MYC promotes fibroblast osteogenesis by regulating ALP and BMP2 to participate in ectopic ossification of ankylosing spondylitis.

BACKGROUND: Ectopic ossification is an important cause of disability in patients with ankylosing spondylitis (AS). Whether fibroblasts can transdifferentiate into osteoblasts and contribute to ossification remains unknown. This study aims to investigate the role of stem cell transcription factors (POU5F1, SOX2, KLF4, MYC, etc.) of fibroblasts in ectopic ossification in patients with AS. METHODS: Primary fibroblasts were isolated from the ligaments of patients with AS or osteoarthritis (OA). In an in vitro study, primary fibroblasts were cultured in osteogenic differentiation medium (ODM) to induce ossification. The level of mineralization was assessed by mineralization assay. The mRNA and protein levels of stem cell transcription factors were measured by real-time quantitative PCR (q-PCR) and western blotting. MYC was knocked down by infecting primary fibroblasts with lentivirus. The interactions between stem cell transcription factors and osteogenic genes were analysed by chromatin immunoprecipitation (ChIP). Recombinant human cytokines were added to the osteogenic model in vitro to evaluate their role in ossification. RESULTS: We found that MYC was elevated significantly in the process of inducing primary fibroblasts to differentiate into osteoblasts. In addition, the level of MYC was remarkably higher in AS ligaments than in OA ligaments. When MYC was knocked down, the expression of the osteogenic genes alkaline phosphatase (ALP) and bone morphogenic protein 2 (BMP2) was decreased, and the level of mineralization was reduced significantly. In addition, the ALP and BMP2 were confirmed to be the direct target genes of MYC. Furthermore, interferon-γ (IFN-γ), which showed high expression in AS ligaments, was found to promote the expression of MYC in fibroblasts in the process of ossification in vitro. CONCLUSIONS: This study demonstrates the role of MYC in ectopic ossification. MYC may act as the critical bridge that links inflammation with ossification in AS, thus providing new insights into the molecular mechanisms of ectopic ossification in AS.

Clinicopathologic predictors of central lymph node metastases in clinical node-negative papillary thyroid microcarcinoma: a systematic review and meta-analysis.

BACKGROUND: The presence of central lymph node metastases (CLNM) has been suggested as a risk factor for poorer prognosis and recurrence in papillary thyroid microcarcinoma (PTMC). However, the clinicopathologic factors for CLNM in clinical node-negative (CN0) PTMC were not well defined. This study aimed to perform a systematic review and meta-analysis to investigate the significant clinicopathologic predictors of CLNM in CN0 PTMC. METHODS: A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Web of Science. Case-control studies on the association of clinicopathologic risk factors with CLNM in CN0 PTMC were included. RESULTS: Thirteen eligible studies involving 6068 patients with CN0 PTMC were included. From the pooled analyses, male (odds ratio [OR]: 2.07, 95% CI: 1.49-2.87, P < 0.001), multifocality (OR: 1.88, 95% CI: 1.54-2.29, P < 0.001), tumor size > 5 mm (OR: 1.84, 95% CI: 1.55-2.18, P < 0.001), and extrathyroidal extension (OR: 1.96, 95% CI: 1.30-2.95, P = 0.001) are significantly associated with increased risk of CLNM in CN0 PTMC. A sample size with a cutoff point of 200 was identified as the source of heterogeneity for sex according to meta-regression (t = 3.18, P = 0.033). Then, the subgroup analysis of male was performed, which illustrated that male increased the risk of CLNM in the small sample group (SG) and the large sample group (LG) by 6.11-folds and 2.01-folds, respectively (SG: OR, 6.11, 95% CI, 3.16-11.81, P < 0.001; LG: OR, 2.01, 95% CI, 1.65-2.46, P < 0.001). CONCLUSIONS: Male, multifocality, tumor size > 5 mm, and extrathyroidal extension may be reliable clinical predictors of CLNM in CN0 PTMC. Moreover, prophylactic central lymph node dissection should be considered in surgical decision-making for CN0 PTMC patients, who are male, multifocal, with tumor size > 5 mm, and with extrathyroidal extension. TRIAL REGISTRATION: CRD42021242211 (PROSPERO).

Clinical implications of Delphian lymph node metastasis in papillary thyroid carcinoma: a single-institution study, systemic review and meta-analysis.

BACKGROUND: To evaluate the possible predictive value and clinicopathological characteristics of Delphian lymph node metastasis in papillary thyroid carcinoma. METHODS: A retrospective analysis of papillary thyroid carcinoma patients with Delphian lymph node metastasis in a single institution and meta-analysis of literature reports were performed. RESULTS: In own series, Delphian lymph node metastasis was detected in 19 (9.9%) of 192 papillary thyroid carcinoma patients and was significantly associated with tumor size≥1 cm (P = 0.003), multifocality (P = 0.006) and extrathyroid extension (P < 0.001) in the multivariate analysis. Female was a protective factor for Delphian lymph node metastasis (P = 0.001). Delphian lymph node metastasis was highly predictive of further central lymph node metastasis (positive predictive value = 89.5%, negative predictive value = 67.6%) and moderately predictive of lateral lymph node metastasis (positive predictive value = 26.3%, negative predictive value = 95.4%). In this meta-analysis, there was a strong correlation between Delphian lymph node metastasis and aggressive clinicopathologic characteristics with regards to multifocality (P = 0.0008), bilaterality (P = 0.04), extrathyroid extension (P < 0.00001), lymphovascular invasion (P < 0.00001), further central lymph node metastasis (P < 0.00001) and lateral lymph node metastasis (P < 0.00001). CONCLUSIONS: This single-institution observational study and meta-analysis identified that Delphian lymph node metastasis was significantly associated with unfavorable clinicopathological characteristics and had a strong predictive power for further disease in the central compartment. TRIAL REGISTRATION: The clinical study was retrospectively registered to UMIN clinical trials registry (the registry number: UMIN000033835 ).

A Single-Center, Randomized, Controlled Comparison of the Transradial vs Transfemoral Approach for Cerebral Angiography: A Learning Curve Analysis.

Purpose: To compare the characteristics and learning curve of the transfemoral approach (TFA) vs the transradial approach (TRA) for cerebral angiography. Materials and Methods: Between February 2016 and April 2017, 101 patients undergoing cerebral angiography were enrolled. Fifty-one patients (mean age 67 years; 40 men) were randomized to TFA and 50 (mean age 68 years; 41 men) to TRA using a computer-generated random table. The patients' demographic and angiographic data were recorded and analyzed. The learning curve of a novice interventionist was analyzed for procedure time, puncture time, fluoroscopy time, and contrast volume as markers of technical proficiency with TFA compared with TRA. Median values are given with the interquartile range (IQR). Results: Procedure time [35 (IQR 30, 47.5) vs 31.0 (IQR 25.0, 48.9) minutes, p=0.16), fluoroscopy time [10.3 (IQR 7.6, 13.9) vs 9.4 (IQR 6.1, 17.6) minutes, p=0.70], contrast volume [105 (IQR 92, 120) vs 95.5 (IQR 90, 111.3) mL, p=0.13), radiation exposure [390.2 (IQR 268.2, 617.9) vs 455.8 (IQR 286.8, 602.3) mGy, p=0.74], and the number of catheter exchanges [1 (IQR 1, 3) vs 1 (IQR 1, 1), p=0.06] were not significantly different between the TFA and TRA groups, respectively, but puncture time was shorter with TFA than with TRA [0.6 (IQR 0.5, 1.1) vs 1 (IQR 0.6, 1.9) minutes, p=0.01]. The learning curve was steeper with TRA than with TFA in the beginning stages of training, but with increasing experience, the procedure and fluoroscopy times were better for TRA than for TFA. Training progress was made earlier in TRA. Conclusion: TRA is a reasonable alternative to TFA for cerebral angiography. TRA has a shorter learning curve for novice interventionists.

Thyroid Antibody Status is Associated with Central Lymph Node Metastases in Papillary Thyroid Carcinoma Patients with Hashimoto's Thyroiditis.

OBJECTIVE: The aim of this study was to explore the impact of thyroid antibody status on central lymph node metastases (CLNM) in papillary thyroid carcinoma (PTC) patients with Hashimoto's thyroiditis (HT). METHODS: A retrospective analysis was performed on 346 PTC patients with HT who underwent thyroidectomy and ipsilateral central lymph node dissection (CLND). Histopathological characteristics of the tumor and serum levels of thyroid hormone, as well as antibodies, were collected and analyzed. RESULTS: The multivariate logistic regression analysis showed that being male [odds ratio (OR) 3.269, 95% confidence interval (CI) 1.240-8.619], tumor size > 1 cm [1 cm < diameter (D) ≤ 2 cm: OR 6.947, 95% CI 2.886-16.722; 2 cm < D: OR 5.880, 1.937-17.846], and antibody status [thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) double negative: OR 3.791, 95% CI 1.391-10.331; TPOAb and TgAb double positive: OR 4.047, 95% CI 1.509-10.856; TgAb single positive: OR 6.024, 95% CI 2.019-17.970] were independent risk factors for CLNM. Additionally, a risk-score scale, including sex, antibody status, and tumor size, was established to predict CLNM. The sensitivity, specificity, positive predictive value, and negative predictive value were 55.7%, 84.4%, 74.4%, and 70%, respectively, when the cut-off point was chosen as 3. CONCLUSIONS: Antibody status is a critical independent risk factor for CLNM in PTC patients with HT. For the CLND strategy, a more conservative option could be considered in a low-risk cohort with the following characteristics: female sex, smaller tumor size, and TPOAb single positive.

A Novel Reverse Branch Technique for Reconstruction of a Renal Artery Perfused by the False Lumen After Thoracic Endovascular Aortic Repair.

PURPOSE: To describe an innovative endovascular technique that successfully reconstructs a renal artery completely perfused by the false lumen after thoracic endovascular aortic repair (TEVAR). CASE REPORT: A 65-year-old patient diagnosed with acute Stanford type B aortic dissection underwent successful TEVAR 4 years ago. Regular follow-up found that the thoracic aorta was well repaired, but the false lumen in the abdominal aorta had enlarged year by year. The left renal artery was supplied entirely by the false lumen, which caused kidney hypoperfusion. The abdominal aorta was successfully remodeled using endovascular aneurysm repair with reconstruction of the left renal artery using Viabahn stent-grafts inserted through the patent false lumen. At 6 months, computed tomography showed false lumen thrombosis and patent Viabahn stent-grafts in the false lumen. CONCLUSION: The false lumen reverse branch technique was feasible in our case, which provides a new idea for dealing with distal dissection involving the renovisceral arteries after TEVAR.