Gaucher disease (GD) is associated with an increased risk for malignancies. Next to hematological malignancies, the development of solid tumors in several organs has been described. The liver is one of the major storage sites involved in GD pathogenesis, and is also affected by liver-specific complications. In this case series, we describe 16 GD type 1 (GD1) patients from eight different referral centers around the world who developed hepatocellular carcinoma (HCC). Potential factors contributing to the increased HCC risk in GD patients are studied. Eleven patients had undergone a splenectomy in the past. Liver cirrhosis, one of the main risk factors for the development of HCC, was present in nine out of 14 patients for whom data was available. Three out of seven examined patients showed a transferrin saturation > 45%. In these three patients the presence of iron overload after histopathological examination of the liver was shown. Chronic hepatitis C infection was present in three of 14 examined cases. We summarized all findings and made a comparison to the literature. We recommend that GD patients, especially those with prior splenectomy or iron overload, be evaluated for signs of liver fibrosis and if found to be monitored for HCC development.

microRNAs are an abundant class of small non-coding RNAs that negatively regulate gene expression. Importantly, microRNA activity has been linked to the control of cellular stress response. In the present study, we investigated whether the expression of hepatic microRNAs is affected by changes in ambient osmolarity. It is shown that hyperosmotic exposure of perfused rat liver induces a rapid upregulation of miR-15a, miR-15b and miR-16, which are members of the miR-15/107 microRNAs superfamily. It was also identified that hyperosmolarity significantly reduces the expression of anti-apoptotic genes including Bcl2, Ccnd1, Mcl1, Faim, Aatf, Bfar and Ikbkb, which are either validated or predicted targets of these microRNAs. Moreover, through the application of NOX and JNK inhibitors as well as benzylamine it is shown that the observed response is mediated by reactive oxygen species (ROS), suggesting that miR-15a, miR-15b and miR-16 are novel redoximiRs. It is concluded that the response of these three microRNAs to osmotic stress is ROS-mediated and that it might contribute to the development of a proapoptotic phenotype.

In patients with 3-hydroxy-3-methylglutaryl (HMG)-CoA lyase deficiency (OMIM 246450), five pregnancies have been described worldwide, which were either terminated or resulted in severe metabolic sequelae during pregnancy or delivery. Here, we report on a patient with HMG-CoA lyase deficiency, who underwent two uncomplicated pregnancies. The 19-year-old patient was admitted because of recurrent vomiting and nausea. Diagnostics revealed pregnancy at week 8 of gestation. Metabolic analyses revealed normal lactate and blood glucose levels and normal acid-base status. Urine organic acid analysis showed an elevated excretion of 3-CH 3 -glutaric acid, 2,3-CH 3 -glutaconic acid, and 3-CH 3 -3-OH-glutaric acid. Oral treatment with carnitine and glucose wes administered intravenously during the period of nausea and vomiting. After clinical recovery, a diet with 0.89 g/kg of protein/d and 38 kcal/kg body weight/d was given. Meals were taken every 3 h. Additionally, 70 g of starch was given at midnight to maintain normoglycemia at night time. Peripartum, a complete parenteral nutrition, was delivered through a central venous catheter. The patient delivered a healthy male infant by Caesarean section at week 38 of gestation (Apgar 9/10/10) and remained metabolically stable throughout the peripartum period. Postpartum nutrition was gradually changed from parenteral to oral diet. Two years later, the patient became pregnant again and presented with hyperemesis gravidarum. With metabolic monitoring and treatment as before no decompensation occurred. At week 38 of gestation, she delivered a healthy female infant by elective Caesarian section (Apgar 9/10/ 10). This case report describes the metabolic and obstetric management of two pregnancies in a patient with HMGCoA lyase deficiency with favorable outcome without metabolic complications.

Background : In recent years, rheumatoid arthritis (RA) uses a “treat to target”  treatment strategy. This strategy requires a valid and accurate tool for assessing disease activity. The most widely used tool is DAS28, which was developed from DAS with the omission of ankle and foot joints. There has been many critization aboutthe accuracy of DAS28 in classifying the state of RA disease. Most importantly, when an active disease state was misclassified as an inactive state (false negative)which lead to under treat and subsequently to disability. The difference between DAS28 and DAS lies mainly in the exclusion of ankle and foot joints, thus DAS28-squeeze, a new and simple tool has been proposed. It comprises the same 28 joints in DAS28 added with a sqeeze test on both metatarsophalangeal joints. However, this new tool has never been validated with any imaging techniques.Objective : To assess the diagnostic values of DAS28 and DAS28-squeeze.Methods : This study comprised a cross-sectional diagnostic study, using Power Doppler sonography as a standard reference in evaluating the diagnostic value ofDAS28 and DAS28-squeeze. This study uses the most sringent sonography criteria of active disease which is an active Doppler signal with a moderate synovial hypertrophy on B-mode. Results : Over the study period, 56 subjects underwent diagnostic tests using DAS28, DAS28-squeeze and Power Doppler sonography. There were 4 false negativecases in DAS28 and 1 case in DAS28-squeeze. The sensitivities of DAS28 and DAS28-squeeze to identify active disease using Power Doppler sonography as reference standard were 73.3% (95%CI ± 11.59) and 93.3% (95%CI ± 6.55), respectively. While the specificities of DAS28 and DAS28-squeeze were 36.6% (95%CI ± 12.62) and 34.1% (95%CI ± 12.42), respectively. Furthermore the negative likelihood ratioof DAS28 and DAS28-squeeze were 0.73 and 0.19, respectively.Conclusion : This study is the first to validate DAS28- squeeze using imaging techniques. From this study the false negative rate of DAS28-squeeze is lower thanDAS28. DAS28-squeeze has a better sensitivity and negative likelihood ratio than DAS28 in identifying RA disease state.Keywords : Rheumatoid Arthritis, DAS28, DAS28-squeeze, treat to target, Power Doppler, squeeze test

Background: The progressivity of chronic kidney disease (CKD) is associated with several clinical conditions which contribute to high morbidity and mortality, including anemia and hypoalbuminemia. This study aimed to assess the association of anemia and hypoalbuminemia with the mortality of CKD patients undergoing routine hemodialysis (HD) in Siloam Hospital Kupang.Methods: We conducted a retrospective cohort study based on Indonesia renal registry data system and hospital medical records. We studied the following variables: gender, age, etiology of CKD, vascular access of HD, and prevalence of anemia and hypoalbuminemia. All analysis was performed using SPSS software version 22.Results: There were 128 patients enrolled in this study. Of the total patients who died, most of them died within the first 3 months since the initiation of HD (62.1%). The majority of patients had anemia (67.2%) and hypoalbuminemia (69.5%). The bivariate analysis showed that anemia (p value=0.192), and hypoalbuminemia (p value=0.336) were not statistically significant associated with mortality among patients undergoing routine HD.Conclusions: Anemia and hypoalbuminemia are not statistically associated with mortality outcome of CKD patients in Siloam Hospital Kupang. However, these conditions may still have prognostic importance for CKD patients undergoing routine HD. Further studies with larger size of cohort and longer period of time are warranted.