Diagnostic Value of the HEAD-US-C Scale for the Knees of Severe Hemophilia A Patients.

OBJECTIVES: This study aimed to assess the reliability of the Hemophilia Early Arthropathy Detection with Ultrasound in China (HEAD-US-C) scale for the knees of severe hemophilia A (SHA) patients and to determine its diagnostic accuracy for assessments of knee-joint lesions in comparison with magnetic resonance imaging (MRI). METHODS: We collected data from 32 knee joints of 21 patients diagnosed with SHA. The knees were evaluated based on the HEAD-US-C scale and the results were compared with the International Prevention Study Group (IPSG) scale. The HEAD-US-C scale was applied independently by two trained ultrasonographers blinded to the MRI results. The IPSG scale was applied independently by two radiologists blinded to the clinical data and ultrasound (US) results. RESULTS: The IPSG and HEAD-US-C scales exhibited good to excellent inter-rater reliability. Additionally, there was good to excellent agreement between the US and MRI results for the detection of knee lesions in SHA patients. The sensitivities of US for joint effusion, synovial hyperplasia, cartilage loss, and bone-surface irregularities in the knees of patients were 92.59, 100, 95.45, and 87.50%, respectively. The HEAD-US-C scale was positively correlated with the IPSG scale. CONCLUSIONS: US is important for evaluating knee lesions in patients with SHA and may potentially replace MRI.

The Correlation Between the HEAD-US-C Score and HJHS in Hemophilic Arthropathy of the Knee.

OBJECTIVES: We aimed to discuss the correlation between the Hemophilia Early Detection Ultrasound in China (HEAD-US-C) score and the Hemophilia Joint Health Score version 2.1 (HJHS 2.1) of the knee joint in patients with hemophilia. METHODS: We included 70 male patients with hemophilia admitted to The Second Hospital of Shanxi Medical University; the patients' bilateral knee joints were evaluated using the HEAD-US-C score and HJHS. We analyzed factors influencing hemophilia arthropathy of the knee and examined the correlation between the HEAD-US-C score and HJHS. RESULTS: The joint injury severity was positively correlated with age and the number of bleeds (P < .001). Further, the HEAD-US-C score and HJHS differed according to the severity (both P < .001), but not type (P = .163 and P = .283, respectively), of hemophilia. There was a significant correlation between the HEAD-US-C score and HJHS (P < .001). CONCLUSIONS: Overall, all joint lesions observed on ultrasound corresponded to clinical joint functional abnormalities. Therefore, the HEAD-US-C is important for hemophilic arthropathy evaluation and is useful in explaining abnormal joint function.

Ineffectiveness of lateral-wedge insoles on the improvement of pain and function for medial knee osteoarthritis: a meta-analysis of controlled randomized trials.

OBJECTIVE: The study aimed to evaluate the role of lateral-wedge insoles in pain reduction and functional improvement among patients with medial knee osteoarthritis. MATERIALS AND METHODS: Three databases including Pubmed, Embase, and Web of science were searched from inception until October 2017 for studies investigating the role of lateral-wedge treatment in pain relief and functional recovery among patients with knee osteoarthritis. Eligible studies were pooled using fixed effect model or random-effects model based on Cochrane Q statistic and I2 test. Moreover, subgroup analysis stratified by research area was performed, and sensitivity analysis was further designed to evaluate the strength of the meta-analysis. RESULTS: Ten studies with a total of 938 patients, of which 478 patients received lateral-wedge insoles and 460 patients were set as control, were included in the meta-analysis. The pooled statistics did not show significant improvement in knee pain (SMD = - 0.21, 95% CI - 0.50, 0.08; P = 0.16) and knee function (SMD = 0.22, 95% CI - 0.27, 0.70; P = 0.38) in lateral-wedge insoles treatment group compared with controls. However, subgroup analysis based on research area revealed a favorable outcome toward Asian patients who received lateral-wedge insoles in pain reduction when compared with control group. (SMD = - 0.88, 95% CI - 1.59, - 0.17; P = 0.02). No significant improvement was observed among patients in USA and other areas. Sensitivity analysis showed unchanged results when we omitted each study. No significant publication bias was observed among the included studies. CONCLUSION: Though for young Asian patients within normal BMI, to some extent, the lateral-wedge insoles seems to be helpful. However, there was no evidence to demonstrate the relationship between race and role of lateral-wedge insoles on pain reduction. All in all, based on current data, lateral-wedge insoles appear to be ineffective at attenuating knee pain and function improvement.

[Combined hepatocellular-cholangiocarcinoma (cholangiolocellular type) with stem-cell features: a clinicopathologic analysis of 26 cases].

OBJECTIVE: To study the clinicopathologic features of combined hepatocellular-cholangiocarcinoma (cholangiolocellular type, CLC type) with stem cell features and its relationship to hepatic progenitor cells (HPCs). METHODS: Clinical and histologic features of 26 cases of combined hepatocellular-cholangiocarcinoma (CLC type) were reviewed. Histochemistry was performed to confirm the type of mucin and immunohistochemical study was carried out for hepatocytic markers (Hep Par-1 and AFP) and biliary/HPCs markers (CK7, CK9, EMA, EpCAM, NCAM, CKIT). RESULTS: The age of patients ranged from 51 to 82 years (mean 64 years). All 26 cases contained CLC and hepatocellular carcinoma components. CLC area was composed of mixtures of small monotonous glands with abundant fibrous stroma and lymphocytic infiltrate. Tumor cells were cuboidal, smaller in size than normal hepatocytes, with basophilic cytoplasm and round nuclei. All cases, especially at the tumor boundary, showed HCC-like trabecular areas characterized by mildly atypical tumor cells with abundant eosinophilic cytoplasm and little stroma. Out of 26 cases, 21 showed definite glandular formation with mucin production, representing intrahepatic cholangiocarcinoma areas. The three distinct areas showed transitional zones merging with each other. The surrounding liver tissue showed cirrhosis and chronic hepatitis with varying degrees of fibrosis and periportal ductular reaction. Immunohistochemistry showed that biliary/HPC markers (CK7, CK9, EMA, EpCAM, NCAM and CKIT) were strongly positive in CLC area in almost all cases, similar to the staining pattern of ductular reaction. In HCC-like areas, CK7 and CK19 were positive in all cases and the expression rates of EMA, EpCAM, NCAM, CKIT, AFP, Hep Par-1 were 80.8% (21/26), 88.5% (23/26), 84.6% (22/26), 88.5% (23/26), 46.2% (12/26) and 53.8% (14/26) respectively, similar to the staining pattern of intermediate hepatocytes. In ICC areas, CK7, CK9, EMA and EpCAM were positive in all cases without the expression of NCAM and CKIT. CONCLUSION: The clinicopathologic findings and immunohistochemical results in this study highly suggest a hepatic progenitor cell origin of combined hepatocellular-cholangiocarcinoma (CLC type).

Molecular mechanism of a novel Ser362Asn mutation causing inherited FX deficiency in a Chinese family.

Factor X (FX) deficiency is an inherited autosomal recessive bleeding disorder. Here, we analyzed a proband with FX deficiency in a Chinese family. Genetic analysis revealed that the proband and his affected sister was homozygous for c.1085G>A mutation, corresponding to a Ser362Asn substitution. In vitro expression experiments showed that the FX Ser362Asn mutation led to a significant reduction in activity levels in the culture medium. This Ser to Asn substitution may change the shape of the active site. Moreover, simulations of molecular dynamics indicated that the binding energy of the FX Ser362Asn to the substrate is higher than that of wild type and the side-chain conformation of the catalytic residue His276 (His42) is changed. This impairs the conformational switch of the protein from zymogen to proteinase, thus causing the functional defect of FX protein. Our findings suggest that the Ser362Asn substitution is a pathogenic mutation that causes inherited FX deficiency.

Evaluation of NCAM and c-Kit as hepatic progenitor cell markers for intrahepatic cholangiocarcinomas.

BACKGROUND: Intrahepatic cholangiocarcinomas (ICCs) are primary liver malignancies and are the second most common type of malignancy after hepatocellular carcinoma. ICCs are heterogeneous in clinical features, genotype, and biological behavior, suggesting that ICCs can initiate in different cell lineages. AIM: We investigated intrahepatic cholangiocarcinoma RBE cell lines for the markers neural cell adhesion molecule (NCAM) and c-Kit, which possess hepatic progenitor cells properties. METHODS: NCAM + c-Kit + cells were tested for hepatic progenitor cell properties including proliferation ability, colony formation, spheroid formation, and invasiveness in NOD/SCID mice. The Agilent Whole Human Genome Microarray Kit was used to evaluate differences in gene expression related to stem cell signaling pathways between NCAM + c-Kit + and NCAM-c-Kit- subset cells. Microarray results were further confirmed by real-time RT-PCR. RESULTS: NCAM + c-Kit + cells showed hepatic progenitor cell-like traits including the abilities to self-renew and differentiate and tumorigenicity in NOD/SCID mice. Differences were observed in the expression of 421 genes related to stem cell signaling pathways (fc ≥ 2 or fc ≤ 0.5), among which 231 genes were upregulated and 190 genes were downregulated. CONCLUSION: NCAM + c-Kit + subset cells in RBE may have properties of hepatic progenitor cells. NCAM combined with c-Kit may be a valuable marker for isolating and purifying ICC stem/progenitor cells.

Musculoskeletal ultrasonography for arthropathy assessment in patients with hemophilia: A single-center cross-sectional study from Shanxi Province, China.

Magnetic resonance imaging (MRI) is currently considered the gold standard for assessing hemophilic arthropathy (HA) severity; however, MRI is often costly, time-consuming, and difficult to perform in children. In the present study, we evaluated the joint status of hemophilic patients from Shanxi Province, China, using musculoskeletal ultrasonography (MSKUS) and identified the factors that most strongly correlated with disease severity.The study included 104 patients with hemophilia, who underwent MSKUS examination. A total of 1248 joints (including the shoulder, elbow, wrist, hip, knee, and ankle joints on both sides) from these patients were evaluated. Effusion, hypertrophy, cartilage modification, and bone erosion were assessed. The chi-square test was used to analyze categorical variables, and multivariate logistic regression was used to analyze the relationship between joint disease and risk factors.MSKUS allowed clear visualization of synovial lesions, effusion, cartilage modification, and bone surface damage; however, it was unable to identify changes deep within bones. The distribution of damaged joints was as follows: shoulder, 2 (1.0%); elbow, 80 (38.5%); wrist, 4 (1.9%); hip, 4 (1.9%); knee, 126 (60.6%); and ankle, 90 (43.3%). Damage was more common in the knee, elbow, and ankle joints than in the shoulder, wrist, and hip joints (P < .001). Among the 1248 joints, 306 showed lesions, which included effusion in 102 (8.2%) joints, synovium hypertrophy in 176 (14.1%), cartilage modification in 193 (15.5%), and bone damage in 176 (14.1%). Many joints had multiple lesions at the same time. The chi-square test and multivariate logistic analysis showed that age and hemophilia severity were significantly associated with joint disease, while type of hemophilia and treatment categories were not associated with joint disease.MSKUS is a convenient and cost-effective examination that can play an important role in the diagnosis and long-term monitoring of HA.