Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: case report and review of the literature

Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence

Weak proactive cognitive/motor brain control accounts for poor children's behavioral performance in speeded discrimination tasks

Background: Motor and inhibitory control rely on frontal cortex activity, which is known to reach full maturation only in late adolescence. The development of inhibitory control has been studied using event-related potentials (ERP), focusing on reactive processing (i.e. the N2 and the P3 components). Scarce information exists concerning pre-stimulus activity as that represented by the Bereinshafstpotential (BP) and by the prefrontal negativity (pN). Further, no literature exists concerning the post-stimulus components originating within the anterior insula (pN1, pP1, pP2). This study aims at associating children performance with these motor-cognitive processing in frontal brain areas. Methods: High-resolution EEG recordings were employed to measure ERPs from 18 children (12 years old) and 18 adults (28 years old) during a visuo-motor discriminative response task. Response time (RT), commission (CE) and omission errors, and RT variability were compared between groups. At brain level, two pre-stimulus (BP and pN) and seven post-stimulus (P1; pN1; N1; pP1; N2; pP2; P3) ERP components were compared between groups. Results: Children showed slower and more variable RTs and poorer inhibition (higher CEs) than adults. At electrophysiological level, children presented smaller BP and pN. After stimulus onset, children showed lower amplitude of N1, pP1, P3, and pP2 components. The P1, pP1, N2 and P3 were delayed compared to adults. Conclusions: Our results demonstrate that children are characterized by less intense task-related proactive activities in frontal cortex, which may account for subsequent poor and delayed reactive processing and, thus, for inaccurate and slow performance

hedgehog pathway influence in the immune escape of tumor cells through pdl 1 modulation

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An Interplay between a Face-Centred Composite Experimental Design and Solid-Phase Microextraction for Wine Aroma GC/MS Analysis

For oenological products, most of the intrinsic and extrinsic drivers of perceived quality are associated with specific aromatic profiles. Aromatic diversity has been recognized as a central element in perceived quality as it is able to transmit the complex interactions between grape variety, geographical characteristics, and viticultural and winemaking practices, including the fermentative process. A comprehensive characterization of flavour compounds by headspace solid-phase microextraction (HS-SPME) and gas chromatography coupled to mass spectrometric analysis is often needed in order to ascertain the quality of wine. HS-SPME requires a proper optimization that can be achieved through an adequate experimental design. Here, a HS-SPME/GC-MS based method was developed to investigate the volatile compounds of wine samples obtained by laboratory-scale fermentations. This was performed by inoculating a commercial Saccharomyces cerevisiae strain, which is used both as single starter and as mixed starter, with an indigenous Hanseniaspora osmophila strain. The experimental conditions of HS-SPME (extraction temperature and time) were optimized by applying a face-centred composite experimental design. Up to 95% of the total variance was explained by the proposed model. The optimized method allowed us to confirm the usefulness of combining the inoculation of grapes with selected yeast strains in co-culture situations in order to improve the wine bouquet

Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in mono-therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis

BACKGROUND: Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first-line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms. OBJECTIVE: We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 microg given once daily, administered in mono-therapy or combined therapy with a H1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season. METHODS: One hundred patients aged 12-50 years (mean+/-SD 31.8+/-9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 microg once daily (n=20) or with FPANS 200 microg once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 microg once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage. RESULTS: All treatments showed significant differences (P<0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P<0.001) and nasal congestion daily (P<0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P<0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P<0.001) and for nasal congestion on daily (P<0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P<0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P<0.001) compared with PLA. Besides, there were significant differences (P<0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK. CONCLUSION: The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis

Intraventricular flow patterns during right ventricular apical pacing

Objectives To assess differences in blood flow momentum (BFM) and kinetic energy (KE) dissipation in a model of cardiac dyssynchrony induced by electrical right ventricular apical (RVA) stimulation compared with spontaneous sinus rhythm. Methods We cross-sectionally enrolled 12 consecutive patients (mean age 74\ub18 years, 60% male, mean left ventricular ejection fraction 58%\ub16 %), within 48 hours from pacemaker (PMK) implantation. Inclusion criteria were: age>18 years, no PMK-dependency, sinus rhythm with a spontaneous narrow QRS at the ECG, preserved ejection fraction (>50%) and a low percentage of PMKstimulation (<20%). All the participants underwent a complete echocardiographic evaluation, including left ventricular strain analysis and particle image velocimetry. Results Compared with sinus rhythm, BFM shifted from 27\ub13.3 to 34\ub17.6\ub0 (p=0.016), while RVA-pacing was characterised by a 35% of increment in KE dissipation, during diastole (p=0.043) and 32% during systole (p=0.016). In the same conditions, left ventricle global longitudinal strain (LV GLS) significantly decreased from 17\ub13.3 to 11%\ub12.8% (p=0.004) during RVA-stimulation. At the multivariable analysis, BFM and diastolic KE dissipation were significantly associated with LV GLS deterioration (Beta Coeff.=0.54, 95% CI 0.07 to 1.00, p=0.034 and Beta Coeff.=0.29, 95% CI 0.02 to 0.57, p=0.049, respectively). Conclusions In RVA-stimulation, BFM impairment and KE dissipation were found to be significantly associated with LV GLS deterioration, when controlling for potential confounders. Such changes may favour the onset of cardiac remodelling and sustain heart failure

Bariatric surgery and diabetes remission: Sleeve gastrectomy or mini-gastric bypass?

AIM: To investigate the weight loss and glycemic control status [blood glucose, hemoglobin A1c (HbA1c) and hypoglycaemic treatment]. METHODS: The primary risk factor for type 2 diabetes is obesity, and 90% of all patients with type 2 diabetes are overweight or obese. Although a remarkable effect of bariatric surgery is the profound and durable resolution of type 2 diabetes clinical manifestations, little is known about the difference among various weight loss surgical procedures on diabetes remission. Data from patients referred during a 3-year period (from January 2009 to December 2011) to the University of Naples "Federico II" diagnosed with obesity and diabetes were retrieved from a prospective database. The patients were split into two groups according to the surgical intervention performed [sleeve gastrectomy (SG) and mini-gastric bypass (MGB)]. Weight loss and glycemic control status (blood glucose, HbA1c and hypoglycaemic treatment) were evaluated. RESULTS: A total of 53 subjects who underwent sleeve gastrectomy or mini-gastric bypass for obesity and diabetes were screened for the inclusion in this study. Of these, 4 subjects were excluded because of surgical complications, 7 subjects were omitted because young surgeons conducted the operations and 11 subjects were removed because of the lack of follow-up. Thirty-one obese patients were recruited for this study. A total of 15 subjects underwent SG (48.4%), and 16 underwent MGB (51.6%). After adjusting for various clinical and demographic characteristics in a multivariate logistic regression analysis, high hemoglobin A1c was determined to be a negative predictor of diabetes remission at 12 mo (OR = 0.366, 95%CI: 0.152-0.884). Using the same regression model, MGB showed a clear trend toward higher diabetes remission rates relative to SG (OR = 3.780, 95%CI: 0.961-14.872). CONCLUSION: Although our results are encouraging regarding the effectiveness of mini-gastric bypass on diabetes remission, further studies are needed to provide definitive conclusions in selecting the ideal procedure for diabetes remission

Development and Validation of a Reversed-Phase HPLC Method with UV Detection for the Determination of L-Dopa in Vicia faba L. Broad Beans

L-Dopa (LD), a substance used medically in the treatment of Parkinson's disease, is found in several natural products, such as Vicia faba L., also known as broad beans. Due to its low chemical stability, LD analysis in plant matrices requires an appropriate optimization of the chosen analytical method to obtain reliable results. This work proposes an HPLC-UV method, validated according to EURACHEM guidelines as regards linearity, limits of detection and quantification, precision, accuracy, and matrix effect. The LD extraction was studied by evaluating its aqueous stability over 3 months. The best chromatographic conditions were found by systematically testing several C-18 stationary phases and acidic mobile phases. In addition, the assessment of the best storage treatment of Vicia faba L. broad beans able to preserve a high LD content was performed. The best LD determination conditions include sun-drying storage, extraction in HCl 0.1 M, chromatographic separation with a Discovery C-18 column, 250 x 4.6 mm, 5 mu m particle size, and 99% formic acid 0.2% v/v and 1% methanol as the mobile phase. The optimized method proposed here overcomes the problems linked to LD stability and separation, thus contributing to the improvement of its analytical determination