94 research outputs found
Kawasaki disease in Sicily: clinical description and markers of disease severity
No full textBackground: Kawasaki disease (KD) is an acute systemic vasculitis of small and middle size arteries; 15-25 % of untreated patients and 5 % of patients treated with intravenous immunoglobulin (IVIG) develop coronary artery lesions (CAL). Many studies tried to find the most effective treatment in the management of resistant KD and to select the risk factors for CAL. Our data are assessed on children from west Sicily, characterized by a genetic heterogeneity. Methods: We studied the clinical data of 70 KD Sicilian children (36 males: 51 %; 34 females: 49 %), analysed retrospectively, including: demographic and laboratory parameters; echocardiographic findings at diagnosis, at 2, 6 and 8 weeks, and at 1 year after the onset of the illness. Results: Forty-seven had Typical KD, three Atypical KD and twenty Incomplete KD. Age at the disease onset ranged from 0.1 to 8.9 years. IVIG were administered 5 ± 2 days after the fever started. Defervescence occurred 39 ± 26 hours after the first IVIG infusion. Fifty-six patients (80 %) received 1 dose of IVIG (responders); 14 patients (20 %) had a resistant KD, with persistent fever after the first IVIG dose (non responders). Ten (14 %) non responders responded to the second dose, 4 (5 %) responded to three doses; one needed treatment with high doses of steroids and Infliximab. Cardiac involvement was documented in twenty-two cases (eighteen with transient dilatation/ectasia, fifteen with aneurysms). Pericardial effusion, documented in eleven, was associated with coronaritis and aneurysms, and was present earlier than coronary involvement in seven. Hypoalbuminemia, D-dimer pre-IVIG, gamma-GT pre-IVIG showed a statistically significant direct correlation with IVIG doses, highlighting the role of these parameters as predictor markers of refractory disease. The persistence of elevated CRP, AST, ALT levels, a persistent hyponatremia and hypoalbuminemia after IVIG therapy, also had a statistical significant correlation with IVIG doses. Non responders showed higher levels of D-dimer and gamma-GT pre-IVIG, persistent high levels of D-dimer, CRP, AST, ALT, hypoalbuminemia and hyponatremia after IVIG. Conclusions: This is the first study on KD in Sicily. We suggest some laboratory parameters as predictive criteria for resistant KD. Patients who show early pericarditis need careful surveillance for coronary lesions
Alterata espressione dei geni coinvolti nel processo di sumoilazione nel carcinoma papillare della tiroide.
No full textLa modificazione post-traslazionale di proteine da parte delle proteine SUMO (small ubiquitin-related modifiers) consiste nella loro coniugazione covalente e reversibile a specifici residui di lisina di proteine bersaglio, con conseguente alterazione della localizzazione subcellulare e dell’attività di queste ultime. La SUMOilazione è implicata in svariati processi biologici tra cui la proliferazione cellulare, l’apoptosi, la riparazione del DNA e la sopravvivenza cellulare. Studi recenti hanno mostrato che la deregolazione del sistema SUMO contribuisce alla trasformazione tumorale modificando l’attività di molteplici oncoproteine e oncosoppressori. Ad oggi, si conosce molto poco riguardo al ruolo della SUMOilazione nel carcinoma papillare della tiroide (PTC). Pertanto, la presente ricerca è stata volta a caratterizzare l’espressione a livello di mRNA di un pannello di geni coinvolti nel processo di SUMOilazione in questo tumore. In particolare, è stata analizzata l’espressione dei geni: a) codificanti per gli enzimi SENP, cistein-proteasi in grado di rimuovere le proteine SUMO dalle proteine bersaglio; b) codificanti per SAE1 e UBA2 che formano un eterodimero attivante le proteine SUMO; c) codificante l’enzima coniugante Ubc9; d) codificanti le E3 ligasi PIAS1-4, RanBP2, NSMCE2, CBX4 e ZMIZ1-2. A tal fine, 20 campioni di tessuto normale e tumorale prelevati da pazienti affetti da PTC sono stati sottoposti a RT-PCR quantitativa, e l’analisi dei dati è stata eseguita con il software Lightcycler Relative Quantification. I risultati ottenuti hanno evidenziato una diminuzione significativa dei livelli di mRNA dei geni SAE1, ZMIZ1, PIAS1, PIAS2 e SENP8. Benché la rilevanza di tali alterazioni nel contesto degli eventi di SUMOilazione debba essere ancora determinata, le nostre osservazioni evidenziano una deregolazione del processo di SUMOilazione nei PTC, che merita ulteriori approfondimenti al fine di accertarne l’eventuale ruolo patogenetico
Kinematics and geologic control of the deep-seated landslide affecting the historic center of Buonalbergo, southern Italy
No full textDeep-seated landslides are important agents of relief shaping and can have substantial impact on human settlements. Many examples are present in the Campania region of southern Italy, where the association of complex lithostratigraphic and structural geologic conditions might have effect on landslide initiation and evolution. On this basis and considering the effect that the deep-seated landslide have had in the last years on the urban settlement, the Buonalbergo landslide was analyzed in terms of decadal kinematics and geological control and insights in prospective evolution were provided. The analysis of data derived by geological and landslide field mapping, settlement damage analysis, Persistent Differential Interferometry SAR data analysis, and Finite Elements stability analysis revealed i) the approximately constant rate movement of the landslide in the last three decades with a consistent enlargement of its area, ii) the presence of a large overturned anticline, characterized by a complex lithostratigraphic arrangement and multiple discontinuity sets, iii) the presence of faults responsible for morphological depression development, iv) a rotational mechanism characterizing the upper sector of the landslide and the ongoing translational sliding of blocks located at its toe and v) the effect of potential pore pressure scenarios on prospective kinematics (i.e. single to multiple stages creep) with the observed constant rate movement potentially related to a pore pressure at the landslide base ranging between 300 and 400 kPa. Result interpretation suggests i) the role of the structural and lithostratigraphic setting of the slope as predisposing factor for landslide development, ii) the potential of fold-related fabric in controlling landslide geometry and fragmentation, iii) the possible occurrence of multiple landslide events affecting the slope affected by the deep-seated landslide and iv) the potential of hydrologic conditions in modulating landslide velocity and evolution toward slope failure. The relevance of results is related to the representativeness of the Buonalbergo landslide as common process in the Apennine context in terms of potential long-term morphologic evolution of the slope and the existence of many landslides that develop in similar geological conditions driving sediment production and inducing persistent topographic changes in mountainsides
PReS-FINAL-2088: Risk of severe adverse events in juvenile idiopathic arthritis and pediatric-onset inflammatory bowel disease, treated with anti-tnf drugs
No full textIntroduction: Severe adverse events have been described in children affected by Juvenile Idiopathic Arthritis (JIA) and Inflammatory Bowel Disease (IBD) treated with anti-tnf drugs.
Objectives: To define the risk of severe adverse events in patients with JIA and IBD treated with anti-tnf drugs.
Methods: This is a retrospective cohort study. All patients with JIA and IBD attending the "IRCCS Burlo Garofolo" of Trieste from 2000 to 2012 were enrolled. They were divided into 2 groups on the basis of the presence or absence of anti-tnf exposure. Severe adverse events were considered the followings: a) infections needing anti-tnf permanent suspension and/or hospitalization; b) autoimmune diseases with present or potential organ damage, except for hepatitis and cholangitis during IBD; c) anaphylaxis; d) malignancies.
Univariate analysis testing the effect of anti-tnf exposure on adverse events appearance was realized.
Results: 323 patients were enrolled (159 with JIA and 164 with IBD). 120 patients were exposed to anti-tnf and 203 were not. Infliximab was the most used anti-tnf (73 patients), followed by etanercept (56 patients) and adalimumab (21 patients). Mean total duration of anti-tnf therapy was 26 months (min.1, max.127). The two cohorts were comparable for sex, age, diagnosis and other therapies assumed.
Severe adverse events occurred in 38 anti-tnf-exposed patients (31.7%) and 22 of the not-exposed group (10.8%), with a statistically significant difference (p = 0.000) and a relative risk (RR) of 2.9 (95% confidence interval, CI, 1.8 to 4.7). Anaphylaxis occured in 11 patients (9.2% of the anti-tnf-treated), all assuming infliximab; in the not-treated group none presented reactions (p = 0.000). Infection rate was 6.7% in the anti-tnf-treated group (8 patients) and 3.5% in the not-exposed group (7 patients) (p = 0.273, RR = 1.9, 95% CI: 0.7 to 5.2). Incidence rate of autoimmune diseases in patients treated with anti-tnf was 18.3% (22 patients) vs 7.9% in not-exposed cohort (p = 0.007, RR = 2.3, 95% CI: 1.3 to 4.2). Uveitis was the most frequent autoimmune disease. Both uveitis and lupus-like syndrome were more likely in the subgroup of patients treated with anti-tnf (p = 0.005, RR = 2.5, 95% CI: 1.1 to 6.0 for uveitis and p = 0.050 for lupus-like syndrome). No patients developed malignancies. The outcome of severe anti-tnf drug reactions was as follows: 2 out of 3 uveitis, all anaphylactic reactions, severe infections and lupus-like syndromes healed without organ damage, whereas the other autoimmune complications have been still treating with a good clinical outcome.
Conclusion: The patients with JIA or IBD treated with anti-tnf have a higher risk of severe adverse events, like anaphylaxis and autoimmune diseases (in particular uveitis and lupus-like syndrome), whereas it seems that this risk does not exist for severe infections. No malignancies were observed during follow up. Our data suggest that, although the risk of severe adverse reactions to anti-tnf therapy is significant, the occurrence of a permanent damage results very low
Targeted Genomic Profiling and Chemotherapy Outcomes in Grade 3 Gastro-Entero-Pancreatic Neuroendocrine Tumors (G3 GEP-NET)
No full textBackground: Grade 3 gastro-entero-pancreatic neuroendocrine tumors (G3 GEP-NET) are poorly characterized in terms of molecular features and response to treatments. Methods: Patients with G3 GEP-NET were included if they received capecitabine and temozolomide (CAPTEM) or oxaliplatin with either 5-fluorouracile (FOLFOX) or capecitabine (XELOX) as first-line treatment (chemotherapy cohort). G3 NET which successfully undergone next-generation sequencing (NGS) were included in the NGS cohort. Results: In total, 49 patients were included in the chemotherapy cohort: 15 received CAPTEM and 34 received FOLFOX/XELOX. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were 42.9%, 9.0 months, and 33.6 months, respectively. Calculating a Ki67 cutoff using ROC curve analysis, tumors with Ki67 ≥ 40% had lower ORR (51.2% vs. 0%; p = 0.007) and shorter PFS (10.6 months vs. 4.4 months; p < 0.001) and OS (49.4 months vs. 10.0 months; p = 0.023). In patients who received FOLFOX/XELOX as a first-line treatment, ORR, PFS, and OS were 38.2%, 7.9 months, and 30.0 months, respectively. In the NGS cohort (N = 13), the most mutated genes were DAXX/ATRX (N = 5, 38%), MEN1 (N = 4, 31%), TP53 (N = 4, 31%), AKT1 (N = 2, 15%), and PIK3CA (N = 1, 8%). Conclusions: FOLFOX/XELOX chemotherapy is active as the first-line treatment of patients with G3 GEP-NET. The mutational landscape of G3 NET is more similar to well-differentiated NETs than NECs
Effects of low-dose aspirin on clinical outcome and disease progression in patients with gastroenteropancreatic neuroendocrine neoplasm
No full textNutritional status and follicular-derived thyroid cancer: An update
No full textThe incidence of differentiated thyroid cancer has been increasing in the last decades all over the world. Such a steady growth cannot be entirely attributable to more intensive thyroid nodule screening and more sensitive diagnostic procedures. Several environmental factors have changed with sufficient rapidity in the same time frame and may represent credible candidates for this increase. They include modified iodine intake, lifestyle-associated risk factors, exposure to various toxic compounds, pollutants and xenobiotics, nutritional deficiencies, eating habits and comorbidities. Foremost, nutritional patterns have gained high interest as possible promoters and modifiable risk factors for thyroid cancer in recent years. The aim of this narrative review is to focus on the relationship between thyroid cancer and nutritional factors, dietary habits and obesity. Low iodine intake has been associated to increased risk of thyroid cancer, favoring the development of more aggressive histotypes. Moreover, correction of iodine deficiency can shift thyroid cancer subtypes toward less aggressive forms, without affecting the overall risk for cancer. Actually, evidence regarding the association between selenium and vitamin D deficiency and thyroid cancer is very limited, despite their well-known anti-cancer potentials, and the clinical usefulness of their supplementation is still uncertain in this setting. Albeit the relationship between single foods and thyroid cancer is difficult to examine, fish and iodine-rich foods, vegetables, and fruits might exert protective effects on thyroid cancer risk. Conversely, no clear association has been found for other foods to date. Lastly, a clear association between obesity and the risk of thyroid cancer, with more aggressive behavior, seems to emerge from most studies, likely involving variations in thyroid function and chronic inflammation mediated by cytokines, insulin, leptin and adiponectins. Although no definite association between dietary factors and thyroid cancer has been firmly established so far, some nutritional patterns, together with excessive weight, seem to play a relevant role in thyroid cancer carcinogenesis as well as in its severity and aggressiveness. These effects may play an additive role to the well-established one exerted by environmental carcinogens, such as pollutants and radiation exposure
The Cretaceous-Paleogene Abortive Rift in the southern Adria domain (southern Apennines, Italy)
No full textThis study provides new data and a reappraisal of the literature concerning the uppermost Cretaceous-Paleogene
stratigraphy, biostratigraphy, tectonics and magmatism in the southern Apennines, with the aim of demonstrating the
occurrence of an Albian to Paleogene abortive rifting stage in the southern Adria domain. This interval marks an important
discontinuity in the tectono-stratigraphic evolution primarily recorded by coeval uplift and drowning of different sectors
of the Apennine and Apulian Platforms, which locally produced a change in the paleoenvironment, from shallow-water
platform to slope and basin facies deposits or the development of thick bauxitic levels. Contemporaneously, in the
surrounding basins a large amount of calciclastic sediments was deposited, testifying for an increased sediment supply
from the emerging sectors of the carbonate platforms. This time interval was also characterized by the occurrence of
anorogenic magmatism and syn-sedimentary extensional faulting that, together with the changed sedimentary facies
distribution, point out for a crustal-scale extensional tectonics. Timing, distance from the actively growing eastern Alps
and, above all, orientation of extensional structures and synchronous anorogenic magmatism poorly fit with a peripheral
bulge stage related with the first pulses of the Alpine collision. We propose an alternative model where such an event is
the result of a rifting episode, characterized by limited anorogenic magmatism, starting in the Albian and reaching its
climax in the uppermost Cretaceous-Eocene times. In the proposed tectonic scenario the extensional tectonics recorded
in several sectors of the Adria domain was synchronous with that affecting the Hyblean (Sicily), Pelagian (Tunisia) and
Sirte Basin Province Rift (Libya) to the south and was part of a single abortive rift system, which extended from the Sirte
Basin up to the southern margin of the Thetyan Ocean to the NW
- …
