6 research outputs found
External Validation of a Predictive Model for Acute Pancreatitis Risk in Patients With Severe Hypertriglyceridemia
Objective: We previously developed a predictive model to assess the risk of developing acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG). In this study, we aimed to externally validate this model.
Methods: The validation cohort included cross-sectional data between 2013 and 2017. Adult patients (≥18 years old) with triglyceride levels ≥1,000 mg/dL were identified. Based on our previous 4-factor predictive model (age, triglyceride [TG], excessive alcohol use, and gallstone disease), we estimated the probability of developing AP. Model performance was assessed using area under receiver operating characteristic curve (AUROC).
Results: In comparison to the original cohort, patients in the validation cohort had more prevalent acute pancreatitis (16.2% versus 9.2%; P<.001) and gallstone disease (7.5% versus 2.1%; P<.001). Other characteristics were comparable and not statistically significant. The AUROCs were almost identical: 0.8337 versus 0.8336 in the validation and the original cohorts, respectively. In univariable analyses, the highest increase in odds of AP was associated with HTG, followed by gallstones, excessive alcohol use, and younger age.
Conclusion: This study externally validates the 4-factor predictive model to estimate the risk of AP in adult patients with severe HTG (TG ≥1,000 mg/dL). Younger age was confirmed to place patients at high risk of AP. The clinical risk categories suggested in this study may be useful to guide treatment options
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Novel targeted therapies and immunotherapy for advanced thyroid cancers
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15–20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced therapies exert their effects by blocking the MAPK pathway, which has been widely correlated to different types of thyroid cancers. While these drugs remain reserved for thyroid cancer patients who failed all treatment options, their ability to improve patients’ overall survival remain hindered by their low efficacy and other molecular factors. Among these factors is the tumor’s ability to activate parallel proliferative signaling pathways other than the cascades blocked by these drugs, along with overexpression of some tyrosine kinase receptors (TKR). These facts urge the search for novel different treatment strategies for advanced thyroid cases beyond these drugs. Furthermore, the growing knowledge of the dynamic immune system interaction with tumor microenvironment has revolutionized the cancer immune therapy field. In this review, we aim to discuss the molecular escape mechanisms of thyroid tumors from these drugs. We also highlight novel therapeutic options targeting other pathways than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and their clinical impact. We also aim to discuss the usage of targeted therapy in restoring thyroid tumor sensitivity to RAI, and finally turn to extensively discuss the role of immunotherapy as a potential alternative treatment option for advanced thyroid diseases. Electronic supplementary material The online version of this article (10.1186/s12943-018-0786-0) contains supplementary material, which is available to authorized users
Additional file 1: of Novel targeted therapies and immunotherapy for advanced thyroid cancers
Table S1. Ongoing clinical trials mentioned. (DOCX 16 kb