Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia.

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes. METHODS: In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause. RESULTS: In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P<0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts. CONCLUSIONS: Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.).

Author Correction: Elevated faecal 12,13-diHOME concentration in neonates at high risk for asthma is produced by gut bacteria and impedes immune tolerance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Minimizing the Relationship Between Early Formula Use and Breastfeeding Cessation by Limiting Formula Volume.

Objective: Early exposure to formula can interfere with successful long-term breastfeeding. The objective of this study was to determine whether limiting the volume of formula used in the first month attenuates formula's detrimental impact on long-term breastfeeding success. Materials and Methods: Using detailed data on dietary intake from a randomized clinical trial, we conducted a secondary analysis of the association between volume of formula received in the first month and breastfeeding cessation before 6 and 12 months of age. We used descriptive statistics and multivariable logistic regression, respectively, to explore this association without and with adjustment for demographic and clinical predictors of infant feeding. Results: Among 199 breastfeeding infants, 80 (40%) received formula daily at 1 month of age, and breastfeeding cessation before 6 and 12 months of age was higher for these infants (46% and 67%) than for those breastfed exclusively (6% and 27%) (p < 0.0005 for each). The risk of cessation did not differ between those who received ≤4 fl oz daily in the first month (11%) and those who did not receive formula in the first month (6%) (p = 0.42). Adjusting for gestational age, race/ethnicity, income, and intention to breastfeed exclusively, the odds ratio for the outcome of cessation before 6 months was 1.15 (95% confidence interval = 0.20-6.67) for infants who received ≤4 fl oz daily compared with those who breastfed exclusively. Conclusion: Limiting formula volumes to ≤4 fl oz daily may attenuate the deleterious association between early formula use and subsequent successful breastfeeding.

Elevated faecal 12,13-diHOME concentration in neonates at high risk for asthma is produced by gut bacteria and impedes immune tolerance.

Neonates at risk of childhood atopy and asthma exhibit perturbation of the gut microbiome, metabolic dysfunction and increased concentrations of 12,13-diHOME in their faeces. However, the mechanism, source and contribution of this lipid to allergic inflammation remain unknown. Here, we show that intra-abdominal treatment of mice with 12,13-diHOME increased pulmonary inflammation and decreased the number of regulatory T (Treg) cells in the lungs. Treatment of human dendritic cells with 12,13-diHOME altered expression of PPARγ-regulated genes and reduced anti-inflammatory cytokine secretion and the number of Treg cells in vitro. Shotgun metagenomic sequencing of neonatal faeces indicated that bacterial epoxide hydrolase (EH) genes are more abundant in the gut microbiome of neonates who develop atopy and/or asthma during childhood. Three of these bacterial EH genes (3EH) specifically produce 12,13-diHOME, and treatment of mice with bacterial strains expressing 3EH caused a decrease in the number of lung Treg cells in an allergen challenge model. In two small birth cohorts, an increase in the copy number of 3EH or the concentration of 12,13-diHOME in the faeces of neonates was found to be associated with an increased probability of developing atopy, eczema or asthma during childhood. Our data indicate that elevated 12,13-diHOME concentrations impede immune tolerance and may be produced by bacterial EHs in the neonatal gut, offering a mechanistic link between perturbation of the gut microbiome during early life and atopy and asthma during childhood.

Pilot Analysis of Early Lactobacillus rhamnosus GG for Infant Colic Prevention.

We conducted a secondary analysis of data from a trial of Lactobacillus rhamnosus GG (LGG) supplementation as a pilot study to assess whether LGG prevents infant colic. For the first 6 months of life, infants received a daily dose of 10 billion colony-forming units of LGG or a control (n = 184). We compared the likelihood of a diagnosis of colic before 4 months of age, based on parent-reported symptoms or a physician diagnosis of colic. Out of the 184 infants, 18 (9.8%) had colic. There were no differences between the 2 groups in the percentage of infants with colic based on symptoms (control 5.4% vs LGG 9.8%; P = 0.19); physician diagnosis (control 3.2% vs LGG 7.6%; P = 0.26); or either symptoms or diagnosis combined (control 6.5% vs LGG 13.0%; P = 0.13). In this pilot study, early infant LGG supplementation does not appear to prevent the later development of colic.

Delayed gut microbiota development in high-risk for asthma infants is temporarily modifiable by Lactobacillus supplementation.

Gut microbiota dysbiosis and metabolic dysfunction in infancy precedes childhood atopy and asthma development. Here we examined gut microbiota maturation over the first year of life in infants at high risk for asthma (HR), and whether it is modifiable by early-life Lactobacillus supplementation. We performed a longitudinal comparison of stool samples collected from HR infants randomized to daily oral Lactobacillus rhamnosus GG (HRLGG) or placebo (HRP) for 6 months, and healthy (HC) infants. Meconium microbiota of HRP participants is distinct, follows a delayed developmental trajectory, and is primarily glycolytic and depleted of a range of anti-inflammatory lipids at 6 months of age. These deficits are partly rescued in HRLGG infants, but this effect was lost at 12 months of age, 6 months after cessation of supplementation. Thus we show that early-life gut microbial development is distinct, but plastic, in HR infants. Our findings offer a novel strategy for early-life preventative interventions.

Postpartum Depression: When Should Health Care Providers Identify Those at Risk?

Maternal postpartum depression (PPD) has an impact on mothers and infants. The American Academy of Pediatrics recommends screening for PPD at well-child visits during the first 6 months. We conducted a secondary data analysis of depression screening data collected each month during months 1 to 12 postpartum for 152 mothers with an infant participating in a randomized controlled trial. We used descriptive statistics to describe the incidence and the cumulative incidence of a positive PPD screen during months 1 to 12 postpartum. The results indicate that the initial positive screen for PPD can occur any time during the first 12 months postpartum and 15% had their first positive screen between months 6 and 12. Additionally, positive PPD screens are consistently high throughout the first year postpartum with the highest rate of positive screens at 12 months postpartum (23%). Our data suggest that PPD screening through 12 months may be most beneficial for families.

Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial.

OBJECTIVES: To determine if probiotic administration during the first 6 months of life decreases childhood asthma and eczema. METHODS: We conducted a randomized, double-blind controlled trial of Lactobacillus rhamnosus GG (LGG) supplementation on the cumulative incidence of eczema (primary end point) and asthma and rhinitis (secondary end points) in high-risk infants. For the first 6 months of life, intervention infants (n = 92) received a daily dose of 10 billion colony-forming units of LGG and 225 mg of inulin (Amerifit Brands, Cromwell, CT), and control infants (n = 92) received 325 mg of inulin alone. We used survival analysis methods to estimate disease incidences in the presence or absence of LGG and to estimate the efficacy of LGG in delaying or preventing these diseases. RESULTS: Infants were accrued over a 6-year period (median follow-up: 4.6 years; 95% retention rate at 2 years). At 2 years of age, the estimated cumulative incidence of eczema was 30.9% (95% confidence interval [CI], 21.4%-40.4%) in the control arm and 28.7% (95% CI, 19.4%-38.0%) in the LGG arm, for a hazard ratio of 0.95 (95% CI, 0.59-1.53) (log-rank P = .83). At 5 years of age, the cumulative incidence of asthma was 17.4% (95% CI, 7.6%-27.1%) in the control arm and 9.7% (95% CI, 2.7%-16.6%) in the LGG arm, for a hazard ratio of 0.88 (95% CI, 0.41-1.87) (log-rank P = .25). CONCLUSIONS: For high-risk infants, early LGG supplementation for the first 6 months of life does not appear to prevent the development of eczema or asthma at 2 years of age.

Television During Meals in the First 4 Years of Life.

The development of children's mealtime television (TV) habits has not been well studied. We assessed whether mealtime TV habits established in infancy will persist into early childhood. We analyzed data collected through parent surveys at birth and at 6-month intervals from a randomized controlled trial. We used t-tests, χ2 tests, and a multivariable logistic regression to determine if family characteristics were associated with mealtime TV. A McNemar test was used to assess whether mealtime TV exposure changed over time. College-educated fathers and families with an annual income >$50 000 were associated with less-frequent TV exposure during children's mealtimes. It was found that 84% of children retained their level of exposure to TV during mealtimes from the first 24 months through 48 months of life. Clinicians should counsel families about mealtime TV use within the first 2 years of life because these habits seem to develop early and persist into at least early childhood.

The Timing of Infant Food Introduction in Families With a History of Atopy.

OBJECTIVE: To describe the timing of introduction and type of food introduced to infants with a family history of atopy. METHODS: We conducted a secondary analysis of foods introduced each month to an interventional birth cohort of 149 infants at risk for atopy. RESULTS: Seven percent of infants received solid food prior to 4 months of age; 13% after 6 months of age. Hyperallergenic foods were introduced on average in the following order: wheat (8.7 months); eggs (11.2 months); soy (13.0 months); fish (13.4 months); peanut (20.2 months); tree nuts (21.8 months); and other seafood (21.8 months). Asian race (odds ratio 3.94; 95% CI 1.14-13.58) and maternal history of food allergy (odds ratio 3.86; 95% CI 1.29-11.56) were associated with late food introduction. CONCLUSION: Variation in timing of food introduction may reflect cultural preferences and/or previous experience with food allergy, as well as the ambiguous state of current recommendations.

Lactobacillus casei abundance is associated with profound shifts in the infant gut microbiome.

Colonization of the infant gut by microorganisms over the first year of life is crucial for development of a balanced immune response. Early alterations in the gastrointestinal microbiota of neonates has been linked with subsequent development of asthma and atopy in older children. Here we describe high-resolution culture-independent analysis of stool samples from 6-month old infants fed daily supplements of Lactobacillus casei subsp. Rhamnosus (LGG) or placebo in a double-blind, randomized Trial of Infant Probiotic Supplementation (TIPS). Bacterial community composition was examined using a high-density microarray, the 16S rRNA PhyloChip, and the microbial assemblages of infants with either high or low LGG abundance were compared. Communities with high abundance of LGG exhibited promotion of phylogenetically clustered taxa including a number of other known probiotic species, and were significantly more even in their distribution of community members. Ecologically, these aspects are characteristic of communities that are more resistant to perturbation and outgrowth of pathogens. PhyloChip analysis also permitted identification of taxa negatively correlated with LGG abundance that have previously been associated with atopy, as well as those positively correlated that may prove useful alternative targets for investigation as alternative probiotic species. From these findings we hypothesize that a key mechanism for the protective effect of LGG supplementation on subsequent development of allergic disease is through promotion of a stable, even, and functionally redundant infant gastrointestinal community.

Examining the hygiene hypothesis: the Trial of Infant Probiotic Supplementation.

The hygiene hypothesis suggests that the absence of infectious exposure at a critical point in immune system development leads to a greater risk for the later development of atopic disease. As a result, it may be possible to devise strategies that can block the onset of atopic diseases such as asthma. This paper outlines the rationale, background and design for the Trial of Infant Probiotic Supplementation study, which is designed to test the effectiveness of a daily infant probiotic supplement in the first 6 months of life in preventing the development of early markers of asthma.