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Background and Objectives: The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods: We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results: In the retrospective cohort, HCV-positive melanoma patients showed an increased risk of early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% vs. 39.8%, p = 0.020), and mortality (65.5% vs. 23.0%, p < 0.001) compared to HCV-negative patients. TriNetX data analysis revealed that HCV-positive patients had a 53% lower risk of developing melanoma (RR = 0.470, 95% CI: 0.443-0.498, p < 0.001). However, HCV-positive melanoma patients had higher all-cause mortality (HR = 1.360, 95% CI: 1.189-1.556, p < 0.001). An in silico analysis identified key molecular players, including IL-6 and CTLA4, in the HCV-melanoma network. Conclusions: While HCV infection may be associated with a lower risk of melanoma development, HCV-positive patients who develop melanoma have poorer outcomes. The identified molecular pathways provide potential targets for future research and therapeutic interventions.

Background/Objectives: The effect of glucagon-like peptide-1 receptor (GLP-1R) agonists on calcium homeostasis is poorly understood. This study aimed to investigate the association between GLP-1R agonist use and the risk of hypocalcemia and/or hypercalcemia, as well as other clinical outcomes. Methods: A retrospective cohort study used de-identified patient data from the TriNetX Global Collaborative Network, including 15,655 adult patients prescribed GLP-1R agonists and 15,655 propensity-matched controls. Outcomes included hypocalcemia, hypercalcemia, emergency visits, hospitalizations, cardiovascular events, and all-cause mortality. Results: GLP-1R agonist use was associated with a reduced risk of hypocalcemia (2.7% vs. 5.5%, RR 0.49, 95% CI: 0.44-0.55) but an increased risk of hypercalcemia (2.3% vs. 1.1%, RR 2.02, 95% CI: 1.69-2.42). The effect on hypocalcemia was most pronounced during the first six months of treatment. Among individual agents, tirzepatide showed the most pronounced effect, reducing hypocalcemia risk by 63% while increasing hypercalcemia risk by 85%. Semaglutide demonstrated similar effects, while dulaglutide and liraglutide showed modest effects. Furthermore, GLP-1R agonist use was associated with reduced risks of emergency visits (RR 0.57, 95% CI: 0.54-0.60), hospitalizations (RR 0.40, 95% CI: 0.36-0.44), cardiovascular events, and all-cause mortality (HR 0.27, 95% CI: 0.21-0.36). Conclusions: GLP-1R agonists exhibit a complex influence on calcium homeostasis, reducing hypocalcemia risk while increasing hypercalcemia risk. Beyond calcium regulation, these medications significantly reduce healthcare utilization, improve cardiovascular outcomes, and decrease mortality. Further research is needed to elucidate the mechanisms behind the differential effects of individual GLP-1R agonists, particularly tirzepatide, to optimize personalized treatment approaches and long-term safety.

Simple Summary: Medullary thyroid cancer is a rare but severe variant of thyroid cancer. The mainstay treatment for this condition is surgery to remove the entire thyroid gland, or total thyroidectomy. However, recent studies have found that a less extensive thyroidectomy may optimize survival outcomes for early localized tumors. We compared the survival and mortality outcomes between patients with such tumors who underwent total thyroidectomy and lobectomy/subtotal thyroidectomy to understand which surgical approach can improve survival rates in early-stage medullary thyroid cancer. Background: The optimal surgical approach for localized T1 medullary thyroid cancer remains unclear. Total thyroidectomy is standard, but lobectomy and subtotal thyroidectomy may minimize mortality while maintaining oncologic control. Methods: This retrospective analysis utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results registry to identify 2702 MTC patients including 398 patients with T1N0/1M0 MTC treated with total thyroidectomy or lobectomy/subtotal thyroidectomy from 2000 to 2019. Cox regression analyses assessed thyroid cancer-specific and overall mortality. Results: The majority (89.7%) underwent total thyroidectomy, while 10.3% had lobectomy/subtotal thyroidectomy. Nodal metastases were present in 29.6%. Over a median follow-up of 8.75 years, no significant difference was observed in cancer-specific mortality (5.7% vs. 8.1%, p = 0.47) or overall mortality (13.2% vs. 12.8%, p = 0.95). On multivariate analysis, undergoing cancer-directed surgery was associated with significantly improved overall survival (HR 0.18, p < 0.001) and cancer-specific survival (HR 0.17, p < 0.001) compared to no surgery. However, no significant survival difference was seen between total thyroidectomy and lobectomy/subtotal thyroidectomy for overall mortality (HR 0.77, p = 0.60) or cancer-specific mortality (HR 0.44, p = 0.23). The extent of surgery also did not impact outcomes within subgroups stratified by age, gender, T stage, or nodal status. Delayed surgery >1 month after diagnosis was associated with worse overall survival (p = 0.012). Conclusions: For localized T1 MTC, lobectomy/subtotal thyroidectomy appears to achieve comparable long-term survival to total thyroidectomy in this population-based analysis. The selective use of limited thyroidectomy may be reasonable for low-risk T1N0/1M0 MTC patients. Delayed surgery is associated with worse survival and additional neck dissection showed no benefit for this select group of patients. [ABSTRACT FROM AUTHOR]

Background: Activating mutations in the BRAF oncogene occur in 45% of papillary thyroid carcinomas (PTCs). Though less studied, K601E may identify a clinically distinct subset of thyroid neoplasms. Methods: A bioinformatics assessment was conducted using the COSMIC database and in silico data analysis. A systematic search was conducted through August 2024 to identify studies reporting BRAF mutation in thyroid neoplasms. Pooled prevalence, histopathological subtype distribution, extrathyroidal extension, lymph node metastasis, recurrence, and survival were extracted/analyzed from 32 studies (13 191 patients). Results: In the COSMIC database, BRAF K601E was found in various tissue types but mainly in the thyroid. In silico data analysis revealed a structural and functional basis for differences between K601E and V600E. Upon systematic review, the BRAF K601E mutation was identified in 2.8% of PTCs compared to 22% with V600E. The stratified analysis revealed geographical differences, with higher rates in Italy (5.23%) and the United States of America (3.31%). The K601E mutant was enriched for follicular‐patterned variants like NIFTP (11.2% of cases). Meta‐analysis demonstrated significantly reduced extrathyroidal extension for K601E versus V600E mutants (RR = 0.22, 95% CI = 0.10–0.50, p = 0.0003). Conclusion: K601E‐mutated neoplasms could be a unique clinicopathological entity associated with low‐risk histology and reduced extrathyroidal extension, consistent with a more indolent course than V600E mutants. Although detecting K601E may potentially guide conservative management, further prospective studies are needed. [ABSTRACT FROM AUTHOR]

Background: Robotic thyroidectomy is gaining popularity, yet its role in completion thyroidectomy remains unclear. We aimed to compare robotic vs conventional completion thyroidectomy for thyroid nodules. Methods: This retrospective study analyzed patients undergoing completion thyroidectomy from 2010-2020, either by conventional open technique (n = 87) or a robotic remote-access approach (n = 44). Outcomes were compared between groups. Results: A total of 131 patients were included. The robotic cohort was younger (45.3 ± 14.0 vs 55.5 ± 14.5 years, P < 0.001) with a lower BMI (25.9 ± 5.5 vs 33.7 ± 7.8 kg/m2, P < 0.001). Operative time was longer for robotic procedures (139 min vs 99 min, P < 0.001). Hospital stay was shorter after robotic surgery, with 25% discharged the same day as compared to 5.7% in the open thyroidectomy cohort (P = 0.006). Overall rates of complication were comparable (P = 0.65). Transient recurrent laryngeal nerve palsy occurred in 4.6% of patients, which was similar between both cohorts (P = 0.66). Conclusion: Robotic completion thyroidectomy appears safe and effective, achieving shorter hospitalization than conventional open approaches despite longer operative times. Appropriate patient selection and surgical technique optimization are key. Larger prospective studies should investigate costs and long-term patient-reported outcomes. [ABSTRACT FROM AUTHOR]