17 research outputs found

    Thyroid Imaging Reporting and Data System Score Combined with the New Italian Classification for Thyroid Cytology Improves the Clinical Management of Indeterminate Nodules

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    The new Italian cytological classification (2014) of thyroid nodules replaced the TIR3 category of the old classification (2007) with two subclasses, TIR3A and TIR3B, with the aim of reducing the rate of surgery for benign diseases. Moreover, thyroid imaging reporting and data system (TI-RADS) score appears to ameliorate the stratification of the malignancy risk. We evaluated whether the new Italian classification has improved diagnostic accuracy and whether its association with TI-RADS score could improve malignancy prediction. We retrospectively analyzed 70 nodules from 70 patients classified as TIR3 according to the old Italian classification who underwent surgery for histological diagnosis. Of these, 51 were available for cytological revision according to the new Italian cytological classification. Risk of malignancy was determined for TIR3A and TIR3B, TI-RADS score, and their combination. A different rate of malignancy (p=0.0286) between TIR3A (13.04%) and TIR3B (44.44%) was observed. Also TI-RADS score is significantly (p=0.003) associated with malignancy. By combining cytology and TI-RADS score, patients could be divided into three groups with low (8.3%), intermediate (21.4%), and high (80%) risk of malignancy. In conclusion, the new Italian cytological classification has an improved diagnostic accuracy. Interestingly, the combination of cytology and TI-RADS score offers a better stratification of the malignancy risk

    Trajectories of Kidney Function in Patients with ATTRv Treated with Gene Silencers

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    Hereditary transthyretin amyloidosis (ATTRv; v for “variant”) is the most common form of hereditary amyloidosis, with an autosomal dominant inheritance and a variable penetrance. This disease has a significant variability in clinical presentation and multiorgan involvement. While kidney involvement in early-onset ATTRv has been reported in one-third of patients, in late-onset ATTRv it has generally been considered rare. In the present study, we describe trajectories of kidney function over time before and after treatment with gene silencing therapies in a cohort of 17 ATTRv patients with different mutations, coming from Italy (nine subjects treated with inotersen and eight patients treated with patisiran). The analysis of estimated glomerular filtration rate (eGFR) slopes revealed that the average change in eGFR was 0.01 mL/min/1.73 m2 per month before initiation and −0.23 mL/min/1.73 m2 per month during follow-up for inotersen and −0.62 mL/min/1.73 m2 per month before initiation and −0.20 mL/min/1.73 m2 per month during follow-up for patisiran. In conclusion, we did not observe any significant difference either between the two groups of treatment or within-group before and after therapy, so gene-silencing therapies may be considered safe for renal function in ATTRv and are not associated with a worsening of eGFR slope

    Joint inversion of the 2011 Tohoku (Japan) earthquake from dinsar and GPS data

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    On March 11, 2011 a Mw 9.0 earthquake hit Honsu island in Japan. The so called \u27Tohoku-Oki\u27 giant earthquake occurred near the northeast coast resulting from thrust faulting on or near the subduction zone plate boundary between the Pacific and North America plates. The rupture zone is roughly centered on the earthquake epicenter alongstrike, while peak slips were up-dip of the hypocenter, towards the Japan Trench axis. The rupture was also responsible of a big tsunami that struck a large portion of the coastal area of Tohoku-Oki region. Soon after the earthquake numerous space remote sensing sensors were tasked to acquire as much as possible information about the situation on ground. In particular, a large numbers of SAR images were collected from the ENVISAT and ERS-2 satellite. For this event, a group of researchers from the Istituto Nazionale di Geofisica e Vulcanologia (INGV), named Tohoku-Oki INGV Team, decided to apply a multidisciplinary approach to carry on some analysis addressed to achieve added value outcomes. In this work we present part of the work done by the Team concerning DInSAR data analysis and the methodology to retrieve the seismic source of this extraordinary and disastrous event. © 2012 IEEE

    Renal Involvement in Hereditary Transthyretin Amyloidosis: An Italian Single-Centre Experience

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    Objective: Hereditary transthyretin amyloidosis (ATTRv) represents a diagnostic challenge considering the great variability of clinical presentation and multiorgan involvement. In the present study, we report the prevalence of kidney involvement and kidney function over time in a cohort of ATTRv patients with different transthyretin gene mutations. Patients and Methods: For this study, we systematically collected data from all patients with a diagnosis of ATTRv followed at the Neurology Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS. Kidney involvement was defined as presence of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 obtained with CKD-EPI equation, abnormal urinary protein excretion (UPE) (>150 mg/24 h) and/or albuminuria > 30 mg/24 h (or mg/g creatinine). The analysis included data from 46 patients with 122 measurements of serum creatinine. Results: Among the 46 patients included in the analysis, kidney involvement was present in 37%, with 15% showing reduced eGFR and 22% abnormal UPE (63% of patients with available UPE data). No single predictor was associated with either eGFR values or its slope over time. Conclusions: Kidney involvement is quite common in patients with ATTRv regardless of the underlying genetic variant. In particular, abnormal UPE appears to be a common feature of the disease

    A Metabolic Signature of Hereditary Transthyretin Amyloidosis: A Pilot Study

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    Hereditary transthyretin amyloidosis is the most common form of hereditary amyloidosis, with an autosomal dominant inheritance and a variable penetrance. ATTRv amyloidosis can present as a progressive, axonal sensory autonomic and motor neuropathy or as an infiltrative cardiomyopathy. The definition of biomarkers for the early diagnosis of ATTRv is particularly important in the current era of emerging treatments. In this sense, metabolomics could be an instrument able to provide metabolic profiles with their related metabolic pathways, and we would propose them as possible fluid biomarkers. The aim of this study is to identify altered metabolites (free fatty acids and amino acids) in subjects with a confirmed pathogenic TTR variant. Out of the studied total free fatty acids and amino acids, the serum values of palmitic acid are significantly lower in the ATTRv patients compared to the recruited healthy subjects. The metabolic remodeling identified in this neurogenetic disorder could be the manifestation of pathophysiological processes of the disease, such as mitochondrial dysfunction and neuroinflammation, and contribute to explaining some of its clinical manifestations

    Nerve Conduction Studies of Dorsal Sural Nerve: Normative Data and Its Potential Application in ATTRv Pre-Symptomatic Subjects

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    The objective of the study is to provide age-related normative values for dorsal sural nerve (DSN) and to analyse its application during follow-up of hereditary transthyretin amyloidosis (ATTRv) pre-symptomatic subjects. We consecutively recruited ATTRv pre-symptomatic carriers in which clinical examination, cardiological evaluation, and nerve conduction studies of the sural nerve and DSN were performed. To provide normative data of DSN, neurophysiologic parameters from healthy controls referred to our service were entered into linear regression analyses to check the relative influence of age and height. A correction grid was then derived. We collected 231 healthy subjects: the mean DSN sensory nerve action potential (SNAP) amplitude was 9.99 ± 5.48 μV; the mean conduction velocity was 49.01 ± 5.31 m/s. Significant correlations were found between age and height with DSN SNAP amplitude. Fifteen ATTRv pre-symptomatic carriers were examined. Sural nerve NCS were normal in 12/15 and revealed low/borderline values in three subjects. Considering our correction grid, we found an abnormal DNS amplitude in 9/15 subjects and low/borderline values in 2/15. In ATTRv, early detection of peripheral nerve damage is crucial to start a disease-modifying treatment. DSN may be easily and reliably included in the routine neurophysiological follow-up of ATTRv pre-symptomatic subjects

    Serum Inflammatory Profile in Hereditary Transthyretin Amyloidosis: Mechanisms and Possible Therapeutic Implications

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    Hereditary transthyretin (ATTRv) amyloidosis is a severe, progressive, and heterogeneous multisystemic condition due to mutations in the TTR gene. Although multiple aspects of its molecular pathophysiological mechanisms have been elucidated over the years, it is possible to hypothesize different pathogenetic pathways. Indeed, we extensively investigated the serum levels of several molecules involved in the immune response, in a cohort of ATTRv patients and healthy controls (HCs). Sixteen ATTRv patients and twenty-five HCs were included in the study. IFN-alpha levels were higher in ATTRv patients than in HCs, as well as IFN-gamma levels. By contrast, IL-7 levels were lower in ATTRv patients than in HCs. No significant difference between groups was found regarding IL-1Ra, IL-6, IL-2, IL-4, and IL-33 levels. Correlation analysis did not reveal any significant correlation between IFN-α, IFN-γ, IL-7, and demographic and clinical data. Larger and longitudinal studies using ultrasensitive methods to perform a full cytokine profiling are needed to better elucidate the role of inflammation in ATTRv pathogenesis and to test the reliability of these molecules as possible biomarkers in monitoring patients’ progression

    A compound score to screen patients with hereditary transthyretin amyloidosis

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    Hereditary transthyretin amyloidosis (ATTRv) is a rare, debilitating and fatal disease, mostly characterized by progressive axonal peripheral neuropathy. Diagnosis is still challenging and diagnostic delay in non-endemic area is about 3-4 years. The aim of this study was to arrange a clinical and electrophysiological score to select patients with axonal neuropathy that deserve screening for TTR mutation

    Gastrointestinal Manifestations in Hereditary Transthyretin Amyloidosis: a Single-Centre Experience

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    Background and Aims: Hereditary transthyretin (ATTRv) amyloidosis represents a diagnostic challenge considering the great variability in clinical presentation and multiorgan involvement. In this study we report the prevalence of gastrointestinal (GI) involvement of patients with hereditary ATTRv amyloidosis from one single center of Italy, a non-endemic area. Methods: We retrospectively analyzed a cohort of 39 patients with hereditary ATTRv amyloidosis followed at the Neurology Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, Italy. All patients had a documented mutation in the gene encoding the thansthyretin. Neurological, cardiological and gastrointestinal manifestations were systematically collected at every monitoring visit. Results: 82% reported at least one GI symptom. Unintentional weight loss was the most frequently reported. Lower GI symptoms were more frequent than upper GI symptoms (66.7% vs. 35.9%, p=0.0122). The first GI symptom was always reported within 5 years since disease onset. Gastrointestinal symptoms were almost always present in patients with Val30Met mutation (93.8%, 15/16), and in more than half of the cases with Phe64Leu mutation (66.7%, 8/12). All cases with a non-Val30Met mutation disclosed almost all GI symptoms within 5 years since disease onset; conversely, patients with Val30Met mutation continued to develop further GI manifestations during the disease course. Conclusions: Prevalence of GI symptoms in our cohort was 82%, resulting in a higher prevalence than reported in the THAOS registry. Gastroenterologists, therefore, play an important role for the management of the disease, and their expertise should be valued for an effective multidisciplinary approach to this condition
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