ABSTRACT
Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.
ABSTRACT
Thyroid hemiagenesis is a rare congenital anomaly that is caused by a developmental defect of a thyroid. Previous reports indicate that thyroid cancer associated with hemiagenesis is extremely rare. A 47-year-old woman presented with single nodule in the right thyroid gland that was incidentally detected during a routine medical checkup. Ultrasonography showed a 1.5×1.2 cm sized ill-defined irregular hypoehoic nodule in the right thyroid and the isthmus was present. However, the left thyroid was not seen and thyroid was disconnected at left paraisthmic area. Fine-needle aspiration cytology confirmed that the right thyroid nodule was papillary thyroid carcinoma. Total thyroidectomy with bilateral central compartment node dissection was performed. Permanent pathologic finding was 1.3×1 cm sized classical type papillary thyroid carcinoma with nodular hyperplasia. There was extensive lymphatic invasion and 3 metastatic lymph nodes out of 4 in central compartment. In conclusion, although thyroid hemiagenesis associated with thyroid carcinoma is extremely rare, treatment strategy is not different with patients with normal anatomy. And the possibility of developing a thyroid carcinoma should be considered in patients with hemiagenesis. Furthermore, it requires awareness of anatomical difference around the thyroid gland during operation.
Subject(s)
Female , Humans , Middle Aged , Biopsy, Fine-Needle , Hyperplasia , Lymph Nodes , Thyroid Gland , Thyroid Neoplasms , Thyroid Nodule , Thyroidectomy , UltrasonographyABSTRACT
PURPOSE: Medullary breast carcinomas (MBC) have been known to represent a rare breast cancer subtype associated with a more favorable prognosis than invasive ductal carcinomas (IDC). The purpose of this study was to compare the clinicopathologic characteristics and outcomes of MBC with those of IDC. METHODS: We retrospectively reviewed medical records of patients with invasive breast cancer who were managed surgically from August 1995 to June 2010. RESULTS: Fifty-two patients were identified with MBC and 5,716 patients were identified with IDC. The clinicopathologic features, disease-free survival (DFS), and overall survival (OS) of patients with MBC were compared with those of patients with IDC. The MBC group presented at a younger age (p=0.005) and had a significant association with a higher histological grade (p=0.003) and nuclear grade (p<0.001) as well as negative estrogen receptor (p<0.001) and progesterone receptor (p<0.001) status. Lymphatic invasion was absent (p<0.001) and lymph node metastasis was rare (p<0.001). The DFS and OS did not differ significantly between the two groups (5-year DFS: 88.0% vs. 89.2%, p=0.920; 5-year OS: 93.4% vs. 94.4%, p=0.503). In multivariate analysis, the factors associated with DFS and OS were nuclear grade, histological grade, tumor size, lymph node metastasis, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status, chemotherapy, and hormone therapy. However, DFS and OS were not significantly different between IDC and MBC according to histological type itself (DFS: hazard ratio 0.85, 95% confidence interval 0.12-6.05, p=0.866; OS: hazard ratio 1.49, 95% confidence interval 0.21-10.77, p=0.692). CONCLUSION: Although MBC has specific clinicopathologic features, its prognosis does not differ from IDC and is determined by prognostic factors such as tumor size and lymph node metastasis. Therefore, patients with MBC also require the same intensive treatment provided for IDC.