Hepatitis G Virus Infection Among Liver Graft Recipients: Anatomoclinical Correlations

Hepatitis G virus (HGV) causes persistent infection in man, but its disease association is controversial. We studied the HGV disease association in 25 liver transplantation (LT) recipients without evidence of hepatitis B and C infection. HGV RNA was tested by semiquantitative RT-PCR in serial serum samples and its presence was correlated with the biochemical and histological evidence of liver damage. The overall prevalence of HGV infection in this population was 9/25 (36%), one patient being HGV RNA positive since before LT, while the other eight apparently acquired de novo infections after LT. In five cases, appearance of HGV was followed by biochemical and histological evidence of liver damage: the liver biopsy showed acute rejection in two cases, acute cholangitis in two, and acute hepatitis in one. At the end of follow-up, histological evidence of chronic hepatitis was found in one HGV-positive patient but also in three HGV-negative patients, whereas the only patient with acute hepatitis at the time HGV RNA was first detected in serum developed an intralobular gigantocellular granuloma. In conclusion, HGV infection after LT may be seldom associated with acute and chronic liver damage, but comparable histological features can be observed also among HGV-negative controls.     

Deferral of assessment of pulmonary embolism

We evaluated a simplified algorithm for safely postponing diagnostic imaging for pulmonary embolism (PE). At the index visit, patients were identified as being at high or low risk of PE; the former received full dosage low molecular weight heparin while the latter were left untreated until performance of diagnostic imaging (max 72 hours). During this period, no thromboembolic events occurred in low-risk patients (0/211, 0.% [upper 95% CI 0.9%]); only one event occurred in those at high-risk (1/125, 0.8% [upper 95% CI, 1.2]). Our study demonstrates that diagnostic imaging for PE can be safely deferred for up to 3 days.     

The use of a telematic connection for the follow-up of hypertensive patients improves the cardiovascular prognosis

BACKGROUND: Inadequate blood pressure (BP) control could be due to incorrect management of hypertensives caused by the lack of interaction between general practitioners (GP) and hypertension specialists. OBJECTIVES: To test the effectiveness on BP and total cardiovascular risk (TCVR) control of an internet-based digital network connecting specialists and GPs. METHODS: We created a network among the Hypertension Clinic, Federico II University (Naples, Italy), 23 hospital-based hypertension clinics and 60 GPs from the area (CampaniaSalute Network, CS). Randomized GPs enrolled in CS could update online records of patients (n = 1979). As a control, we included 2045 patients referred to the specialist clinics by GPs from outside the network. All patients completed a 2-year follow-up. RESULTS: CS provided a larger reduction in BP [systolic/diastolic BP (SBP/DBP): 7.3 +/- 0.4/5.4 +/- 0.3 versus 4.1 +/- 0.4/3.1 +/- 0.26 mmHg, CS versus control; P < 0.001 for both] and percentage of patients with BP < 140/90 mmHg (CS versus control: baseline, 33 versus 34%, NS; end of follow-up, 51 versus 47%, chi = 13.371; P < 0.001). A European Society of Hypertension-European Society of Cardiology (ESH/ESC) TCVR score was calculated [from 1 (average) to 5 (very high TCVR)]. The CS group showed a reduction in the mean TCVR score (CS: from 3.5 +/- 0.02 to 3.2 +/- 0, P < 0.01, ANOVA; control group: 3.5 +/- 0.03 to 3.4 +/- 0.03, NS) and, accordingly, fatal and non-fatal major cardiovascular events (MACE) were less frequent (2.9 versus 4.3%; chi = 5.047, P < 0.02). CS predicts fewer MACE in multiple binary regression analysis (beta:-7.27, P < 0.008) reducing the risk for MACE compared to control [odds ratio (OR): 0.838; 95% confidence interval (CI): 0.73-0.96]. CONCLUSION: Our results support the idea that telemedicine can achieve better control of BP and TCVR.     

Quantifying the Severity of a Delirium Episode Throughout Hospitalization: the Combined Importance of Intensity and Duration

Background

The ability to determine which episodes of delirium are likely to lead to poor clinical outcomes has remained a major area of challenge.

Objective

To quantify delirium severity and course over an entire hospitalization using several measures, and to evaluate their predictive validity for 30- and 90-day outcomes post-discharge.

Design

Two prospective cohort studies.

Participants

Analysis was conducted in two independent cohorts of adult patients aged ≥70.

Main Measures

Nine delirium episode severity measures were examined: (1) measures reflecting delirium intensity (peak Confusion Assessment Method-Severity [CAM-S] and mean CAM-S score), (2) a measure reflecting delirium intensity and duration (sum of all CAM-S scores, sum of all CAM-S scores on delirium days only, peak CAM-S score x days with delirium), (3) measures requiring information on delirium duration and delirium at discharge (total number of delirium days, percentage of delirium days, delirium at discharge), and (4) a measure of cognitive change. Associations of the delirium episode severity measures with 30- and 90-day post-hospital outcomes (death, nursing home placement, and readmission) relevant to delirium were examined.

Key Results

The delirium episode severity measure that required information on both delirium intensity and duration (sum of all CAM-S scores) was the most strongly associated with 30- and 90-day post-hospital outcomes. Using this measure, the relative risk [95 % confidence interval] for death at 30-days increased across levels of sum of all CAM-S scores from 1.0 (referent) to 2.1 [0.8, 5.4] for ‘low,’ to 2.9 [1.2, 7.1] for ‘moderate,’ to 6.4 [2.9, 14.0] for ‘high’ (p for trend <.01).

Conclusions

The delirium episode severity measure that included both intensity and duration had the strongest association with important post-hospital outcomes.

     

Age-associated changes in functional response to CXCR3 and CXCR5 chemokine receptors in human osteoblasts

The expression and functional activity of CXC chemokine receptors were evaluated in human osteoblasts (OB) obtained post-trauma from old donors compared to very young donors. It was found that CXCR1 and CXCR4 were only expressed by old but not young donors' cells. In contrast, CXCR3 and CXCR5 were expressed by both young and old donors. We functionally evaluated CXCR3/CXCL10 and CXCR5/CXCL13 receptor/ligand pairs by analysing cell proliferation and the release of N-acetyl-β-D-glucosaminidase (NAG), an enzyme that degrades glycosaminoglycans and hyaluronic acid. CXCL10 and CXCL13 induced a dose-dependent increase of cell proliferation in OB from young donors while cell proliferation of OB in old donors was not affected. By contrast, CXCL10 and CXCL13 induced a significantly higher NAG release in OB from old donors compared to young ones. These data demonstrate a significant age-dependent difference in the response of OB to CXCL10 and CXCL13 stimulation. These chemokines induce an inverse response of OB from old and young donors, which suggests a role of ageing in the modulation of cellular response of bone cells. This revised version was published online in July 2006 with corrections to the Cover Date.     

Cardiac expression of adenine nucleotide translocase-1 in transgenic mice overexpressing bovine GH

Heart hypertrophy is a common finding of acromegaly, a syndrome due to GH excess. Impairment of adenine nucleotide translocase-1 (ANT-1) gene, the main mitochondrial ADP/ATP exchanger, leads to cardiac hypertrophy. The aim of the study was to evaluate cardiac expression and the functional role of ANT-1 in 1- to 12-month-old transgenic mice overexpressing bovine GH (acromegalic mice, Acro) and littermate controls (wild-type mice, Wt). GH specificity of protein degree variation was assessed treating Acro with pegvisomant, a GH receptor competitor. Tissue levels of ANT-1, NF-kappaB, ATP, and lactic acid were evaluated by western blot, bioluminescence, and Fourier transform infrared spectroscopy respectively. The degree of ANT-1 expression was higher in 1-month-old Acro than in Wt (47+/-5% OD vs 33+/-4% OD, P<0 01). On the contrary, ANT-1 expression was lower in 3- to 12-month-old Acro than in Wt (P<0 03). Changes in ANT-1 expression were associated with consistent changes of cellular ATP content, increasing at 1 month (P<0 05) and reducing thereafter in Acro when compared with Wt (P<0 04). Treatment with pegvisomant abolished ANT-1 and ATP changes observed in 1- and 3-month-old Acro, thus supporting a GH-dependent mechanism. Reduced ATP generation in hypertrophied hearts of older Acro was associated with increased lactic acid levels suggesting that part of energy was due to glycolysis. Variations in ANT-1 expression were linked to GH through changes in NF-kappaB, the levels of which changed accordingly. In conclusion, 1-month-old acromegalic mice had increased ANT-1 expression and higher degree of ATP production. Long-standing disease was associated with a consistent reduction of ANT-1 and ATP tissue levels, which became GH-independent in older animals. This study demonstrated a direct effect of GH on key proteins involved in energy metabolism of acromegalic hearts.     

Hypertransaminasemia in childhood as a marker of genetic liver disorders

Background The widespread use of routine biochemical assays has led to increased incidental findings of hypertransaminasemia. We aimed to evaluate the prevalence of different causes of raised aminotransferase levels in children referred to a university department of pediatrics.Methods We investigated 425 consecutive children (age range, 1–18 years) with isolated hypertransaminasemia. All patients had raised aminotransferase levels on at least two occasions in the last month before observation. Cases due to major hepatotropic viruses were excluded.Results During the first 6 months of observation, 259 children showed normalized liver enzymes. Among the remaining 166 patients with hypertransaminasemia lasting for more than 6 months, 75 had obesity-related liver disease; 51, genetic disorders; 7, autoimmune hepatitis; 5, cholelithiasis; 3, choledochal cyst; and 3, celiac disease. Among the 51 children with genetic disorders, 18 had Wilson disease; 14, muscular dystrophy; 4, alpha-1-antitrypsin deficiency; 4, Alagille syndrome; 4, hereditary fructose intolerance; 3, glycogen storage disease (glycogenosis IX); 2, ornithine transcarbamylase deficiency; and 2, Shwachman’s syndrome. In 22 children, the hypertransaminasemia persisted for more than 6 months in the absence of a known cause.Conclusions Genetic disease accounted for 12% of cases of isolated hypertransaminasemia observed in a tertiary pediatric department. A high level of suspicion is desirable for an early diagnosis of these disorders, which may present with isolated hypertransaminasemia and absence of typical clinical signs.     

Apoptosis and immaturity in acute myeloid leukemia

The primary cause of treatment failures in acute myeloid leukemia (AML) is the emergence of both resistant disease and early relapse. Among the most frequent agents of these phenomena are defects in the mitochondrial-mediated apoptotic pathway. This pathway is regulated by bcl-2 family of anti-apoptotic (bcl-2, bcl-xl, mcl-1) and pro-apoptotic proteins (bax, bad, bak). In particular, bcl-2 dimerizes with several members of bcl-2 family of proteins, altering the threshold of cell death. The flow cytometric quantitative measurement of bcl-2 and bax expression for the determination of bax/bcl-2 ratio provided crucial clinical information in AML: in our hands, lower bax/bcl-2 ratio conferred a very poor prognosis with decreased rates of complete remission (CR) and overall survival (OS). Moreover, striking correlations were found between lower bax/bcl-2 ratio and higher progenitor marker expression, such as CD34, CD117 and CD133 antigens, confirming the link between this apoptotic index and the maturation pathways. However, the capacity of bax/bcl-2 ratio to clearly identify patients with different prognosis with regard to CR and OS within the CD34+, CD117+ and CD133+ subgroups implies that other mechanisms, such as proliferation and/or cell cycle dysregulation may be involved to explain its clinical significance. Finally, small molecules that target both the receptor- and mitochondrial-mediated pathway of apoptosis are providing encouraging results in patients with relapsed and/or refractory disease (i.e. CDDOMe, bcl-2 antisense oligonucleotides, CEP-701, etc), confirming the key role of apoptotic mechanisms on the outcome of AML patients.