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Background/AimsSeveral noninvasive methods have recently been developed for the evaluation of liver fibrosis. The accuracy of transient elastography (TE), acoustic-radiation-force impulse (ARFI) elastography, and real-time elastography (RTE) in predicting liver fibrosis were evaluated.MethodsSeventy-four patients who had undergone a liver biopsy within the previous 6 months were submitted to evaluation with TE, ARFI, and RTE on the same day.ResultsThere were significant correlations between fibrosis stage and liver stiffness measurement (LSM) using the three tested methods: TE, r2=0.272, P=0.0002; ARFI, r2=0.225, P=0.0017; and RTE, r2=0.228, P=0.0015. The areas under the receiver operating characteristic curves (AUROC) for the diagnosis of significant fibrosis (≥F2, Metavir stage) by TE, ARFI, RTE, TE/platelet count (PLT), velocity of shear wave (Vs)/PLT, and elasticity score (Es)/PLT were 0.727, 0.715, 0.507, 0.876, 0.874, and 0.811, respectively. The AUROC for the diagnosis of cirrhosis by TE, ARFI, RTE, TE/PLT, Vs/PLT, and Es/PLT were 0.786, 0.807, 0.767, 0.836, 0.819, and 0.838, respectively. Comparisons of AUROC between all LSMs for predicting significant fibrosis (≥F2) produced the following results: TE vs. RTE, P=0.0069; ARFI vs. RTE, P=0.0277; and TE vs. ARFI, P=0.8836. Applying PLT, the ability of each LSM to predict fibrosis stage significantly increased: TE/PLT vs. TE, P=0.0004; Vs/PLT vs. ARFI, P=0.0022; and Es/PLT vs. RTE, P<0.0001. However, the ability to predict cirrhosis was not enhanced, combining LSM and PLT.ConclusionsTE and ARFI may be better methods for predicting significant liver fibrosis than RTE. This predictive ability increased significantly when accounting for platelet count. However, all of the measures had comparable efficacies for predicting cirrhosis.

BackgroundThe purpose of this study was to evaluate the association between blood manganese levels and the prevalence of chronic diseases in the Korean population.MethodsThis was a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNAHNES). The study included 3996 participants 20 years of age or older whose blood manganese levels had been measured. The participants were also evaluated for the presence of five chronic diseases: diabetes, renal dysfunction, hypertension, ischemic heart disease, and stroke.ResultsBlood manganese levels were significantly lower in the diabetes group compared with the non-diabetes group (1.26 ± 0.02 vs. 1.35 ± 0.01 μg/dL; p = 0.001) and the renal dysfunction group compared with those with normal renal function (1.28 ± 0.03 vs. 1.35 ± 0.01 μg/dL; p = 0.04). There was no significant association between blood manganese levels and the presence of ischemic heart disease or stroke. A multivariate logistic regression analysis adjusted for age, sex, and body mass index was performed; the odds ratio was 0.652 (95% CI: 0.46–0.92) for diabetes and 0.589 (95% CI: 0.39–0.88) for renal dysfunction when comparing the higher quartiles (Q2-4) with the lowest quartile (Q1) of blood manganese level. The prevalence of diabetes was 7.6% in Q1 and 5.3% in Q2-4 (p = 0.02). Similarly, the prevalence of renal dysfunction was 6.8% in Q1, compared with 4.6% in Q2-4 (p = 0.02).ConclusionThe prevalence of diabetes and renal dysfunction increased in participants with low blood manganese levels, suggesting that blood manganese may play a role in glucose homeostasis and renal function.

BACKGROUND: The severe forms of thalassemia are the most common inherited anemias managed with regular blood transfusion therapy. Transfusion policies and complications are critical to quality of life and survival, but there is a lack of standardized care. STUDY DESIGN AND METHODS:A survey of 58 items was completed in 2016 by 11 centers in California, Washington, Oregon, Nevada, and Arizona providing long-term care for thalassemia. The questionnaire addressed demographic information, transfusion practices and complications, and educational needs. RESULTS:The centers followed 717 patients with β-thalassemia (314, 43.8%) or α-thalassemia (394, 55%). One-third (34.7%) of patients were transfusiondependent. Indications and goals of transfusion therapy differed between centers. Prestorage leukoreduction was universal, while routine irradiation of units was limited to one site. Red blood cell antigen phenotype was determined before the first transfusion and patients received Rh/Kell-matched units. However, more than half of the transfused patients had received blood at multiple hospitals within or outside the United States. Alloantibodies were seen in 16.9% of transfused group, but management of such patients was variable. Unusual or emerging transfusion-transmitted pathogens were not observed. Multiple educational needs were recognized, with iron overload as the biggest challenge; the approach to iron chelation varied within the group.CONCLUSION: This study identified many patients not included in earlier surveys limited to major national centers, suggesting that the thalassemia population in the United States is vastly underestimated. Lack of evidence-based guidelines is a barrier to optimal care, which should be addressed through regional consortia of thalassemia centers.ABBREVIATIONS: LIC = liver iron concentration; NTD = non-transfusion dependent. From the Human subjects protectionCompletion of the surveys was acknowledged as a quality improvement activity exempt from the need for approval by institutional review boards. Each center provided only summary data and did not share patient-level information or identifiers. Statistical analysisResponses from all centers were summarized as tables and the proportion of individual responses were calculated.

The CKD-EPI equation showed that blood lead and cadmium levels were associated with renal dysfunction in the Korean adult population. This finding has significant implications for environmental institutional strategies regarding heavy metal exposure.

BackgroundNeuroblastoma is the second most common extracranial cancer in children. Current therapies for neuroblastoma, which use a combination of chemotherapy drugs, have limitations for high-risk subtypes and can cause significant long-term adverse effects in young patients. Therefore, a new therapy is needed. In this study, we investigated the transcription factor MXD3 as a potential therapeutic target in neuroblastoma.MethodsMXD3 expression was analyzed in five neuroblastoma cell lines by immunocytochemistry and quantitative real time reverse transcription PCR and in 18 primary patient tumor samples by immunohistochemistry. We developed nanocomplexes using siRNA and superparamagnetic iron oxide nanoparticles to target MXD3 in neuroblastoma cell lines in vitro as a single agent therapeutic and in combination with doxorubicin, vincristine, cisplatin, or maphosphamide, common drugs used in current neuroblastoma treatment.ResultsMXD3 was highly expressed in neuroblastoma cell lines and in patient tumors that had high-risk features. Neuroblastoma cells treated in vitro with the MXD3 siRNA nanocomplexes showed MXD3 protein knockdown and resulted in cell apoptosis. Furthermore, combining MXD3 siRNA nanocomplexes with each of the four drugs, all showed additive efficacy.ConclusionsThese results indicate that MXD3 is a potential new target and MXD3 siRNA nanocomplexes are a novel therapeutic approach for neuroblastoma.

The exponential rise in molecular and genomic data has generated a vast array of therapeutic targets. Oligonucleotide-based technologies to down regulate these molecular targets have promising therapeutic efficacy. However, there is relatively limited success in translating this into effective in vivo cancer therapeutics. The primary challenge is the lack of effective cancer cell-targeted delivery methods, particularly for a systemic disease such as leukemia. We developed a novel leukemiatargeting compound composed of a monoclonal antibody directly conjugated to an antisense oligonucleotide (ASO). Our compound uses an ASO that specifically targets the transcription factor MYC-associated factor X (MAX) dimerization protein 3 (MXD3), which was previously identified to be critical for precursor B-cell (preB) acute lymphoblastic leukemia (ALL) cell survival. The MXD3 ASO was conjugated to an anti-cluster of differentiation-22 (CD22) antibody (αCD22 Ab) that specifically targets most preB ALL. We demonstrated that the αCD22 Ab-ASO conjugate treatment showed MXD3 protein knockdown and leukemia cell apoptosis in vitro. We also demonstrated that the conjugate treatment showed cytotoxicity in normal B cells, but not in other hematopoietic cells, including hematopoietic stem cells. Furthermore, the conjugate treatment at the lowest dose tested (0.2 mg/kg Ab for 6 doses -twice a week for 3 wks) more than doubled the mouse survival time in both Reh (median survival time 20.5 versus 42.5 d, p < 0.001) and primary preB ALL (median survival time 29.3 versus 63 d, p < 0.001) xenograft models. Our conjugate that uses αCD22 Ab to target the novel molecule MXD3, which is highly expressed in preB ALL cells, appears to be a promising novel therapeutic approach.

The β thalassemia syndromes constitute the most frequent inherited anemia managed with chronic red cell transfusions around the world. 1,2 The prevalence of thalassemia in the United States was underestimated in past surveys that were limited only to the major specialty centers. 3 Recent data show that the aggregate number of patients followed at smaller centers and community practices surpasses those at the major centers. 4 A precise estimate of the total number of individuals with thalassemia in the U.S. is unavailable due to the lack of either a state or national database. Surveys have shown that 10 large thalassemia centers in the country collectively follow about 1100 patients, while additional 1500 patients are estimated to receive care at other hospitals. 4,5 The Thalassemia Western Consortium (TWC) study showed that of the 717 patients, 44% of patients had β thalassemia syndromes (including 15% with HbE β thalassemia) and 55% had various α thalassemia disorders. Transfusion-dependent patients comprised 35% of the population, 9% had received 1 or more life-time transfusions, and 56% had never been transfused. Thus,