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Background:Rituximab (RTX), a chimeric human-murine anti-CD20 monoclonal antibody, has been used for treatment of active moderate-severe Graves' orbitopathy (GO) since 2004 as second-line therapy in patients unresponsive to intravenous steroids. We conducted an open-label prospective study (EUDRACT 2012-001980-53) in which patients were treated with a single infusion of only 100 mg RTX to analyze the efficacy and safety of this low dose.Methods:Seventeen patients, of whom nine had disease that was unresponsive to intravenous methylprednisolone and eight with newly diagnosed GO, were enrolled. Disease activity was assessed with the clinical activity score (CAS) and severity with a composite ophthalmic score. Long-term surgical treatment and quality of life were also assessed, as well as treatment-related adverse events.Results:Mean baseline CAS was 4.56 ± 0.96 and decreased to 1.25 ± 1.14 at 24 weeks (p= 0.001). Disease inactivation occurred within 24 weeks in >90% of patients and was unrelated to disease duration. Severity improved in about 60% of patients, with no relapses. All patients showed peripheral depletion of CD20+and CD19+cells at the end of RTX infusion (60 minutes). Two patients required surgical orbital decompression because of optic neuropathy (ON). Among adverse events observed, there was one patient who developed a cytokine release syndrome.Conclusions:A dose of 100 mg RTX is effective in patients with active moderate-severe GO. Low doses are better tolerated, expose patients to immune suppression for a shorter period of time, and are extremely cost effective, compared with higher doses. This dose, consistently with all other immunosuppressants, does not prevent the progression of GO to dysthyroid ON.

Background:The overall changes of ocular motility in Graves' orbitopathy (GO) are not easily quantifiable with the methods currently available, especially in clinical studies. The aim of the present study was to calculate parameters that quantify the changes of ocular motility in GO in relation to the Gorman score for diplopia.Methods:We studied 100 GO patients (Group 1) and 100 controls (Group 2). We also included 30 patients treated with intravenous methylprednisolone (iv-MP), assessed at baseline and after 12 and 24 weeks (Group 3), and 66 patients submitted to squint surgery, assessed at baseline and after 12 weeks (Group 4). Ocular ductions were measured in four gaze directions by a perimeter arc and were used to calculate a total motility score (TMS) as the sum of ductions in each direction; a biocular TMS (b-TMS) as the sum of the TMS of two eyes; and an asymmetry ratio (AR) as the sum of the differences of the corresponding ductions between the two fellow eyes divided by the mean difference found in controls. Quality of life was accessed by a specific questionnaire (Graves' orbitopathy quality of life [GO-QoL] questionnaire).Results:TMS and b-TMS were lower, while AR was higher, in Group 1 compared with controls (p< 0.001). In Group 1, TMS and b-TMS were inversely correlated with the Gorman score (p< 0.001) and AR was higher in patients with constant diplopia compared with the others (p< 0.001). In Group 3, TMS and b-TMS increased after treatment in responders to iv-MP (p< 0.001). In Group 4, TMS and b-TMS improved in all patients after surgery (p< 0.01), while AR and GO-QoL score improved only in those without residual constant diplopia (p< 0.001).Conclusion:We describe a quantitative method to assess eye motility dysfunction in any stage of GO to be used as an outcome measure in clinical studies.

The seismic sequence that in May 2012 struck a large area of the river Po Valley (Emilia-Romagna region, Northern Italy) triggered significant fractures and deformations in a number of riverbanks located close to the earthquake epicenter. Among them, one of the most severely damaged structures turned out to be the banks of an irrigation canal known as Canale Diversivo di Burana, flowing through the small village of Scortichino (Municipality of Bondeno), near the historic town of Ferrara. Large, longitudinally-oriented ground cracks were observed along a 3 km bank stretch, causing in turn severe structural damages to a large part of the approximately one hundred houses and productive activities built on the bank crown. In order to interpret the response of such soil structure during the 2012 earthquake by identifying possible damage causes as well as to suggest relevant remedial measures and seismic risk mitigation actions towards possible future earthquakes, the Emilia-Romagna regional authority launched an in-depth study carried out by a number of research groups from various Italian universities in cooperation with technical experts of the Geological, Seismic and Soil Survey Regional Department. To this purpose, a number of geotechnical investigations were performed (in situ and laboratory tests) and an accurate geotechnical model for the seismic stability analyses was thus defined. Potential liquefaction phenomena of the shallow sandy soils, in the foundation subsoil, were taken into account in the analyses. The paper describes the main features of the extensive study carried out by the working group and summarizes the most significant achievements of the analyses.

La sequenza sismica che ha colpito la pianura padana emiliana nel 2012, con scosse principali il 20 e 29 maggio, ha prodotto diffusi ed estesi dissesti in alcuni rilevati arginali che, in qualche caso, hanno determinato l’inagibilità di edifici e la chiusura di strade. Uno degli argini maggiormente colpiti è quello del canale diversivo in località Scortichino, frazione del Comune di Bondeno, sede di oltre 400 tra unità abitative e produttive, molte delle quali classificate inagibili proprio a causa dei dissesti verificatisi nell’argine. La Regione Emilia-Romagna, su richiesta dell’Amministrazione Comunale, ha costituito un Gruppo di Lavoro in cui l’Associazione Geotecnica Italiana, con diversi gruppi di ricerca già coinvolti nella rete di laboratori ReLuis, ha affiancato i tecnici della Regione con l’obiettivo di analizzare la risposta sismica dell’argine durante la sequenza sismica del 2012, comprendere le cause dei dissesti osservati e suggerire le necessarie azioni di mitigazione ed eventuali interventi di messa in sicurezza nei confronti di terremoti futuri. A questo scopo è stata condotta un’ampia campagna sperimentale di indagini in sito, sia geofisiche che geotecniche, e di prove di laboratorio, finalizzate alla ricostruzione di un accurato modello geotecnico per la valutazione delle condizioni di stabilità dell’argine in condizioni sismiche, portando in conto anche l’eventuale insorgenza di fenomeni di liquefazione nei terreni sabbiosi superficiali costituenti la fondazione del corpo arginale. La presente memoria intende dare conto delle attività del Gruppo di Lavoro e sintetizzare i principali risultati conseguiti.

On May 20, 2012 an earthquake of magnitude ML=5.9 struck the Emilia Romagna Region of Italy and a little portion of Lombardia Region. Successive earthquakes occurred on May 29, 2012 with ML=5.8 and ML=5.3. The earthquakes caused 27 deaths, of which 13 on industrial buildings. The damage was considerable. 12,000 buildings were severely damaged; big damages occurred also to monuments and cultural heritage of Italy, causing the collapse of 147 campaniles. The damage is estimated in about 5-6 billions of euro. To the damage caused to people and buildings, must be summed the indirect damage due to loss of industrial production and to the impossibility to operate for several months. The indirect damage could be bigger than the direct damage caused by the earthquake. The resilience of the damaged cities to the damage to the industrial buildings and the lifelines was good enough, because some industries built a smart campus to start again to operate in less of one month and structural and geotechnical guidelines were edited to start with the recovering the damage industrial buildings. In the paper a damage survey is presented and linked with the ground effects. Among these, soil amplification and liquefaction phenomena are analyzed, basing on the soil properties evaluation by field and laboratory tests. Particular emphasis is devoted to the damaged suffered by the industrial buildings and to the aspects of the remedial work linked with the shallow foundation inadequacy and to the liquefaction mitigation effects.

The Po River is the major Italian watercourse. Over half its length is controlled with embankments as protection measures against heavy floodings. Recently, the Italian Government has funded a project for the evaluation of the seismic stabil-ity of about 90 km of embankments of the Po River. The project mainly aims at the seismic stability analyses of the river banks, with assessment of local site response and evaluation of the liquefaction potential. Hundreds of geotechnical investigations within the study area were performed and the water level variations in the embankment and subsoil were investigated using piezometers. This paper describes the methodology and the main results of the analyses. The safety of 43 significant sections in static and seismic conditions was investigated using limit equilibrium analyses. Dynamic effects in the seismic condition were considered using the pseudostatic method. Local seismic hazard and effects of site conditions on the ground motion are taken into account in the definition of the expected seismic action. Eventually, the analysis results are summarized in a static and seismic stability map of the investigated area, a useful tool for the local Authority in the prevention and mitigation.

OBJECTIVE The differential diagnosis of congenital hypothyroidism (CH) is aimed to distinguish transitory from permanent forms, to optimize L-thyroxine (L-T4) therapy to replacement or TSH-suppressive regimens, and to reach accurate definition of the clinical and biochemical phenotype for subsequent genetic investigations and counselling. Therefore, L-T4 therapy is presently withdrawn in most instances and investigations are performed in a disturbing hypothyroid state. DESIGN The availability of recombinant human TSH (rhTSH) prompted us to assess its efficacy in the differential diagnosis of CH during L-T4 therapy. PATIENTS AND MEASUREMENTS Eight adult patients with permanent CH remained on L-thyroxine and underwent a new protocol for rhTSH (Thyrogen) testing with injections [4 mug/kg/day intramuscularly (i.m.)] at days 1, 2 and 3. At day 3, I-123 was administered and uptake obtained after 2 and 24 h. Serum TSH and thyroglobulin (Tg) levels were measured at days 1-4. Neck ultrasound was carried out in all cases. RESULTS Serum TSH reached levels > 20 mU/I at day 2 and remained above 30 mU/I on days 3 and 4. Stimulation of Tg levels was seen in five patients with peak at day 4. Lingual thyroid was documented at scintigraphy (TS) in three Tg- responsive patients who were previously diagnosed as having thyroid agenesia. In one patient with dyshormonogenesis and high Tg, TS confirmed the presence of goitre with positive perchlorate test. TS was negative in the remaining four cases. All tests indicated complete agenesia in one, whereas a minimal Tg response was marker of nearly complete agenesia in another. The last two TS-negative patients had hypoplastic glands at ultrasound, and refractoriness to TSH stimulation was confirmed by absent Tg response. CONCLUSIONS We report the first application of rhTSH for differential diagnosis of patients with permanent CH, avoiding the undesirable transient hypothyroidism consequent to L-T4 withdrawal. The data obtained led to the change of the diagnosis at presentation in 4/8 patients and to a more accurate description of the clinical picture in all patients. The proposed protocol has been proved to cause Tg increases even in the presence of small amounts of responsive thyroid cells. The rhTSH testing led to the desired disease characterization, thus allowing specific management and targeted genetic analyses

On May 20, 2012 an earthquake of magnitude ML=5.9 struck the Emilia Romagna Region of Italy and a little portion of Lombardia Region. Successive earthquakes occurred on May 29, 2012 with ML=5.8 and ML=5.3. The earthquakes caused 27 deaths, of which 13 on industrial buildings. The damage was considerable. 12,000 buildings were severely damaged; big damages occurred also to monuments and cultural heritage of Italy, causing the collapse of 147 campaniles. The damage is estimated in about 5-6 billions of euro. To the damage caused to people and buildings, must be summed the indirect damage due to loss of industrial production and to the impossibility to operate for several months. The indirect damage could be bigger than the direct damage caused by the earthquake. The resilience of the damaged cities to the damage to the industrial buildings and the lifelines was good enough, because some industries built a smart campus to start again to operate in less of one month and structural and geotechnical guidelines were edited to start with the recovering the damage industrial buildings. In the paper a damage survey is presented and linked with the ground effects. Among these, soil amplification and liquefaction phenomena are analyzed, basing on the soil properties evaluation by field and laboratory tests. Particular emphasis is devoted to the damaged suffered by the industrial buildings and to the aspects of the remedial work linked with the shallow foundation inadequacy and to the liquefaction mitigation effects.

The differential diagnosis of congenital hypothyroidism (CH) is aimed to distinguish transitory from permanent forms, to optimize L-thyroxine (L-T4) therapy to replacement or TSH-suppressive regimens, and to reach accurate definition of the clinical and biochemical phenotype for subsequent genetic investigations and counselling. Therefore, L-T4 therapy is presently withdrawn in most instances and investigations are performed in a disturbing hypothyroid state.The availability of recombinant human TSH (rhTSH) prompted us to assess its efficacy in the differential diagnosis of CH during L-T4 therapy.Eight adult patients with permanent CH remained on L-thyroxine and underwent a new protocol for rhTSH (Thyrogen) testing with injections [4 g/kg/day intramuscularly (i.m.)] at days 1, 2 and 3. At day 3, 123I was administered and uptake obtained after 2 and 24 h. Serum TSH and thyroglobulin (Tg) levels were measured at days 1-4. Neck ultrasound was carried out in all cases.Serum TSH reached levels20 mU/l at day 2 and remained above 30 mU/l on days 3 and 4. Stimulation of Tg levels was seen in five patients with peak at day 4. Lingual thyroid was documented at scintigraphy (TS) in three Tg-responsive patients who were previously diagnosed as having thyroid agenesia. In one patient with dyshormonogenesis and high Tg, TS confirmed the presence of goitre with positive perchlorate test. TS was negative in the remaining four cases. All tests indicated complete agenesia in one, whereas a minimal Tg response was marker of nearly complete agenesia in another. The last two TS-negative patients had hypoplastic glands at ultrasound, and refractoriness to TSH stimulation was confirmed by absent Tg response.We report the first application of rhTSH for differential diagnosis of patients with permanent CH, avoiding the undesirable transient hypothyroidism consequent to L-T4 withdrawal. The data obtained led to the change of the diagnosis at presentation in 4/8 patients and to a more accurate description of the clinical picture in all patients. The proposed protocol has been proved to cause Tg increases even in the presence of small amounts of responsive thyroid cells. The rhTSH testing led to the desired disease characterization, thus allowing specific management and targeted genetic analyses.