Potential Replacements for Antibiotic Growth Promoters in Poultry: Interactions at the Gut Level and Their Impact on Host Immunity.

The chicken gastrointestinal tract (GIT) has a complex, biodiverse microbial community of ~ 9 million bacterial genes plus archaea and fungi that links the host diet to its health. This microbial population contributes to host physiology through metabolite signaling while also providing local and systemic nutrients to multiple organ systems. In a homeostatic state, the host-microbial interaction is symbiotic; however, physiological issues are associated with dysregulated microbiota. Manipulating the microbiota is a therapeutic option, and the concept of adding beneficial bacteria to the intestine has led to probiotic and prebiotic development. The gut microbiome is readily changeable by diet, antibiotics, pathogenic infections, and host- and environmental-dependent events. The intestine performs key roles of nutrient absorption, tolerance of beneficial microbiota, yet responding to undesirable microbes or microbial products and preventing translocation to sterile body compartments. During homeostasis, the immune system is actively preventing or modulating the response to known or innocuous antigens. Manipulating the microbiota through nutrition, modulating host immunity, preventing pathogen colonization, or improving intestinal barrier function has led to novel methods to prevent disease, but also resulted in improved body weight, feed conversion, and carcass yield in poultry. This review highlights the importance of adding different feed additives to the diets of poultry in order to manipulate and enhance health and productivity of flocks.

Management of isolated distal deep-vein thrombosis with direct oral anticoagulants in the RIETE registry.

Isolated distal deep-vein thrombosis (DVT, infra-popliteal DVT without pulmonary embolism) is a common presentation of venous thromboembolism (VTE), but was an exclusion criterion from the pivotal trials that validated the use of direct oral anticoagulants (DOACs) for VTE management. Using data from the international RIETE registry, we analyzed and compared trends in DOACs prescription between January 2011 and June 2019 in patients with distal vs. proximal DVT. We also assessed DOACs' prescriptions and compared the outcomes (VTE recurrence, bleeding and death) of distal DVT patients treated with DOACs vs. those on vitamin K antagonists (VKAs). 2308 patients with distal DVT and 11,364 patients with proximal DVT were included in the current analysis. DOACs were more frequently prescribed in patients with distal than proximal DVT (25% vs. 16%, p < 0.001). DOACs use increased sharply during the observation period (P < 0.001 for trend). In 2018, 56% of patients with distal DVT received DOACs. Distal DVT patients treated with rivaroxaban or edoxaban received the dose recommended for VTE management in most (> 85%) cases. Patients treated with apixaban were older, more likely to have underlying conditions than patients treated with rivaroxaban and, in most cases (> 75%), did not receive the recommended 1-week loading dose for acute VTE management. Outcomes between distal DVT patients treated with VKAs or DOACs appeared to be similar. In patients with distal DVT, DOACs have become the most common anticoagulant regimen. Specific trials are needed to determine the optimal DOACs dose regimen for treatment of distal DVT.

Use of 1,470 nm laser for treatment of superficial venous insufficiency.

BACKGROUND: There are several ways to treat varicose veins of the lower limbs, among which use of 1470nm diode lasers stands out. This technique can be used to treat patients in outpatient settings, with early return to work, good esthetic results, and low rates of complications. However, variables such as the laser wavelength, the power administered in each area, the type of fiber, and the linear intravenous energy density (LEED) are still extensively discussed. OBJECTIVES: To analyze the results of superficial venous insufficiency treatment with a 1470nm diode laser. METHODS: Retrospective study conducted at a private clinic in a private hospital in Florianopolis, based on a database collected prospectively. The sample comprised 287 patients who underwent surgery to treat superficial venous insufficiency with 1470nm diode laser, from January 2016 to December 2018, totaling 358 great saphenous veins (GSVs) and 84 small saphenous veins (SSVs) treated. RESULTS: The total occlusion rates after 12 months of surgery were 94.4% in the GSVs, with an average LEED of 45.90 J/cm, and 96.4% in the SSVs, with an average LEED of 44.07 J/cm. CONCLUSIONS: During the follow-up period, the 1470nm diode laser proved to be a safe treatment, with great efficacy and low rates of complications (pain, edema, bruising, deep vein thrombosis, and endothermal heat-induced thrombosis - EHIT).

Performance and intestinal microbiota of chickens receiving probiotic in the feed and submitted to antibiotic therapy.

The purpose of this study was to verify the ability of a probiotic in the feed to maintain the stability of the gut microbiota in chickens after antibiotic therapy and its association with growth performance. One thousand six hundred twenty 1-day-old Cobb male were housed in floor pens (36 pens, 45 birds/pen) and were fed corn-/soya bean meal-based diets supplemented with or without probiotic (Bacillus subtilis) during the entire rearing phase. From 21 to 24 days of age (three consecutive days), the chickens were submitted to antibiotic therapy via drinking water (bacitracin and neomycin) in order to mimic a field treatment and induce dysbiosis. Growth performance was monitored until 42 days of age. At 2, 4 and 6 days after antibiotic therapy, three chickens from each pen were euthanized and the contents of the small intestine and caeca were collected and pooled. The trial was conducted with four treatments and nine replicates in a 2 × 2 factorial arrangement for performance characteristics (with and without probiotic × with and without antibiotic therapy); for the intestinal microbiota, it was in a 2 × 2 × 3 factorial arrangement (with and without probiotic × with and without antibiotic therapy × 2, 4 and 6 days after the antibiotic therapy) with three replicates per treatment. Terminal restriction length polymorphism (T-RFLP) analysis showed that the structure of gut bacterial community was shaped by the intestinal segment and by the time after the antibiotic therapy. The number of 16S rDNAs copies in caecum contents decreased with time after the therapeutic treatment. The antibiotic therapy and dietary probiotic supplementation decreased richness and diversity indexes in the caecal contents. The improved performance observed in birds supplemented with probiotic may be related to changes promoted by the feed additive in the structure of the intestinal bacterial communities and phylogenetic groups. Antibiotic therapy modified the bacterial structure, but did not cause loss of broiler performance.

Double aneurysm of the superior mesenteric artery: case report.

Superior mesenteric artery aneurysms are rare, accounting for less than 0.5% of all intra-abdominal aneurysms. They are mainly caused by atherosclerosis and septic emboli resulting from bacterial endocarditis. Although uncommon, these aneurysms are considered dangerous because of possible complications such as rupture with hemorrhage and intestinal ischemia. Since the consequences can be very serious, early diagnosis and treatment are essential to improve outcomes. Although there is no well-defined consensus, recommended treatments include open surgery, endovascular therapy, and watchful waiting with periodic examinations. In this article we report the case of an asymptomatic 58-year-old man with an incidental and unusual finding of two superior mesenteric artery aneurysms. Since anatomy was not favorable for an endovascular approach, open surgery was performed, using a dacron graft to successfully repair the artery.

Tomographic Measurement of Gutters and Analysis of the Conformability of Stent Grafts in the Octopus Technique for Endovascular Thoracoabdominal Aneurysm Repair.

BACKGROUND: The Octopus technique is an off-label and off-the-shelf strategy used as an option in the management of some specific and selected cases of thoracoabdominal aortic aneurysms (TAAA). We sought to compare 2 different methods of measurements on computed tomography (CT) slices and to evaluate the accommodation and conformability, before and after ballooning, of the components used in the Octopus technique. METHODS: The CT gutter analysis between the 3 stent grafts within the short docking limb of the Excluder(®) was made using Viabahns(®) of 8, 7, and 6 mm in diameter. Each of the 10 possible combinations underwent a CT established protocol. The best axial image of the docking limb was submitted for an evaluation by 2 independent analysts, using 2 different methods. We also performed a postballooning evaluation, and the same CT protocol was used. RESULTS: There was no significant difference between the formats of measurement type "A" and type "B." Furthermore, there was no significant difference between the measurements made by the independent analysts. The tomography analyses demonstrated that the combination of stent grafts (Viabahn) of 8 and 7 mm diameter, inside the short docking limb of the bifurcated endoprosthesis, had the best possible relationship between the diameters used. These combinations showed better conformability and juxtaposition, with smaller areas of gutters and theoretically less possibility of endoleak. In addition, we found that postimplant balloon dilatation impaired the conformability and juxtaposition of the stent grafts (Viabahn) in the optimum combinations. CONCLUSIONS: In this analysis, we demonstrated a feasible, reliable, and reproducible form of CT measurement of the gutters in the Octopus technique for endovascular repair of TAAAs. Based on these measurements, there is a preferable combination of Viabahn sizes to be used in the Octopus technique and that postdilatation impairs the conformability and juxtaposition.

Endovascular treatment of ruptured abdominal aortic aneurysm with aortocaval fistula based on aortic and inferior vena cava stent-graft placement.

A ruptured abdominal aortic aneurysm (RAAA), complicated by an aortocaval fistula (ACF), is usually associated with high morbidity and mortality during open operative repair. We report a case of endovascular treatment of an RAAA with ACF. After accessing both common femoral arteries, a bifurcated aortic stent graft was placed. Subsequently, we accessed the fistula from the right femoral vein and a cava vein angiography showed a persistent massive flow from the cava to the excluded aneurysm sac. We proceeded by covering the fistula with an Excluder aortic stent-graft cuff to prevent pressurization of the aneurysm sac and secondary endoleaks. This procedure is feasible and may reduce the chances of posterior endoleaks.

A microbial muramidase improves growth performance and reduces inflammatory cell infiltration in the intestine of broilers chickens under Eimeria and Clostridium perfringens challenge.

The objective of the present studies was to evaluate muramidase (MUR) supplementation in broilers under Eimeria and/or Clostridium perfringens challenge. For this, 2 experiments were conducted. Experiment 1. A total of 256 one-day old male Cobb 500 chicks were placed in battery cages in a completely randomized design, with 5 treatment groups, 7 replicate cages per treatment and 8 birds per cage. The treatments were: nonchallenged control (NC), challenged control (CC), CC + MUR at 25,000 or 35,000 LSU(F)/kg, and CC + Enramycin at 10 ppm (positive control-PC). Challenge consisted of 15× the recommended dose of coccidiosis vaccine at placement, and Clostridium perfringens (108 CFU/bird) inoculation at 10, 11, and 12 d. Macro and microscopic evaluation, immunohistochemistry, and gene expression were evaluated at 7, 14, 21, and 28 d of age. Experiment 2. A total of 1,120 one-day old male Cobb 500 chicks were placed in floor pens with fresh litter in a completely randomized design, with 4 treatment groups, 8 replicate pens per treatment, and 35 birds per pen. The treatments were: Control, supplementation of MUR at 25,000 or 45,000 LSU(F)/kg, and a positive control (basal diet plus Enramycin). At 10, 11, and 12 d of the experiment all the birds were inoculated by oral gavage with a fresh broth culture of a field isolate Clostridium perfringens (0.5 mL containing 106 CFU/bird). It was observed that in Experiment 1 MUR supplementation reduced the infiltration of macrophages and CD8+ lymphocytes in the liver and ileum of infected birds, downregulated IL-8 and upregulated IL-10 expression. In Experiment 2, MUR linearly improved the growth performance of the birds, increased breast meat yield, and improved absorption capacity. MUR supplementation elicited an anti-inflammatory response in birds undergoing a NE challenge model that may explain the improved growth performance of supplemented birds.

Total endovascular repair of aberrant left subclavian artery with Kommerell's diverticulum using a customized branched device.

We describe a case of Kommerell's diverticulum involving the distal portion of a right-sided aortic arch and the origin of an aberrant left subclavian artery (LSA). The patient underwent a total endovascular repair with the use of a modified Valiant endograft (Medtronic, Minneapolis, Minn) to which a branch was attached to keep LSA patency. Postoperative computed tomography showed complete exclusion of the lesion, without endoleaks. The use of "customized off-label" devices to treat special conditions was feasible in this case, keeping patency of the LSA without risk of arm claudication or the requirement for a complementary surgical bypass.

Microbiome modulation, microbiome protein metabolism index, and growth performance of broilers supplemented with a precision biotic.

The objectives of the present studies were to evaluate: 1) the in vivo impact of the supplementation with a precision biotic (PB) on the growth performance and microbiome modulation of broiler chickens; 2) the role of PB on the modulation of functional pathways of the microbiome collected from animals with low and high body weight gain, and 3) to develop a Microbiome Protein Metabolism Index (MPMI) derived from gut metagenomic data to link microbial protein metabolism with performance. The in vivo work consisted of 2 experiments with 2 treatments: Control vs. PB at 1.1 kg/MT of PB with 21 or 14 replicates of 40 birds per replicate, in experiments 1 and 2, respectively. Growth performance was evaluated in both experiments, and from experiment 1, cecal samples from one bird/replicate was collected on d 21 and 42 (n = 21/treatment) to evaluate the microbiome through whole genome sequencing. In the ex vivo assay, 6 cecal samples were collected from low body weight (BW) birds (at 10% below average), and 6 samples from high BW birds (at least 10% above average). The samples were incubated in the presence or absence of PB. After incubation, DNA was isolated to develop a functional genomic assay and the supernatant was separated to measure short-chain fatty acid (SCFA) production. The MPMI is the sum of beneficial genes in the pathways related to protein metabolism. In the in vivo grow out experiments, it was observed that the supplementation improved the BW gain by 3% in both studies, and the corrected feed conversion ratio (cFCR) by 3.7 and 3.4% in studies 1 and 2, respectively (P < 0.05). The functional microbiome analysis revealed that the PB shifted the microbiome pathways toward a beneficial increase in protein utilization, as shown by higher MPMI. In the ex vivo experiment, the PB increased the abundance of genes related to the beneficial metabolism of protein (quantitative MPMI), and the concentration of SCFA, regardless of the underline BW of the birds. Taken together, the microbiome metabolic shift observed in the in vivo study and higher MPMI, plus the observations from the ex vivo assay with higher SFCA production, may explain the improvement in growth performance obtained with the supplementation of PB.

A meta-analysis of the effect of Eimeria spp. and/or Clostridium perfringens infection on the microbiota of broiler chickens.

Coccidiosis in chickens is caused by Eimeria spp. The infection provides a growth advantage to Clostridium perfringens (CP), frequently leading to necrotic enteritis. One approach to alleviate the negative impacts of the diseases is to improve the bacterial composition in chickens, and many experiments investigating chicken enteric health in recent years include the characterization of the bacterial microbiota. This meta-analysis synthesized the data of studies investigating the intestinal microbiota after infection with coccidia and/or CP to provide a basis for future research. Inclusion criteria were that experiments contained a group infected with one or both pathogens and an uninfected control group, the use of 16SrRNA Illumina sequencing and the availability of raw data. A total of 17 studies could be included. Meta-analyses of 3 different data sets were performed: 1 on data of 9 experiments on chickens infected with coccidia only; the second on data of 4 studies on chickens infected with CP only; the third on raw data of 8 experiments with chickens infected with coccidia and CP. The meta-analysis of relative abundance and alpha diversity of the data sets was performed in R using the SIAMCAT and metafor packages. The number of families of interest identified by the analyses of experiments with infection with coccidia only, CP only and the combined infection were 23, 2, and 29, respectively. There was an overlap of 13 families identified by analyses of experiments with infection with coccidia only and of experiments with the combined infections. Machine learning was not able to find a model to predict changes of the microbiota in either 1 of the 3 analyses. Meta-analyses of functional profiles showed a more uniform reaction to the infections with the relative abundance of many pathways significantly altered. Alpha diversity was not affected by infection with either pathogen or the combination. In conclusion, the heterogeneity of these microbiota studies makes recognizing common trends difficult, although it seems that coccidia infection affects the microbiota more than an infection with CP. Future studies should focus on the bacterial functions that are changed due to these infections using metagenome techniques.

Microbiome modulation by a precision biotic in broilers chickens: a commercial study validation.

Precision biotics (PBs) are chemically synthesized complex glycans that modulate specific microbiome metabolic functions. The objective of the present study was to evaluate the effect of the supplementation of PB on the growth performance, and cecal microbiome modulation of broiler chickens raised under commercial conditions. A total of 190,000-day-old Ross 308 straight-run broilers were randomly assigned to 2 dietary treatments. There were 5 houses per treatment with 19,000 birds per house. In each house, there were 6 rows of battery cages with 3 tiers. The 2 dietary treatments included a control diet (a commercial broiler diet) and a PB supplemented diet at 0.9 kg/MT. On a weekly basis, 380 birds were randomly selected for body weight (BW) determination. At 42 d of age, the BW and feed intake (FI) of each house were recorded, the feed conversion ratio (cFCR) was calculated and corrected with the final BW, and the European production index (EPI) was calculated. Additionally, 8 birds per house (40 birds/experimental group) were randomly selected to collect cecal content for microbiome analysis. The supplementation of PB significantly improved (P < 0.05) the BW of the birds at 7, 14, and 21 d and numerically improved the BW of the birds by 64 and 70 g at 28 and 35 d of age, respectively. At 42 d, the PB numerically improved BW by 52 g, and significantly improved (P < 0.05) the cFCR by 2.2 points and the EPI by 13 points. The functional profile analysis showed a clear and significant difference in the cecal microbiome metabolism between control vs. PB supplemented birds. A higher abundance of pathways was modulated by PB which were associated with amino acid fermentation and putrefaction, particularly from lysine, arginine, proline, histidine, and tryptophane which led to a significant increase (P = 0.0025) in the Microbiome Protein Metabolism Index (MPMI) compared to nonsupplemented birds. In conclusion, the supplementation of PB efficiently modulated pathways related to protein fermentation and putrefaction, resulting in higher MPMI and improved growth performance of broilers.

Clinical Significance and Outcome in Patients with Asymptomatic Versus Symptomatic Subsegmental Pulmonary Embolism.

The clinical significance and optimal therapy of patients with subsegmental pulmonary embolism (SSPE) remain controversial. We used the data in the RIETE Registry to compare the baseline characteristics, treatment, and outcomes during anticoagulation and after its discontinuation in patients with asymptomatic vs. symptomatic SSPE. From January 2009 to September 2022, there were 2135 patients with a first episode of SSPE, of whom 160 (7.5%) were asymptomatic. Most patients in both subgroups received anticoagulant therapy (97% vs. 99.4%, respectively). During anticoagulation, 14 patients developed symptomatic pulmonary embolism (PE) recurrences, 28 lower-limb deep vein thrombosis (DVT), 54 bled, and 242 died. The patients with asymptomatic SSPE had similar rates of symptomatic PE recurrences (hazard ratio (HR): 2.46; 95% CI: 0.37-9.74), DVT (HR: 0.53; 95% CI: 0.03-2.80), or major bleeding (HR: 0.85; 95% CI: 0.21-2.42) to those with symptomatic SSPE, but had a higher mortality rate (HR: 1.59; 95% CI: 1.25-2.94). The rate of major bleeding outweighed the rate of PE recurrences (54 major bleeds vs. 14 PE recurrences), and the rate of fatal bleeds outweighed the rate of fatal PE recurrences (12 vs. 6 deaths). After discontinuing anticoagulation, the patients with asymptomatic SSPE had a similar rate of PE recurrences (HR: 1.27; 95% CI: 0.20-4.55) and a non-significantly higher mortality rate (HR: 2.06; 95% CI: 0.92-4.10). The patients with asymptomatic SSPE had similar rates of PE recurrences to those with symptomatic SSPE, during and after discontinuing anticoagulation. The unexpectedly higher rate of major bleeding than recurrences highlights the need for randomized trials to find the best management.

Effect of microbial muramidase supplementation in diets formulated with different fiber profiles for broiler chickens raised under various coccidiosis management programs.

The objective of the present study was to determine the effects of muramidase (MUR) supplemented to diets formulated with different fiber sources (inert or fermentable) on the growth performance and intestinal parameters of broiler chickens raised under different coccidiosis management programs. A total of 2,208 male Ross 308 broilers were housed in 96 floor pens and distributed into a 2 × 3 × 2 factorial arrangement in a completely randomized block design with 2 sources of fiber (inert or fermentable fiber), 3 coccidiosis management programs (none, vaccine, or Salinomycin), and with or without supplementation of MUR at 35,000 LSU(F)/kg of diet. Body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were calculated for each feeding phase (d 0-14, d 14-28, d 28-36) and from d 0 to 36. On d 17 and d 31, samples were taken to analyze several parameters. The experimental data were analyzed with 3-way ANOVA considering the main effect of fiber source, coccidiosis program, inclusion of MUR, and their interactions using JMP 16.2. 16S rDNA sequencing of the ileal and cecal content was carried out to analyze the diversity, composition, and predictive function of the microbiota. From d 0 to 36, BWG increased (P = 0.05) by 2.5% in birds supplemented with Salinomycin (P = 0.04), and by 2.2% with MUR supplementation (P = 0.02). Salinomycin and MUR improved FCR (P < 0.0001) when compared to nonsupplemented birds. The supplementation of MUR, regardless of the coccidiosis management program, reduced the intestinal viscosity (P = 0.03). On d 31, the highest blood concentration of carotenoids was observed in chickens fed diets supplemented with Salinomycin. MUR led to significant changes in the diversity, composition, and predictive function of the ileal microbiota, mainly on d 31. The results observed herein further explain the positive effects of MUR on the growth performance of broiler chickens.

Evaluation of a Precision Biotic on the Growth Performance, Welfare Indicators, Ammonia Output, and Litter Quality of Broiler Chickens.

A dietary glycan-based precision biotic (Glycan PB) was evaluated on the performance, welfare indicators, and litter characteristics of broiler chickens. In Trial 1, the main effects of Glycan PB dose (0, 250 and 500 g/metric ton (MT)) and xylanase supplementation (0 or 100 g/MT) were tested, as was their interaction. In Trial 2, pens located inside a commercial house were used to test the effect of Glycan PB supplementation (500 g/MT) versus a control diet. In Trial 1, Glycan PB supplementation at 250 and 500 g/MT improved feed conversion ratio (FCR) by 7 and 11 points when compared to diets without Glycan PB (p < 0.001). At 35 d, Glycan PB reduced the pH and ammonia concentration in diets with xylanase. In Trial 1, the supplementation with 500 g of Glycan PB/MT of feed reduced litter scores (p < 0.05). In both trials, 500 g of Glycan PB/MT of feed increased the proportions of birds without footpad lesions (Trial 1: 72.2% vs. 82.7%; p < 0.001; Trial 2: 14 to 27.3% (p = 0.05) or gait defects (Trial 1: 96.1% vs. 98.4%; p < 0.001) and decreased the proportion of birds with footpad lesions (Trial 2: 86% vs. 72.7%; p = 0.05).

Laboratory "In-vitro" Evaluation of the Parallel Stent Graft Association for the Iliac Sandwich Technique.

OBJECTIVES: The Iliac Sandwich is an off-label technique that uses parallel stent grafts to treat aortoiliac aneurysms. The purpose of this experimental study is to evaluate the conformability and juxtaposition of stent grafts combinations used in this technique through in-vitro mechanical evaluation, computed tomography (CT) analyses, and a controlled pulsatile flow system. METHODS: The combinations of two Viabahn® ("V-V") or Viabahn® and Excluder® iliac extension ("V-E") were analysed using CT imaging with measurement of the gutter area by two independent analysts before and after balloon angioplasty. In a second phase, the parallel stent combinations were also evaluated using CT imaging after being implanted in the aortic aneurysm model with a pulsatile flow system with controlled temperature, viscosity, and density. RESULTS: The "V-E" group had a better conformability when compared to the "V-V" group, ensuring smaller gutter areas (0.0064 cm2 ± 0.01 vs. 0.0228 cm2 ± 0.03, p < 0.001). Post dilatation with two non-compliant balloons resulted in enlargement of the gutter area (Area A, p 0.065; Area B, p 0.071). Conversely, post dilatation with a non-compliant balloon for the internal iliac component and a compliant balloon for the external iliac device reduced the gutter area (Area A, p 0.008; Area B, p 0.010). CONCLUSION: The combination of Viabahn® and Excluder® iliac extension device ("V-E") had a smaller gutter area compared to two Viabahn® parallel stents for the Iliac Sandwich Technique. Post dilatation using a non-compliant balloon for the internal iliac device and a compliant balloon for the external iliac provided superior conformability and juxtaposition.

Evaluation of a Novel Precision Biotic on Enterohepatic Health Markers and Growth Performance of Broiler Chickens under Enteric Challenge.

This study evaluated the supplementation of a precision biotic (PB) on the enterohepatic health markers and growth performance of broiler chickens undergoing an enteric challenge. In the first study, three treatments were used: Unchallenged Control (UC); Challenged Control (CC; dietary challenge and 10× dose of coccidia vaccine); and a challenged group supplemented with PB (1.3 kg/ton). In the second study, three treatments were used: control diet, diet supplemented with Avilamycin (10 ppm), and a diet supplemented with PB (0.9 kg/ton). All the birds were exposed to natural challenge composed by dietary formulation and reused litter from a coccidiosis positive flock. In Trial 1, PB decreased ileal histological damage, increased villi length, and the expression of SLC5A8 in ileal tissue versus CC; it reduced ileal expression of IL-1ß compared to both UC and CC treatments. PB increased the expression of cell cycling gene markers CCNA2 and CDK2 in the ileum compared to CC. In Trial 2, PB improved the growth performance, intestinal lesion scores and intestinal morphology of broiler chickens. These results indicate that birds supplemented with PB are more resilient to enteric challenges, probably by its action in modulating microbiome metabolic pathways related to nitrogen metabolism and protein utilization.

Effects of a microbial muramidase on the growth performance, intestinal permeability, nutrient digestibility, and welfare of broiler chickens.

The objective of these studies was to evaluate the inclusion of a microbial muramidase (MUR) in the diets of broiler chickens on the growth performance, intestinal permeability (IP), total blood carotenoid content, apparent ileal digestibility (AID), and foot pad dermatitis (FPD). In Experiment 1, a total of 1,000 one-day-old chicks were placed in floor-pens with reused litter, and randomly distributed into 4 treatments with 10 replicates each. Treatments were a basal diet (control), or basal diet supplemented with 15,000; 25,000 or 35,000 LSU (F)/kg of MUR. Feed intake (FI), body weight gain (BWG), and feed conversion ratio (FCR) were evaluated at d 21 and 43. Intestinal permeability was evaluated on d 35 by FITC-d, and FPD and AID on d 43. In Experiment 2, a total of 800 one-day-old chicks were placed in floor-pens with fresh litter, and randomly distributed into 4 treatments with 8 replicates each. Treatments were a basal diet (control), or basal diet supplemented with 25,000 or 35,000 LSU (F)/kg of MUR, and a fourth group where the basal diet was supplemented with enramycin. The birds were induced to a mild intestinal challenge. Feed intake, BWG, and FCR were evaluated on d 21 and d 42, and total blood concentration of carotenoids was evaluated on d 28. In experiment 1, 35,000 LSU (F)/kg of MUR promoted the best FCR (P < 0.05). Muramidase supplementation linearly increased the AID of dry matter, ash, and fat (P < 0.01), and regardless of the dose, MUR decreased the IP (P < 0.05). In Experiment 2, the supplementation of 35,000 LSU (F)/kg of MUR improved BWG and FCR in the entire cycle (1-42 d) and increased the concentration of carotenoids in the blood on d 28 compared to the control group (P < 0.05). These studies show that MUR improves growth performance of broilers by improving intestinal permeability, digestibility of dry matter, ash and fat, absorption of carotenoids, and reducing FPD.

Safety and Efficacy of Rivaroxaban as Extended-Phase Anticoagulation in Patients with Cancer and Venous Thromboembolism: A Preliminary Data Analysis from the Mac Project.

Extended-phase anticoagulation with direct oral Xa inhibitors (OAXI) is suggested in patients with cancer-associated venous thromboembolism (CAT). We report on patients enrolled in the MAC (Monitoring AntiCoagulants) Project, given rivaroxaban as extended-phase anticoagulation after CAT. The primary efficacy outcome was the incidence of symptomatic recurrent VTE; the primary safety outcomes were incidence of major and non-major clinically relevant bleeding, adverse events, and all-cause mortality. The mean patients' follow-up was 19 months (SD 16); 64/604 (11%) had CAT. Recurrent VTE occurred in 9.3% and in 8.1% of patients with and without CAT (OR 1.2, 95% CI 0.5 to 2.9; p = 0.6). Major bleeding occurred in 4.7% and in 2.6%, respectively (OR = 1.8, 95% CI 0.5 to 6.6, p = 0.4), and non-major clinically-relevant bleeding in 4.7% and in 4.1% (OR = 1.2, 95% CI 0.3 to 3.9, p = 0.7). The relative figures for fatal haemorrhage and all-cause death were 1.6% versus 0%, and 1.6% versus 0.4%. Rivaroxaban appears to be effective and safe as extended-phase anticoagulation in patients with CAT. The mean treatment period was 3-times the standard 6-month course.

Safety and Efficacy of Rivaroxaban for Extended-Phase Anticoagulation of Patients with Unprovoked or Recurrent Venous Thromboembolism: Real-Life Data from the MAC Project.

Venous thromboembolism (VTE) is a major cause of death in the world. After the acute-phase treatment, the optimal duration of anticoagulation is still debatable. The latest guidelines suggest maintaining long-term anticoagulation in patients with cancer-associated thrombosis (CAT) or with unprovoked VTE and a low bleeding risk. Methods: The MAC Project is an ongoing prospective-cohort, multi-center, observational study in Italy. The project aims to collect real-life clinical information in unselected patients given oral anticoagulants for VTE over a 5-year follow-up period. There were no exclusion criteria, except for life expectancy <6 months and refusal to sign the informed consent form or to attend the planned follow-up visit. All patients were followed-up prospectively with clinical controls scheduled at 3, 6, and 12 months after the index event, and then annually for up to 5 years. The primary efficacy and safety outcomes were symptomatic recurrent VTE and major bleeding. Results: We analyzed 450 consecutive patients treated with rivaroxaban and referred them to the MAC Project database for unprovoked or recurrent VTE. Of these, 267 (55%) were unprovoked VTE, and 377 (87%) were symptomatic. We followed up with the patients for a mean of 22 months (Q1 10.7; Q3 37.4 months). Recurrent VTE occurred in 12 patients on rivaroxaban treatment (IR 1.7 per 100 person-years). Males had more recurrence than women. During the follow-up period, we recorded 13 (2.9%) major bleeding, 12 (2.7%) clinically relevant non-major bleeding, 8 minor bleeding, and no fatal bleeding events. Overall, bleeding events occurred in 33 (7.3%) patients, most occurring within the first 2 years of treatment. In addition, we observed a statistically significant higher incidence of bleeding in patients with a baseline HAS-BLED score of 3 to 4 compared with those with a score of 0 to 2, with most events occurring during the first 3 months of treatment (RR 5.9). Discussion: Rivaroxaban appears to be safe and effective for the long-term treatment of patients with recurrent or unprovoked VTE. Our results match previously published data, and we are confident that the continuation of the follow-up for up to 5 years will confirm these outcomes.