Bemarituzumab plus mFOLFOX6 as first-line treatment in East Asian patients with FGFR2b-overexpressing locally advanced or metastatic gastric/gastroesophageal junction cancer: subgroup of FIGHT final analysis.

BACKGROUND: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. METHODS: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29-0.87); median OS (95% CI) was 24.7 months (13.8-33.1) vs 12.9 months (9.3-21.4), respectively (HR 0.56, 95% CI 0.32-0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. CONCLUSION: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6.

New insights into ATR inhibition in muscle invasive bladder cancer: The role of apolipoprotein B mRNA editing catalytic subunit 3B.

Background: Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC. Methods: Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin. Conclusion: There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Conclusion: Our study shows that APOBEC3B's higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

Supplemental effect of Pediococcus acidilactici CNCM I-4622 probiotic on the laying characteristics and calcium and phosphorus metabolism in laying hens.

The close link between intestinal microbiota and bone health ('gut-bone' axis) has recently been revealed: the modulation of the amount and nature of bacteria present in the intestinal tract has an impact on bone health and calcium (Ca) metabolism. Probiotics are known to favorably impact the intestinal microbiota. The objective of this study was to investigate the effect of Pediococcus acidilactici CNCM I-4622 (PA) on laying performance, egg/eggshell quality, Ca metabolism and bone mineralization and resistance in relatively old layers (50 wks old at the beginning of the experiment) during 14 weeks. 480 Hy Line brown layers were divided into 2 groups (CON and PA: 3 layers/rep, 80 rep/group) and fed with a diet formulated to be suboptimal in calcium (Ca) and phosphorus (P) (- 10% of the requirements). The total egg weight was improved by 1.1% overall with PA, related to an improvement of the weight of marketable eggs (+ 0.9%). PA induced a decreased % of downgraded eggs, mainly broken eggs (- 0.4 pts) and FCR improvement (- 0.8% for all eggs, - 0.9% for marketable eggs). PA also led to higher Haugh units (HU: + 7.4%). PA tended to decrease crypt depth after the 14 weeks of supplementation period in the jejunum (- 25.2%) and ileum (- 17.6%). As a consequence, the VH/CD ratio appeared increased by PA at the end of the trial in the jejunum (+ 63.0%) and ileum (+ 48.0%). Ca and P retention were increased by 4 pts following PA supplementation, translating into increased bone hardness (+ 19%), bone cohesiveness (+ 43%) and bone Ca & P (+ 1 pt) for PA-supplemented layers. Blood Ca and P were respectively improved by 5% and 12% with PA. In addition, blood calcitriol and osteocalcin concentrations were respectively improved by + 83% and + 3% in PA group at the end of the trial, compared to CON group. There was no difference between the 2 groups for ALP (alkaline phosphatase) and PTH (parathyroid hormone). PA significantly decreased the expression of the following genes: occludin in the small intestine, calbindin 1 in the ovarian tissue and actin B in the bone. PA therefore improved zootechnical performance of these relatively old layers, and egg quality. The parallel increase in Ca and P in the blood and in the bone following PA supplementation suggests an improvement of the mineral supply for eggshell formation without impacting bone integrity, and even increasing bone resistance.

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

Copper-Nanoparticle-Decorated Hydrothermal Carbonaceous Carbon-Polydimethylsiloxane Nanocomposites: Unveiling Potential in Simultaneous Light-Driven Interfacial Water Evaporation and Power Generation.

This study introduces a hydrothermal synthesis method that uses glucose and Cu2+ ions to create a Cu-nanoparticle (NP)-decorated hydrothermal carbonaceous carbon hybrid material (Cu-HTCC). Glucose serves both as a reducing agent, efficiently transforming Cu2+ ions into elemental Cu nanostructures, and as a precursor for HTCC microstructures. An enhanced plasmon-induced electric field resulting from Cu NPs supported on microstructure matrices, coupled with a distinctive localized π-electronic configuration in the hybrid material, as confirmed by X-ray photoelectron spectroscopic analysis, lead to the heightened optical absorption in the visible-near-infrared range. Consequently, flexible nanocomposites of Cu-HTCC/PDMS and Cu-HTCC@PDMS (PDMS = polydimethylsiloxane) are designed as 2 and 3D structures, respectively, that exhibit broad-spectrum solar absorption. These composites promise efficient photo-assisted thermoelectric power generation and water evaporation, demonstrating commendable mechanical stability and flexibility. Notably, the Cu-HTCC@PDMS composite sponge simultaneously exhibits commendable efficiency in both water evaporation (1.47 kg m-2 h-1) and power generation (32.1 mV) under 1 sunlight illumination. These findings unveil new possibilities for innovative photothermal functional materials in diverse solar-driven applications.

Dietary rutin alleviated the damage by cold stress on inflammation reaction, tight junction protein and intestinal microbial flora in the mice intestine.

Low temperature is a common stress source for the poultry industry in the north of China. However, the low energy consuming and economical way to reduce the negative effects from cold stress is still limited. Therefore, the aim of this study was to investigate the effect of rutin on intestinal barrier in mice under low temperature. The cold stress model was established at 4°C for 3 h each day and the experiment lasted for 21 days. Forty Balb/c mice were randomly divided into four treatments: CON, normal temperature with the basal diet; RUT, normal temperature with the basal diet +150 mg/kg body weight (BW) of rutin; CS, mice under cold stress with basal diet; CR, 150 mg/kg of BW rutin under cold stress. Rutin supplementation significantly increased the ileum villus-to-crypt ratio compared with these non-supplemented treatments. Rutin attenuated the hypothermia induced morphological damage in the ileum. In addition, rutin improved the antioxidant capacity of mice under cold stress. Rutin supplementation significantly increased the trypsin activity and inhibited the lipase in cold stressed mice. Rutin supplementation significantly inhibited the production of inflammatory factors induced by cold stress. Rutin induced the inhibition of TLR4 and NF-кB, thereby reducing the expression of inflammation-related genes. In addition, rutin improved the reduction of the intestinal claudin-1 and occludin expression in those mice in the cold stress (P < .05) and improved the intestinal ZO-1 expression in cold stressed mice. Finally, rutin alleviated the dysregulation of intestinal microflora in the mice under cold stress.

The Role of Pretreatment Serum Interleukin 6 in Predicting Short-Term Mortality in Patients with Advanced Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its aggressive progression and dismal survival rates, with this study highlighting elevated interleukin 6 (IL-6) levels in patients as a key marker of increased disease severity and a potential prognostic indicator. Analyzing pre-treatment serum from 77 advanced PDAC patients via ELISA, the research determined optimal cutoff values for IL-6 and the IL-6:sIL-6Rα ratio using receiver operating characteristic curve analysis, which then facilitated the division of patients into low and high IL-6 groups, showing significantly different survival outcomes. Notably, high IL-6 levels correlated with adverse features such as poorly differentiated histology, higher tumor burden, and low albumin levels, indicating a stronger likelihood of poorer prognosis. With a median follow-up of 9.28 months, patients with lower IL-6 levels experienced markedly better median overall survival and progression-free survival than those with higher levels, underscoring IL-6's role in predicting disease prognosis. Multivariate analysis further confirmed IL-6 levels, alongside older age, and elevated neutrophil-to-lymphocyte ratio, as predictors of worse outcomes, suggesting that IL-6 could be a critical biomarker for tailoring treatment strategies in advanced PDAC, warranting further investigation into its role in systemic inflammation and the tumor microenvironment.

Effects of dietary supplementation of illite on growth performance, nutrient digestibility, and meat-carcass grade quality of growing-finishing pigs.

This study investigated the impact of clay mineral 'illite' (IL) on the growth performance, apparent total tract digestibility, and meat-carcass grade quality in growing-finishing pigs. One hundred fifty pigs were divided into two groups with fifteen pens/group and five pigs/pen, a control group that was fed with a corn-soybean meal-based diet and IL treated group were fed a meal-based diet supplemented with 0.5% IL. Compared to the control, IL supplementation increased average daily feed intake (ADFI) and reduce gain to feed ratio (G:F) in the pigs during days 43 to 70 and 99 to 126 and increased dry matter during days 42 and 126, and backfat thickness on day 98 (p < 0.05). The drip loss was reduced on day 7, meat firmness tended to increase with dietary IL supplementation. In summary, dietary 0.5% IL supplementation improved ADFI, nutrient utilization of dry matter, and firmness and reduced G:F and drip loss of growing-finishing pigs.

Effect of dietary Achyranthes japonica extract on growth performance of growing pigs and absorption rate of quercetin in blood.

This study was done to investigate the effects of the incorporation of Achyranthes japonica extracts (AJE) in diet on the production parameters of growing pigs. Exp 1: Total, 105 crossbred pigs (average body weight: 24.47 ± 2.46 kg) were used in a 6-week feeding trial. Pigs (seven replicates, five pigs per pen) were allotted randomly to three treatments. Dietary treatments: CON (basal diet); basal diet with 0.025% AJE, and basal diet + 0.050% AJE). Growth performance, nutrient digestibility, fecal microbial count, and fecal noxious gas were assessed in this study. Average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) were not affected by the addition of up to 0.05% AJE. In the case of apparent total tract digestibility (ATTD), dry matter (DM), nitrogen (N), and digestible energy (DE) were not changed in 3rd and 6th weeks of the feeding trial through the addition of AJE up to 0.05% in the growing pig diet. In microbial count, Lactobacillus and Escherichia coli count at 3rd and 6th week was similar in all the treatment diets. The inclusion of AJE at levels up to 0.05% in growing pig diet had no effect on the production of NH3, H2S, acetic acid, and CO2 in the feces. After ending the Exp 1, a total of nine pigs were divided into three treatment groups. Treatment diets were included, TRT1, basal diet + powder quercetin 30 g; TRT2, basal diet + powder quercetin 150 g; TRT3, basal diet + powder quercetin 300g. Rate of absorption in blood was increased with the higher dose of quercetin. The results suggested incorporation of AJE up to 0.05% has no significant effect on ADG, ADFI, and G:F, as well as DM, N, and DE digestibility, fecal microbial count, and fecal noxious gas emission in growing pigs, even though no negative effect was found.

Comparison of the effects of zinc oxide and zinc aspartic acid chelate on the performance of weaning pigs.

In this research, the growth efficiency, nutritional utilization, fecal microbial levels, and fecal score of weaned pigs were evaluated using therapeutic zinc oxide (ZnO) and zinc aspartic acid chelate (Zn-Asp). In a 42-day feeding trial, 60 weaned pigs ([Yorkshire × Landrace] × Duroc) were arbitrarily allotted (age: 21 days; 7.01 ± 0.65 kg preliminary body weight) to 3 different treatment groups with 5 repetitions (2 male and 2 female piglets) in each pen. The trial had 2 different phases, including 1-21 days as phase 1, and 22-42 days as phase 2. The nutritional treatments were: basal diet as control (CON), basal diet incorporated with 3,000 ppm ZnO as TRT1, and basal diet incorporated with 750 ppm Zn-Asp as TRT2. In comparison to the CON group, the pigs in the TRT1 and TRT2 groups had greater (p < 0.05) body weight on day 42; an average daily gain, and an average daily feed intake on days 22-42. Furthermore, during days 1-42, the average daily gain in the treatment groups trended higher (p < 0.05) than in the CON group. Additionally, the fecal score decreased (p < 0.05) at week 6, the lactic acid bacteria count tended to increase (p < 0.05), and coliform bacteria presented a trend in reduction (p < 0.05) in the TRT1 and TRT2 groups compared to the CON group. However, there was no difference in nutrient utilization (p > 0.05) among the dietary treatments. Briefly, the therapeutic ZnO and Zn-Asp nutritional approaches could decrease fecal score and coliform bacteria, increase lactic acid bacteria, and improve growth efficiency; moreover, Zn-Asp (750 ppm) can perform a comparable role to therapeutic ZnO (3,000 ppm). So we can use Zn-Asp (750 ppm) instead of therapeutic ZnO (3,000 ppm) for the better performance of weaning pigs and the reduction of environmental pollution, as therapeutic ZnO is responsible for environmental pollution.

Dietary eubiotics of microbial muramidase and glycan improve intestinal villi, ileum microbiota composition and production trait of broiler.

BACKGROUND: Optimal gut health is important to maximize growth performance and feed efficiency in broiler chickens. A total of 1,365 one-day-old male Ross 308 broiler chickens were randomly divided into 5 treatments groups with 21 replicates, 13 birds per replicate. The present research investigated effects of microbial muramidase or a precision glycan alone or in combination on growth performance, apparent total tract digestibility, total blood carotenoid content, intestinal villus length, meat quality and gut microbiota in broiler chickens. Treatments included: NC: negative control (basal diet group); PC: positive control (basal diet + 0.02% probiotics); MR: basal diet + 0.035% microbial muramidase; PG: basal diet + 0.1% precision glycan; and MRPG: basal diet + 0.025% MR + 0.1% PG, respectively. RESULTS: MRPG group increased the body weight gain and feed intake (P < 0.05) compared with NC group. Moreover, it significantly increased total serum carotenoid (P < 0.05) and MRPG altered the microbial diversity in ileum contents. The MRPG treatment group increased the abundance of the phylum Firmicutes, and family Lachnospiraceae, Ruminococcaceae, Oscillospiraceae, Lactobacillaceae, Peptostreptococcaceae and decreased the abundance of the phylum Campilobacterota, Bacteroidota and family Bacteroidaceae. Compared with the NC group, the chickens fed MRPG showed significantly increased in duodenum villus length at end the trial. CONCLUSION: In this study, overall results showed that the synergetic effects of MR and PG showed enhancing growth performance, total serum carotenoid level and altering gut microbiota composition of broilers. The current research indicates that co-supplementation of MR and PG in broiler diets enhances intestinal health, consequently leading to an increased broiler production.

The effects of synbiotics-glyconutrients on growth performance, nutrient digestibility, gas emission, meat quality, and fatty acid profile of finishing pigs.

Glyconutrients help in the body's cell communication. Glyconutrients and synbiotics are promising options for improving immune function. Therefore, we hypothesized that combining synbiotics and glyconutrients will enhance pig nutrient utilization. 150 pigs (Landrace × Yorkshire × Duroc), initially weighing 58.85 ± 3.30 kg of live body weight (BW) were utilized to determine the effects of synbiotics-glyconutrients (SGN) on the pigs' performance, feed efficiency, gas emission, pork traits, and composition of fatty acids. The pigs were matched by BW and sex and chosen at random to 1 of 3 diet treatments: control = Basal diet; TRT1 = Basal diet + SGN 0.15%; TRT2 = Basal diet + SGN 0.30%%. The trials were conducted in two phases (weeks 1-5 and weeks 5-10). The average daily gain was increased in pigs fed a basal diet with SGN (p = 0.036) in weeks 5-10. However, the apparent total tract digestibility of dry matter, nitrogen, and gross energy did not differ among the treatments (p > 0.05). Dietary treatments had no effect on NH3, H2S, methyl mercaptans, acetic acids, and CO2 emissions (p > 0.05). Improvement in drip loss on day 7 (p = 0.053) and tendency in the cooking loss were observed (p = 0.070) in a group fed basal diets and SGN at 0.30% inclusion level. The group supplemented with 0.30% of SGN had higher levels of palmitoleic acid (C16:1), margaric acid (C17:0), omega-3 fatty acid, omega-6 fatty acid, and ω-6: ω-3 ratio (p = 0.034, 0.020, 0.025, 0.007, and 0.003, respectively) in the fat of finishing pigs. Furthermore, group supplemented with 0.30% of SGN improved margaric acid (C17:0), linoleic acid (C18:2n6c), arachidic acid (C20:0), omega 6 fatty acid, omega-6 to omega-3 ratio, unsaturated fatty acid, and monounsaturated fatty acid (p = 0.037, 0.05, 0.0142, 0.036, 0.033, 0.020, and 0.045, respectively) in the lean tissues of finishing pigs compared to pigs fed with the control diets. In conclusion, the combination of probiotics, prebiotics, and glyconutrients led to higher average daily gain, improved the quality of pork, and more favorable fatty acid composition. Therefore, these results contributed to a better understanding of the potential of SGN combinations as a feed additive for pigs.

Strategies for reducing noxious gas emissions in pig production: a comprehensive review on the role of feed additives.

The emission of noxious gases is a significant problem in pig production, as it can lead to poor production, welfare concerns, and environmental pollution. The noxious gases are the gasses emitted from the pig manure that contribute to air pollution. The increased concentration of various harmful gasses can pose health risks to both animals and humans. The major gases produced in the pig farm include methane, hydrogen sulfide, carbon dioxide, ammonia, sulfur dioxide and volatile fatty acids, which are mainly derived from the fermentation of undigested or poorly digested nutrients. Nowadays research has focused on more holistic approaches to obtain a healthy farm environment that helps animal production. The use of probiotics, prebiotics, dietary enzymes, and medicinal plants in animal diets has been explored as a means of reducing harmful gas emissions. This review paper focuses on the harmful gas emissions from pig farm, the mechanisms of gas production, and strategies for reducing these emissions. Additionally, various methods for reducing gas in pigs, including probiotic interventions; prebiotic interventions, dietary enzymes supplementation, and use of medicinal plants and organic acids are discussed. Overall, this paper provides a comprehensive review of the current state of knowledge on reducing noxious gas in pigs and offers valuable insights for pig producers, nutritionists, and researchers working in this area.

Dietary inclusion of micelle silymarin enhances egg production, quality, and lowers blood cholesterol in Hy-line brown laying hens.

This study aimed to evaluate the effect of micelle silymarin (MS) supplementation on productive performance, egg quality, and blood biochemical parameters in laying hens. A total of 384 (Hy-Line brown, 28-week-old) laying hens were randomly distributed into one of four dietary treatment groups (eight replication per treatment; 12 hens per replicate) for a 12-week long feeding trial. Hens were fed a basal diet with the addition of 0%, 0.02%, 0.04%, and 0.06% of MS respectively. The results expressed that egg production percentage and egg weight were linearly (p < 0.05) enhanced at Weeks 0-6, 7-12, and 0-12, when 0%, 0.02%, 0.04%, and 0.06% of MS were added to laying hen diets. The feed conversion ratio and feed intake improved (p < 0.05) linearly at Weeks 0-6, 7-12, and 0-12 with increasing levels of MS supplementation in laying hens. The eggshell thickness and eggshell strength were linearly (p < 0.05) improved at weeks 4, 8, and 12 with an MS-supplemented diet. Additionally, eggshell colour, Haugh unit, and albumin height had no significant (p > 0.05) difference throughout the experimental period with different levels of MS-supplemented diet. The yolk colour of eggs showed significant (p < 0.05) differences at weeks 8 and 12 with levels of the MS-supplemented diet. However, at the end of the trial, the blood profile indicated that cholesterol levels decreased (p < 0.05) linearly, and triglyceride levels showed a tendency to decrease (p < 0.10) with MS supplementation. In conclusion, increasing the level of MS addition in the laying hen diet improved the egg production percentage and egg quality, reducing cholesterol levels in Hy-Line brown hens. However, this study indicates that MS can be added to the diet of laying hens up to 0.06% for improved egg production and egg quality.

Bemarituzumab as first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial.

BACKGROUND: We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2-negative gastric or gastroesophageal junction cancer (GC). METHODS: Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval [CI]) was 9.5 months (7.3-13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7-8.4) with placebo-mFOLFOX6 (hazard ratio [HR], 0.72; 95% CI 0.49-1.08); median OS (95% CI) was 19.2 (13.6-24.2) and 13.5 (9.3-15.9) months, respectively (HR 0.77; 95% CI 0.52-1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26-0.73); OS: HR 0.52 (95% CI 0.31-0.85). No new safety findings were reported. CONCLUSIONS: In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626). CLINICAL TRIAL REGISTRATION: NCT03694522.

Comparative effects of dietary herbal mixture or guanidinoacetic acid supplementation on growth performance, cecal microbiota, blood profile, excreta gas emission, and meat quality in Hanhyup-3-ho chicken.

Phytogenic feed additives are renowned for their growth promotion, gut health enhancement, and disease prevention properties, which is important factors for sustaining prolonged poultry rearing. The study aimed to evaluate the effect of herbal mixture (mixture of ginseng and artichoke) or guanidinoacetic acid (GAA) on growth performance, cecal microbiota, excretal gas emission, blood profile, and meat quality in Hanhyup-3-ho chicken. A total of 360 one-day-old chickens (half males and half females) were allocated into one of 3 dietary treatments (12 replicate cages/treatment; 10 broilers/replicate cage) for 100 d of age. Experimental diets were CON: basal diet; TRT1: basal diet combined with 0.05% herbal mixture; and TRT2: basal diet combined with 0.06% GAA. All birds received a basal diet during the first 30 d, but from d 31 to 100, an experimental diet was supplied. The addition of 0.05% herbal mixture improved the average body weight gain and feed conversion ratio from d 31 to 100 as well as the overall experimental period. The cecal Lactobacillus, Escherichia coli, and Salmonella count remained consistent across all dietary treatments. Blood albumin and Superoxide Dismutase (SOD) levels increased in the herbal mixture supplemented diet. Additionally, there was a notable reduction in excretal NH3 and H2S emissions in the herbal mixture group. Furthermore, the herbal mixture group exhibited increased breast muscle weight, improved breast muscle color, improved water holding capacity, and a decrease in abdominal fat compared to the control group. Additionally, the supplementation of 0.06% GAA did not demonstrate any statistically significant impact on any evaluated parameter throughout the experiment. The results from the present investigation underscore the potential of ginseng together with artichoke extract supplementation as a viable feed additive, conferring improvements in growth performance, feed efficiency, excreta gas emission, meat quality parameters, and defense mechanism against oxidative stress in Hanhyup-3-ho chicken.

Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06).

BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).

Dietary Bacillus spp. supplementation to both sow and progenies improved post-weaning growth rate, gut function, and reduce the pro-inflammatory cytokine production in weaners challenged with Escherichia coli K88.

BACKGROUND: The use of probiotics (PRO) in late gestation sow and their impact on progenies' performance during the post-weaning stage has received more attention from the researchers recently. This study aimed to analyze the effect of probiotic mixture (Bacillus subtilis and Bacillus licheniformis) on both sow and offspring's performance. METHODS: First experiment (Exp.1) was conducted from the 100th day of gestation through to post-weaning. A total of twenty sows and their litters were assigned to one of two dietary treatments, Control (CON) based diet and PRO- CON+ 0.05% probiotic mixture. Dietary treatments were arranged in a split-plot pattern with sow and weaner treatment (CON and PRO diet) as the main and sub plot. Exp.2. E. coli challenge study was carried out two weeks after weaning with 40 piglets. Dietary treatments remained same while all pigs were orally administered with a 1.5 ml suspension of 1010 CFU of K88 strain of E. coli per ml. RESULT: PRO group sow showed significantly decreased backfat thickness difference and body weight difference after farrowing and at the end of weaning d21. The nutrient digestibility of PRO group sows was significantly higher at the end of weaning. Moreover, piglets born from PRO group sow showed higher weaning weight and tend to increase average daily gain at the end of d21. The addition of mixed probiotic in sow and weaner diet had suppressed the production of TNF-α and interleukin-6 in E. coli challenged pigs. The phyla Firmicutes and Bacteroidetes in E. coli -challenged pigs were highly abundant while, the relative abundance of clostridium_sensu_stricto_1 at genus level was significantly reduced by the inclusion of probiotic in both the sow and weaner diet. Also, taxonomic distribution analysis showed significantly lower prevalence of Clostridium and Brachyspira and higher prevalence of Lactobacilli in E. coli-challenged pigs that were born from PRO group sow and fed CON and PRO weaner diet. CONCLUSION: This study reveals that the inclusion of 0.05% mixed probiotics (Bacillus spp.) to both sow and their progenies diet would be more beneficial to enhance the post-weaning growth rate, gut health, and immune status of E. coli challenged pigs.

Assessing the potential of phytogenic feed additives: A comprehensive review on their effectiveness as a potent dietary enhancement for nonruminant in swine and poultry.

Phytogenic feed additives (PFAs) often referred to as phytobiotics or botanical feed additives, are natural compounds derived from various plants, herbs, spices and other botanical sources. These feed additives are intended to serve a variety of purposes, including an immune system regulator, an antimicrobial, an antimutagenic, an antioxidant and a growth promoter. They are composed of bioactive compounds extracted from plants, including essential oils, polyphenols, terpenoids and flavonoids. They are mostly utilized as substitute antibiotic growth promoters in nonruminant (swine and poultry) livestock production, owing to the prohibition of antibiotic usage in the feed industry. It has been thoroughly examined to ascertain their impact on intestinal health and activity, correlation with animals' effective health and well-being, productivity, food security and environmental impact. The potential uses of these feed additives depend on the properties of herbs, the comprehension of their principal and secondary components, knowledge of their mechanisms of action, the safety of animals and the products they produce. They are gaining recognition as effective and sustainable tools for promoting animal health and performance while reducing the reliance on antibiotics in nonruminant nutrition. Their natural origins, multifaceted benefits and alignment with consumer preferences make them a valuable addition to modern animal farming process. However, because of their inconsistent effects and inadequate knowledge of the mechanisms of action, their usage as a feed additive has been limited. This review offers a comprehensive assessment of the applications of PFAs as an effective feed supplement in swine and poultry nutrition. In summary, this comprehensive review provides current knowledge, identifies gaps in research and emphasizes the potential of phytogenic additives to foster sustainable and healthier livestock production systems while addressing the global concerns associated with antibiotic use in livestock farming.