Whiteheadladegaard5662

CONCLUSIONS Although overlapping syndromes are rare, we report positive GFAP-IgG in 2 cases with NMOSD or RP. Both patients had clinical features of GFAP astrocytopathy, but diagnosis of the condition was very challenging because of the overlapping presentation. © 2020 S. Karger AG, Basel.INTRODUCTION The tumor microenvironments of different organs often differ and thus may affect the immunotherapy response. OBJECTIVE This study elucidated that the efficacy of programmed cell death protein-1 (PD-1) inhibitors varies across different metastatic sites among individuals with advanced hepatocellular carcinoma (HCC). METHODS We retrospectively analyzed treatment outcomes in advanced HCC patients receiving PD-1 inhibitors with or without a combination of tyrosine kinase inhibitors (TKIs). Both the overall response rate (ORR) and organ-specific response rate (OSRR) were assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. A survival analysis and its predictors were determined using a multivariate analysis. RESULTS We analyzed 42 advanced HCC patients (median age 58.0 years; 78.6% males). Thirty (71.4%) patients were sorafenib-experienced and 27 (64.3%) were administered a combination of TKIs. The ORR was 14.3% and the disease control rate was 33.3%. The median overall survival (OS) and progression-free survival (PFS) were 12.0 and 2.9 months, respectively. The OSRRs were 14.7, 23.8, 28.6, and 50.0% for the liver, lungs, lymph nodes, and vascular response, respectively. The multivariate analysis indicated that the vascular response was significantly associated with PFS. ECOG performance status was a significant independent predictor of OS. CONCLUSIONS PD-1 inhibitors improved OS and PFS in advanced HCC patients. Their efficacies varied among the metastatic locations regardless of the combination of TKIs; in particular, a higher response in vascular metastases was correlated with a longer PFS. PD-1 inhibitors may deliver a synergistic benefit in patients undergoing traditional therapy and progression in other organs in vascular responders. © 2020 S. Karger AG, Basel.BACKGROUND It is necessary to investigate the frequency of BRCA1 and BRCA2 mutations in Hakka populations due to the variations in breast cancer epidemiology and genetics. METHODS 359 breast cancer patients and 66 ovarian cancer patients were included in this retrospective clinical study. Mutations of BRCA1 and BRCA2 were detected in blood samples by semiconductor sequencing. RESULTS The sensitivity of tumor markers including CEA, CA15-3, CA12-5, and CA199 for screening breast cancer was 16.44, 15.11, 8.44, and 7.56%, the combination of these 4 tumor markers reached the highest sensitivity index (31.11%). For ovarian cancer, the tumor markers were CA12-5 (54.05%), HE-4 (54.05%), CA72-4 (51.35%), and CEA (2.70%) in order of decreasing sensitivity. Moreover, the combination of these 4 tumor markers has the best sensitivity (75.68%) for screening ovarian cancer. In breast cancer patients, we found 5 (1.39%) patients with mutations in BRCA1, 13 (3.62%) mutations in BRCA2, and the total carrier rate is 5.01% (18/359). For ovarian cancer patients, the corresponding results were 3 (4.54%) mutations, 2 (3.03%) mutations, and 7.58% (5/66), respectively. The proportion of BRCA mutations was 5.41% (23/425) in breast and ovarian cancer patients of a Hakka population. The pathogenic, likely pathogenic, and benign mutations, and mutations of uncertain significance in this study mainly occurred in exon 14 of the BRCA1 gene, and exon 10 and exon 11 of the BRCA2 gene. CONCLUSIONS Understanding the spectrum and frequency of BRCA1 and BRCA2 mutations in a Hakka population will assist in the prevention and control of hereditary breast and ovarian cancers in this population. © 2020 S. Karger AG, Basel.FAM20C (family with sequence similarity 20 - member C) is a protein kinase that phosphorylates secretory proteins, including the proteins that are essential to the formation and mineralization of calcified tissues. Previously, we reported that inactivation of Fam20c in mice led to hypophosphatemic rickets/osteomalacia along with increased circulating fibroblast growth factor 23 (FGF23) levels and dental defects. In this study, we examined whether a high-phosphate (hPi) diet could rescue the skeletal defects in Fam20c-deficient mice. Fam20c conditional knockout (cKO) mice were generated by crossing female Fam20c-floxed mice (Fam20cfl/fl) with male Sox2-Cre;Fam20cfl/+ mice. The pregnant female Fam20cfi/fl mice were fed either a normal or hPi diet until the litters were weaned. The cKO and control offspring were continuously given a normal or hPi diet for 4 weeks after weaning. click here Plain X-ray radiography, micro-CT, histology, immunohistochemistry (FGF23, DMP1, OPN, and SOX9), and in situ hybridization (type II and type X collagen) analyses were performed to evaluate the effects of an hPi diet on the mouse skeleton. Plain X-ray radiography and micro-CT radiography analyses showed that the hPi diet improved the shape and mineral density of the Fam20c-deficient femurs/tibiae, and rescued the growth plate defects in the long bone. Histology analyses further demonstrated that an hPi diet nearly completely rescued the growth plate-widening defects in the long bone and restored the expanded hypertrophic zone to nearly normal width. These results suggested that the hPi diet significantly improved the skeletal development of the Fam20c-deficient mice, implying that hypophosphatemia partially contributed to the skeletal defects in Fam20c-deficient subjects. © 2020 S. Karger AG, Basel.INTRODUCTION Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage and fibrosis of the skin and internal organs. The major complications are lung fibrosis, pulmonary artery hypertension, scleroderma renal crisis, and cardiac involvement. OBJECTIVE The aim of this study was to assess renal and cardiac involvement in asymptomatic SSc patients using renal Doppler ultrasound (RDU) and cardiac magnetic resonance (CMR). MATERIALS AND METHODS We enrolled 26 consecutive SSc patients (21 female) according to 2013 ACR/EULAR criteria. Biochemical analysis, clinical evaluation, RDU with intrarenal hemodynamic parameters (renal resistive index [RRI], pulsatility index [PI], systolic/diastolic [S/D] ratio), and CMR with late gadolinium enhancement (LGE) were investigated at the time of enrollment. RESULTS The median PI value was significantly (p = 0.007) higher in SSc patients with LGE than in SSc patients without LGE (1.37 [1.28-1.58] vs. 1.12 [1.06-1.26]). The median RRI value was significantly (p = 0.