We used a double-blind, placebo-controlled trial to study the efficacy of WC3 rotavirus vaccine administered to 104 infants (ages, three to 12 months) before the rotavirus season. Forty-nine infants received vaccine; 55 received placebo. Rotavirus disease during this season was predominantly caused by a serotype 1 strain. In placebo recipients there were 14 cases of rotavirus diarrhea (attack rate, 25%); 11 were moderate to severe (attack rate, 20%). Vaccinees experienced only three cases of rotavirus disease (attack rate, 6.1%), all mild. When all cases (whether associated with rotavirus or not) of clinically significant diarrhea (CSD) were evaluated, WC3 vaccine provided statistically significant (P less than .01) protection against the total number of episodes of CSD and reduced the number of days of CSD-associated diarrhea, vomiting, fever, or illness. Seventy-one percent of the WC3-vaccinated infants had serum antibody responses to the vaccine. The 14 placebo recipients who experienced natural disease predominantly had antibody responses to serotype 1. Sera taken after the rotavirus season revealed a nearly identical rate (40%) of natural rotavirus infection in the vaccinated and placebo groups.
By releasing vasoactive substances into the circulation, carcinoid tumors can cause right-sided valvular heart disease. Factors associated with the progression of carcinoid heart disease are poorly understood. We conducted a retrospective study to identify such factors.Our sample included 71 patients with the carcinoid syndrome who underwent serial echocardiographic studies performed more than one year apart and 32 patients referred directly for surgical intervention after an initial echocardiographic evaluation. A score for carcinoid heart disease was determined on the basis of an assessment of valvular anatomy and function and the function of the right ventricle. An increase of more than 25 percent in the score between studies was considered suggestive of disease progression. Tumor progression was assessed on the basis of abdominal computed tomographic scans and changes in the level of urinary 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin.Of the patients with serial echocardiographic studies, 25 (35 percent) had an increase of more than 25 percent in the cardiac score. As compared with patients whose score changed by 25 percent or less, these patients had higher urinary peak 5-HIAA levels (median, 265 mg per 24 hours [interquartile range, 209 to 593] vs. 189 mg per 24 hours [interquartile range, 75 to 286]; P=0.004) and were more likely to have biochemical progression (10 of 25 patients vs. 9 of 46, P=0.05) and to have received chemotherapy (13 of 25 vs. 10 of 46, P=0.009). Logistic-regression analysis showed that a higher peak urinary 5-HIAA level and previous chemotherapy were predictors of an increase in the cardiac score that exceeded 25 percent (odds ratio for each increase in 5-HIAA of 25 mg per 24 hours, 1.08 [95 percent confidence interval, 1.03 to 1.13]; P=0.009); odds ratio associated with chemotherapy, 3.65 [95 percent confidence interval, 1.74 to 7.48]; P=0.001).Serotonin is related to the progression of carcinoid heart disease, and the risk of progressive heart disease is higher in patients who receive chemotherapy than in those who do not.
Background Two-dimensional strain echocardiography (2D-SE) calculates tissue velocities via frame-to-frame tracking of unique acoustic markers within the image and provides strain parameters in two dimensions. Novel 2D-SE software allows semi-automated strain measurements and increased averaging capabilities optimizing signal–noise ratio.
To assess left atrial (LA) function and determine the prevalence of LA dysfunction in AL amyloidosis (AL) using conventional and strain echocardiography.LA ejection fraction, LA filling fraction, LA ejection force, peak LA systolic strain rate (LAsSR), and LA systolic strain (LA epsilon) were determined in 95 AL patients (70 with and 25 without echocardiographic evidence of cardiac involvement, abbreviated CAL and NCAL, respectively), 30 age-matched controls (CON), and 20 patients with diastolic dysfunction and LA dilatation (DD). Peak LAsSR >2 standard deviations below mean CON value was used as the cut-off for normal LA function. LA ejection fraction was lower in CAL when compared with CON (40.4+/-13.6 vs. 67.0+/-6%, P=0.01). Left atrial septal strain rate and strain were lower in CAL (0.8+/-0.5 s(-1) and 5.5+/-4%, respectively) compared with CON (1.8+/-0.8 s(-1) and 14+/-4%, respectively, P=<0.0001), NCAL (1.6+/-0.8 s(-1) and 13+/-7%, respectively, P<0.0001) and DD (1.3+/-0.4 s(-1) and 10+/-2%, respectively, P<0.0001). Based on peak LA systolic strain rate criteria, the cut-off values for normal LA function were -1.1 s(-1) and -1.05 s(-1) for lateral and septal walls. Using these criteria, LA dysfunction was identified in 32% (lateral LA criteria) and 60% (septal LA criteria) of CAL patients. Lateral and septal LAsSR were lower in CAL patients with vs. those without symptoms of heart failure. Inter- and intra-observer agreement was high for LA strain echocardiography.LA function assessment using strain echocardiography is feasible with low intra- and inter-observer variability. LA dysfunction is observed in AL patients without other echocardiographic features of cardiac involvement and may contribute to cardiac symptoms in CAL.
Background: Despite the availability of potent LDL-C-lowering therapies, patients with mixed dyslipidemia (MD) remain at high risk of cardiovascular (CV) disease due to residual risk from triglyceride (TG)-rich atherogenic lipoproteins (TRLs), ie, remnant cholesterol and/or VLDL-C. Inhibition of APOC3 has emerged as a promising therapeutic strategy for reducing this residual CV risk. Aim: We report interim results through Week 24 from MUIR, an ongoing, randomized, placebo-controlled, Phase 2b study (NCT04998201) evaluating the effects of ARO-APOC3 in patients with MD (fasting TGs 150 to 499 mg/dL and either LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL). Methods: Eligible subjects (n=353) were randomized 3:1 to receive either subcutaneous injections of 10, 25, or 50 mg ARO-APOC3 or matched placebo on Day 1 and at Week 12 or 50 mg ARO-APOC3 on Day 1 and Week 24. Subjects were on a stable diet and optimal lipid-lowering therapies. The primary endpoint was the percent change from baseline in fasting TGs at Week 24. Statistically significant differences were determined using mixed model repeat measures analysis. Results: At Week 24, when dosed on Day 1 and Week 12, ARO-APOC3 significantly decreased APOC3 in a dose-dependent manner up to 80% (p<0.0001). Least squares (LS) mean TGs were significantly reduced by 52 to 64% (p<0.0001). Least squares (LS) mean atherogenic lipoproteins were reduced by up to 27% for non-HDL-C, 19% for apolipoprotein B, and 55% for remnant cholesterol. LS mean HDL-C was increased by up to 51%. The most frequent adverse events were COVID-19 infection, worsening of glycemic control, and upper respiratory infection. Conclusions: By silencing APOC3 expression, ARO-APOC3 significantly reduced circulating TGs and atherogenic TRLs in patients with MD. The effect of ARO-APOC3 on CV relative risk reduction will be evaluated in an upcoming outcomes trial.
