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Mini-Mental State Examination (MMSE) lacks of sensitivity in detecting cognitive deficits associated with subcortical damage. The HIV-Dementia Scale (HDS), a screening tool originally created for detecting cognitive impairment due to subcortical damage in HIV + patients, has proved to be useful in other neurological diseases. Until now, an Italian version of the HDS is not available. We aimed at: (1) validating the HDS Italian version (HDS-IT) in a cohort of cognitively healthy subjects (CN); (2) exploring the suitability of HDS-IT in detecting cognitive impairment due to subcortical damage (scCI). The psychometric properties of the HDS-IT were assessed in 180 CN (mean age 67.6 ± 8.3, range 41–84) with regard to item-total correlation, test–retest reliability and convergent validity with MMSE. Item-total correlations ranged 0.44–0.72. Test–retest reliability was 0.70 (p p scCI subjects (mean age 64.9 ± 10.6, range 41–84). Mean HDS-IT total score was close to the original version and significantly lower in the scCI group compared to CN (8.6 ± 3.6 vs. 12.6 ± 2.5, p p

Background Brain-derived neurotrophic factor (BDNF) is a neurotrophine that plays a key role in the regulation of both central and peripheral nervous system. Moreover, BDNF is secreted in multiple tissues and exerts systemic, autocrine, and paracrine effects in the cardiovascular system. Of importance, BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries and may be involved in thrombus formation. Thus, BDNF has been suggested as an important link between inflammation and thrombosis, potentially involved in the pathogenesis of acute coronary syndrome (ACS). Purpose In our study we aimed at assessing serum levels of BDNF in patients with ACS, evaluating differences according to clinical presentation [ST-segment elevation myocardial infarction (STEMI) vs. Non-ST-segment elevation ACS (NSTE-ACS)]. Moreover, we assessed the presence of optical coherence (OCT)-defined macrophage infiltrates (MØI) in the culprit vessel of ACS patients and evaluated their relationship with BDNF levels. Methods ACS patients were prospectively selected. Blood samples were collected at admission and serum levels of BDNF were subsequently assessed. Presence of OCT-defined MØI along the culprit vessel was assessed. Results 166 ACS patients were enrolled [mean age 65.3±11.9 years, 125 (75.3%) male, 109 STEMI, 57 NSTE-ACS]. Serum levels of BDNF were higher among STEMI patients compared with NSTE-ACS [median (IQR) 2.48 pg/mL (1.54–3.34) vs. 2.12 pg/mL (1.34–2.47), p=0.007], while C-reactive protein levels did not differ between the two groups. OCT assessment was performed in 53 patients and MØI were detected in 27 patients. Of importance, patients with MØI in the culprit vessel had higher levels of BDNF compared with patients without MØI [median (IQR) 2.23 pg/mL (1.38–2.53) vs. 1.41 pg/mL (0.93–2.07), p=0.023], while C-reactive protein levels did not differ between the two groups. Of note, at multivariate regression analysis BDNF levels were independent predictor of MØI [OR: 2.20; 95% CI (1.02–4.74), p=0.043]. Conclusions Serum levels of BDNF may reliable identify the presence of local macrophage inflammatory infiltrates in patients with ACS. Moreover, BDNF levels are higher in patients with STEMI compared with NSTE-ACS. Taken together, these data suggest that BDNF may represent an interesting link between local inflammatory activation and enhanced thrombosis in ACS. BDNF serum levels Funding Acknowledgement Type of funding source: None

Background Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS). Inflammatory activation is considered a key mechanism of plaque instability in patients with plaque rupture through the release of metalloproteinases and the inhibition of collagen synthesis that in turns lead to fibrous cap degradation. However, the clinical relevance of macrophage infiltration has never been investigated in patients with PE. Purpose In our study, we aimed at assessing the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. Methods ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site and in non-culprit segments along the culprit vessel was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03–2.58) years]. Results We included 153 patients [median age (IQR) 64 (53–75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. In particular, culprit lesion analysis demonstrated that patients with PE with MØI had a significantly thinner fibrous cap [median (IQR) 100 (60–120) μm vs. 160 (95–190) μm, p Conclusion Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with a more aggressive phenotype of coronary atherosclerosis with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up. These findings are of the utmost importance in the era of precision medicine because clearly show that macrophage infiltrates may identify patients with a higher cardiovascular risk requiring more aggressive secondary prevention therapies and a closer clinical follow-up. Prognosis Funding Acknowledgement Type of funding source: None

We present a 47-year-old, South-African origin, woman with a background of stable monoclonal gammopathy of unknown significance (MGUS) who attended A&E with a history of coryzal symptoms associated with persistent fever, lymphadenopathy and a new onset of rash, not responding to antibiotics and paracetamol. A trial of high-dose steroids resolved symptoms. Bone marrow biopsy confirmed a progression of MGUS into multiple myeloma and her axillary lymph node biopsy analysis supported a diagnosis of Kikuchi-Fujimoto disease (KFD). This is an unusual presentation where KFD has been noted alongside MGUS progression to multiple myeloma. Haematology follow-up is underway.

Our objective was to describe incidence and clinical features of ALS from a prospective population-based study in Emilia Romagna Region (ERR). From 2009 onwards, a prospective registry recorded all incident cases of ALS among residents in the ERR (population, 4.4 million inhabitants), involving 17 neurological departments. For each patient, detailed demographic and clinical information was collected by caring physicians. Results showed that from 1 January 2009 to 31 December 2011, 347 patients received a new diagnosis of ALS with a crude incidence rate of 2.63/100,000/year. There was micro-geographic heterogeneity throughout ERR, with higher incidence rates in the low density population (3.27/100,000) (p < 0.01). ALS patients have been more frequently employed in agriculture than the general ERR population (8.64\% vs. 4.6\%, p < 0.01). Clinical features were similar to those described in previous population based studies. In conclusion, we report incidence rates similar to those reported by European registries, reflecting good accuracy of our prospective study. We confirmed previous studies reporting higher incidence rates in rural areas and among agricultural workers. Although genetics has been gaining increasing importance in ALS aetiology, some epidemiological data are still unexplained. Identifying geographical areas or populations with high incidence rates can be a starting point for identifying environmental risk factors. Further studies having this specific aim can shed light on these topics.

Carp ( Cyprinus carpio ) is one of important freshwater cultivated fish species in Indonesia. Aeromonas hydrophila is accounted as potential pathogenic bacteria in Carp, Hence the control for the infection of A. hydrophila is very important. In this study we investigated the effectiveness of crude extract of Dayak onions (Eleutherine palmifolia (L.) Merr) for the treatment of A. hydrophila infected fish. Furthermore, alteration of histophatology of several organs, gills, kidney, liver and muscle were also investigated. Crude Extract of Dayak Onion ( E leutherine palmifolia (L) Merr. (CEDO) with the doses of 50, 60, 70 and 80 ppm were used for treatment of A. hydrophila infected carp for 11 days. Prior to investigation of histopatology of gills, kidneys, hearts, muscle, the Carp was moved to fresh-non infected fish tank. The Result indicated that gill experienced Hyperplasia, Fusion, Necrosis. Kidney experienced Degeneration, Congestion, Necrosis. Liver experienced the vacuole degeneration, congestion, Melano macrophages, necrosis. Muscle experienced Edema and necrosis. But fish treated with 80 ppm treatment showed less damage and tissue repair. Keywords : E. palmfolia (L.) Merr, A. hydrophila , C. carpio , Histopathology, Gills, Kidney, Liver, Muscle

Background: Clinical and molecular factors are essential to define the prognosis in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of surgical resection are the most relevant prognostic factors. Our investigation of the role of gender in predicting prognosis shows a slight survival advantage for female patients. Methods: We performed a prospective evaluation of the Project of Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors in patients with GBM who received standard treatment. Results: A total of 169 patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively. MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival was longer in the methylated females compared with the methylated males (P = 0.028) but was not significantly different between the unmethylated females and the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT methylation status considered together (methylated females vs. methylated males; hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017), age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI, 0.948-0.982; P < 0.001) were significantly correlated with survival. Conclusions: Survival was consistently longer among MGMT methylated females compared with males. Gender can be considered as a further prognostic factor.

Introduction Current treatment options for myelofibrosis (MF) are diverse; apart from rare patients who are eligible for allogeneic transplantation, active treatments are focused on controlling MF-related symptoms and are not disease modifying. Patients who are initially asymptomatic and those at low risk for progression are usually observed without active treatment (watch and wait) until the appearance of symptoms or progression. There are limited real-world data on the management of patients with MF in the United Kingdom (UK). The REALISM UK study documented the early management pathways for patients with MF in routine clinical practice. Method REALISM UK was a multi-centre, retrospective, non-interventional study in 15 UK secondary care centres. Eligible patients were those aged ≥18 years at diagnosis of MF, with diagnosis >6 months and ≤5 years prior to data collection and with ≥1 follow-up visit. Data on patient demographics, clinical characteristics, MF management strategies and outcomes were collected from patients' medical records; the observation period was from the date of MF diagnosis until data collection. The primary endpoint was the time from diagnosis to active treatment. Watch and wait strategies included supportive therapies (blood transfusions, erythropoiesis-stimulating agents, and steroids). Results A total of 200 patients were recruited (63% [n=126/200] with primary MF (PMF); 37% [n=74/200] with secondary MF). The median age at MF diagnosis was 69.7 years (interquartile range [IQR] 63.5-75.7) and 71% (n=141/200) had a JAK2 mutation. At diagnosis, 52% (n=104/200) of patients had International Prognostic Scoring System (IPSS) categories of intermediate-2 (Int-2) or high. Common documented features of disease at diagnosis included an enlarged spleen (47%, n=94/200), anaemia (44%, n=88/200), and constitutional symptoms (e.g. night sweats, unexplained fever, or weight loss [30%, n=60/200]). The median (IQR) time to first active treatment was 46 days (range 0-350) in the total population; patients with higher risk disease were prescribed active treatment sooner: IPSS low, 136.5 days (range 0-625; n=26); IPSS Int-1, 90 days (range 0-494; n=70); IPSS Int-2, 0 days (range 0-252; n=65); IPSS high: 0 days (0-216; n=39). The choice of first management strategy by IPSS at diagnosis is shown in Table 1. During the study period, watch and wait was the first management strategy for 54% (n=107/200) of patients, with the median (IQR) time from diagnosis to active treatment in this group being 322 (130-610) days. Constitutional symptoms were recorded in 20% (n=21/107) of patients for whom watch and wait was the first management strategy. Active treatment was started at diagnosis for 47% (n=93/200) of patients, with the most commonly used medications being hydroxycarbamide (22.5% [n=45/200]) and ruxolitinib (17.5% [n=35/200]). The median (IQR) treatment duration during the study observation window was 346 days (range 121-768) for hydroxycarbamide and 375 days (range 172-691) for ruxolitinib. In total, 5.5% (n=11/200) of patients were recorded as having undergone allogenic stem cell transplantation during the observation period. Conclusion Clinicians in the UK apply a broad range of management strategies for the treatment of patients with MF. Many patients were observed without active treatment following diagnosis, despite having symptomatic disease. The most common active treatments as first management strategies were hydroxycarbamide and ruxolitinib. Disclosures Mead: Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel/accommodation expenses, Research Funding, Speakers Bureau; Bristol Myers-Squibb: Consultancy. Somervaille:Novartis: Consultancy, Honoraria. Butt:Novartis: Consultancy, Honoraria, Speakers Bureau. Whiteway:Novartis: Consultancy, Honoraria, Speakers Bureau. Kirkpatrick:Novartis: Consultancy, Honoraria. Roughley:Novartis: Consultancy, Honoraria. Ewing:Novartis: Honoraria, Other: Meeting attendance sponsorship ; Bristol Myers-Squibb: Other: Meeting attendance sponsorship . Garg:Novartis: Consultancy, Honoraria. Harrison:Promedior: Honoraria; Shire: Speakers Bureau; Sierra Oncology: Honoraria; Celgene: Honoraria, Speakers Bureau; Roche: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Incyte: Speakers Bureau; Gilead: Speakers Bureau; CTI: Speakers Bureau; AOP: Honoraria; Janssen: Speakers Bureau. Bains:Novartis: Employment. Chiu:Novartis: Employment. Hickey:OPEN VIE: Employment.

The last 20 years have observed the proposal of several minimally invasive techniques for non-surgical treatment of thyroid nodules. This chapter describes, on the basis of our experience and of a brief literature review, the efficacy, safety, cost-effectiveness and current clinical indications of the first of these procedures: percutaneous ethanol injection (PEIT).

Summary. A multicentre cross-sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1–1.3, P

A letter to the editor is presented related to the case where GATA1 is overexpressed in patients with essential thrombocythemia and polycythemia vera, but not in patients with primary myelofibrosis or chronic myelogenous leukemia.

Reduction strategies of blood pressure, as a modifiable cardiovascular risk, are currently based on office assessment of brachial artery blood pressure. However, antihypertensive treatment based on brachial BP values reduces cardiovascular risk but cannot completely reverse the hypertension-induced risk of morbidity events. As is well known, BP varies in different arterial systems and invasive and non-invasive studies have demonstrated that brachial BP does not necessarily reflect central aortic BP. Emerging evidences now suggest that central pressure may predict cardiovascular diseases better than brachial BP; moreover, it may differently respond to certain antihypertensive drugs. The potential effects beyond peripheral BP control may be due to specific protective properties of different antihypertensive drugs in affecting central aortic pressure and arterial stiffness. Although data on direct cardiovascular benefit impact of central blood pressure treatment in randomized clinical trials are still lacking, it is likely that the improvement of quality of care and the individualized assessment of the hypertension-associated cardiovascular risk are achievable with the use of central hemodynamics. Therefore, basing antihypertensive treatment guidance on central pressures rather than on peripheral blood pressure may be the key for future antihypertensive strategies.

To propose a test to evaluate endothelial function, based on VO(2) on-transition kinetics in sub-anaerobic threshold (AT) constant load exercise, we tested healthy subjects and patients with ischemic-hypertensive cardiopathy by two cardiopulmonary tests on a cycle ergometer endowed with an electric motor to overcome initial inertia: a pre-test and, after at least 24 h, one 6 min constant load exercise at 90 % AT. We measured net phase 3 VO(2)-on kinetics and, by phase 2 time constant (tau), valued endothelial dysfunction. We found shorter tau in repeated tests, shorter time between first and second test, by persisting endothelium-dependent arteriolar vasodilatation and/or several other mechanisms. Reducing load to 80 % and 90 % AT did not produce significant changes in tau of healthy volunteers, while in heart patients an AT load of 70 %, compared to 80 % AT, shortened tau (delta=4.38+/-1.65 s, p=0.013). In heart patients, no correlation was found between NYHA class, ejection fraction (EF), and the two variables derived from incremental cycle cardio-pulmonary exercise, as well as between EF and tau; while NYHA class groups were well correlated with tau duration (r=0.92, p=0.0001). Doxazosin and tadalafil also significantly reduced tau. In conclusion, the O(2) consumption kinetics during the on-transition of constant load exercise below the anaerobic threshold are highly sensitive to endothelial function in muscular microcirculation, and constitute a marker for the evaluation of endothelial dysfunction.

Background: Cytotoxic regimens used in induction treatments for acute myeloid leukemia (AML) almost always include standard or high-dose cytarabine (Ara-C). During or soon after induction therapy, leukemic patients frequently develop gastroenteric complications, characterized by abdominal pain and diarrhea. The association ofthese symptoms with f and melena is typical ofnecrotizing enterocolitis (NE), a life-threathening condition that can be documented by ultrasound abdominal scan. Patients and methods: We analyzed retrospectively the clinical course of169 adult patients with AML treated by standard dose Ara-C-containing induction regimens, either by continuous venous infusion (group 1) or subcutaneous injection (group 2). Ultrasonography was employed as early diagnostic tool in a majority ofpatients with gastroenteric complications. Bowel wall thickening was accurately measured and used to confirm the diagnosis of necrotizing enterocolitis. Results: In the first group of 115 patients (median age, 51 years), gastroenteric complications were observed in 55 patients (48%), and 10 patients (9%) received diagnosis ofNE, which was fatal in four. Patients with NE had a median age older than that of patients without gastroenteric symptoms, and a more prolonged neutropenia. In the second group of54 patients (median age, 60 years), gastroenteric events were observed in 14 patients (26%), and no case of NE was recorded. Conclusions: This retrospective analysis shows that NE is a serious complication occurring mainly in patients treated by Ara-C administered as continuous i.v. infusion. The Hematology Journal (2003) 4, 346–350. doi:10.1038/sj.thj.6200304

Background As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. Methods Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. Results Two hundred sixty-seven GBM patients (median age, 64 y; range, 29–84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2–12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0–18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248–0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388–0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328–0.986; P = .0446). Conclusions The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

Although the clinical relevance of brachial blood pressure (BP) measurement for cardiovascular (CV) risk stratification is nowadays widely accepted, this approach can nevertheless present several limitations. Pulse pressure (PP) amplification accounts for the notable increase in PP from central to peripheral arterial sites. Target organs are more greatly exposed to central hemodynamic changes than peripheral organs. The pathophysiological significance of local BP pulsatility, which has a role in the pathogenesis of target organ damage in both the macro- and the microcirculation, may therefore not be accurately captured by brachial BP as traditionally evaluated with cuff measurements. The predictive value of central systolic BP and PP over brachial BP for major clinical outcomes has been demonstrated in the general population, in elderly adults and in patients at high CV risk, irrespective of the invasive or non-invasive methods used to assess central BP. Aortic stiffness, timing and intensity of wave reflections, and cardiac performance appear as major factors influencing central PP. Great emphasis has been placed on the role of aortic stiffness, disturbed arterial wave reflections and their intercorrelation in the pathophysiological mechanisms of CV diseases as well as on their capacity to predict target organ damage and clinical events. Comorbidities and age-related changes, together with gender-related specificities of arterial and cardiac parameters, are known to affect the predictive ability of central hemodynamics on individual CV risk.

Background Tachykinins (TKs) have been shown to be involved in the excitatory enteric motor pathway. This study aimed to examine the direct and nerve-mediated effect of specific NK 1 , NK 2 and NK 3 receptor agonists and antagonists in colonic preparations from control subjects and patients with idiopathic chronic constipation (ICC). Materials and methods Cumulative concentrations of Sar 9 Met(O 2 ) 11 substance P (selective NK 1 receptor agonist), [Ala 5 ,b-Ala 8 ]-neurokinin A (4-10) (selective NK 2 receptor agonist) and [MePhe 7 ]-neurokinin B (selective NK 3 receptor agonist) were tested on colonic circular muscle strips to evaluate the direct drug effects. In addition, in the presence of atropine, the role of TKs in the off-contraction that follows the typical inhibitory response evoked by low frequencies of electrical field stimulation (0.5-10 Hz, 20 V, 1 ms pulse trains lasting 1 min) was investigated. Results In control preparations, the rank order of potency was: NK 2 receptor-selective agonist > NK 3 receptor-selective agonist > NK 1 receptor-selective agonist. The off-contraction was found to be reduced by about 30-40% in colonic circular muscle from ICC patients with respect to controls. Incubation with the NK 1 receptor agonist did not modify the off-contraction measurements in either control or ICC preparations. Conversely, both NK 2 and NK 3 receptor agonists significantly (P < 0.01) increased the off-contraction in ICC preparations only. This increased response was fully antagonized by MEN-10627, a NK 2 and NK 3 receptor antagonist depending on the dose. Conclusions We may conclude that ICC is hyporesponsive to TKs and that the contractile reflex to distension is greatly reduced in ICC disease, but can be restored by incubation with NK 2 and NK 3 receptor agonists.

Background Erythromycin has been shown to have profound prokinetic effects on the gastrointestinal tract of humans and animals, probably through its action on endogenous motilin receptors. The purpose of this study was to determine both the direct and indirect effects (‘off contraction’) of erythromycin and motilin on ex vivo circular muscle strips of the distal colon from patients with or without idiopathic chronic constipation (ICC). Materials and methods Cumulative concentrations of erythromycin (1–20 μM) and motilin (0.05–1 μM) were tested in both control and ICC preparations in order to evaluate the direct drugs effect. A range doses of both erythromycin (0.5–10 μM) and motilin (0.05–0.5 μM) were tested on their ability to affect the off-contraction that follows the typical inhibitory response evoked by low frequencies of Electrical Field Stimulation (EFS) (1–5 Hz, 20 V, 1 msec pulse trains lasting 1 min). Results The direct effect of both erythromycin and motilin was a slight increase (less than 10% of the maximal ACh-induced contraction) in the basal tension, with no dose–response relationship. The off-contraction, evoked by EFS, was not affected by drugs pretreament in control preparations. Conversely, in ICC preparations both drugs significantly increased the off-contraction (about 30%). Conclusions Erythromycin causes mainly an indirect contractile effect in circular muscle strips from ICC patients. This effect may be related to the activation of inhibitory neuronal motilin receptors. This activation might potentiate NANC relaxation, proportionally increasing the circumferential reflex contraction that follows the EFS-induced relaxation.

The aim of our study was to further investigatethe pathophysiological mechanism underlying idiopathicchronic constipation (ICC), a disorder of colonicmotility. A possible alteration of excitatory and inhibitory neurotransmission and also the roleof inhibitory neurotransmitters such as nitric oxide(NO), 5′-adenosine triphosphate (ATP), andvasoactive intestinal peptide (VIP) has been evaluatedon preparations of distal colon from patients with or withoutICC. The isometric tension was recorded from isolatedcircular muscle strips of both experimental groupsduring pharmacological and electrical field stimulation (EFS). The contractile response obtained byacetylcholine (ACh 20 μM), EFS (20 Hz, 20 V, 1 msec,pulse trains lasting 1 min) and substance P (SP 1 μM)was significantly lower in ICC than in controlpreparations. The effect of inhibitory nonadrenergic,noncholinergic innervation was evaluated using EFS atlow frequencies (0.5-8 Hz), after cholinergic andsympathetic blockade with atropine (3 μM) andguanethidine (3 μM). The maximum relaxation valueexpressed as percentage of inhibition of SP-inducedcontraction was significantly higher in ICC than incontrol preparations (87 ± 2.4 and 67 ±6.3, respectively; P < 0.05). Experiments with substances thatantagonize or reduce the effect of putative inhibitorymediators (VIP 6-28, apamin andNG-nitro-L-arginine) suggest that analteration in NO and ATP release is present in ICC preparations. In particularat a higher inhibitory frequency NO-mediated relaxationis enhanced in ICC vs control, supporting the hypothesisthat excessive NO production may be involved in pathophysiological mechanism ofconstipation.

The Burkholderia cepacia complex (Bcc) is a group of phenotypically similar, genetically distinct, motile, freeliving, glucose-non-fermentative, gram-negative bacilli that can be found in soil or water, and it has emerged as an important lung pathogen for patients with cystic fibrosis [1]. Many strains of Bcc are transmissible. Although it is capable of occasionally contaminating hospital environments [1], Bcc rarely causes community-acquired infections in immunocompetent patients. The prospective study described here investigated the nasal microbiology of 48 patients with sinonasal polyposis and 24 patients with chronic sinusitis who consecutively underwent functional endoscopic sinus surgery (FESS). The nasal microbiology of a control group of ten patients without rhinologic abnormalities was also considered. The significant rate of Bcc isolation in our sinonasal polyposis group is discussed. The records of 72 consecutive patients with chronic sinonasal disease treated with FESS at the Section of Otolaryngology of Padova University, a tertiary referral academic hospital, were reviewed. None of the patients had immunosuppression or cystic fibrosis in their medical history, but one had diabetes mellitus. All patients considered for inclusion in the study were admitted on the day of surgical intervention. Nasal swabs were obtained in the operating room before the administration of local nasal anesthesia; a second nasal swab was performed on an outpatient basis 1 month after FESS, during follow-up nasal endoscopy. One nasal middle meatal bacterial swab was taken from each patient under rigid endoscope control. Postoperatively, intravenous antibiotic treatment (ampicillin/sulbactam 1.5 g four times a day in 50 patients; cefazolin 1 g three times a day in 14 patients) was administered for 2–3 days in 64 patients, and oral antibiotic treatment (levofloxacin 500 mg once a day) was administered in eight patients. After discharge, the patients received a 7-day course of antibiotic treatment, consisting of oral amoxicillin-clavulanate (1 g three times per day) in 58 cases, levofloxacin (500 mg once a day) in seven cases, or ceftibuten (400 mg twice a day) in seven cases. Nasal irrigation with either sulphurous-arsenical-ferruginous thermal water (Levico Terme, Trento, Italy) (40 cases) or isotonic sodium chloride solution (32 cases) was performed for at least 1 month after surgery. Histological evaluation of surgical specimens confirmed the diagnosis of sinonasal polyposis in 48 of 72 patients. In the clinical history of these patients, allergy was present in 15 cases, asthma in eight and acetylsalicylic acid intolerance in five. A control group of ten patients without rhinologic abnormalities ruled out by rigid nasal endoscopy also underwent nasal swabbing. Nasal swabs were plated onto sheep blood agar (COS; bioMerieux, Marcy l’Etoile, France) and chocolate agar with PolyVitex (bioMerieux). Plates were incubated for 24 and 48 h. Gram staining was performed. The isolates were Eur J Clin Microbiol Infect Dis (2007) 26:73–75 DOI 10.1007/s10096-006-0233-9

OBJECTIVE: To determine whether a multisystemic bioenergetic deficit is an underlying feature of familial hypobetalipoproteinaemia. METHODS: Brain and skeletal muscle bioenergetics were studied by in vivo phosphorus MR spectroscopy (31P-MRS) in two neurologically affected members (mother and son) and in one asymptomatic member (daughter) of a kindred with familial hypobetalipoproteinaemia. Plasma concentrations of vitamin E and coenzyme Q10 (CoQ10) were also assessed. RESULTS: Brain 31P-MRS disclosed in all patients a reduced phosphocreatine (PCr) concentration whereas the calculated ADP concentration was increased. Brain phosphorylation potential was reduced in the members by about 40%. Skeletal muscle was studied at rest in the three members and during aerobic exercise and recovery in the son and daughter. Only the mother showed an impaired mitochondrial function at rest. Both son and daughter showed an increased end exercise ADP concentration whereas the rates of postexercise recovery of PCr and ADP were slow in the daughter. The rate of inorganic phosphate recovery was reduced in both cases. Plasma concentration of vitamin E and CoQ10 was below the normal range in all members. CONCLUSIONS: Structural changes in mitochondrial membranes and deficit of vitamin E together with reduced availability of CoQ10 can be responsible for the multisystemic bioenergetic deficit. Present findings suggest that CoQ10 supplementation may be important in familial hypobetalipoproteinaemia.

Introduction: Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma. Case Presentation: We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy®), a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), as second-line treatment after progression with dacarbazine, for (wild-type BRAF) metastatic melanoma. The patient was referred to us for several painful lumps on his right arm. A biopsy of one of them revealed melanoma. CT and PET scans did not show any other lesions or a primary site. The patient was started on first-line chemotherapy with dacarbazine 850 mg/m2 on day 1, every 3 weeks. After 3 cycles, the patient showed disease progression with an increase in size of the skin metastasis. Second-line treatment was started with ipilimumab 3 mg/kg on day 1, every 3 weeks. At the end of the treatment, after 4 cycles, we documented a complete clinical response with total resolution of the skin metastasis. At the time of writing this paper, our patient had finished his treatment more than 9 months earlier and is still in complete remission. Conclusion: This is a paradigmatic case where, despite extensive metastatic disease, treatment with ipilimumab has confirmed its efficacy. It is still an open question why only a minority of patients have such a remarkable response, and further trials are warranted to address this important question.

Intracranial extramedullary haematopoiesis (EMH) is very rare. We report the case of EMH with intracranial involvement which developed after trauma in a 73-year-old lady affected by JAK2 mutated myelofibrosis (MF). She was diagnosed with MF in 2005 and treated with low-dose-steroids (prednisolone and oxymethalone) for about 5 years with anexcellent response on full blood count and splenomegaly. In June 2011, she fell from the stairs and sustained minor trauma to the forehead. Six weeks later, the patient had a gradually enlarging and moderately painful lump in the centre of her forehead. A contrast-enhanced CT scan of the head was performed, showing a small fracture in the frontal bone infiltrated and surrounded by a soft tissue mass extending intracranially and invading the skin extracranially (Figures 1 and 2). A metastatic deposit from an occult tumour was suspected. In August 2011, we performed a CT-guided trucut biopsy of the forehead mass. The histology report confirmed extramedullary haematopoiesis according to the patchy expression of myeloid (CD45, CD43, myeloperoxidase) and megakaryocytic markers (CD68, CD42b). We concluded that the trauma caused a small fracture which triggered the bone marrow tissue reaction resulting in production of extramedullary haematopoiesis in the site of the trauma. The patient underwent local radiotherapy resulting in complete resolution of the lesion.

Ultrasound-guided ethanol injection (PEI) is an effective treatment of autonomously functioning thyroid nodules (AFTN) but little is known about the tissue lesions induced by alcohol. We report morphological changes of an AFTN which was removed after successful PEI treatment. At histological evaluation, the adenoma showed multiple areas of coagulative necrosis with eosinophilic ghost follicles, hemorrhages, small vessel thrombosis and a wedge-shaped hemorrhagic infarction. The peripheral adenomatous tissue and the surrounding thyroid parenchyma were free of regressive changes and/or lympho-monocytic inflammatory reactions. Enzyme histochemistry confirmed the hyperfunctioning character of the lesion and showed reduction of succinic dehydrogenase and cytochrome-c-oxydase activity in the viable tissue surrounding the central necrotic areas. By electron microscopy, the hyperfunctioning follicular epithelium showed submicroscopical alterations of the adenomatous cells surrounding the areas of coagulative necrosis. These results suggest that control of hyperthyroidism, after PEI, is due to: a) directly induced, irreversible damage (coagulative necrosis and vascular thrombosis with hemorrhagic infarction) in the central areas of the lesion; b) potentially reversible damage (reduction of intracellular enzyme activity and ultrastructural changes) in the peripheral areas.

Background: Patellar tumors are rare; only a few series have been described in the literature and radiographic diagnosis can be challenging. We reviewed all patellar tumors at one institution and reviewed the literature. Materials and methods: In an evaluation of the database at one institution from 1916 to 2009, 23,000 bone tumors were found. Of these, 41 involved the patella. All had imaging studies and microscopic diagnostic confirmation. All medical records, imaging studies, and pathology were reviewed. Results: There were 15 females and 26 males, ranging from 8 to 68 years old (average 30). There were 30 benign tumors; eight giant cell tumors, eight chondroblastomas, seven osteoid osteomas, two aneurysmal bone cysts, two ganglions, one each of chondroma, exostosis, and hemangioma. There were 11 malignant tumors: five hemangioendotheliomas, three metastases, one lymphoma, one plasmacytoma, and one angiosarcoma. Conclusion: Patellar tumors are rare and usually benign. As the patella is an apophysis, the most frequent lesions are giant cell tumor in the adult and chondroblastoma in children. Osteoid osteomas were frequent in our series and easily diagnosed. Metastases are the most frequent malignant diagnoses in the literature; in our series malignant vascular tumors were more common. These lesions are often easily analyzed on radiographs. CT and MR define better the cortex, soft tissue extension, and fluid levels. This study presents the imaging patterns of the more common patellar tumors in order to help the radiologist when confronted with a lesion in this location. © 2011 Elsevier Ireland Ltd. All rights reserved.

Item does not contain fulltext BACKGROUND: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS: In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. RESULTS: At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. CONCLUSIONS: Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Cushing's syndrome may remain unrecognized among patients referred for metabolic syndrome; thus, a proactive screening has been suggested in certain patient populations with features of the disorder. However, conflicting data have been reported on the prevalence of Cushing's syndrome in patients with type 2 diabetes.Our aim was to evaluate the prevalence of unsuspected Cushing's syndrome among outpatients with type 2 diabetes.This was a cross-sectional prospective study in 24 diabetes clinics across Italy.Between June 2006 and April 2008, 813 patients with known type 2 diabetes without clinically overt hypercortisolism were evaluated. Follow-up of the study was closed in September 2010. Patients were not selected for characteristics conferring a higher pretest probability of hypercortisolism. Patients underwent a first screening step with the 1-mg overnight dexamethasone suppression test.Forty patients failed to suppress serum cortisol less than 5.0 μg/dl (138 nmol/liter) and underwent a standard 2-d, 2-mg dexamethasone suppression test, after which six patients (0.6% of the overall series) failed to suppress cortisol less than 1.8 μg/dl (50 nmol/liter), receiving a definitive diagnosis of Cushing's syndrome that was adrenal dependent in five patients. Four patients were cured, being able to discontinue, or reduce, the glucose-lowering agents.The present data do not support widespread screening of patients with type 2 diabetes for Cushing's syndrome; however, the disorder is less rare than previously thought when considering epidemiology of type 2 diabetes. Our results support a case-finding approach in patients with uncontrolled diabetes and hypertension despite appropriate treatment.

International audience; Transformation to acute myeloid leukemia (AML) is a known complication of myeloproliferative neoplasia (MPN). Recent studies reported the high incidence (53%) of JAK2 negative blasts from transformed JAK2V617F-MPN. We collected, by cell sorting, blast cells and mature cells (GRA) from total bone marrow (BM) of 34 patients newly diagnosed of secondary AML. At MPN diagnosis (PMF n = 18; PV n = 9; ET n = 7), JAK2 was mutated in 22 of 34 patients. Twenty of 22 JAK2V617F-MPN (91%) maintained the mutation in blasts and GRA after leukemic switch, while in 2 of 22 patients the selected compartments lost the mutation. Surprisingly we also found the first case of JAK2V617F-AML from a wild type (WT)-MPN. In contrast to the previous study, we conclude that JAK2V617F-MPN yields rarely (9%) a JAK2WT-AML and any JAK2-status modification/persistence involves always the entire BM during leukemic transformation.

The involvement of the small bowel in systemic forms of amyloidosis may be diffuse or very rarely focal.? Some cases of focal amyloidomas of the duodenum and jejunum without extraintestinal manifestations have been reported. The focal amyloidomas consisted of extensive amyloid infiltration of the entire intestinal wall thickness. Radiological barium studies, ultrasound and computed tomography (CT) patterns of diffuse small bowel amyloidosis have been described: the signs are non-specific and may include small-bowel dilatation, symmetric bowel wall thickening, mesenteric infiltration, and mesenteric adenopathy. No data are available about the positron emission tomography (PET)/CT and magnetic resonance imaging (MRI) patterns of intestinal amyloidosis. We report two cases of small bowel amyloidosis: the former characterized by focal deposition of amyloid proteins exclusively within blood vessel walls of the terminal ileum, the latter characterized by diffuse intestinal involvement observed on MRI and PET/CT studies.

High performance liquid chromatography (HPLC) with electrochemical detection proves to be a reliable method for determination of plasma catecholamines (CA) to assess the possible role of the sympathetic nervous system (SNS) in essential hypertension (EH). The present investigation in a group of 15 normotensive (N) and 13 stable EH patients, homogeneous for age and duration of hypertension, was carried out without treatment in the supine position, up-right position and during a personalized bicycle exercise. Mean blood pressure, mean heart rate, plasma renin activity and plasma aldosterone were also evaluated at the various exertion phases. Norepinephrine (NE) and epinephrine (E) showed a progressive increase in N and in EH patients, reaching the highest values at maximum effort. However, EH patients showed higher E plasma levels than N before maximum effort. Dopamine (DA) reached the highest values in N at maximum effort and in EH patients at recovery time. These findings allow us to foresee the possibility of a better characterization of the SNS role in EH.

Background Left ventricular hypertrophy (LVH) is an independent and powerful risk factor for cardiovascular events and death. Serum uric acid (SUA) may induce LVH, on one hand, through an inflammatory effect which promotes cardiac hypertrophy and, on the other, through an activation of the renin-angiotensin-aldosterone system which generates hypertrophy and hyperplasia of myocytes and fibrosis of the heart Objectives Aim of the study was to investigate the correlation between SUA levels and left ventricular mass in a group of hypertensive patients Methods We evaluated 51 patients (mean age 74±10 years; range 49-87, F 37.7%; M 62.3%) with essential hypertension. Each patient underwent a standardized medical history and clinical examination, laboratory tests and echocardiographic assessment with the determination of left ventricular mass index (LVMI) Results Mean value of SUA was 6.68±2 mg/dl. Mean blood pressure (MAP) was 95±12 mmHg. A positive significant correlation between SUA and LVMI (P=0.029) was observed. After adjusting for MAP and age in standard multiple linear regression analysis, SUA level remains independently associated with LVMI suggesting that increased urate levels are associated with a higher myocardial mass. Conclusions Our results demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH could be a powerful predictor of cardiovascular events References Yoshio Iwashima, Takeshi Horio, Kei Kamide, Hiromi Rakugi, Toshio Ogihara and Yuhei Uric Acid, Left Ventricular Mass Index, and Risk of Cardiovascular Disease in Essential Hypertension. Hypertension 2006;47:195-202; Ayako Yoshimura, Hisashi Adachi, Yuji Hirai, Mika Enomoto, Ako Fukami, Eita Kumagai, Kyoko Ohbu, Sachiko Nakamura, Aya Obuchi, Yume Nohara, Tsutomu Imaizumi. Serum Uric Acid Is Associated With the Left Ventricular Mass Index in Males of a General Population. Int Heart J, January 2014 Cristiana Catena, GianLuca Colussi, Frine Capobianco, Gabriele Brosolo and Leonardo A. Sechi. Uricaemia and left ventricular mass in hypertensive patients. Eur J Clin Invest 2014;44(10):972-981 Disclosure of Interest None declared

Background: Polycythemia vera (PV) is characterized by erythrocytosis, thrombocytosis, and/or leukocytosis and a broad range of disease-related symptoms. In high-risk patients, the most common first-line treatment is hydroxyurea (HU). The open-label RESPONSE trial demonstrated that ruxolitinib (RUX), a JAK1/JAK2 inhibitor, provided superior efficacy compared with best available therapy in patients with PV who were resistant to or intolerant of HU according to modified European LeukemiaNet (ELN) criteria. This study (RELIEF) was conducted in patients receiving a stable dose of HU and who were generally well controlled but reporting disease-associated symptoms, comparing the change in PV-related symptom burden in patients continuing their HU therapy with those switching to RUX treatment. Methods: RELIEF was a randomized, multicenter, double-blind, double-dummy, phase 3b study of patients with PV aged ≥18 years on a stable dose of HU monotherapy and reporting PV-related symptoms. Patients were required to be receiving HU for ≥12 weeks prior to enrollment and on the same dose level for the last 4 weeks, and have a score ≥8 on the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) cytokine total symptom score (TSS-C). The TSS-C comprised symptoms of itching, tiredness, muscle ache, night sweats, and sweats while awake; each symptom was rated on a scale of 0=absent to 10=worst imaginable, with a maximum TSS-C score of 50. Patients also had to meet one of the following: ≤1 phlebotomy in the previous 6 months or no palpable splenomegaly. Those eligible were randomized 1:1 to receive RUX 10 mg BID and HU-placebo, or HU at the same dose/schedule and RUX-placebo. Dose adjustments were permitted for safety and efficacy. After Week 16, patients could receive open-label RUX until Week 48. The primary endpoint was the proportion of patients with a ≥50% reduction in TSS-C at Week 16; secondary endpoints included proportion of patients with a ≥50% reduction in individual TSS-C symptoms and safety. Results: Overall, 54 and 56 patients were randomized to RUX and HU, respectively; 87.0% and 89.3% remained on treatment through Week 16. At baseline, the median age (range) was 64 (36-87) in the RUX group and 66 (19-85) in the HU group; 44% and 61% were men. The majority of patients in the RUX and HU groups did not have baseline platelet counts or WBC above ELN thresholds: platelets >400 and ≤600 x 109/L (RUX 31.5%, HU 28.6%), >600 x 109/L (3.7%, 8.9%); WBC >10 and ≤15 x 109/L (16.7%, 16.1%), >15 x 109/L (11.1%, 14.3%). In the RUX and HU groups, the mean TSS-C at screening (22.4, 23.1) was higher than that at baseline (16.7, 18.0); the ratio of screening to baseline TSS-C was 1.7 and 1.6. The proportion of patients achieving a ≥50% reduction from baseline in TSS-C at Week 16 (primary endpoint) was 43.4% in the RUX group and 29.6% in the HU group (P=0.139; OR, 1.82; 95% CI, 0.82-4.04). The proportions of patients in the RUX vs HU groups achieving a ≥50% reduction in scores for itching and tiredness at Week 16 were 40.0% vs 26.4% and 54.2% vs 32.0%, respectively. Median percentage changes in individual TSS-C symptoms are shown in Table 1. Additional analyses found no correlation between individual changes in HU dose from baseline to Weeks 13-16 and percentage change in TSS-C in the HU arm (r2=0.030). Even patients maintaining the same HU dose from prior to study entry through Week 16 reported symptom improvement: 12/35 (34.3%) with no dose change, 4/12 (33.3%) with a dose increase, and 0/9 (0%) with a dose decrease had a ≥50% reduction in TSS-C. The most common nonhematologic adverse events in the RUX arm on randomized treatment were fatigue (20.4% RUX vs 10.7% HU), headache (16.7% vs 5.4%), and dizziness (13.0% vs 8.9%). The most common adverse events on HU were diarrhea (9.3% RUX vs 19.6% HU) and constipation (7.4% vs 12.5%); most events were grade 1 or 2. Grade 3 or 4 anemia or thrombocytopenia (lab values) were not reported in the RUX group; two patients in the RUX group had grade 3 or 4 neutropenia. Conclusion: In generally well controlled PV patients receiving a stable dose of HU, there was a positive trend in symptom improvement for patients switched to RUX therapy versus those continuing on HU therapy, although this was not statistically significant. The 34% response rate among patients who continued to receive a stable HU dose suggests a placebo effect that led to an underpowered study. Further analyses are required to better interpret these findings. Disclosures Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Vannucchi:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Yacoub:Alexion Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Membership on an entity's Board of Directors or advisory committees. Koschmieder:Novartis Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Byrne:Novartis Pharmaceuticals: Honoraria. Verstovsek:Incyte Corporation: Research Funding. Hunter:Incyte Corporation: Employment, Equity Ownership. Jones:Incyte Corporation: Employment, Equity Ownership. He:Incyte Corporation: Employment, Equity Ownership. Morozov:Novartis Pharmaceuticals: Employment, Equity Ownership.

Our retrospective experience underscores the ability of Doppler echocardiography to detect the cardiotoxicity of chemotherapy (functional and pericardial abnormalities, heart involvement) and points out the need for an accurate echocardiographic follow-up of hematologic patients.

To establish the role of percutaneous ethanol injection (PEI) treatment in benign thyroid lesions by evaluating: (1) the long-term efficacy and side effects of the treatment, (2) the factors predictive of efficacy of PEI, and (3) the cost effectiveness of the procedure.Fifty-eight recurrent cystic nodules, 95 autonomously functioning nodules (AFTN), and 17 hyperfunctioning nodules causing thyrotoxicosis (toxic nodules) were treated by PEI from 1990 to 1996 in our center. Ultrasound (US) and color flow doppler (CFD) examinations were carried out before and after each treatment. In patients with AFTN, serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb) levels were tested before and after PEI. All patients were independently reexamined by two external reviewers after a minimum follow-up of 5 years (median, 6.9 years).The median number of treatments was 2.0 (range, 1.0-4.0) for cystic nodules, 4 (range, 2.0-6.0) for AFTN, and 5 (range, 3.0-7.0) for toxic nodules. At the 5-year evaluation cystic nodules showed a volume reduction greater than 75% versus baseline in 86.2% of cases and an improvement of local symptoms in 91.4% of cases. AFTN presented serum TSH within normal limits in 60.0% of patients. Toxic nodules showed a detectable serum TSH and normal FT3 and FT4 values in 35.3% of cases. Two cases of transient dysphonia were observed. In cystic lesions no significant correlation was found between the baseline and the final volume (r2 = 0.17) and no significant predictor of treatment efficacy was found. However, unilocularity was associated with a lower number of treatments than multilocularity (median, 2.0 vs. 3.0). Independent predictors of clinical efficacy in both AFTN and toxic nodules were a baseline volume less than 5.0 mL and a fluid component greater than 30% (odds ratio [OR] = 6.1 and 3.3, respectively).Most recurrent cystic lesions of the thyroid can be cured by PEI, which should become the first line of treatment. The majority of AFTN and toxic nodules with volume less than 5.0 mL presented a marked volume decrease and normal serum TSH levels when treated by PEI, which seems a valid alternative to clinical follow-up alone in patients refusing 131I. PEI is not indicated in large or toxic nodules, for which 131I is the treatment of choice.

The Authors describe a cutaneous recurrence of a thyroid follicular cancer, immediately above the thyroid nodule, in a 76-year-old woman with advanced multiple myeloma, 8 mo after a fine-needle axpiration biopsy performed with 22-gauge needles. © 1994 Wiley-Liss, Inc.

The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1) the relative importance of US features as risk factors of malignancy; and 2) a cost-effective management of nonpalpable thyroid nodules. Four hundred ninety-four consecutive patients with nonpalpable thyroid nodules (8-15 mm) were evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology were excluded from the study. All patients with suspicious or malignant cytology underwent surgery, whereas subjects with benign cytology had clinical and US control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). Extracapsular growth (pT(4)) was present in 35.5%, and nodal involvement in 19.4% of neoplastic lesions, with no significant differences between tumors greater or smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87% of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83), intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were independent risk factors of malignancy. FNA performed on hypoechoic nodules with at least one risk factor was able to identify 87% of the cancers at the expence of cytological evaluation of 38.4% of nonpalpable lesions. The majority of nonpalpable thyroid tumors can be identified by cytological evaluation of lesions presenting hypoechoic appearance in conjunction with one independent risk factor. Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis, US-FNA should be performed on all 8-15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions of the thyroid without risk factors should be followed by means of clinical and US evaluation.

Liver metastases from differentiated thyroid tumors are unusual clinical findings, and are only rarely hyperfunctioning. We report a case of thyrotoxicosis caused by a huge and surgically unresectable liver metastasis from follicular thyroid cancer, unresponsive to treatment with large doses of thionamides. To avoid the hazardous side effects of (131)I treatment in a severely thyrotoxic patient, a preliminary debulking of the liver mass was performed by means of percutaneous interstitial laser photocoagulation. Three treatments (total energy delivery: 7200 J) were performed under ultrasound guidance, with no serious complications, during a 2-week period. One month later, serum thyroid hormones had decreased, general condition was improved, and magnetic resonance evaluation revealed large and well-defined areas of necrosis of metastatic tissue. During the following 10 months, the patient underwent 3 radioiodine treatments. Eighteen months after diagnosis, thyroid hormones were within normal levels, liver mass decreased, and the clinical condition markedly improved. The combination of percutaneous interstitial laser photocoagulation treatment and radioiodine therapy made possible the effective management of a hyperfunctioning and surgically untreatable liver metastasis from thyroid follicular carcinoma, avoiding the side effects of (131)I therapy in a thyrotoxic patient and increasing the effectiveness of radioiodine-induced neoplastic tissue ablation.