Using FIB-4 score as a screening tool in the assessment of significant liver fibrosis (F2) in patients with transfusion dependent beta thalassaemia: a cross sectional study

Objective To evaluated the performance of FIB-4 score as a screening tool to detect significant liver fibrosis (F2) compared to transient elastography (TE) among chronic transfusion-dependent beta-thalassemia (TDT) patients, in a resource-poor setting. Design A cross-sectional study Setting Adolescent and Adult Thalassaemia Care Center (University Medical Unit) Kiribathgoda Sri Lanka. Participants 45 TDT patients who have undergone more than 100 blood transfusions with elevated serum ferritin more than 2000ng/mL were selected for the study. Patients who were serologically positive for hepatitis C antibody were excluded. Outcome measures TE and FIB-4 score were estimated at the time of recruitment in all participants. Pre-defined cut-off values for F2 extracted from previous studies for TE and FIB-4 score were compared. A new cut-off value for FIB-4 score was estimated using ROC curve analysis to improve the sensitivity for F2 prediction. Results Of the selected 45 TDT patients 22(49%) were males. FIB-4 score showed a significant linear correlation with TE (r= 0.52 p< 0.0003). The FIB-4 score was improbable to lead to a false classification of TDT patients to have F2 when the FIB-4 cut-off value was 1.3. On the other hand it had a very low diagnostic yield in missing almost all (except one) of those who had F2. Using a much-lowered cut-off point of 0.32 for FIB-4 we improved the pick-up rate of F2 to 72%. Conclusions Regardless of the cut-off point FIB-4 score cannot be used as a good screening tool to pick-up F2 in patients with TDT irrespective of their splenectomy status. On the contrary at 1.3 cut off value though FIB-4 is a very poor detector for F2 fibrosis it will not erroneously diagnose F2 fibrosis in those who do not have it.

Sellar germinoma mimicking IgG4-related hypophysitis: a case report

Background The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis. Case presentation A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible. Conclusion Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis.

Sex differences in the involvement of skeletal and cardiac muscles in myopathic Ano5-/- mice.

Limb-girdle muscular dystrophy R12 (LGMD-R12) is caused by recessive mutations in the Anoctamin-5 gene (ANO5, TMEM16E). Although ANO5 myopathy is not X-chromosome linked, we performed a meta-analysis of the research literature and found that three-quarters of LGMD-R12 patients are males. Females are less likely to present with moderate to severe skeletal muscle and/or cardiac pathology. Because these sex differences could be explained in several ways, we compared males and females in a mouse model of LGMD-R12. This model recapitulates the sex differences in human LGMD-R12. Only male Ano5-/- mice had elevated serum creatine kinase after exercise and exhibited defective membrane repair after laser injury. In contrast, by these measures, female Ano5-/- mice were indistinguishable from wild type. Despite these differences, both male and female Ano5-/- mice exhibited exercise intolerance. While exercise intolerance of male mice can be explained by skeletal muscle dysfunction, echocardiography revealed that Ano5-/- female mice had features of cardiomyopathy that may be responsible for their exercise intolerance. These findings heighten concerns that mutations of ANO5 in humans may be linked to cardiac disease.

Altered Functional Mitochondrial Protein Levels in Plasma Neuron-Derived Extracellular Vesicles of Patients With Gadolinium Deposition

The retention of the heavy metal, gadolinium, after a Gadolinium-Based Contrast Agent-assisted MRI may lead to a symptom cluster termed Gadolinium Deposition Disease. Little is known of the disorder’s underlying pathophysiology, but a recent study reported abnormally elevated serum levels of pro-inflammatory cytokines compared to normal controls. As a calcium channel blocker in cellular plasma and mitochondrial membranes, gadolinium also interferes with mitochondrial function. We applied to sera from nine Gadolinium Deposition Disease and two Gadolinium Storage Condition patients newly developed methods allowing isolation of plasma neuron-derived extracellular vesicles that contain reproducibly quantifiable levels of mitochondrial proteins of all major classes. Patients’ levels of five mitochondrial functional proteins were statistically significantly lower and of two significantly higher than the levels in normal controls. The patterns of differences between study patients and controls for mitochondrial dynamics and mitochondrial proteins encompassing neuronal energy generation, metabolic regulation, ion fluxes, and survival differed from those seen for patients with first episode psychosis and those with Major Depressive Disorder compared to their controls. These findings suggest that mitochondrial dysfunction due to retained gadolinium may play a role in causing Gadolinium Deposition Disease. Larger samples of both GDD and GSC patients are needed to allow not only testing the repeatability of our findings, but also investigation of relationships of specific mitochondrial protein deficiencies or excesses and concurrent cytokine, genetic, or other factors to GDD’s neurological and cognitive symptoms. Studies of neuronal mitochondrial proteins as diagnostic markers or indicators of treatment effectiveness are also warranted.

Body mass index was linked with multi-cardiometabolic abnormalities in Chinese children and adolescents: a community-based survey

Background Evidence on how body mass index (BMI) influence cardiometabolic health remains sparse in Chinese children and adolescents, especially in south China. We aim to investigate the effect of overweight and/or obesity on high blood pressure (HBP), dyslipidemia, elevated serum uric acid (SUA) and their clustering among children and adolescents in an island in South China. Methods Using multi-stage cluster sampling method, 1577 children and adolescents aged 7–18 in Hainan province, south China, participated in the survey. The association between body mass index and cardiometabolic indexes were explored. Overweight and obesity were classified according to criteria of World Health Organization for children and adolescents aged 5 to 19. Restricted cubic spline models were used to examine the possible non-linear association between BMI and cardiometabolic profiles. Multivariable logistic regression models were fitted to examine the effect size of BMI on cardiometabolic disorders including HBP, elevated SUA and dyslipidemia. Comorbidity of at least two cardiometabolic abnormalities (HBP, dyslipidemia, elevated SUA) was defined as clustering of cardiometabolic risk factors. Results Comparing with normal weight and underweight subjects, overweight/obese youths had higher levels of BP, SUA, triglyceride, low-density lipoprotein but lower level of high-density lipoprotein. Overweight/obese youth had higher risk of dyslipidemia (OR:2.89, 95%CI: 1.65–5.06), HBP (OR:2.813, 95%CI: 1.20–6.59) and elevated SUA (OR: 2.493, 95%CI: 1.45–4.27), respectively, than their counterparts. The sex-, age-adjusted prevalence of abnormalities clustering was 32.61% (95% CI: 20.95% to 46.92%) in overweight/obesity group, much higher than in the under/normal weight group (8.85%, 95%CI: 7.44% to 10.48%). Conclusion Excess adiposity increased the risk of elevated serum uric acid, serum lipids, blood pressure and their clustering among children and adolescents in south China.