Detection of myeloma cell-derived microvesicles: a tool to monitor multiple myeloma load.

The persistence of tumor load in multiple myeloma (MM) lead to relapse in patients achieving complete remission (CR). Appropriate and effective methods of myeloma tumor load monitoring are important for guiding clinical management. This study aimed to clarify the value of microvesicles in monitoring MM tumor load. Microvesicles in bone marrow and peripheral blood were isolated by differential ultracentrifugation and detected by flow cytometry. Western blotting was applied to assess myosin light chain phosphorylation levels. Flow cytometry to detect Ps+CD41a-, Ps+CD41a-CD138+, Ps+CD41a-BCMA+ microvesicles from bone marrow can be used to predict myeloma burden, furthermore, Ps+CD41a- microvesicles may as a potential index to MRD test. Mechanistically, the releasing of microvesicles from MM cell was regulated by Pim-2 Kinase via Phosphorylation of MLC-2 protein.

SYTL5 Promotes Papillary Thyroid Carcinoma Progression by Enhancing Activation of the NF-κB Signaling Pathway.

The function and mechanism of SYTL5 in papillary thyroid carcinoma (PTC) are still unclear. In this research, we found that SYTL5 was significantly overexpressed in PTC tissues compared with normal thyroid tissues. SYTL5 downregulation significantly weakened the proliferative, migratory, and invasive abilities of PTC cells. In addition, upregulated SYTL5 could promote cancer progression by activating the NF-κB signaling pathway. RAC1b expression is positively associated with SYTL5, and overexpressed RAC1b abrogated the antitumor effect after SYTL5 inhibition. In conclusion, our findings identify the oncogenic role of SYTL5 in PTC by activation of the NF-κB signaling pathway, thus facilitating PTC development and progression.

Primary Vitreoretinal Lymphoma: A Retrospective Study of 20 Eyes.

Purpose: This study aimed to describe and analyze the clinical features of 20 eyes of 15 primary vitreoretinal lymphoma (PVRL) patients. Methods: This was a retrospective case series and a review of the literature. Fifteen PVRL patients (20 affected eyes) referred between February 2011 and December 2019 were recruited, and their medical records were retrospectively reviewed. Results: Among these 15 PVRL patients, seven were men (46.67%), and five had bilateral PVRL (33.33%). The median onset age was 66 ± 9.26 years and six (40%) patients had central nervous system (CNS) involvement, and two of them died of CNS-related complications. The ocular symptoms varied from decreased vision to binocular diplopia. The ocular manifestations were diverse and involved both the anterior and posterior segments, including the vitreous cells, subretinal white-yellow lesions, cotton-wool spots, and ophthalmoplegia. The rate of misdiagnosis and failure to diagnose was 100%, and 30% of them were misdiagnosed as uveitis. We found five cases revealing rare characteristics of this malignancy. Among them, there were two cases with mild hypertensive retinopathy exhibiting cotton-wool spots, one case mimicking age-related macular degeneration (AMD), one case with systemic lupus erythematosus (SLE), and one patient had extraocular muscle involvement. To the best of our knowledge, we reported PVRL exhibiting cotton-wool spots as the main manifestation and coexisting with extraocular myopathy for the first time. Conclusions: PVRL is a rare intraocular malignancy that commonly masquerades as uveitis. As the clinical signs and symptoms are atypical, ophthalmologists must carefully examine patients to avoid misdiagnosis or a failure to diagnose. Cotton-wool spots and extraocular myopathy might be the dominant initial symptoms in PVRL patients, and AMD should be considered a differential diagnosis of PVRL. SLE patients under immunosuppressive treatment could have spontaneous PVRL.

Is Epstein-Barr Virus Infection Associated With Thyroid Tumorigenesis?-A Southern China Cohort Study.

Background: Epstein-Barr virus (EBV) is associated with many epithelial malignancies. A few reports on the association between EBV and thyroid tumorigenesis have been investigated. However, the conclusion is highly contradictory. We aimed to explore the role of EBV in thyroid nodule development and its clinical significance in a cohort from southern China. Method: We conducted a retrospective data abstraction study of patients who underwent thyroidectomy between December 2017 and June 2018. We retrospectively analyzed the clinicopathological parameters and EBV infection status (serological antibodies and in situ hybridization). Result: The cohort comprised 384 patients with newly diagnosed thyroid diseases, including 261 papillary thyroid carcinomas, 87 nodular goiters, 21 follicular adenomas, 12 follicular thyroid carcinomas, and 3 medullary thyroid carcinomas. Forty-two (10.9%) patients were identified as being serological antibody positive. However, there was no association between the clinicopathological parameters and serological antibody positivity. Additionally, none of the patients showed EBER expression in thyroid normal/cancer cell nuclei in in situ hybridization. Conclusion: In this study, no correlation between EBV and thyroid diseases was found in a cohort from southern China.

Treatment-related adverse effects with TKIs in patients with advanced or radioiodine refractory differentiated thyroid carcinoma: a systematic review and meta-analysis.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been administered to advanced or radio-iodine refractory differentiated thyroid carcinoma (RR-DTC) patients for years. We performed a pooled analysis to explore the frequency of severe adverse effects in advanced or RR-DTC patients treated with sorafenib and lenvatinib. METHODS: We performed a comprehensive search of computerized databases, including PubMed, Web of Science, Ovid, EMASE, and the Cochrane Library, from the drugs' inception to July 2018 to identify clinical trials. All grade and severe adverse events (AEs; grade ≥3) were analyzed. This meta-analysis was conducted in accordance with PRISMA guidelines. RESULTS: In total, seve studies published from 2012-2018 with 657 patients were eligible for this study. We included two studies (238 patients) that received 200 mg sorafenib twice and five studies (419 patients) that received 24 mg lenvatinib daily. The frequency of AEs was different among the two drugs. Patients in the sorafenib group had a significantly higher frequency of all grade hand-foot syndrome, hypocalcemia, rash, elevated alanine aminotransferase (ALT), and elevated aspartate aminotransferase (AST). Conversely, the lenvatinib group experienced more frequent all grade voice change, hypertension, nausea, and vomiting compared with those with sorafenib. For grade ≥3 adverse effects, hand-foot syndrome, hypocalcemia, and elevated ALT were more frequent in sorafenib-treated patients. Moreover, lenvatinib-treated patients had a significantly higher incidence of severe weight loss, hypertension, and nausea. CONCLUSION: Significant differences in common adverse effects, such as all-grade and severe AEs, were detected between sorafenib and lenvatinib in the current study. Early intervention and management of treatment-related AEs (TRAEs) can minimize the impact on patients' quality-of-life, and avoid unnecessary dose reductions and treatment-related discontinuations.