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Ferreri A.J.M.,San Raffaele Scientific Institute
The Lancet Oncology | Year: 2014

Extranodal lymphomas constitute a heterogeneous group of malignancies, accounting for roughly 60% of all non-Hodgkin lymphomas. The extranodal organ where lymphomas arise is an important determining factor of biological, molecular, and aetio-pathogenic features, and of presentation, dissemination pattern, and outcome. An increased risk of CNS involvement, an uncommon but lethal event, has been suggested in some extranodal lymphomas, but the absolute risk is still debatable for most of these malignancies. This debate is because of the presence of selection biases and other confounding factors in related literature, which inevitably has led to conflicting recommendations. The identification of extranodal lymphomas at increased risk of CNS dissemination is an important unmet clinical need; affected patients could benefit from early CNS assessment by neuroimaging and cerebrospinal fluid analysis and adequate CNS prophylaxis, avoiding unnecessary prophylaxis and related toxicity in low-risk patients. This Review discusses relevant confounding factors and identifies high-risk extranodal lymphomas analysing histopathological category, involved organ, and other specific risk factors, which could be helpful for result interpretation and patient stratification in future clinical trials. Finally, a recommendation is provided for CNS-directed management of high-risk extranodal lymphoma patients in daily practice. © 2014 Elsevier Ltd. Source

Camaschella C.,San Raffaele Scientific Institute
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2013

To avoid iron deficiency and overload, iron availability is tightly regulated at both the cellular and systemic levels. The liver peptide hepcidin controls iron flux to plasma from enterocytes and macrophages through degradation of the cellular iron exporter ferroportin. The hepcidin-ferroportin axis is essential to maintaining iron homeostasis. Genetic inactivation of proteins of the hepcidin-activating pathway causes iron overload of varying severity in human and mice. Hepcidin insufficiency and increased iron absorption are also characteristic of anemia due to ineffective erythropoiesis in which, despite high total body iron, hepcidin is suppressed by the high erythropoietic activity, worsening both iron overload and anemia in a vicious cycle. Hepcidin excess resulting from genetic inactivation of a hepcidin inhibitor, the transmembrane protease serine 6 (TMPRSS6) leads to a form of iron deficiency refractory to oral iron. Increased hepcidin explains the iron sequestration and iron-restricted erythropoiesis of anemia associated with chronic inflammatory diseases. In mice, deletion of TMPRSS6 in vivo has profound effects on the iron phenotype of hemochromatosis and beta-thalassemia. Hepcidin manipulation to restrict iron is a successful strategy to improve erythropoiesis in thalassemia, as shown clearly in preclinical studies targeting TMPRSS6; attempts to control anemia of chronic diseases by antagonizing the hepcidin effect are ongoing. Finally, the metabolic pathways identified from iron disorders are now being explored in other human pathologic conditions, including cancer. Source

Hedlund P.,San Raffaele Scientific Institute
Neurourology and Urodynamics | Year: 2014

Aims: To review knowledge on cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction. Methods: Review of MEDLINE using defined search terms, and manual analysis. Articles published in English were included. Results: and Discussion Components of the endocannabinoid system - cannabinoid (CB) receptor types 1 and 2, anandamide, and fatty acid amide hydrolase (FAAH), which degrades anandamide and related fatty-acid amides - have been located to lower urinary tract tissues of mice, rats, monkeys, and humans. Studies have located CB receptors in urothelium and sensory nerves and FAAH in the urothelium. CB receptor- and FAAH-related activities have also been reported in the lumbosacral spinal cord. Data on supraspinal CB functions in relation to micturition are lacking. Cannabinoids are reported to reduce sensory activity of isolated tissues, cause antihyperalgesia in animal studies of bladder inflammation, affect urodynamics parameters reflecting sensory functions in animals models, and appear to have effects on storage symptoms in humans. FAAH inhibitors have affected sensory bladder functions and reduced bladder overactivity in rat models. Cannabinoids may modify nerve-mediated functions of isolated lower urinary tract tissues. Conclusions: Evidence suggests components of the endocannabinoid system are involved in regulation of bladder function, possibly at several levels of the micturition pathway. It is unclear if either CB receptor has a dominant role in modification of sensory signals or if differences exist at peripheral and central nervous sites. Amplification of endocannabinoid activity by FAAH inhibitors may be an attractive drug target in specific pathways involved in LUTS. © 2013 Wiley Periodicals, Inc. Source

Tortoli E.,San Raffaele Scientific Institute
Clinical Microbiology Reviews | Year: 2014

Nontuberculous mycobacteria (NTM) are present in the environment, mainly in water, and are occasionally responsible for opportunistic infections in humans. Despite the fact thatNTMare characterized by a moderate pathogenicity, the diseases caused by NTM at various body sites are increasing on a worldwide level. Among over 150 officially recognized NTM species, only two or three dozen are familiar to clinicians, and even to most microbiologists. In this paper, approximately 50 new species described in the last 8 years are reviewed, and their role in human infections is assessed on the basis of reported clinical cases. The small number of reports concerning most of the “new” mycobacterial species is responsible for the widespread conviction that they are very rare. Their role is actually largely underestimated, mainly because they often remain unrecognized and misidentified. Aiming to minimize such bias, emphasis has been placed on more common identification pitfalls. Together with new NTM, new members of the Mycobacterium tuberculosis complex described in the last few years are also an object of the present review. © 2014, American Society for Microbiology. All Rights Reserved. Source

Dzavik V.,University of Toronto | Colombo A.,San Raffaele Scientific Institute
JACC: Cardiovascular Interventions | Year: 2014

Objectives This study sought to evaluate the feasibility of performing contemporary bifurcation techniques with the Absorb everolimus-eluting bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, California) (BVS). Background The feasibility of using the BVS in bifurcation lesions is unknown. Methods We performed bifurcation stenting procedures including main-vessel stenting with ballooning of the side branch through the BVS struts, T-stenting and crush and culotte procedures, in a synthetic arterial model. Low-pressure final kissing balloon (FKB) inflation was performed to complete the procedures. Results Single-stent procedures optimally opened the side-branch ostium without deforming the main vessel BVS. T-stenting completely covered the side-branch ostium. In crush cases, we could easily re-cross the crushed BVS with the wire and balloon and achieve good results after deployment of the main-vessel BVS and FKB inflation. A 2-BVS culotte resulted in good paving of the main vessel. Disruption of 1 BVS strut was observed after FKB inflation with the 2 balloons inflated beyond the recommended limit of the BVS, as calculated by Finet's law. Conclusions Intervention of bifurcation lesions using the Absorb BVS using modern bifurcation techniques appears feasible in a coronary bifurcation model. Provisional stenting is recommended in the majority, with sequential balloon inflations and FKB inflation only when necessary. T or T-stenting and small protrusion stenting with a metal drug-eluting stent is preferable in case of crossover. A 2-BVS, T-stent technique can be performed in a high-angle bifurcation; otherwise, crush or culotte should be considered, using metal DES in the side branch. Two-BVS crush and culotte require careful evaluation, and should only be considered in patients with large-caliber main vessels. © 2014 by the American College of Cardiology Foundation. Source

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