Introduction—heterogeneity in clinical outcomes and survival was observed in patients with papillary thyroid cancer (PTC) and distant metastases. Here, we investigated the effect of distant metastases sites on survival in PTC patients. Methods—patients with a diagnosis of PTC and known metastases were identified using the Surveillance, Epidemiology, and End Results database (1975–2016). Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on thyroid cancer-specific survival (TCSS) and overall survival (OS). Results—from 89,694 PTC patients, 1819 (2%) developed distant metastasis at the initial diagnosis, of whom 26.3% presented with the multiple-organ disease. The most common metastatic sites were lung (53.4%), followed by bone (28.1%), liver (8.3%), and brain (4.7%). In metastatic patients, thyroid cancer-specific death accounted for 73.2%. Kaplan–Meier curves showed decreased OS in patients with metastases to the brain (median OS = 5 months) and liver (median OS = 6 months) compared to lung (median OS = 10 months) and bone (median OS = 23 months). Moreover, multiple organ metastasis had a higher mortality rate (67.4%) compared to single organ metastasis (51.2%, p < 0.001). Using multivariate analysis, risk factors that significantly influence TCSS and OS were male gender (HR = 1.86, 95% CI = 1.17–2.94, p < 0.001, and HR = 1.90, 95% CI = 1.40–2.57, p = 0.009), higher tumor grade (HR = 7.31, 95% CI = 2.13–25.0, p < 0.001 and HR = 4.76, 95% CI = 3.93–5.76, p < 0.001), multiple organ involvement (HR = 6.52, 95% CI = 1.50–28.39, p = 0.026 and HR = 5.08, 95% CI = 1.21–21.30, p = 0.013), and brain metastasis (HR = 1.82, 95% CI = 1.15–2.89, p < 0.001 and HR = 4.21, 95% CI = 2.20–8.07, p = 0.010). Conclusion—the pattern of distant metastatic organ involvement was associated with variability in OS in PTC. Multi-organ metastasis and brain involvement are associated with lower survival rates in PTC. Knowledge of the patterns of distant metastasis is crucial to personalize the treatment and follow-up strategies.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated significant efficacy in obesity treatment beyond their original development for type-2 diabetes management. This comprehensive study investigated the relationship between GLP-1RA use and cancer incidence in individuals with obesity across a 5-year follow-up period. Methods: We conducted a large-scale cohort study using the TriNetX US Collaborative Network database (2013–2023) examining adult patients with obesity. The study utilized propensity score matching to pair GLP-1RA-treated patients with controls (1:1) using the nearest neighbor method. Cancer incidence served as the primary outcome measure over the 5-year follow-up, with subgroup analyses considering individual GLP-1RA agents, patient sex, and BMI categories. Results: Analysis revealed significant cancer-risk reductions associated with GLP-1RA use across multiple cancer types compared to matched controls. Notable risk reductions were observed in gastrointestinal (HR 0.67, 95% CI 0.59–0.75), skin (HR 0.62, 95% CI 0.55–0.70), breast (HR 0.72, 95% CI 0.64–0.82), female genital (HR 0.61, 95% CI 0.53–0.71), prostate (HR 0.68, 95% CI 0.58–0.80), and lymphoid/hematopoietic cancers (HR 0.69, 95% CI 0.60–0.80). Semaglutide demonstrated superior protective effects, particularly in gastrointestinal cancers (HR 0.45, 95% CI 0.37–0.53). Conversely, liraglutide showed increased risks for thyroid (HR 1.70, 95% CI 1.03–2.82) and respiratory cancers (HR 1.62, 95% CI 1.13–2.32). Conclusions: This research provides compelling evidence for GLP-1RA’s potential role in cancer-risk reduction, with semaglutide showing particularly promising results. The differential effects observed among GLP-1RA agents emphasize the importance of personalized medicine approaches. These findings suggest significant implications for clinical practice and future research in both obesity management and cancer prevention.

A meta‐analysis was performed to identify patients with coronavirus disease 2019 (COVID‐19) presenting with gastrointestinal (GI) symptoms during the first and second pandemic waves and investigate their association with the disease outcomes. A systematic search in PubMed, Scopus, Web of Science, ScienceDirect, and EMBASE was performed up to July 25, 2020. The pooled prevalence of the GI presentations was estimated using the random‐effects model. Pairwise comparison for the outcomes was performed according to the GI manifestations' presentation and the pandemic wave of infection. Data were reported as relative risk (RR), or odds ratio and 95% confidence interval. Of 125 articles with 25,252 patients, 20.3% presented with GI manifestations. Anorexia (19.9%), dysgeusia/ageusia (15.4%), diarrhea (13.2%), nausea (10.3%), and hematemesis (9.1%) were the most common. About 26.7% had confirmed positive fecal RNA, with persistent viral shedding for an average time of 19.2 days before being negative. Patients presenting with GI symptoms on admission showed a higher risk of complications, including acute respiratory distress syndrome (RR = 8.16), acute cardiac injury (RR = 5.36), and acute kidney injury (RR = 5.52), intensive care unit (ICU) admission (RR = 2.56), and mortality (RR = 2.01). Although not reach significant levels, subgroup‐analysis revealed that affected cohorts in the first wave had a higher risk of being hospitalized, ventilated, ICU admitted, and expired. This meta‐analysis suggests an association between GI symptoms in COVID‐19 patients and unfavorable outcomes. The analysis also showed improved overall outcomes for COVID‐19 patients during the second wave compared to the first wave of the outbreak.

Circulatory tumor-derived exosomal microRNAs (miRNAs) play key roles in cancer development/progression. We aimed to assess the diagnostic/prognostic value of circulating exosomal miRNA in thyroid cancer (TC). A search in PubMed, Scopus, Web of Science, and Science Direct up to 22 May 2021 was performed. The true/false positive (TP/FP) and true/false negative (TN/FN) rates were extracted from each eligible study to obtain the pooled sensitivity, specificity, positive/negative likelihood ratios (PLR/NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95%CIs). The meta-analysis included 12 articles consisting of 1164 Asian patients and 540 controls. All miRNAs were quantified using qRT-PCR assays. The pooled sensitivity was 82% (95%CI = 77–86%), pooled specificity was 76% (95%CI = 71–80%), and pooled DOR was 13.6 (95%CI = 8.8–21.8). The best biomarkers with high sensitivity were miR-16-2-3p (94%), miR-223-5p (91%), miR-130a-3p (90%), and miR182-5p (94%). Similarly, they showed high specificity, in addition to miR-34c-5p. Six panels of two to four exosomal miRNAs showed higher diagnostic values with an area under the curve (AUC) ranging from 0.906 to 0.981. The best discriminative ability to differentiate between cancer and non-cancer individuals was observed for miR-146b-5p + miR-223-5p + miR-182-5p (AUC = 0.981, sensitivity = 93.8% (84.9–98.3), specificity = 92.9% (76.5–99.1)). In conclusion, the expression levels of exosomal miRNAs could predict TC.

Background: Previously, we have demonstrated that nuclear BRAF^V600E is associated with melanoma aggressiveness and vemurafenib resistance. However, the underlying mechanisms of how nuclear localization of BRAF^V600E promotes cell aggressiveness have not yet been investigated. Despite therapeutic advancements targeting cutaneous melanoma, unknown cellular processes prevent effective treatment for this malignancy, prompting an urgent need to identify new biological targets. This study aims to explore the association of inducible heme oxygenase 1 (HMOX-1) with nuclear BRAF^V600E in promoting melanoma aggressiveness. Methods: Proteomics analysis was performed to identify the interacting partner(s) of nuclear BRAF^V600E. Immunohistochemistry was applied to evaluate the levels of HMOX-1 and nuclear BRAF^V600E expression in melanoma and adjacent healthy tissues. Immunofluorescence assessed the nuclear localization of BRAF^V600E in vemurafenib-resistant A375R melanoma cells. Further study of HMOX-1 knockdown or BRAF^V600E overexpression in melanoma cells suggested a role for HMOX-1 in the regulation of cell proliferation in vivo and in vitro. Finally, Western blot analysis was performed to confirm the pathway by which HMOX-1 mediates Akt signaling. Results: Proteomics results showed that HMOX-1 protein expression was 10-fold higher in resistant A375R cells compared to parental counterpart cells. In vitro and in vivo results illustrate that nuclear BRAF^V600E promotes HMOX-1 overexpression, whereas HMOX-1 reduction represses melanoma cell proliferation and tumor growth. Mechanistic studies revealed that HMOX-1 was associated with nuclear BRAF^V600E localization, thus promoting melanoma proliferation via a persistent activation of the AKT pathway. Conclusions: Our results highlight a previously unknown mechanism in which the nuclear BRAF^V600E/HMOX-1/AKT axis plays an essential role in melanoma cell proliferation. Targeting HMOX-1 could be a novel method for treating melanoma patients who develop BRAF inhibitor resistance.