Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study.

OBJECTIVES: Nucleotide analogues may promote renal and bone toxicity. The aim of the present study was to evaluate markers of osteorenal toxicity in patients affected by hepatitis B virus-related chronic hepatitis treated with lamivudine plus adefovir who were switched to tenofovir. PATIENTS AND METHODS: We evaluated 60 consecutive patients at the time of the switch of treatment and after 1, 3, 6, 9 and 12 months. The mean baseline estimated glomerular filtration rate (eGFR) was 89.3 ± 19.0 mL/min/1.73 m(2). RESULTS: During the study period we observed a reduction in mean eGFR up to 6 months after switching to tenofovir, and this remained stable for the last two timepoints. At the end of study, the mean eGFR was 82.6 ± 21.5 mL/min/1.73 m(2), a reduction of 7.5%. The mean baseline proteinuria was 202.6 ± 237.6 mg/24 h. Microhaematuria was observed in 22.6% of patients and hypophosphataemia in 18.6%. After 1 month of tenofovir, we observed a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24 h proteinuria. After 3 and 12 months of tenofovir, these data tended to recover to baseline levels. A total of 92.6% of patients at baseline had hypovitaminosis D. After supplementation with cholecalciferol, this percentage decreased significantly. We observed a reduced bone mineral density (BMD) in 52.7% of patients at baseline; this increased to 77.8% after 6 months of tenofovir, but at the last timepoint the percentage of patients with a reduced BMD had fallen to a level above the baseline. CONCLUSIONS: In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment.

Capillaroscopic Skin Ulcers Risk Index (CSURI) calculated with different videocapillaroscopy devices: how its predictive values change.

INTRODUCTION: Digital ulcers (DU) occur in about 50% of systemic sclerosis (SSc) patients. Scleroderma DU are responsible for chronic pain and disability with the need of systemic and local treatments. Recently, capillaroscopic skin ulcer risk index (CSURI) has been validated as useful tool in predicting the appearance of new scleroderma ulcers and/or persistence of non-healing lesions, within 3 months from capillaroscopy evaluation. OBJECTIVES: Since the image length of 1.57 mm might represent a critical factor for CSURI calculation, the present study aimed to evaluate the reliability of CSURI using three different videocapillaroscopy devices with distinct image widths. METHODS: One hundred and seventy-six unselected SSc patients were consecutively enrolled for the study during a six-month period, using three different capillaroscopy devices (image widths of 1.33, 1.57, and 1.70 mm). RESULTS: After a three month-follow-up new DU or persisting non-healing ulcers were observed in 46/176 patients (26.1%). The receiver operating characteristic curve analysis for CSURI showed an area under curve respectively of 0.705 for the image width of 1.33 mm, 0.786 for the image of 1.70 mm, and 0.888 for the image width of 1.57 mm. CONCLUSIONS: The good sensitivity, specificity and positive predictive value of CSURI was confirmed in the whole patients' series, as well as in the three subgroups on different image widths obtained with various available devices. In addition, the negative predictive value of the capillaroscopic index remained very high regardless of the picture length adopted.

Digital laser doppler flowmetry may discriminate "limited" from "diffuse" systemic sclerosis.

OBJECTIVES: To investigate skin blood flux and microvascular functional changes by laser Doppler flowmetry (LD) in patients with systemic sclerosis (SSc) at baseline and following dynamic stimulations. METHODS: Skin blood flux of the dorsal hands was recorded by LD at baseline and after the cold test and the post-occlusive hyperemia test in 59 SSc patients (49 limited cutaneous, 10 diffuse cutaneous). Twenty-five patients with primary Raynaud's phenomenon (PRP), and 31 healthy donors (HD) were studied as controls. RESULTS: After the cold test, SSc patients had a significantly higher reduction of the blood flux (-38.4%+/-28) than PRP (-21.1%+/-37) and HD (-22.1%+/-23) subjects (p<0.05). Within the SSc group, the cold test flux was significantly reduced in limited-SSc (-399%+/-28, p<0.05), but not in diffuse-SSc (-31.2%+/-29), whereas, the time needed to recover the basal flux after the occlusive/ischemic test was significantly longer in diffuse-SSc (18.8s+/-21)than in limited-SSc (4.5s+/-4, p<0.01) or HD (2.2s+/-2, p<0.01) or PRP (0.4s+/-0.7, p<0.01). CONCLUSIONS: These data clearly indicate an impairment of vascular tone regulatory mechanisms in SSc and suggest that a peculiar pathogenic mechanism may be involved in different SSc subset. Nevertheless, it has clear that PRP and SSc-associated RP have a distinct pattern at LD evaluation, and monitoring patients with PRP could be helpful to understand whether a change in the LD pattern might predict the development of SSc.

Functional impairments of microcirculation in HIV-positive patients: a laser Doppler fluxometry-based investigation.

PURPOSE: The aim of our study was to investigate the morphologic and functional characteristics of microcirculation in HIV-positive patients. Microcirculation was investigated by means of capillaroscopy and laser Doppler fluxometry (LDF). The results were compared with those obtained from healthy subjects and patients affected by sclerodermia. METHOD: We evaluated 140 subjects: 69 HIV-positive, 48 sclerodermic, and 23 healthy individuals. The groups were compared for resting flow (RF), mean flow during cold test, mean flow during the recovery, postocclusive reaction, and time of recovery after reactive hyperaemia. RESULTS: RF (p = .0035), flow during the cold test (p = .008), recovery (p = .03), and postocclusive reaction (p = .007) results were higher in HIV-1 positive patients with respect to the other two groups. Recovery after postocclusive reaction in HIV-positive patients was longer than in healthy individuals. Time from diagnosis and a pathologic electromyography were significantly related to a vasospasm reduction induced by the cold test (p = .022). The recovery was also influenced by the time from disease diagnosis (p = .0016). CONCLUSIONS: HIV patients seem to have an altered microcirculation regulation, with increased perfusion of the capillary territory. This could be related to the length of period of infection and a coexisting neuropathy.

Microscopic polyangiitis associated with primary biliary cirrhosis.

We describe a patient with microscopic polyangiitis and primary biliary cirrhosis (PBC) who presented with a non-erosive polyarthritis followed by pulmonary and renal involvement and signs of liver disorder. Detection of pANCA and antimitochondrial antibodies with results of renal and liver biopsies allowed a diagnosis of microscopic polyangiitis and PBC. To our knowledge, this is the first report of an association between the 2 diseases.