Glioblastoma multiforme (GBM) is the most malignant and aggressive type of brain tumor with an average life expectancy of less than 15 months. This is mostly due to the highly mutated genome of GBM, which is characterized by the deregulation of many key signaling pathways involving growth, proliferation, survival, and apoptosis. It is critical to explore novel diagnostic and therapeutic strategies that target these pathways to improve the treatment of malignant glioma in the future. This review summarizes the most common and important pathways that are highly mutated or deregulated in GBM and discusses potential therapeutic strategies targeting these pathways.
Introduction
Pancreatic cancer has the worst survival rate of all cancers. The current standard care for metastatic pancreatic cancer is gemcitabine, however, the success of this treatment is poor and overall survival has not improved for decades. Drug resistance (both intrinsic and acquired) is thought to be a major reason for the limited benefit of most pancreatic cancer therapies.
Areas covered
Previous studies have indicated various mechanisms of drug resistance in pancreatic cancer, including changes in individual genes or signaling pathways, the influence of the tumor microenvironment, and the presence of highly resistant stem cells. This review summarizes recent advances in the mechanisms of drug resistance in pancreatic cancer, and potential strategies to overcome this.
Expert Opinion
Increasing drug delivery efficiency and decreasing drug resistance is the current aim in pancreatic cancer treatment, and will also benefit the treatment of other cancers. Understanding the molecular and cellular basis of drug resistance in pancreatic cancer will lead to the development of novel therapeutic strategies with the potential to sensitize pancreatic cancer to chemotherapy, and to increase the efficacy of current treatments in a wide variety of human cancers.
Background:
The long incubation period and asymptomatic spread of COVID-19 present considerable challenges for health-care institutions. The identification of infected individuals is vital to prevent the spread of illness to staff and other patients as well as to identify those who may be at risk for disease-related complications. This is particularly relevant with the resumption of elective orthopaedic surgery around the world. We report the results of a universal testing protocol for COVID-19 in patients undergoing orthopaedic surgery during the coronavirus pandemic and to describe the postoperative course of asymptomatic patients who were positive for COVID-19.
Methods:
A retrospective review of adult operative cases between March 25, 2020, and April 24, 2020, at an orthopaedic specialty hospital in New York City was performed. Initially, a screening questionnaire consisting of relevant signs and symptoms (e.g., fever, cough, shortness of breath) or exposure dictated the need for nasopharyngeal swab real-time quantitative polymerase chain reaction (RT-PCR) testing for all admitted patients. An institutional policy change occurred on April 5, 2020, that indicated nasopharyngeal swab RT-PCR testing for all orthopaedic admissions. Screening and testing data for COVID-19 as well as relevant imaging, laboratory values, and postoperative complications were reviewed for all patients.
Results:
From April 5, 2020, to April 24, 2020, 99 patients underwent routine nasopharyngeal swab testing for COVID-19 prior to their planned orthopaedic surgical procedure. Of the 12.1% of patients who tested positive for COVID-19, 58.3% were asymptomatic. Three asymptomatic patients developed postoperative hypoxia, with 2 requiring intubation. The negative predictive value of using the signs and symptoms of disease to predict a negative test result was 91.4% (95% confidence interval [CI], 81.0% to 97.1%). Including a positive chest radiographic finding as a screening criterion did not improve the negative predictive value of screening (92.5% [95% CI, 81.8% to 97.9%]).
Conclusions:
A protocol for universal testing of all orthopaedic surgery admissions at 1 hospital in New York City during a 3-week period revealed a high rate of COVID-19 infections. Importantly, the majority of these patients were asymptomatic. Using chest radiography did not significantly improve the negative predictive value of screening. These results have important implications as hospitals anticipate the resumption of elective surgical procedures.
Level of Evidence:
Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
A significant volume of surgical care is being delivered at county hospitals throughout Liberia. The density and quality of appropriately trained personnel and infrastructure remain critically low. There is strong evidence for continued development of emergency and essential surgical services, as well as improved surgical outcomes tracking, at county hospitals in Liberia. These results serve to inform the international community and donors of the ongoing global surgical and anesthesia crisis.
In order to meet the immense demand for surgical care in Bangladesh, public hospitals must address critical shortages in skilled human resources, inadequate physical infrastructure, and low availability of equipment and essential medications. This study identified numerous areas in which the international community can play a vital role in increasing surgical and anesthesia capacity in Bangladesh and ensuring safe surgery for all in the country.
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