The role of 18F fluorodeoxyglucose (FDG)-positron emission tomography (PET) in follicular lymphoma (FL) staging is not yet determined.
The aim of the present study was to investigate the role of PET ...in the initial staging of FL patients enrolled in the FOLL05-phase-III trial that compared first-line regimens (R-CVP, R-CHOP and R-FM). Patients should have undergone conventional staging and have available PET baseline to be included.
A total of 142 patients were analysed. PET identified a higher number of nodal areas in 32% (46 of 142) of patients and more extranodal (EN) sites than computed tomography (CT) scan. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score increased in 18% (26 of 142) and decreased in 6% (9 of 142) of patients. Overall, the impact of PET on modifying the stage was highest in patients with limited stage. Actually, 62% (15 of 24) of cases with limited disease were upstaged with PET.
The inclusion of PET among staging procedures makes the evaluation of patients with FL more accurate and has the potential to modify therapy decision and prognosis in a moderate proportion of patients. Further prospective clinical trials on FL should incorporate PET at different moments, and the therapeutic criteria to start therapy should be re-visited in the views of this new tool.
A workflow for editing and rendering 360° images (also called spherical or equirectangular images) is illustrated and discussed. The aim was to develop a novel procedure able to overcome limitations ...induced by deformations in images acquired with low-cost 360° cameras. Editing and rendering are carried on equirectangular projections using a dynamic procedure that turns images into traditional central perspectives, enabling the user to change viewing directions, modify digital content, and store the changes in the original files. Integration of the rendered projections with traditional outputs of digital recording operations as well as other deliverables of the architectural restoration project is also discussed. Finally, the development of a web-GIS application that stores and shares multiple deliverables (including the newly proposed renders) is presented.
Ethmoidal dural arteriovenous fistulae are rare vascular malformations associated with a high risk of bleeding. We present a multicenter contemporary series of patients treated with microsurgical and ...endovascular techniques. Sixteen consecutive patients were evaluated and/or treated between 2008 and 2015 at four centers with large experience in the endovascular and surgical treatment of cerebrovascular diseases. We analyzed demographic and clinical data, risk factors for dural fistulas, treatment type, peri- and post-operative morbidity, clinical and radiological outcomes, rates of occlusion, and long-term neurological outcome. Sixteen patients (81 % men, mean age of 58 years) with ethmoidal dural fistulas were included in the analysis. Seven patients had suffered an intracranial hemorrhage; the remaining presenting with neurological signs and symptoms or the fistula was an incidental finding. Three patients were managed conservatively. Among patients who underwent intervention (
n
= 13), 46.1 % were treated with endovascular therapy and 53.9 % were treated surgically. Complete angiographic obliteration was achieved in 100 % immediately after treatment and at last follow-up evaluation. All patients experienced a favorable neurological recovery (mRS 0–2) at the last follow-up visit (12 months). Ethmoidal dural AVFs are found mostly in male patients. Nowadays, due to wider use of non-invasive imaging, AVFs are discovered with increasing frequency in patients with minimal or no symptoms. Traditionally, these fistulas were considered “surgical.” However, in the modern endovascular era, selected patients can be effectively and safely treated with embolization although surgical ligation continues to have an important role in their management.
Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) in the CheckMate 040 study at ...30.7-month median follow-up. Here, we present 5-year results from this cohort.
Patients were randomized 1 : 1 : 1 to arm A nivolumab 1 mg/kg plus ipilimumab 3 mg/kg Q3W (four doses) or arm B nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W (four doses), each followed by nivolumab 240 mg Q2W, or arm C (nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W). The primary objectives were safety, tolerability, investigator-assessed objective response rate (ORR), and duration of response (DOR) per RECIST version 1.1.
A total of 148 patients were randomized across treatment arms. At 60-month minimum follow-up (62.6-month median follow-up), the ORR was 34% (n = 17), 27% (n = 13), and 29% (n = 14) in arms A, B, and C, respectively. The median DOR was 51.2 months 95% confidence interval (CI) 12.6 months-not estimable (NE), 15.2 months (95% CI 7.1 months-NE), and 21.7 months (95% CI 4.2 months-NE), respectively. The median overall survival (OS) was 22.2 months (34/50; 95% CI 9.4-54.8 months) in arm A, 12.5 months (38/49; 95% CI 7.6-16.4 months) in arm B, and 12.7 months (40/49; 95% CI 7.4-30.5 months) in arm C; 60-month OS rates were 29%, 19%, and 21%, respectively. In an exploratory analysis of OS by response (6-month landmark), the median OS was meaningfully longer for responders versus nonresponders for all arms. No new safety signals were identified with longer follow-up. There were no new discontinuations due to immune-mediated adverse events since the primary analysis.
Consistent with the primary analysis, the arm A regimen of nivolumab plus ipilimumab continued to demonstrate clinically meaningful responses and long-term survival benefit, with no new safety signals in patients with advanced HCC following sorafenib treatment, further supporting its use as a second-line treatment in these patients.
•After 5 years, nivolumab plus ipilimumab continued to show clinically meaningful benefit in sorafenib-treated advanced HCC.•The ORR in arm A nivolumab 1 mg/kg + ipilimumab 3 mg/kg Q3W (four doses), then nivolumab 240 mg Q2W was 34%.•Responses were durable (median DOR 51.2 months) and long-term survival benefit was achieved (5-year OS rate 29%) in arm A.•No new safety signals were identified, and there were no additional discontinuations due to immune-mediated adverse events since primary analysis.•These results further support the use of the arm A regimen of nivolumab plus ipilimumab for sorafenib-treated advanced HCC.
The high hygroscopicity of gentamicin (G) as raw material hampers the production of respirable particles during aerosol generation and prevents its direct use as powder for inhalation in patients ...suffering from cystic fibrosis (CF). Therefore, this research aimed to design a new dry powder formulation of G studying dispersibility properties of an aminoacid, l-leucine (leu), and appropriate process conditions. Spray-dried powders were characterized as to water uptake, particle size distribution, morphology and stability, in correlation with process parameters. Aerodynamic properties were analyzed both by Single Stage Glass Impinger and Andersen Cascade Impactor. Moreover, the potential cytotoxicity on bronchial epithelial cells bearing a CFTR F508/F508 mutant genotype (CuFi1) were tested. Results indicated that leu may improve the aerosol performance of G-dried powders. The maximum fine particle fraction (FPF) of about 58.3% was obtained when water/isopropyl alcohol 7:3 system and 15–20% (w/w) of leu were used, compared to a FPF value of 13.4% for neat G-dried powders. The enhancement of aerosol efficiency was credited both to the improvement of the powder flowability, caused by the dispersibility enhancer (aminoacid), and to the modification of the particle surface due to the influence of the organic co-solvent on drying process. No significant degradation of the dry powder was observed up to 6 months of storage. Moreover, particle engineering did not affect either the cell viability or cell proliferation of CuFi1 over a 24h period.
The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute ...promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-α (PML-RARα) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARα transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P=0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RARα transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P=0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.
The present study aimed to test the capability of real-time three-dimensional echocardiography (RT3DE) in characterizing early abnormalities of left ventricular (LV) structure and function in native, ...untreated hypertensive patients.
Thirty-eight newly diagnosed, never-treated hypertensives (H) and 38 healthy controls (C) underwent both standard echo-Doppler and RT3DE assessment. LV volumes and ejection fraction (EF), sphericity index, LV mass index (LVMi), global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were calculated by RT3DE. The two groups were comparable for age and heart rate. Body mass index and blood pressure (BP) were significantly higher in H. LV volumes, EF, and sphericity index calculated by RT3DE did not differ significantly between the two groups, while LVMi was higher in H than in C (P< 0.0001). GAS (-29.1 ± 2.5% in H vs. -33.6 ± 3.4% in C), GLS, and GRS (all P< 0.0001) were lower in H, but GCS was not significantly different between the two groups. Among the different 3D strain components, GAS showed the best independent associations with mean BP (β = -0.502, P< 0.0001) and LVMi (β = -0.385, P< 0.001; cumulative R(2) = 0.55, P< 0.0001) in the pooled population.
RT3DE identifies early functional LV changes in native hypertensive patients. GAS is precociously reduced, and longitudinal and radial strain impaired, while circumferential strain is still preserved, supporting a normal LV chamber systolic function. Reduction of GAS is independently associated with both pressure overload and magnitude of the LV mass.
Background Dual-release hydrocortisone (DR-HC) improves metabolism in patients with adrenal insufficiency. The aims of this study were to compare the cardiovascular and metabolic effects of ...conventional glucocorticoids (GCs) vs. DR-HC and of high vs. low doses of GCs, after 48 months of observation. Methods We selected 27 patients on hydrocortisone (mean dose 17.5 ± 4.2 mg/day) and 20 patients on cortisone acetate (mean dose 37.5 ± 12.1 mg/day) who maintained this treatment (group A) and 53 patients switched to DR-HC (mean dose 22 ± 4.8 mg/day) (group B). At baseline and after 48 months, clinical and metabolic parameters and Framingham Risk Score (FRS) were obtained. Results After 48 months, patients in group A had a significant increase from baseline in BMI (P < 0.001), waist circumference (P = 0.001), systolic blood pressure (P = 0.001), LDL cholesterol (P = 0.018), HbA1c (P = 0.020) and FRS (P = 0.002). By contrast, patients in group B had a significant decrease in BMI (P = 0.002), waist circumference (P = 0.015), diastolic blood pressure (P = 0.031), total (P = 0.006) and LDL cholesterol (P = 0.005), HbA1c (P < 0.001) and FRS (P = 0.015) compared to baseline. No significant differences between high and low doses of both conventional GCs and DR-HC were observed. Conclusions DR-HC is associated with an improvement of metabolic parameters and cardiovascular risk compared to conventional GCs, which are associated with a worsening of these parameters, regardless of the dose used.
The zoonotic tapeworm Echinococcus granulosus sensu lato (s.l.) represents a species complex encompassing multiple causative agents of cystic echinococcosis, a neglected tropical disease affecting ...more than one million people in the world. At least eight genotypes, grouped in five species, are currently recognized within this species complex, and they differ in terms of relative public health impact. Here we present a molecular method that first identifies the common E. granulosus sensu stricto (s.s.) (genotypes G1 and G3) based on a PCR-RFLP assay, and can further identify the remaining species based on a multiplex PCR assay. We demonstrate the applicability of the method to DNA extracted from parasitic cyst material of human and animal origin, preserved in ethanol or frozen. The method has been developed and validated at the European Union Reference Laboratory for Parasites (EURLP), according to the ISO/IE 17025.
•A protocol for the detection of E. granulosus sensu lato is described.•This method represents a practical tool for diagnosis of human and animal CE.•This method represents an alternative approach to sequencing.•This protocol was developed and validated according to the ISO/IEC 17025.
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