the lamina propria has been considered the sine qua non of malignancy and hence a pre-requisite for the diagnosis of cancer in the West. In Korea, although the incidence of gastric cancer is similar to Japan, the diagnostic approach to GED or cancer seems to lie midway between Western and Japanese criteria. In this review, we will discuss the difference in the diagnosis of GED and cancer between two pathologists working in the comprehensive cancer center located in Japan and Korea, one of the most prevalent areas in the world for gastric cancer

Anterior Abdominal Stab Injury: A Comparison of Self-Inflicted and Intentional Third-Party Stabbings

Background: There is minimal literature comparing self-inflicted (SI) with non–self-inflicted (NSI) anterior abdominal stab wounds (AASW). Methods: Adult patients treated at a level 1 trauma center from 2006 through 2011 with an AASW were reviewed. Results: There were 215 patients with an AASW; 20% were SI. NSI patients had more nonabdominal injuries (47% vs 16%, P \u3c .01) and disposition directly to the operating room (45% vs 26%, P = .02). Intra-abdominal injury rates were similar. One hundred twenty-eight patients had isolated AASWs; 28% were SI. SI patients had higher admission rates (86% vs 63%, P = .01). One hundred three patients had isolated stable/asymptomatic AASWs; 31% were SI. SI patients had more admissions (84% vs 52%, P \u3c .01), had higher intensive care unit admission rates (23% vs 5%, P = .01), longer LOS (3.2 vs 1.4, P \u3c .01), and higher hospital charges ($18,000 vs$11,000, P \u3c .01). The rates of intra-abdominal injury were again similar. Conclusions: Controlling for extra-abdominal injuries, SI AASW patients have similar rates of intra-abdominal injury but use more resources

Anterior Abdominal Stab Injury: A Comparison of Self-Inflicted and Intentional Third-Party Stabbings

Background: There is minimal literature comparing self-inflicted (SI) with non–self-inflicted (NSI) anterior abdominal stab wounds (AASW). Methods: Adult patients treated at a level 1 trauma center from 2006 through 2011 with an AASW were reviewed. Results: There were 215 patients with an AASW; 20% were SI. NSI patients had more nonabdominal injuries (47% vs 16%, P \u3c .01) and disposition directly to the operating room (45% vs 26%, P = .02). Intra-abdominal injury rates were similar. One hundred twenty-eight patients had isolated AASWs; 28% were SI. SI patients had higher admission rates (86% vs 63%, P = .01). One hundred three patients had isolated stable/asymptomatic AASWs; 31% were SI. SI patients had more admissions (84% vs 52%, P \u3c .01), had higher intensive care unit admission rates (23% vs 5%, P = .01), longer LOS (3.2 vs 1.4, P \u3c .01), and higher hospital charges ($18,000 vs$11,000, P \u3c .01). The rates of intra-abdominal injury were again similar. Conclusions: Controlling for extra-abdominal injuries, SI AASW patients have similar rates of intra-abdominal injury but use more resources

An Exploratory Study on the Microbiome of Northern and Southern Populations of \u3ci\u3eIxodes scapularis\u3c/i\u3e Ticks Predicts Changes and Unique Bacterial Interactions

The black-legged tick (Ixodes scapularis) is the primary vector of Borrelia burgdorferi, the causative agent of Lyme disease in North America. However, the prevalence of Lyme borreliosis is clustered around the Northern States of the United States of America. This study utilized a metagenomic sequencing approach to compare the microbial communities residing within Ix. scapularis populations from northern and southern geographic locations in the USA. Using a SparCC network construction model, we performed potential interactions between members of the microbial communities from Borrelia burgdorferi–infected tissues of unfed and blood-fed ticks. A significant difference in bacterial composition and diversity was found between northern and southern tick populations. The network analysis predicted a potential antagonistic interaction between endosymbiont Rickettsia buchneri and Borrelia burgdorferi sensu lato. The network analysis, as expected, predicted significant positive and negative microbial interactions in ticks from these geographic regions, with the genus Rickettsia, Francisella, and Borreliella playing an essential role in the identified clusters. Interactions between Rickettsia buchneri and Borrelia burgdorferi sensu lato need more validation and understanding. Understanding the interplay between the microbiome and tick-borne pathogens within tick vectors may pave the way for new strategies to prevent tick-borne infections

An Exploratory Study on the Microbiome of Northern and Southern Populations of \u3ci\u3eIxodes scapularis\u3c/i\u3e Ticks Predicts Changes and Unique Bacterial Interactions

The black-legged tick (Ixodes scapularis) is the primary vector of Borrelia burgdorferi, the causative agent of Lyme disease in North America. However, the prevalence of Lyme borreliosis is clustered around the Northern States of the United States of America. This study utilized a metagenomic sequencing approach to compare the microbial communities residing within Ix. scapularis populations from northern and southern geographic locations in the USA. Using a SparCC network construction model, we performed potential interactions between members of the microbial communities from Borrelia burgdorferi–infected tissues of unfed and blood-fed ticks. A significant difference in bacterial composition and diversity was found between northern and southern tick populations. The network analysis predicted a potential antagonistic interaction between endosymbiont Rickettsia buchneri and Borrelia burgdorferi sensu lato. The network analysis, as expected, predicted significant positive and negative microbial interactions in ticks from these geographic regions, with the genus Rickettsia, Francisella, and Borreliella playing an essential role in the identified clusters. Interactions between Rickettsia buchneri and Borrelia burgdorferi sensu lato need more validation and understanding. Understanding the interplay between the microbiome and tick-borne pathogens within tick vectors may pave the way for new strategies to prevent tick-borne infections

A proposed approach to monitor private-sector policies and practices related to food environments, obesity and non-communicable disease prevention

Private-sector organizations play a critical role in shaping the food environments of individuals and populations. However, there is currently very limited independent monitoring of private-sector actions related to food environments. This paper reviews previous efforts to monitor the private sector in this area, and outlines a proposed approach to monitor private-sector policies and practices related to food environments, and their influence on obesity and non-communicable disease (NCD) prevention. A step-wise approach to data collection is recommended, in which the first (‘minimal’) step is the collation of publicly available food and nutrition-related policies of selected private-sector organizations. The second (‘expanded’) step assesses the nutritional composition of each organization’s products, their promotions to children, their labelling practices, and the accessibility, availability and affordability of their products. The third (‘optimal’) step includes data on other commercial activities that may influence food environments, such as political lobbying and corporate philanthropy. The proposed approach will be further developed and piloted in countries of varying size and income levels. There is potential for this approach to enable national and international benchmarking of private-sector policies and practices, and to inform efforts to hold the private sector to account for their role in obesity and NCD prevention