Reduction of volumetric bone mineral density in postmenopausal women with hepatitis C virus-correlated chronic liver disease: A peripheral quantitative computed tomography (pQCT) study

BackgroundThe prevalence of osteoporosis in chronic liver disease (CLD) varies considerably among the studies, depending on patient selection and diagnostic criteria. We aimed to measure bone turnover markers and volumetric bone mineral density (BMD) in a group of postmenopausal women with CLD using both dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), in comparison with age-matched healthy subjects.MethodsThirty-five postmenopausal patients with HCV-correlated CLD and 35 healthy postmenopausal women, as controls, underwent a DXA scan at lumbar and femoral level and a pQCT measurement of the nondominant forearm. Serum concentrations of biochemical markers relevant to bone turnover were also measured.ResultsPatients showed no differences in DXA values either at lumbar or femoral level compared to controls. On the contrary, pQCT geometrical (cortical cross-sectional area) and volumetric (total and trabecular volumetric BMD) parameters were significantly reduced in the CLD women. Also the Strength–Strain Index (SSI), an estimate of diaphyseal bone resistance to bending and torsion, was significantly lower in patients than in controls. Patients with CLD presented an unbalanced bone turnover, with increased bone resorption markers.ConclusionsThe bone geometrical and volumetric parameters measured in our CLD postmenopausal women, by pQCT, show a reduced bone mineral quality and stiffness. Conversely, DXA-measurements seem unable to appreciate the bone alterations in these patients. This would encourage further studies to validate pQCT analysis as a diagnostic tool for a correct estimate of bone involvement in CLD.     

Role of hepatic vein catheterisation and transient elastography in the diagnosis of idiopathic portal hypertension

Background

Idiopathic portal hypertension is a rare cause of portal hypertension, frequently misdiagnosed as cryptogenic cirrhosis. This study evaluates specific findings at hepatic vein catheterisation or liver stiffness in idiopathic portal hypertension.

Methods

39 cases of idiopathic portal hypertension patients were retrospectively reviewed. Hepatic vein catheterisation and liver stiffness measurements were compared to matched patients with cirrhosis and portal hypertension, and non-cirrhotic portal vein thrombosis, included as controls.

Results

Hepatic vein-to-vein communications were found in 49% idiopathic portal hypertension patients precluding adequate hepatic venous pressure gradient measurements in 12. In the remaining 27 patients, mean hepatic venous pressure gradient (HVPG) was 7.1 ± 3.1 mmHg. Only 5 patients had HVPG ≥ 10 mmHg. HVPG was markedly lower than in cirrhosis (17 ± 3 mmHg, p < 0.001). Mean liver stiffness in idiopathic portal hypertension was 8.4 ± 3.3 kPa; significantly higher than in non-cirrhotic portal vein thrombosis (6.4 ± 2.2 kPa, p = 0.009), but lower than in cirrhosis (40.9 ± 20.5 kPa, p = 0.005). Only 2 idiopathic portal hypertension patients had liver stiffness >13.6 kPa.

Conclusions

Patients with idiopathic portal hypertension frequently have hepatic vein-to-vein communications and, despite unequivocal signs of portal hypertension, HVPG and liver stiffness values much lower than the cut-off for clinical significant portal hypertension in cirrhosis. These findings oblige to formally rule-out idiopathic portal hypertension in the presence of signs of portal hypertension.     

Electron microscopic findings in skin biopsies from patients with infantile osteopetrosis and neuronal storage disease

Infantile osteopetrosis with neuronal storage disease is a rare lysosomal storage disorder. It is an autosomal recessive disease that is associated with mutations in the OSTM1 and chloride channel ClCN-7genes. So far mutations in the OSTM1 gene have been identified in only 8 patients. To date, the clinical and morphological features of nine patients with infantile osteopetrosis with neuronal storage have been reported, but no ultrastructural findings of skin have been described in these patients. Skin biopsy is a cost-effective tool for the diagnosis of lysosomal storage disease. The purpose of this report is to define the ultrastructure of affected cells seen in skin biopsies of 2 boys whose mutation of OSTM1 has been characterized. The children presented in infancy with severe osteopetrosis and neurological deficiencies whose predominant symptoms were marked cerebral atrophy, decreased myelinization, and severe central nervous system involvement. Because of the difficulties in distinguishing this disorder from some lysosomal storage diseases such as mucopolysaccharidosis that have both neurological and skeletal abnormalities, the authors elected to examine skin biopsies from these children. Ultrastructural examination revealed the presence of swollen unmyelinated axons containing spheroids, reduced numbers of myelinated axons, and the presence of secondary lysosomes in Schwann cells containing lipofuscin. This study demonstrates that electron microscopy of skin biopsy is a useful diagnostic method to identify patients with clinical features of osteopetrosis with neuronal storage disease.     

Increased susceptibility to amyloid toxicity in familial Alzheimer's fibroblasts

Much experimental evidence suggests that an imbalance in cellular redox status is a major factor in the pathogenesis of Alzheimer's disease (AD). Our previous data showed a marked increase in membrane lipoperoxidation in primary fibroblasts from familial AD (FAD) patients. In the present study, we demonstrate that when oligomeric structures of Abeta 1-40 and Abeta 1-42 are added to the culture media, they accumulate quicker near the plasma membrane, and are internalized faster and mostly in APPV717I fibroblasts than in age-matched healthy cells; this results in an earlier and sharper increase in the production of reactive oxygen species (ROS). Higher ROS production leads in turn to an increase in membrane oxidative-injury and significant impairment of cellular antioxidant capacity, giving rise to apoptotic cascade activation and finally to a necrotic outcome. In contrast, healthy fibroblasts appear more resistant to amyloid oxidative-attack, possibly as a result of their plasma membrane integrity and powerful antioxidant capacity. Our data are consistent with increasing evidence that prefibrillar aggregates, compared to mature fibrils, are likely the more toxic species of the peptides. These findings provide compelling evidence that cells bearing increased membrane lipoperoxidation are more susceptible to aggregate toxicity as a result of their reduced ability to counteract amyloid oligomeric attack.     

Monitoring HCV RNA viral load by locked nucleic acid molecular beacons real time PCR

Locked nucleic acids (LNA) based real time PCR was used in particular situations where there are difficulties in primer design due to sequence complexity. In this study a new real time RT-PCR assay was developed using LNA modified primers and LNA molecular beacon probes to monitor hepatitis C virus (HCV) viral load in plasma and serum samples. The technique did not suffer from an heterogeneity of the HCV genome and, in addition, an internal RNA control was amplified in the same reaction tube with different short primers and beacon probe. Due to the short consensus LNA primers length, the PCR efficiency was close to 100% with no formation of hairpin loop structures. In summary a new LNA molecular beacon based real time RT-PCR assay was used successfully to measure quantitatively the total level of HCV RNA in both experimental and clinical specimens. The high sensitivity (50 IU/ml), the wide range of genotype detection, increased specificity and robustness obtained with this test are particularly useful for screening large number of specimens and measuring viral loads to monitor the progress of the disease.     

Neuropsychiatric clinical manifestations in elderly patients treated with hydroxychloroquine: a review article

Little is known about the development of psychosis during hydroxychloroquine (HCQ) treatment, especially in elderly patients affected by rheumatic diseases, with multiple comorbidities and treatments. To summarize the available evidence on HCQ-induced psychosis in elders, we performed a literature review. Additionally, individual case safety reports sent to the European Pharmacovigilance database (EudraVigilance) with HCQ as suspected drug and related to adverse events belonging to the System Organ Class ‘Psychiatric disorders’ were shown. Over the years, evidence was published about the risk of neuropsychiatric clinical manifestations during HCQ treatment for rheumatic diseases, but few of them were related to elderly patients. These adverse events can include less severe clinical manifestations such as affect lability and nervousness or more severe conditions such as actual psychosis and suicidal tendencies, which frequency are actually unknown. The presence of risk factors in these patients may precipitate HCQ-induced psychosis and their precocious detection could be associated with a risk minimization. Among predisposing risk factors, there are the co-exposure to interacting drugs, alcohol intake, familial history of psychiatric diseases, female gender, and the concomitant use of low-dose glucocorticoids. In some cases it was possible to reverse psychotic behaviour with the antipsychotic treatment or with HCQ suspension.