In the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only ...categorically (<40 mg/dL). We sought to better characterize the nature, duration, and treatment for hypoglycemia.
Secondary analysis of infants from ALPS, a multicenter trial randomizing women at risk for late preterm delivery to betamethasone or placebo. This study was a reabstraction of all available charts from the parent trial, all of which were requested. Unreviewed charts included those lost to follow-up or from sites not participating in the reabstraction. Duration of hypoglycemia (<40 mg/dL), lowest value and treatment, if any, were assessed by group. Measures of association and regression models were used where appropriate.
Of 2,831 randomized, 2,609 (92.2%) were included. There were 387 (29.3%) and 223 (17.3%) with hypoglycemia in the betamethasone and placebo groups, respectively (relative risk RR: 1.69, 95% confidence interval CI: 1.46-1.96). Hypoglycemia generally occurred in the first 24 hours in both groups: 374/385 (97.1%) in the betamethasone group and 214/222 (96.4%) in the placebo group (
= 0.63). Of 387 neonates with hypoglycemia in the betamethasone group, 132 (34.1%) received treatment, while 73/223 (32.7%) received treatment in placebo group (
= 0.73). The lowest recorded blood sugar was similar between groups. Most hypoglycemia resolved by 24 hours in both (93.0 vs. 89.3% in the betamethasone and placebo groups, respectively,
= 0.18). Among infants with hypoglycemia in the first 24 hours, the time to resolution was shorter in the betamethasone group (2.80 interquartile range: 2.03-7.03) vs. 3.74 (interquartile range: 2.15-15.08) hours;
= 0.002. Persistence for >72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo,
= 0.18).
In this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure.
· Hypoglycemia was transient and approximately two-thirds received no treatment.. · Neonates in the ALPS trial who received betamethasone had a shorter time to resolution than those with hypoglycemia in the placebo group.. · Prolonged hypoglycemia occurred in approximately 2 out of 100 late preterm newborns, irrespective of antenatal steroid exposure..
Abstract Despite remarkable improvements in survival of extremely premature infants, the burden of BPD among survivors remains a frustrating problem for parents and caregivers. Advances, such as ...antenatal steroids and surfactant replacement, which have dramatically improved survival, have not reduced BPD among survivors. Other advances that have significantly improved the combined outcome of death or BPD, such as vitamin A and avoidance of mechanical ventilation, have had smaller magnitude effects on the outcome of BPD alone. Postnatal steroids have a clear beneficial effect on BPD, but the optimal preparation, dose, and timing for maximizing benefit and minimizing harm have yet to be determined. This persistent burden of BPD among the most immature survivors remains a challenge for the NRN and other researchers in neonatal medicine.
Antenatal administration of glucocorticoids such as betamethasone (BMZ) during the late preterm period improves neonatal respiratory outcomes. However, glucocorticoids may elicit programming effects ...on immune function and gene regulation. Here, we test the hypothesis that exposure to antenatal BMZ alters cord blood immune cell composition in association with altered DNA methylation and alternatively expressed Exon 1 transcripts of the glucocorticoid receptor (GR) gene in cord blood CD4
T-cells. Cord blood was collected from 51 subjects in the Antenatal Late Preterm Steroids Trial: 27 BMZ, 24 placebo. Proportions of leukocytes were compared between BMZ and placebo. In CD4+ T-cells, methylation at CpG sites in the GR promoter regions and expression of GR mRNA exon 1 variants were compared between BMZ and placebo. BMZ was associated with an increase in granulocytes (51.6% vs. 44.7% p = 0.03) and a decrease in lymphocytes (36.8% vs. 43.0% p = 0.04) as a percent of the leukocyte population vs. placebo. Neither GR methylation nor exon 1 transcript levels differed between groups. BMZ is associated with altered cord blood leukocyte proportions, although no associated alterations in GR methylation were observed.
Leishmania parasites infect macrophages, cells normally involved in innate defense against pathogens. Leishmania amazonensis and Leishmania major cause severe or mild disease, respectively, ...consistent with each parasite's ability to survive within activated macrophages. The mechanisms underlying increased virulence of L. amazonensis are mostly unknown. We show that L. amazonensis promotes its own survival by inducing expression of CD200, an immunoregulatory molecule that inhibits macrophage activation. L. amazonensis does not form typical nonhealing lesions in CD200(-/-) mice and cannot replicate in CD200(-/-) macrophages, an effect reversed by exogenous administration of soluble CD200-Fc. The less virulent L. major does not induce CD200 expression and forms small, self-healing lesions in both wild-type and CD200(-/-) mice. Notably, CD200-Fc injection transforms the course of L. major infection to one resembling L. amazonensis, with large, nonhealing lesions. CD200-dependent iNOS inhibition allows parasite growth in macrophages, identifying a mechanism for the increased virulence of L. amazonensis.
To investigate the relationships among blood pressure (BP) values, antihypotensive therapies, and in-hospital outcomes to identify a BP threshold below which antihypotensive therapies may be ...beneficial.
Prospective observational study of infants 23(0/7) to 26(6/7) weeks' gestational age. Hourly BP values and antihypotensive therapy use in the first 24 hours were recorded. Low BP was investigated by using 15 definitions. Outcomes were examined by using regression analysis controlling for gestational age, the number of low BP values, and illness severity.
Of 367 infants enrolled, 203 (55%) received at least 1 antihypotensive therapy. Treated infants were more likely to have low BP by any definition (P < .001), but for the 15 definitions of low BP investigated, therapy was not prescribed to 3% to 49% of infants with low BP and, paradoxically, was administered to 28% to 41% of infants without low BP. Treated infants were more likely than untreated infants to develop severe retinopathy of prematurity (15% vs 8%, P = .03) or severe intraventricular hemorrhage (22% vs 11%, P < .01) and less likely to survive (67% vs 78%, P = .02). However, with regression analysis, there were no significant differences between groups in survival or in-hospital morbidity rates.
Factors other than BP contributed to the decision to use antihypotensive therapies. Infant outcomes were not improved with antihypotensive therapy for any of the 15 definitions of low BP investigated.
Although opioid agonist therapy (OAT) is associated with positive health outcomes, including improved HIV management, long-term retention in OAT remains low among patients with opioid use disorder ...(OUD). Using data from the Veterans Aging Cohort Study (VACS), we identify variables independently associated with OAT retention overall and by HIV status. Among 7,334 patients with OUD, 13.7% initiated OAT, and 27.8% were retained 12-months later. Likelihood of initiation and retention did not vary by HIV status. Variables associated with improved likelihood of retention included receiving buprenorphine (relative to methadone), receiving both buprenorphine and methadone at some point over the 12-month period, or diagnosis of HCV. History of homelessness was associated with a lower likelihood of retention. Predictors of retention were largely distinct between patients with HIV and patients without HIV. Findings highlight the need for clinical, systems, and research initiatives to better understand and improve OAT retention.
To identify genetic variants associated with sepsis (early-onset and late-onset) using a genome-wide association (GWA) analysis in a cohort of extremely premature infants.
Previously generated GWA ...data from the Neonatal Research Network's anonymised genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole-genome-amplified DNA was genotyped for 1.2 million single-nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. p Values and false discovery rates (FDRs) were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p<10
. Secondary analyses assessed associations of SNPs with pathogen type. Pathway analyses were also run on primary and secondary end points.
Data from 757 extremely premature infants were included: 351 infants with sepsis and 406 infants without sepsis. No SNPs reached genome-wide significance levels (5×10
); two SNPs in proximity to FOXC2 and FOXL1 genes achieved target levels of significance. In secondary analyses, SNPs for ELMO1, IRAK2 (Gram-positive sepsis), RALA, IMMP2L (Gram-negative sepsis) and PIEZO2 (fungal sepsis) met target significance levels. Pathways associated with sepsis and Gram-negative sepsis included gap junctions, fibroblast growth factor receptors, regulators of cell division and interleukin-1-associated receptor kinase 2 (p values<0.001 and FDR<20%).
No SNPs met genome-wide significance in this cohort of extremely low birthweight infants; however, areas of potential association and pathways meriting further study were identified.
Scope
IL‐1RI‐mediated inflammatory signaling alters metabolic tissue responses to dietary challenges (e.g., high‐fat diet HFD). Recent work suggests that metabolic phenotype is transferrable between ...mice in a shared living environment (i.e., co‐housing) due to gut microbiome exchange. The authors examine whether the metabolic phenotype of IL‐1RI−/− mice fed HFD or low‐fat diet (LFD) could be transferred to wild‐type (WT) mice through gut microbiome exchange facilitated by co‐housing.
Methods and results
Male WT (C57BL/J6) and IL‐1RI−/− mice are fed HFD (45% kcal) or LFD (10% kcal) for 24 weeks and housed i) by genotype (single‐housed) or ii) with members of the other genotype in a shared microbial environment (co‐housed). The IL‐1RI−/− gut microbiome is dominant to WT, meaning that co‐housed WT mice adopted the IL‐1RI−/− microbiota profile. This is concomitant with greater body weight, hepatic lipid accumulation, adipocyte hypertrophy, and hyperinsulinemia in co‐housed WT mice, compared to single‐housed counterparts. These effects are most evident following HFD. Primary features of microbiome differences are Lachnospiraceae and Ruminococcaceae (known producers of SCFA).
Conclusion
Transfer of SCFA‐producing microbiota from IL‐1RI−/− mice highlights a new connection between diet, inflammatory signaling, and the gut microbiome, an association that is dependent on the nature of the dietary fat challenge.
High‐fat diet (HFD) impacts IL‐1RI‐signaling altering metabolic tissue function. This study demonstrates that the IL‐1RI‐/‐ microbiome dominates in a shared‐living environment, wherein transmission of SCFA‐producing bacteria and metabolic phenotype from IL‐1RI‐/‐ to wild‐type mice is enabled. These effects are more significant following a HFD challenge vs. a low‐fat diet. Results highlight a novel connection between diet, the gut, and inflammatory‐signaling.
Purpose Adverse event reporting is poorly classified and nonstandardized in the urological literature. We report adverse event data and associated risk factors using standardized reporting methods ...and Common Terminology Criteria for Adverse Events, version 3.0 to minimize interpretation bias and allow reliable comparisons with other populations. Materials and Methods We retrospectively reviewed consecutive radical cystectomies done for urothelial bladder carcinoma at our institution between January 2004 and September 2006. Adverse events within 90 days postoperatively were recorded. We explored the association of important risk factors with the overall complication rate and specific complications. Results A total of 283 patients were included in the study. Complete 90-day followup data were available on 90% of patients. Median age was 70 years (IQR 62–75). Median body mass index was 26.8 kg/m2 (IQR 24.4–31.0). At least 1 adverse event was observed in 152 patients (54.0%) and a grade 3–4 adverse event was observed in 40.3%. The most common grade 4 adverse events were myocardial infarction in 3.5% of cases, septic shock in 2.8% and pulmonary embolism in 1.8%. No patient died during followup. An association between body mass index, and any and major adverse events was found after adjusting for confounding variables. Conclusions More than 50% of patients experience an adverse event after radical cystectomy and 40% are major. Body mass index is independently associated with adverse events in these patients. These findings are important for individualized risk assessment, patient counseling and uniform assessment of quality care.
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