S.13.1 Safety and efficacy of rituximab in SSc: an analysis from the European Scleroderma Trial and Research Group

Objectives. Objective of this multicentre, observational study was to assess effects and safety of rituximab (RTX) using the European Scleroderma Trial and Research Group (EUSTAR) cohort. Methods. EUSTAR centres were asked to provide specific data about SSc patients treated with RTX. Primary endpoints were predefined for different disease manifestations and compared between baseline and follow-up. Normally distributed data, analysed by paired t-test, are shown as mean (s.d.), and non-parametric data, analysed by Wilcoxon matched paired signed-rank test, are shown as median and interquartile range. Results. Data on 72 SSc patients treated with RTX were captured from 27 EUSTAR centres (51 females/21 males, 52 diffuse/19 limited, age 51 (44-60) years, disease duration 6 (3-10) years, 47 anti-Scl-70 positive). The most frequent RTX application scheme was 1000 mg × 2 within 2 weeks (57/72 patients). Co-treatment with other immunosuppressive drugs was reported in 28 patients. The modified Rodnan skin score (mRSS) significantly decreased vs baseline at 7 (5-9) months follow-up (n = 47, 18.2 + 10.9 vs 14.5 + 9.9, P = 0.0002). This was true for both patients with later disease stages and also for patients with earlier, extended skin fibrosis (dSSc with mRSS >16 at baseline, n = 26; 26.5 + 6.8 vs 20.4 + 8.9, P < 0.0001, reduction by 29.9%). S-HAQ was unchanged, but the European SSc activity score improved after rituximab treatment [n = 10; 3.7 (2.6-6.4) vs 1.7 (0.9-2.5), P = 0.01]. RTX had no effects on lung fibrosis (FVC, DLCO, TLC, HRCT score) in n = 11 patients with evidence for SSc-ILD. In SSc-polyarthritis patients, the DAS-28 declined at 6 months follow-up without reaching statistical significance [n = 8; 4.8 (2.5-7.5) vs 3.7 (2.6-6.6); p = 0.3]. Of 8, 5patients were RF and/or anti-CCP antibody positive. Similar results were obtained for secondary outcome measures (tender and swollen joint count, VAS, CRP, ESR). Additional positive effects of RTX were seen on SSc-related myopathy (CK levels, 273 + 177 vs 184 + 139; n = 12, P = 0.03) and on digital ulcers [total number per patient 1 (1-3) vs 0 (0-1); n = 23; P = 0.0086]. During RTX treatment 14 patients had infections, 3 serum sickness, 2 allergic reactions and 1 lung fibrosis aggravation, 29 fatigue and 9 nausea. Four patients died, one possibly related to RTX treatment (pneumonia and cardiac failure 1.5 months after RTX infusion). Conclusion. This large EUSTAR cohort study points at positive effects of RTX in particular on skin fibrosis, and suggests randomized controlled trial in SSc patient

Linee guida per l’elaborazione del modello idrogeologico concettuale

Introduzione. Il presente quaderno tecnico affronta il tema del modello idrogeologico concettuale, ovvero di quel passaggio dalle categorie storicamente qualitative, naturalistiche della geologia classica, a quelle di un inquadramento stringente, coerente e quantificato dell’idrogeologia applicata e dei suoi corollari numerici. Vengono di seguito descritti metodi, strumenti e concetti per una corretta elaborazione del modello concettuale, ovvero come conglobare l’informazione meteo-climatica, idrochimica, geochimica, agronomica, litologica, petro- chimica ed idrologica in uno schema coerente che consenta la sintesi olistica della dinamica delle acque sotterranee e di quanto esse veicolano, in un quadro comprensibile anche ad altre categorie tecnico-professionali. Un modello concettuale, correttamente concepito, agevola la comprensione dei fenomeni accaduti e la previsione di cosa potrà succedere anche, ma non solo, in conseguenza di azioni antropiche in atto o in programmazione. Si è quindi affrontato anche il tema delle normative che trattano la materia in riferimento alla programmazione ter- ritoriale, alla progettazione di manufatti ed opere ed alla tutela ed al risanamento dell’ambiente. Il modello concettuale è base imprescindibile per ogni successiva valutazione quantitativa. In assenza di un modello verificato e robusto, non solo il passaggio all’implementazione di un modello numerico è velleitario, ma anche i semplici calcoli deterministico-analitici, più ampiamente diffusi ed applicati, rischiano di perdere ogni significato pratico. Ovviamente il quaderno non ha alcuna pretesa di esaustività né di formulare codici, ma cerca semplicemente di for- nire ai colleghi una traccia utile, ancorché insufficiente se non corredata dagli approfondimenti che ciascuno di noi è sempre tenuto a fare, per soddisfare in scienza e coscienza le esigenze dei committenti. Il paragrafo bibliografia e l’annesso glossario servono proprio a questo

[Ultrasound lung comets: new echographic sign of lung interstitial fibrosis in systemic sclerosis].

Objective: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are common complications of systemic sclerosis (SSc). Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC), i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILaD and PAH by integrated cardiac and chest ultrasound in SSc. Methods: We enrolled 30 consecutive SSc patients (age= 54±13 years, 23 females) in the Rheumatology Clinic of Pisa University. In all, we assessed systolic pulmonary arterial pressure (SPAP), from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space). All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70), and antiicentromere associated with development of pulmonary involvement. Twenty-eight patients also underwent high resolution computed tomography, HRCT (from 0= no fibrosis to 3= honey combing). Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence Scl-70 antibodies. ULC number was similar in localized or diffuse forms (16±20 vs 21±19, p=ns) and was unrelated to SPAP (r=0.216, p=ns). Conclusions: Chest sonography assessment and ULC allow a complete, simple, radiation-free characterization of interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies

Linee guida di idrogeologia: approccio ai progetti

Da Cap. Introduzione: Lavorare in idrogeologia significa studiare il moto delle acque sotterranee, la geometria degli acquiferi, la dinamica dell’interazione fra acque sotterranee di differenti acquiferi e fra queste e le acque superficiali; non solo, significa anche comprendere come e perché opere antropiche, sia intenzionalmente che involontariamente, interagiscono con la risorsa acqua e conoscere metodologie e tecniche per progettare in modo ecosostenibile e nel rispetto della risorsa stessa. Nessun progetto di opera che interagisce, intenzionalmente o meno, poco o tanto, con le acque sotterranee può prescindere da un adeguato studio idrogeologico. I capitoli che seguono non pretendono il titolo di manuale, né aspirano a quello di “Bignami” di idrogeologia; le stesse parole “linee guida” presenti nel titolo, lungi dal presumere ogni valore normatorio, hanno solo carattere esplicativo, non una regola, ma piuttosto una traccia, anche perché la “dinamicità” con cui i quadri normativi comunitari, nazionali, regionali e locali si sono recentemente evoluti non permette di confrontarsi con un ambito di leggi e consuetudini collaudato e consolidato. Scopo esclusivo del documento è quello di fornire una guida ai colleghi, liberi professionisti o funzionari che siano, alle prese con la preparazione di studi, relazioni, istruttorie, controlli in materia di risorsa idrica. La prima parte dell’elaborato sintetizza i metodi e gli strumenti dell’idrogeologia (dal rilievo geologico alla geofisica, alla geochimica, ai metodi modellistici), puntualizzando i contenuti indispensabili e opzionali della relazione idrogeologica e della carta idrogeologica; la seconda parte tratta, più specificamente, di normativa e supporto idrogeologico per alcuni selezionati campi di attività (siti inquinati e discariche, viabilità ed infrastrutture lineari, ricerca idrica, pianificazione, attività estrattive). Il documento, privo di qualsiasi pretesa di esaustività sulle problematiche trattate, ha mirato comunque, approfittando della ricchezza di punti di vista derivante dalla vasta gamma di ruoli svolti nella professione dai colleghi della commissione, ad armonizzare le posizioni in un documento tecnico, forse dissonante nello stile, ma univoco negli scopi. Il capitolo 9 “Viabilità ed infrastrutture lineari” tratta del supporto idrogeologico per viabilità, in galleria o meno, di una certa rilevanza regionale; gli stessi approfondimenti, ovviamente tarati sull’importanza dell’opera, sono validi anche per le viabilità Provinciali e Comunali e per le minori. Un accenno a parte per il capitolo 10 “Ricerca idrica ed opere di approvvigionamento idrico” dove è stato ripreso in toto il documento della Commissione Pozzi del 2005, aggiornandolo ed aggiungendo un capitolo relativo alle sorgenti ed un capitolo su problematiche ambientali in cui fra l’altro si è affrontato il critico argomento, purtroppo in Italia ad oggi sottostimato (garbatissimo eufemismo), della definizione, mantenimento e ripristino della separazione fra falde idriche naturalmente distinte. Per quanto concerne le sorgenti, la trattazione tecnico-scientifica è stata privilegiata rispetto a quella burocratico-procedurale, soprattutto perché, nel 90% dei casi, l’iter burocratico per autorizzazioni e concessioni per le sorgenti è identico a quello per i pozzi, alla cui trattazione quindi si rimanda. Riguardo alla Pianificazione (capitolo 11), si è scelto di trattare a grandi linee solo la pianificazione a scala comunale nella Regione Toscana. Il settore pianificazione idrogeologica, che non poteva ovviamente essere omesso in un documento che tratta di idrogeologia, è un settore che in Italia è stato sviluppato, con un certo grado di approfondimento, solo in alcune regioni del nord, regioni che hanno dovuto affrontare gravi emergenze; per il resto, in genere, esso è sempre considerato, quando sia preso in considerazione, come appendice della pianificazione urbanistico-edilizia. La mancanza di norme specifiche in materia rende necessario un approccio di tipo scientifico-tecnico ed una trattazione ben più vasta ed articolata di quella necessaria per semplici linee guida quali sono, o per lo meno vorrebbero essere, quelle che seguono

Five decades of terrestrial and freshwater research at Ny-Ålesund, Svalbard

For more than five decades, research has been conducted at Ny-Ålesund, in Svalbard, Norway, to understand the structure and functioning of High-Arctic ecosystems and the profound impacts on them of environmental change. Terrestrial, freshwater, glacial and marine ecosystems are accessible year-round from Ny-Ålesund, providing unique opportunities for interdisciplinary observational and experimental studies along physical, chemical, hydrological and climatic gradients. Here, we synthesize terrestrial and freshwater research at Ny-Ålesund and review current knowledge of biodiversity patterns, species population dynamics and interactions, ecosystem processes, biogeochemical cycles and anthropogenic impacts. There is now strong evidence of past and ongoing biotic changes caused by climate change, including negative effects on populations of many taxa and impacts of rain-on-snow events across multiple trophic levels. While species-level characteristics and responses are well understood for macro-organisms, major knowledge gaps exist for microbes, invertebrates and ecosystem-level processes. In order to fill current knowledge gaps, we recommend (1) maintaining monitoring efforts, while establishing a long-term ecosystem-based monitoring programme; (2) gaining a mechanistic understanding of environmental change impacts on processes and linkages in food webs; (3) identifying trophic interactions and cascades across ecosystems; and (4) integrating long-term data on microbial, invertebrate and freshwater communities, along with measurements of carbon and nutrient fluxes among soils, atmosphere, freshwaters and the marine environment. The synthesis here shows that the Ny-Ålesund study system has the characteristics needed to fill these gaps in knowledge, thereby enhancing our understanding of High-Arctic ecosystems and their responses to environmental variability and change

Five decades of terrestrial and freshwater research at Ny-Ålesund, Svalbard

For more than five decades, research has been conducted at Ny-Alesund, in Svalbard, Norway, to understand the structure and functioning of High Arctic ecosystems and the profound impacts on them of environmental change. Terrestrial, freshwater, glacial and marine ecosystems are accessible year-round from Ny-Alesund, providing unique opportunities for interdisciplinary observational and experimental studies along physical, chemical, hydrological and climatic gradients. Here, we synthesize terrestrial and freshwater research at Ny-Alesund and review current knowledge of biodiversity patterns, species population dynamics and interactions, ecosystem processes, biogeochemical cycles and anthropogenic impacts. There is now strong evidence of past and ongoing biotic changes caused by climate change, including negative effects on populations of many taxa and impacts of rain-on-snow events across multiple trophic levels. While species-level characteristics and responses are well understood for macro-organisms, major knowledge gaps exist for microbes, invertebrates and ecosystem-level processes. In order to fill current knowledge gaps, we recommend (1) maintaining monitoring efforts, while establishing a longterm ecosystem-based monitoring programme; (2) gaining a mechanistic understanding of environmental change impacts on processes and linkages in food webs; (3) identifying trophic interactions and cascades across ecosystems; and (4) integrating long-term data on microbial, invertebrate and freshwater communities, along with measurements of carbon and nutrient fluxes among soils, atmosphere, freshwaters and the marine environment. The synthesis here shows that the Ny-Alesund study system has the characteristics needed to fill these gaps in knowledge, thereby enhancing our understanding of High-Arctic ecosystems and their responses to environmental variability and change

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies