Epidemiology and geographic clustering of Erdheim-Chester disease in Italy and France.

This geoepidemiological study, performed in Italy and France, shows that Erdheim-Chester disease is increasingly diagnosed and cases cluster in specific geographic areas, namely southern Italy and central France. Disease frequency inversely correlates with the Human Development Index.

State-of-the-Art of Endomyocardial Biopsy on Acute Myocarditis and Chronic Inflammatory Cardiomyopathy.

PURPOSE OF REVIEW: Histologic evidence of myocardial inflammatory infiltrate not secondary to an ischemic injury is required by current diagnostic criteria to reach a definite diagnosis of myocarditis. Endomyocardial biopsy (EMB) is therefore often indicated for the diagnosis of myocarditis, although it may lack sufficient sensitivity considering the limited possibility of myocardial sampling. Improving the diagnostic yield and utility of EMB is of high priority in the fields of heart failure cardiology and myocarditis in particular. The aim of the present review is to highlight indications, strengths, and shortcomings of current EMB techniques, and discuss innovations currently being tested in ongoing clinical studies, especially in the setting of acute myocarditis and chronic inflammatory cardiomyopathy. RECENT FINDINGS: EMB provides unique diagnostic elements and prognostic information which can effectively guide the treatment of myocarditis. Issues affecting the diagnostic performance in the setting of acute myocarditis and chronic inflammatory cardiomyopathies will be discussed in this review in the light of recent expert consensus documents on the management of these conditions and on indication to EMB. Recent innovations using electroanatomic mapping (EAM)-guided EMB and fluoroscopic-guided EMB during temporary mechanical circulatory support have improved the utility of the procedure. EMB remains an important diagnostic test whose results need to be interpreted in the context of (1) clinical pre-test probability, (2) timing of sampling, (3) quality of sampling (4) site of sampling, (5) histologic type of myocarditis, and (6) analytic methods that are applied. Herein we will review these caveats as well as perspectives and innovations related to the use of this diagnostic tool.

OCT findings of radiotherapy-induced coronary artery disease: A "two-hit combined hypothesis".

Radiotherapy-induced coronary artery disease (RT-CAD) is a well-known late complication of anti-neoplastic treatment. Although definitive diagnosis requires standard coronary angiography, modern intracoronary imaging techniques, such as optical coherence tomography (OCT), are able to provide detailed morphological characteristics of RT-CAD lesions. We report the case of a 42-year-old male with a previous history of treated Hodgkin's lymphoma who complained of typical chest pain on minimal exertion. Coronary angiography showed significant 2-vessel disease. Use of OCT documented the fibro-fatty nature of coronary lesions, showing a constrictive pattern, compatible with RT-CAD. The patient underwent successful revascularization of both lesions. .

Effect of beta- and alpha-glucans on immune modulating factors expression in enterocyte-like Caco-2 and goblet-like LS 174T cells.

Glucans are complex polysaccharides consisting of repeated units of d-glucose linked by glycosidic bonds. The nutritional contribution in α-glucans is mainly given by starch and glycogen while in ß-glucans by mushrooms, yeasts and whole grains, such as barley and spelt well represented in the Mediterranean Diet. Numerous and extensive studies performed on glucans highlighted their marked anti-tumor, antioxidant and immunomodulatory activity. It has recently been shown that rather than merely being a passive barrier, the intestinal epithelium is an essential modulator of immunity. Indeed, epithelial absorptive enterocytes and mucin secreting goblet cells can produce specific immune modulating factors, driving innate immunity to pathogens as well as preventing autoimmunity. Despite the clear evidence of the effects of glucans on immune system cells, there are only limited data about their effects on immune activity of mucosal intestinal cells strictly related to intestinal barrier integrity. The aim of the study was to evaluate the effects of α and ß glucans, alone or in combination with other substances with antioxidant properties, on reactive oxygen species (ROS) levels, on the expression of ROS-generating enzyme DUOX-2 and of the immune modulating factors Tumor Necrosis Factor (TNF-α), Interleukin 1 ß (IL-1ß) and cyclooxygenase-2 (COX-2) in two intestinal epithelial cells, the enterocyte-like Caco-2 cells and goblet cell-like LS174T. In our research, the experiments were carried out incubating the cells with glucans for 18 h in culture medium containing 0.2% FBS and measuring ROS levels fluorimetrically as dihydrodichlorofluoresce diacetate (DCF-DA) fluorescence, protein levels of DUOX-2 by Western blotting and mRNA levels of, TNF-α, IL-1ß and COX-2 by qRT-PCR. α and ß glucans decreased ROS levels in Caco-2 and LS 174T cells. The expression levels of COX-2, TNF-α, and IL-1ß were also reduced by α- and ß-glucans. Additive effects on the expression of these immune modulating factors were exerted by vitamin C. In Caco-2 cells, the dual oxidase DUOX-2 expression is positively modulated by ROS. Accordingly, in Caco-2 or LS174T cells treated with α and ß-glucans alone or in combination with Vitamin C, the decrease of ROS levels was associated with a reduced expression of DUOX-2. The treatment of cells with the NADPH oxidase (NOX) inhibitor apocynin decrease ROS, DUOX-2, COX-2, TNF-α and IL-1ß levels indicating that NOX dependent ROS regulate the expression of immune modulating factors of intestinal cells. However, the combination of vitamin C, α and ß-glucans with apocynin did not exert an additive effect on COX-2, TNF-α and IL-1ß levels when compared with α-, ß-glucans and Vitamin C alone. The present study showing a modulatory effect of α and ß-glucans on ROS and on the expression of immune modulating factors in intestinal epithelial cells suggests that the assumption of food containing high levels of these substances or dietary supplementation can contribute to normal immunomodulatory function of intestinal barrier.

Current strategies to minimize toxicity of oxaliplatin: selection of pharmacogenomic panel tests.

Oxaliplatin is an anticancer drug routinely used to treat colorectal, gastroesophageal, ovarian, breast, head/neck, and genitourinary cancers. Discontinuation of oxaliplatin treatment is mostly because of peripheral neuropathy, more often than for tumor progression, potentially compromising patient benefit. Several strategies to prevent neurotoxicity have so far been investigated. To overcome this life-threatening side effect, while taking advantage of the antineoplastic activities of oxaliplatin, we describe in detail recent findings on the underlying mechanisms of genetic variants associated with toxicity and resistance to oxaliplatin-based chemotherapy in colorectal cancer. A comprehensive panel of eight polymorphisms, previously validated as significant markers related to oxaliplatin toxicity, is proposed and discussed. In addition, the most common available strategies or methods to prevent/minimize the toxicity were described in detail. Moreover, an early outline evaluation of the genotyping costs and methods was taken in consideration. With the availability of individual pharmacogenomic profiles, the oncologists will have new means to make treatment decisions for their patients that maximize benefit and minimize toxicity. With this purpose in mind, the clinician and lab manager should cooperate to evaluate the advantages and limitations, in terms of costs and applicability, of the most appropriate pharmacogenomic tests for routine incorporation into clinical practice.

Iodized salt improves the effectiveness of L-thyroxine therapy after surgery for nontoxic goitre: a prospective and randomized study.

OBJECTIVE: To investigate whether the addition of iodized salt to daily diet in thyroidectomized patients for nontoxic goitre could influence the effectiveness of nonsuppressive L-thyroxine (L-T4) therapy on thyroid remnant size, during 12 months' follow-up after thyroid surgery. DESIGN AND PATIENTS: A consecutive series of selected 139 patients (26 males, 113 females; median age 45 years, range 30-69 years) living in a moderate iodine-deficient area, and undergoing thyroid surgery for nontoxic multinodular goitre, was enrolled. Patients were assigned randomly to two different therapeutic regimens: 70 patients received L-T4 therapy alone (Gr. L-T4), while the remaining 69 patients took iodized salt on a daily basis in addition to L-T4 treatment (Gr. L-T4 + I). In both groups, the initial L-T4 dose was 1.5 microg/kg/day, which, in our experience, has been shown to be intermediate between suppressive and replacement doses. To avoid the risks of mild thyrotoxicosis and to limit the excessive TSH stimulation of the thyroid remnant, the L-T4 dose was adjusted in those patients with serum TSH levels outside the lowest two-thirds of the normal range (0.3-2.5 mU/l). An ultrasound evaluation of thyroid remnant size was performed after thyroid surgery and 12 months later. RESULTS: After surgery, the median thyroid remnant volume was 3.5 ml (range 0.4-13.9 ml) in Gr. L-T4 and 4.6 ml (range 0.5-12.7 ml) in Gr. L-T4 + I (P = 0.06). After 1 year of follow-up, the patients treated with L-T4 + I obtained a remnant volume reduction (-39.7%, range -87.0% to +91.2%) significantly (P = 0.006) greater than that observed in patients assuming L-T4 alone (-10.2%, range -89.4% to +85.0%). However, the percentage of patients showing an increase in remnant size in the months following surgery was higher in Gr. L-T4 than in Gr. L-T4 + I (22/60 vs. 9/66; P = 0.01). In Gr. L-T4 patients the thyroid remnant volume variation throughout 12 months of treatment was correlated significantly with the size of the thyroid remnant found at the first ultrasound evaluation (R(2) = 0.3; P < 0.001). No such correlation was found in Gr. L-T4 + I patients, for whom the therapy maintains a similar effectiveness in patients with either a large or a small postsurgery thyroid remnant. In patients treated with L-T4 alone, the remnant volume variation was correlated significantly with the median serum TSH values attained in the course of treatment (R2 = 0.4; P < 0.001). The highest reduction in remnant volume was observed only by lowering the serum TSH concentrations. In patients treated with L-T4 plus iodine, instead, the thyroid remnant volume reduction occurred independently of the plasma TSH levels attained in the course of treatment. CONCLUSIONS: Our short-term prospective and randomized study leads us to conclude that, in patients living in a moderate iodine-deficient area and undergoing thyroid surgery for nontoxic goitre: (1) the iodine prophylaxis improves the effects of postsurgery nonsuppressive L-T4 therapy on thyroid remnant size. (2) In patients treated with L-T4 alone the therapeutic effectiveness decreases in the presence of a large postsurgery thyroid remnant. With the addition of iodine, the L-T4 maintains a similar efficacy in patients with either a large or a small remnant. (3) During treatment with L-T4 alone the highest therapeutic effectiveness is attained by lowering the plasma TSH concentration. With the addition of iodized salt to the daily diet the effects of L-T4 on remnant size are relevant independently of the TSH levels.