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 materialThe online version of this article (10.1186/s12943-018-0786-0) contains supplementary material, which is available to authorized users.

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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 yearsold) with triglyceride levels ≥ 1,000 mg/dL were identified. Based on our previous four factors-predictive model (age, 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% vs 9.2%, p<0.001) and gallstone disease (7.5% vs 2.1%, p<0.001). 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 four-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.

Background Western Australia (WA) public health measures to eradicate SARS‐CoV‐2 resulted in a secondary reduction in paediatric respiratory syncytial virus (RSV) admissions. Following an absent expected 2020 winter peak, RSV‐positive admissions surged during the summer of 2020. Aim This report examines the number of RSV‐positive admissions and severities across 36 months to better understand this out‐of‐season epidemic. Methods A retrospective observational study was performed assessing the number and severity of RSV‐related respiratory hospitalisations at a peripheral paediatric centre from March 2018 to February 2021. Data were extracted from the hospital clinical database. Results The total number of included participants was n = 294. The total number of RSV hospitalisations in SY (study year) 2018 (March 2018 to February 2019), SY 2019 (March 2019 to February 2020) and SY 2020 (March 2020 to February 2021) was 67, 98 and 129, respectively. Prior to SARS‐CoV‐2, RSV hospitalisations were highest during the winter months. In SY 2020, there were 0 RSV hospitalisations during winter, while 101 admissions in the following summer season. The proportion of admissions requiring respiratory support was significantly reduced in SY 2020 (34.1%) compared to SY 2018 (46.9%, P = 0.050) and SY 2019 (55.2%, P = 0.004). The median length of stay (LOS) in 2020 was 2.0 which was significantly reduced from 2018 and 2019 which was 3.0, P = 0.001; and 3.0, P < 0.001, respectively. Conclusion Following a period of RSV absence, there was an unprecedented surge in admission, however, with lower severity and shorter LOS.