Thymic volume predicts long-term immune reconstitution in HIV-infected children treated with highly active antiretroviral therapy

Highly active antiretroviral therapy (HAART) suppresses viral replication and augments CD4 T cell counts. HAART-associated immune restoration is often difficult to predict. We verified whether increases in CD4 cells, and particularly in cells of the naive phenotype, would be associated in HAART-treated children with thymic volume. Long-term immune reconstitution is significantly better in children with bigger thymuses at the initiation of HAART. Thymic volume has a strong predictive value for the immunological effect of HAART

Comparative evaluation of seven resistance interpretation algorithms and their derived genotypic inhibitory quotients for the prediction of 48 week virological response to darunavir-based salvage regimens

Background: the darunavir genotypic inhibitory quotient (gIQ) has been suggested as one of the predictors of virological response to darunavir-containing salvage regimens. Nevertheless, which resistance algorithm should be used to optimize the calculation of gIQ is still debated. The aim of our study was to compare seven different free-access resistance algorithms and their derived gIQs as predictors of 48 week virological response to darunavir-based salvage therapy in the clinical setting. Methods: patients placed on two nucleoside reverse transcriptase inhibitors\u200a+\u200a600/100 mg of darunavir/ritonavir twice daily \u200a\ub1\u200a enfuvirtide were prospectively evaluated. Virological response was assessed at 48 weeks. Darunavir resistance interpretation was performed according to seven different algorithms, of which two were weighted algorithms. Analysis of other factors potentially associated with virological response at 48 weeks was performed. Results: fifty-six treatment-experienced patients were included. Overall, 35 patients (62.5%) had a virological response at 48 weeks. Receiver operator characteristic curve analysis showed that De Meyer's weighted score (WS) and its derived gIQ (gIQ WS) were the most accurate parameters defining virological response, and related cut-offs showed the best sensitivity/specificity pattern. In univariate logistic regression analysis, baseline log viral load (P = 0.028), optimized background score 65 2 (P = 0.048), WS >5 (P = 0.001) and WS gIQ 65 600 (P\u200a<\u200a0.0001) were independently associated with virological response. In multivariate analysis, only baseline log viral load (P = 0.008) and WS gIQ 65 600 (P < 0.0001) remained in the model. Conclusions: in our study, although different resistance interpretation algorithms and derived gIQs were associated with virological response, gIQ WS was the most accurate predictive model for achieving a successful virological response

Le manifestazioni epatobiliari nella colite ulcerosa

La colangite sclerosante primitiva (Primary Sclerosing Cholangitis, PSC) rappresenta la manifestazione epatobiliare di maggiore rilevanza associata alla rettocolite ulcerosa (RCU), in termini di frequenza e severit\ue0 clinica. I pazienti con PSC ed RCU presentano un aumentato rischio di sviluppo di neoplasie epatiche ed extraepatiche, in particolare di colangiocarcinoma e neoplasia colorettale. Dati recenti indicano che, nella PSC, la terapia con acido ursodesossicolico ad alte dosi si \ue8 dimostrata in grado di indurre un miglioramento radiologico e della fibrosi epatica (staging bioptico); l\u2019impatto sulla sopravvivenza rimane da valutare. Il trapianto di fegato costituisce ad oggi l\u2019unica terapia curativa per i pazienti affetti da PSC in stadio avanzato e consente di ottenere un tasso di sopravvivenza a 5 anni dell\u201985% circa; il timing pi\uf9 appropriato resta tuttavia da definire. Steatosi epatica, epatite cronica, cirrosi, amiloidosi, ascessi epatici, trombosi portale e sindrome di Budd-Chiari rappresentano altre manifestazioni epatobiliari associate alla RCU

Bone grafting: historical and conceptual review, starting with an old manuscript by Vittorio Putti.

Vittorio Putti has been recognized as one of the founders of orthopedic science. He wrote a number of original papers on different topics from his vast experience of orthopedics. In a paper on bone grafting dated 1912, Putti demonstrated his modern way of thinking by his ability to study past experiences critically and by his willingness to compare his own experiences with those of other orthopedic surgeons. Putti's paper proposes principles that still apply today, and which can be considered as the basis of the modern science of grafting. The results of his work can be summarized as follows: a) The uniformity of bone graft integration processes, and a marked reduction in integration capacity in heteroplastic grafts. b) The osteogenetic incapability of the graft as opposed to the osteogenetic capability of the periosteum. c) Marked reduction in the biological capability of bone that has been treated with preservatives, boiled, or macerated. d) The importance of the quality of the tissues in which the bone graft is inserted, including the mechanical characteristics of the graft and its fixation. e) The importance of asepsis. f) The importance of functional exercise. These important experiences were achieved without Putti having any knowledge of immunology, vascular surgery, tissue preservation or non decalcified histology techniques

A labeled tableaux system for the Distributed Temporal Logic DTL

DTL is a distributed temporal logic for reasoning about temporal properties of distributed systems from the local point of view of the system's agents, which are assumed to execute sequentially and to interact by means of synchronous event sharing. We present a sound and complete labeled tableaux system for future-time DTL. To achieve this, we first formalize a labeled tableaux system for reasoning locally at each agent, which provides a system for full future-time LTL, and afterwards we combine the local systems into a global one by adding rules that capture the distributed nature of DTL

Mechanisms of disease : the role of aldosterone in kidney damage and clinical benefits of its blockade

In the past 10 years, many widely accepted concepts relating to aldosterone production and its pathogenetic role have changed. We now know that aldosterone is produced not only by the zona glomerulosa of the adrenal cortex, but also in the heart, blood vessels, kidney and brain; such extra-epithelial production occurs mainly during tissue repair. Also, increased aldosterone levels contribute to vessel inflammation, oxidative stress, endothelial dysfunction and organ damage. As such, aldosterone has a key role in the development of myocardial fibrosis. Anti-aldosterone treatment has proven effective in patients with heart failure. Experimental evidence regarding the role of aldosterone in kidney damage has accumulated. Aldosterone infusion can counteract the beneficial effects of treatment with angiotensin-converting-enzyme inhibitors, causing more-severe proteinuria and an increased number of vascular and glomerular lesions; treatment with aldosterone antagonists can reverse these alterations. Preliminary observations in pilot studies in humans confirm the experimental findings, supporting the hypothesis that aldosterone antagonists are renoprotective in clinical practice. Studies in larger populations with longer follow-up are needed to confirm this theory