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BackgroundTo determine whether granulocyte colony-stimulating factor (G-CSF) improves clinical outcomes after large ST-elevation myocardial infarction (STEMI) when administered early in patients with left ventricular (LV) dysfunction after successful percutaneous coronary intervention (PCI).MethodsSTEM-AMI OUTCOME was designed as a prospective, multicentre, nationwide, randomised, open-label, phase III trial (ClinicalTrials.gov ID: NCT01969890) to demonstrate the efficacy and safety of early G-CSF administration in reducing 2-year cardiac mortality and morbidity in patients with STEMI with LV ejection fraction ≤45% after PCI. The primary outcome was a composite of all-cause death, recurrence of myocardial infarction and hospitalisation for heart failure. Due to low recruitment and event rates, the study was discontinued and did not achieve adequate statistical power to verify the hypothesis.ResultsPatients were randomly allocated to G-CSF (n=260) or standard of care (SOC; n=261). No difference was found in the composite primary outcome between study groups (HR 1.20; 95% CI 0.63 to 2.28). The 2-year mortality was 2.31% in the G-CSF and 2.68% in the control group (HR 0.88; 95% CI 0.29 to 2.60). Adverse events did not differ between the G-CSF (n=65) and SOC groups (n=58; OR 1.17; 95% CI 0.78 to 1.75). In post hoc analyses on the intervention group, we observed a trend towards fewer composite primary outcomes in patients with low bone marrow (BM) cell mobilisation (n=108) versus those with high mobilisation (n=152, with peak leucocyte count >50×109/L; HR 2.86; 95% CI 0.96 to 8.56). Primary outcomes were lower in patients with severe LV systolic dysfunction at discharge treated with G-CSF than in controls (interaction β±SE, −0.08±0.04; p=0.034).ConclusionsAlthough inconclusive, this is the largest trial in the field of cell-based cardiac repair after STEMI providing evidence of the tolerability and long-term safety of G-CSF treatment. The results prompt further studies to understand which patient can benefit most from BM cell mobilisation.Trial registration number NCT01969890.

Objective: To compare in a prospective, randomised, multicentre trial the relative merits of pre-discharge exercise ECG and early pharmacological stress echocardiography concerning risk stratification and costs of treating patients with uncomplicated acute myocardial infarction. Design: 262 patients from six participating centres with a recent uncomplicated myocardial infarction were randomly assigned to early (day 3–5) pharmacological stress echocardiography (n  =  132) or conventional pre-discharge (day 7–9) maximum symptom limited exercise ECG (n  =  130). Results: No complication occurred during either stress echocardiography or exercise ECG. At one year follow up there were 26 events (1 death, 5 non-fatal reinfarctions, 20 patients with unstable angina requiring hospitalisation) in patients randomly assigned to early stress echocardiography and 18 events (2 reinfarctions, 16 unstable angina requiring hospitalisation) in the group randomly assigned to exercise ECG (not significant). The negative predictive value was 92% for stress echocardiography and 88% for exercise ECG (not significant). Total costs of the two strategies were similar (not significant). Conclusion: Early pharmacological stress echocardiography and conventional pre-discharge symptom limited exercise ECG have similar clinical outcome and costs after uncomplicated infarction. Early pharmacological stress echocardiography should be considered a valid alternative even for patients with interpretable baseline ECG who can exercise.

In a randomized trial, 1442 patients with a history of atrial fibrillation were assigned to receive either valsartan, an angiotensin II–receptor blocker, or placebo. Antiarrhythmic therapy was administered according to the treating physician's preference. At 1 year, there was no difference between the groups in the rate of either a first recurrence or multiple recurrences of atrial fibrillation. Patients with a history of atrial fibrillation were assigned to receive either valsartan or placebo. At 1 year, there was no difference between the groups in the rate of either a first recurrence or multiple recurrences of atrial fibrillation. Atrial fibrillation is the most common cardiac arrhythmia. 1 – 5 Antiarrhythmic drugs have only moderate efficacy in preventing recurrences of atrial fibrillation and sometimes cause serious adverse reactions. 6 – 8 Ablation is a costly procedure, and accepted indications are limited. 9 , 10 Thus, new approaches to the management of atrial fibrillation continue to be the subject of interest and investigation. Some studies have shown that the recurrence of atrial fibrillation after cardioversion may be partially related to a biologic phenomenon known as remodeling, in which the electrical, mechanical, and structural properties of atrial tissue and cardiac cells are progressively and irreversibly altered, creating . . .

The hypothesis that a therapeutic strategy aimed at lowering systolic blood pressure (SBP) below 130 mm Hg is superior to a conventional strategy targeted at below 140 mm Hg in hypertensive subjects has never been tested in randomized intervention studies. The Studio Italiano Sugli Effetti Cardiovascolari del Controllo della Pressione Arteriosa Sistolica (Cardio-Sis) is a multi-centre study in non-diabetic, treated hypertensive subjects aged >55 years with uncontrolled SBP (⩾150 mm Hg) and at least one additional cardiovascular risk factor (ClinicalTrials.gov identifier: NCT00421863). Subjects are randomized to an SBP goal <140 mm Hg (conventional) or <130 mm Hg (aggressive), independently of baseline and achieved diastolic blood pressure (BP). Anti-hypertensive drugs dispensed for the study are restricted to a list of specific drugs. The primary outcome of the study is based on regression of left ventricular hypertrophy (LVH) using electrocardiography (ECG). The hypothesis is that subjects without LVH regression or with new development of LVH 2 years after randomization are 19% with conventional strategy and 12% with aggressive strategy. Secondary outcome is a composite pool of pre-specified fatal and non-fatal events. Randomization of 1111 subjects was completed by February 2007. Mean age of subjects (41% men) at entry was 67 years. BP was 158/87 mm Hg (systolic/diastolic) and prevalence of LVH by ECG was 21.0%. Cardio-Sis is the first randomized study specifically designed to compare two different SBP goals. Results will be broadly applicable to subjects with uncontrolled SBP under anti-hypertensive treatment.

Selenium (Se) is an essential trace mineral important for immune function and overall health of cattle. The nasopharyngeal microbiota in cattle plays an important role in overall respiratory health, especially when stresses associated with weaning, transport, and adaptation to a feedlot affect the normal respiratory defenses. Recent evidence suggests that cattle diagnosed with bovine respiratory disease complex have significantly less bacterial diversity. The objective of this study was to determine whether feeding weaned beef calves Se-enriched alfalfa (Medicago sativa) hay for 9 weeks in a preconditioning program prior to entering the feedlot alters nasal microbiota. Recently weaned beef calves (n = 45) were blocked by sex and body weight, randomly assigned to 3 treatment groups with 3 pens of 5 calves per treatment group, and fed an alfalfa hay based diet for 9 weeks. Alfalfa hay was harvested from fields fertilized with sodium selenate at a rate of 0, 45.0 or 89.9 g Se/ha. Blood samples were collected biweekly and analyzed for whole-blood Se concentrations. Nasal swabs were collected during week 9 from one or two calves from each pen (total n = 16). Calculated Se intake from dietary sources was 3.0, 15.6, and 32.2 mg Se/head/day for calves consuming alfalfa hay with Se concentrations of 0.34 to 2.42 and 5.17 mg Se/kg dry matter, respectively. Whole-blood Se concentrations after 8 weeks of feeding Se-fertilized alfalfa hay were dependent upon Se-application rates (0, 45.0, or 89.9 g Se/ha) and were 155, 345, and 504 ng/mL (PLinear < 0.0001). Microbial DNA was extracted from nasal swabs and amplified and sequenced. Alpha rarefaction curves comparing the species richness (observed OTUs) and overall diversity (Chao1, Observed OTU, and Shannon index) between calves fed selenium-biofortified alfalfa hay compared with control calves showed that Se-supplementation tended to be associated with an enriched nasal microbiota. ANOSIM of unweighted UniFrac distances showed that calves fed high Se-biofortified alfalfa hay clustered separately when compared with control calves in the PCoA plot (R = 0.216, P = 0.04). The bacterial orders Lactobacillales and Flavobacteriales were increased in healthy control calves compared with Clostridiales and Bacteroidales being increased in calves fed Se-biofortified alfalfa hay. Although there were strong trends, no significant differences were noted for any of the bacterial taxa. Based upon these findings, we suggest that weaned beef calves fed Se-biofortified hay tend to have an enriched nasal microbiota. Feeding Se-biofortified alfalfa hay to weaned beef calves prior to entering the feedlot is a strategy for increasing nasopharyngeal microbial diversity.

We previously reported that feeding Se-biofortified alfalfa hay to weaned beef calves in a preconditioning program decreases morbidity and mortality during the feedlot period. To understand the mode of action by which supranutritional Se supplementation supports calf health, we examined the effect of agronomic Se-biofortification on nasal microbiome and fecal parasites. Recently weaned Angus-cross beef calves (n = 30) were randomly assigned to two groups and fed an alfalfa hay-based diet for 9 weeks in a preconditioning program. Alfalfa hay was harvested from fields fertilized with sodium selenate at a rate of 0 or 90 g Se/ha. Calculated Se intake from dietary sources was 1.09 and 27.45 mg Se/calf per day for calves consuming alfalfa hay with Se concentrations of 0.06 and 3.47 mg Se/kg dry matter, respectively. Feeding Se-biofortified alfalfa hay for 9 weeks was effective at increasing whole-blood Se concentrations (556 ± 11 vs 140 ± 11 ng/mL; P < 0.001) and increasing body weight ( P Treatment , = 0.03) in weaned beef calves. Slaughter yield grades were higher for calves that had been fed Se-enriched alfalfa hay during the preconditioning period ( P Treatment = 0.008). No significant differences were observed in fecal parasite load, which remained low. The nasal microbiome and microbiota diversity within calves and across calves expanded from weaning (week 0) to the feedlot period (week 12), which was promoted by feeding Se-biofortified alfalfa hay. Especially concerning was the expansion of nasal Mycoplasmataceae in the feedlot, which reached over 50% of the total microbiota in some calves. In conclusion, we identified dietary Se-biofortified alfalfa hay as a potential promoter of nasal microbiome genome and microbiota diversity, which may explain in part high-Se benefits for prevention of bovine respiratory disease complex in beef calves.

Cerebral embolic protection (CEP) devices may be a tool to mitigate the perioperative stroke risk in cardiac surgery. However, studies are limited. The aim of this study was to analyze the feasibility, safety, and efficacy of CEP use in high-risk cardiac surgery. Ten high-risk surgical candidates with native valvular heart disease (mainly mitral with severe MAC) or failed bioprosthesis were consecutively enrolled between March 2023 and April 2024. All participants underwent open-heart surgery with use of Sentinel CEP. The CEP device was successfully deployed and recaptured in all cases without any Sentinel-related complications reported. Clearly visible, large deposits of calcium debris were captured. No significant neurological deficits (above mild neurological dysfunction; NIHSS > 5) were reported in any of the patients. Nine patients suffered postprocedural complications ranging from new-onset left bundle branch block to cardiogenic shock. One individual gradually deteriorated and ultimately died. Importantly, her neurological status remained intact throughout the course of the hospitalization. All other patients were discharged in good standing. The current study extends the early experience demonstrating the feasibility and safety of Sentinel CEP in high-risk cardiac surgery. Particularly in the highest-risk patient sub-sets CEP devices may offer advantages reducing the risk of periprocedural episodes and improving outcomes.

Dietary selenium (Se) alters whole-blood Se concentrations in sheep, dependent upon Se source and dosage administered, but little is known about effects on immune function. We used footrot (FR) as a disease model to test the effects of supranutritional Se supplementation on immune function. To determine the effect of Se-source (organic Se-yeast, inorganic Na-selenite or Na-selenate) and Se-dosage (1, 3, 5 times FDA-permitted level) on FR severity, 120 ewes with and 120 ewes without FR were drenched weekly for 62 weeks with different Se sources and dosages (30 ewes/treatment group). Innate immunity was evaluated after 62 weeks of supplementation by measuring neutrophil bacterial killing ability. Adaptive immune function was evaluated by immunizing sheep with keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. At baseline, FR-affected ewes had lower whole-blood and serum-Se concentrations; this difference was not observed after Se supplementation. Se supplementation increased neutrophil bacterial killing percentages in FR-affected sheep to percentages observed in supplemented and non-supplemented healthy sheep. Similarly, Se supplementation increased KLH antibody titers in FR-affected sheep to titers observed in healthy sheep. FR-affected sheep demonstrated suppressed cell-mediated immunity at 24 hours after intradermal KLH challenge, although there was no improvement with Se supplementation. We did not consistently prevent nor improve recovery from FR over the 62 week Se-treatment period. In conclusion, Se supplementation does not prevent FR, but does restore innate and humoral immune functions negatively affected by FR.

Selenium (Se) is an essential micronutrient in cattle, and Se-deficiency can affect morbidity and mortality. Calves may have greater Se requirements during periods of stress, such as during the transitional period between weaning and movement to a feedlot. Previously, we showed that feeding Se-fertilized forage increases whole-blood (WB) Se concentrations in mature beef cows. Our current objective was to test whether feeding Se-fertilized forage increases WB-Se concentrations and performance in weaned beef calves. Recently weaned beef calves (n = 60) were blocked by body weight, randomly assigned to 4 groups, and fed an alfalfa hay based diet for 7 wk, which was harvested from fields fertilized with sodium-selenate at a rate of 0, 22.5, 45.0, or 89.9 g Se/ha. Blood samples were collected weekly and analyzed for WB-Se concentrations. Body weight and health status of calves were monitored during the 7-wk feeding trial. Increasing application rates of Se fertilizer resulted in increased alfalfa hay Se content for that cutting of alfalfa (0.07, 0.95, 1.55, 3.26 mg Se/kg dry matter for Se application rates of 0, 22.5, 45.0, or 89.9 g Se/ha, respectively). Feeding Se-fertilized alfalfa hay during the 7-wk preconditioning period increased WB-Se concentrations (P Linear<0.001) and body weights (P Linear = 0.002) depending upon the Se-application rate. Based upon our results we suggest that soil-Se fertilization is a potential management tool to improve Se-status and performance in weaned calves in areas with low soil-Se concentrations.

Low selenium (Se) concentrations in soils and plants pose a health risk for ruminants consuming locally-grown forages. Previous studies have shown that Se concentrations in forages can be increased using soil-applied selenate amendments. However, the effects of foliar selenate amendments applied with traditional nitrogen-phosphorus-potassium-sulfur (NPKS) fertilizers on forage yields, and nutrient contents, and agronomic efficiencies are unknown. Using a split plot design, we determined the effects of springtime sodium selenate foliar amendment rates (0, 45, and 90 g Se ha ) and NPKS application (none, NPK for grasses/PK for alfalfa, and NPKS/PKS fertilization at amounts adapted to meet local forage and soil requirements) on forage growth and N, S, and Se concentrations, yields, and agronomic efficiencies. This 2-year study was conducted across Oregon on four representative forage fields: orchardgrass ( L.) in Terrebonne (central Oregon), grass-clover mixture in Roseburg (southwestern Oregon), and both grass mixture and alfalfa ( L.) fields in Union (eastern Oregon). Grasses grew poorly and were low in N content without NPK fertilization. Fertilization with NPK/PK promoted forage growth, increased forage N concentrations, and had to be co-applied with S when plant available S was low. Without Se amendment, forage Se concentrations were low and further decreased with NPKS/PKS fertilization. Selenate amendment linearly increased forage Se concentration without adversely affecting forage yields, N and S concentrations, or N and S agronomic efficiencies. Importantly, S fertilization did not interfere with Se uptake in Se amended plots. In conclusion, co-application of NPKS/PKS fertilizers and foliar sodium selenate in springtime is an effective strategy to increase forage total Se concentrations, while maintaining optimal growth and quality of Oregon forages.