Lymph-vascular Space Involvement and Outer One-third Myometrial Invasion Are Strong Predictors of Distant Haematogeneous Failures in Patients with Stage I-II Endometrioid-type Endometrial Cancer

The aim of this retrospective study was to assess the predictive value of different clinicopathological variables (patient age, tumour size, FIGO grade, myometrial invasion, lymph-vascular space involvement [LVSI], invasion margins, peri-tumour phlogistic infiltrate and mitotic activity) for the risk of distant haematogenous recurrences in patients with endometrioid-type stage Ib-II endometrial cancer. Between August 1990 and April 2005, 259 patients had undergone laparotomy, peritoneal washing, total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without pelvic +/- para-aortic lymphadenectomy for endometrioid-type endometrial cancer. Thirty-six (13.9%) patients had developed recurrent disease after a median time of 17 months (range, 2-128 months). The relapse had been locoregional in 9, distant in 21 and both locoregional plus distant in 6 cases. This study assessed 12 patients with FIGO stage Ib-II disease who had developed distant haematogenous recurrences and 20 randomly chosen control patients with FIGO stage Ib-II disease who had remained recurrence-free after a median follow-up of 52 months (range, 37-66 months). Adjuvant therapy had been: no further treatment in 15 patients, external pelvic irradiation in 14 patients, adjuvant external pelvic irradiation plus brachytherapy in 2 patients and platinum-based chemotherapy followed by external pelvic irradiation in I patient. The site of distant failure had been the lung in 9 patients, liver in 2 patients and lung plus liver in I patient. A concomitant locoregional relapse (vagina or lymph nodes) had occurred in 3 patients. The median interval between surgery and the development of distant failure had been 16.5 months (range, 5-113 months). On univariate analysis, a higher incidence of FIGO grade 3 (50% versus 10%, p=0.0114), outer one-third myometrial invasion (91.7% versus 35.0%, p=0.0051) and LVSI (75.0.% versus 20.0%, p=0.0022) was found in the patients who had developed distant haematogeneous metastases compared to the recurrence-free women. Multivariate analysis showed that LVSI (p=0.0264) and deep myometrial invasion (p=0.0345) were independent predictive variables for the risk of distant haematogeneous failure. Patients with these pathological findings should be enrolled in randomised trials designed to assess the role of adjuvant chemotherapy alone or combined with sequential and /or concomitant external pelvic irradiation

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction

Debittering of Grape Juice by Electrospun Nylon Nanofibrous Membranes: Impact of Filtration on Physicochemical, Functional, and Sensory Properties

The effect of electrospun nylon-6 nanofibrous membranes (NFMs) on the concentration of bitter compounds and antioxidants of grapefruit juices during dead-end filtration processes was studied. Filtration experiments with aqueous standard solutions of different molecules showed that NFMs retain low molecular weight antioxidants (i.e., ascorbic and caffeic acids) only at early filtration stages, whereas they remove bitter glycosylated phenolics (i.e., naringin and narirutin) at a more stable ratio, variable according to the membrane thickness. Experiments with fresh grapefruit juice of two varieties (pink and yellow) showed that NFM-filtration reduces (17 to 30%) flavanones associated with the immediate bitterness and allows for the complete removal (>99.9%) of limonin, responsible for the persistent bitterness of many citrus juices. In contrast, the same process causes a lower loss of ascorbic acid (5%) and does not affect acidity, nor sugar concentration. The results confirmed that NFMs feature permselectivity towards bitterness-related compounds. This work highlights the NFM potential as filter devices for the selective reduction of the bitter terpenoid (limonin) and glycosylated flavonoids (naringin and narirutin) from grape juice citrus juices in the production of industrially-relevant beverages