A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Microalgae supplementation to late gestation sows and its effects on the health status of weaned piglets fed diets containing high- or low-quality protein sources.

Maternal stress, such as a bacterial infection occurring in late gestation, may predispose offspring to a variety of diseases later in life. It may also alter programming of developing systems within the fetus, such as the hypothalamic-pituitary-adrenal (HPA) axis and immune system. Dietary supplementation during the last trimester of pregnancy with immune-modulating compounds may be a means of reducing potential adverse effects of maternal stress on the developing fetus. Essential omega-3 polyunsaturated fatty acids (n-3 PUFA) such as docosahexanoic acid (DHA) and eicosapentanoic acid are well-known for their immune-modulating and anti-inflammatory properties. Sources of these n-3 PUFA include fish products such as fish oil and microalgae, which may be a suitable alternative to fish-based products. The aim of this study was to determine the effect of supplementing gestating sow diets with n-3 PUFA and inducing an immune stress challenge in late gestation on piglet growth and immune responsiveness when placed on either a high- or low-quality protein diet after weaning. Forty-eight sows were fed gestation diets containing either 3.12% microalgae, 3.1% fish oil or a corn oil control diet containing 1.89% corn oil starting on gestation day (gd) 75. On gd112, half the sows in each treatment were immune stress challenged with bacterial lipopolysaccharide (LPS) endotoxin (10 µg/kg administered i.m). After farrowing, piglet BW gain was monitored weekly during lactation and pigs were weaned at 21 days of age. One week after weaning, four piglets per sow were immune stress challenged with LPS (40 µg/kg administered i.m.). At the same time, four piglets per sow were vaccinated with the novel antigens chicken ovalbumin (OVA) and Candida cellular antigen (CAA) and received booster vaccinations two weeks later. Four weeks after the initial vaccination, a transdermal hypersensitivity immune challenge was performed using the same antigens. Blood samples were also collected to quantify IgG antibody responses to both antigens. PUFA enrichment in sow blood and piglet brain was detected after sows were on feed for 40 days. Piglet growth was increased in pigs fed a high-quality diet in nursery phase 1. Concentrations of the cytokines IL-1ra, IL-6 and IL-10 were elevated in pigs fed a high-quality protein diet following LPS immune challenge. Overall, it appears that in the current study piglet nursery diet quality was more important for determining piglet health and growth than maternal diet and immune stress.

Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw.

UNLABELLED: The administration of teriparatide (TPTD) in conjunction with periodontal care could provide faster and more favorable clinical outcomes in previously refractory bisphosphonate-related osteonecrosis of the jaws (BRONJ) cases compared to conventional dental care, combination of surgery and antimicrobial treatment. We also found that underlying vitamin D levels might influence the response to TPTD treatment. INTRODUCTION: Treatment of BRONJ is quite challenging and there are no standard treatment modalities. In this retrospective, longitudinal study, we examined whether additional TPTD administration could be beneficial for the resolution of BRONJ lesions compared to conservative management, such as antimicrobial treatment with or without surgery, and also studied the factors influencing the response to TPTD. METHODS: Twenty-four cases of intractable BRONJ were included: 15 subjects were assigned to the TPTD group and the other 9 subjects, who refused TPTD administration, were assigned to the non-TPTD group. All subjects in both groups continued calcium and vitamin D supplementation and the TPTD group additionally received a daily subcutaneous injection of 20 µg TPTD for 6 months. RESULTS: While 60.0% of the non-TPTD group showed one stage of improvement in BRONJ, 40.0% of the group did not show any improvement in disease status. In the TPTD group, 62.5% of the treated subjects showed one stage of improvement and the other 37.5% demonstrated a marked improvement, including two stages of improvement or complete healing, and there was not a single case that did not improve. The clinical improvement of BRONJ was statistically better in the TPTD group after the 6-month treatment (p < 0.05). Moreover, patients with higher baseline serum 25(OH)D levels showed better clinical therapeutic outcomes with TPTD. CONCLUSIONS: We observed the beneficial effects of TPTD on BRONJ, and subjects with optimal serum vitamin D concentrations seemed to reap the maximum therapeutic effects of TPTD. A prospective, randomized, controlled trial should be needed to further evaluate the therapeutic efficacy of TPTD in the resolution of BRONJ.

Antioxidant nutrient intakes and corresponding biomarkers associated with the risk of atopic dermatitis in young children.

BACKGROUND/OBJECTIVES: To investigate the association of antioxidant nutritional status with the risk of atopic dermatitis (AD) in young children in a case-control, population-based study. SUBJECTS/METHODS: Identified from preschools by using the Korean version of the International Study of Asthma and Allergies in Childhood (ISAAC). Final analysis included 180 AD (mean age 5.3+/-0.9 years) and 242 non-AD (mean age 5.2+/-1.0 years) children. Diet was assessed using a validated semi-quantitative food frequency questionnaire. Fasting blood samples were used for analyses of fat-soluble vitamins (retinol, alpha-tocopherol, and beta-carotene) and vitamin C. RESULTS: AD was associated negatively with intakes of antioxidant-related nutrients. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) were 0.44 (0.22-0.88) for the highest (vs lowest) quintile of beta-carotene. A similar association was observed for dietary vitamin E (OR=0.33, 95% CI=0.16-0.67), folic acid (OR=0.37, 95% CI=0.18-0.73), and iron (OR=0.39, 95% CI=0.19-0.79). Reduced AD risk was found with 1 s.d. increase of serum alpha-tocopherol [OR=0.64, 95% CI=0.41-0.98) and retinol (OR=0.74, 95% CI=0.58-0.96) concentrations, and marginally with that of serum beta-carotene levels (P=0.0749 for trend). There was no relationship of AD risk with dietary and plasma vitamin C as well as nutrient supplement intake regardless of nutrient type. AD was predicted better by the intake measure than the corresponding blood biomarker regarding vitamin E and beta-carotene. CONCLUSIONS: These findings suggest that higher antioxidant nutritional status reduces the risk of AD and that such risk-reduction effects depend on nutrient type.

Ether fraction of methanol extracts of Gastrodia elata, a traditional medicinal herb, protects against kainic acid-induced neuronal damage in the mouse hippocampus.

Gastrodia elata (GE) has been used traditionally for the treatment of convulsive diseases such as epilepsy in oriental countries including South Korea and still occupies an important place in traditional medicine in Asia. We studied the anticonvulsive effect and protective effect of the ether fraction of methanol extracts (EFME) of GE against hippocampal neuronal damage after kainic acid administration in mice. Mice were treated with the EFME of GE (200 or 500 mg/kg per day, p.o.) for 14 days before kainic acid injection (45 mg/kg, i.p.). The EFME of GE (at the dose of 500 mg/kg) delayed the onset time of neurobehavioral change (P<0.01) and reduced the severity of convulsions (P<0.05) and hippocampal neuronal damage in the CA1 (P<0.01) and CA3 (P<0.05) regions. Our results show that The EFME of GE has anticonvulsive effect and putative neuroprotective effect against excitotoxicity induced by kainic acid.

IgE binding components in Tetranychus urticae and Panonychus ulmi-derived crude extracts and their cross-reactivity with domestic mites.

BACKGROUND: Recent investigation has revealed that spider mites such as Tetranychus urticae and Panonychus ulmi are important allergens in the development of occupational asthma among apple farmers. OBJECTIVE: To evaluate IgE binding components in T. urticae and P. ulmi-derived crude extracts and their cross-reactivity with Panonychus citri, Tyrophagus putrescentiae and Dermatophagoides pteronyssinus in apple cultivating farmers. METHODS: Thirty-one apple farmers with positive skin responses to T. urticae or P. ulmi were randomly recruited, and specific IgE levels in their sera were measured using ELISA. Cross-reactivity was evaluated by ELISA inhibition. IgE binding components were evaluated by IgE immunoblotting. RESULTS: A total of 11 IgE binding components in T. urticae and 10 in P. ulmi were found. Among them, the 17 kDa, 27 kDa, 33 kDa, 37 kDa, 41 kDa, 56 kDa, and 75 kDa allergens in T. urticae, and the 33 kDa, 41 kDa, and 51 kDa allergens in P. ulmi were identified as dominant allergens. T. urticae-specific IgE binding was completely inhibited by 100 microg/mL of T. urticae (99.7%), but only partially inhibited by P. citri (83.0%), P. ulmi (71.6%), T. putrescentiae (69.7%), and D. pternonyssinus (60.1%). P. ulmi-specific IgE binding was completely inhibited by additions of P. citri (92.3%) and P. ulmi (91.2%), but only partially inhibited by the addition of T. urticae (61.5%), T. putrescentiae (57.7%), and D. pteronyssinus (54.4%). CONCLUSION: There were seven dominant allergens found in T. urticae and three in P. ulmi. T. urticae- and P. ulmi-specific IgE bindings were partially inhibited by crude extracts derived from D. pteronyssinus and T. putrescentiae.

Effect of dietary cholesterol and degree of fat unsaturation on plasma lipid levels, lipoprotein composition, and fecal steroid excretion in normal young adult men.

Effect of four test diets differing in the ratio of polyunsaturated to saturated fats (P/S, 1.8 vs 0.28) and two cholesterol levels (1,000 vs 300 mg/day) for each level of the P/S ratio was determined on plasma lipid levels, lipoprotein compositions and concentrations, and fecal steroid excretion in a controlled diet study with 11 normal young men using a crossover design. Plasma cholesterol levels were significantly decreased by the diets high in P/S ratio regardless of the dietary cholesterol levels (14% decrease by high cholesterol and 20% in low cholesterol) while the diets low in P/S ratio increased cholesterol by an average of 24 and 22% in presence of high and low cholesterol, respectively. Lipids and apoproteins of lower-density lipoproteins were changed in accordance with those of plasma cholesterol but changes in high-density lipoprotein (HDL) appear to depend on both cholesterol content and P/S ratio. Dietary cholesterol level profoundly influenced the excretion of neutral sterols and diets high in P/S ratio significantly (p less than 0.05) increased fecal bile acid extraction. The present study demonstrated that dietary polyunsaturated fats, when a moderate amount was consumed, were effective and beneficial hypocholesterolemic nutrients without reducing HDL-cholesterol.