Laktoferrin som tilskudd for å forhindre sepsis hos premature

BACKGROUND: Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in neonatal intensive care units (NICUs) worldwide, with a high morbidity and related mortality. Lactoferrin is a mammalian milk glycoprotein involved in innate immunity. Recent data show that bovine lactoferrin (bLF) prevents late-onset sepsis in preterm very low birth weight (VLBW) neonates. METHODS: This is a secondary analysis of data from a multicenter randomized controlled trial where preterm VLBW neonates randomly received bLF, bLF + Lactobacillus rhamnosus GG, or placebo. Her I analyze the incidence rates of the primary outcome late-onset sepsis, but also the secondary outcomes including incidence of urinary tract infections, fungal colonization, invasive fungal colonization, rate of progression from colonization to infection, necrotizing enterocolitis, threshold retinopathy of prematurity, severe intraventricular hemorrhage and bronchopulmonary dysplasia and adverse effects or intolerance in all groups. RESULTS: This study included 472 low birth weight infants whose clinical, nutritional, and demographical characteristics were similar. A statistically significant reduction in late-onset sepsis was observed in groups that received either lactoferrin alone (RR 0.34, 95% CI 0.17, 0.70; P=0,002) or in combination with Lactobacillus rhamnosus GG (RR 0.27, 95% CI 0.12, 0.60; P<0.001). In subgroup analyses, infants weighing less than 1000 g had significant reduction in late-onset sepsis after oral lactoferrin supplementation alone. Invasive fungal colonization was significantly decreased in the group receiving bLF (P=0.004). Prophylaxis with oral lactoferrin alone did not reduce the incidence of NEC (P=0.09), but there were a significant reduction in threshold retinopathy of prematurity in the group receiving oral lactoferrin alone (P=0.02). No adverse effects or intolerances occurred. CONCLUSIONS: Prophylactic oral administration of bLF reduces the incidence of late-onset sepsis in infants weighing less than 1500 g and most effective in infants weighing less than 1000 g. Oral lactoferrin prophylaxis also reduces the incidence of invasive fungal infection in preterm VLBW neonates and the incidence retinopathy of prematurity. Well-designed, randomized trials should address dosing, duration, type of lactoferrin (bovine or human) prophylaxis in prevention of sepsis and other invasive infections

Thyroid Signaling Biomarkers in Female Symptomatic Hypothyroid Patients on Liothyronine versus Levothyroxine Monotherapy: A Randomized Crossover Trial

Background. Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5–10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid signaling pathway, in addition to adverse effects, in patients with residual hypothyroid symptoms. Methods. Fifty-nine female hypothyroid patients, with residual symptoms on LT4 monotherapy or LT4/liothyronine (LT3) combination therapy, were randomly assigned in a non-blinded crossover study and received LT4 or LT3 monotherapy for 12 weeks each. Measurements, including serum analysis of a number of biochemical and hormonal parameters, were obtained at the baseline visit and after both treatment periods. Results. Free thyroxine (FT4) was higher in the LT4 group, while free triiodothyronine (FT3) was higher in the LT3 group. The levels of reverse triiodothyronine (rT3) decreased after LT3 treatment compared with LT4 treatment. Both low-density lipoprotein (LDL) and total cholesterol levels were reduced, while sex hormone-binding globulin (SHBG) increased after LT3 treatment compared with LT4 treatment. The median TSH levels for both treatment groups were within the reference range, however, lower in the LT4 group than in the LT3 group. We did not find any differences in pro-B-type natriuretic peptide (NT pro-BNP), handgrip strength, bone turnover markers, or adverse events between the two treatment groups. Conclusion. We have demonstrated that FT4, FT3, rT3, cholesterol, and SHBG show significantly different values on LT4 treatment compared with LT3 treatment in women with hypothyroidism and residual symptoms despite normal TSH levels. No differences in general or bone-specific adverse effects were demonstrated. This trial is registered with NCT03627611 in May 2018

Effect of Liothyronine Treatment on Dermal Temperature and Activation of Brown Adipose Tissue in Female Hypothyroid Patients: A Randomized Crossover Study

Background Thyroid hormones are essential for the full thermogenic response of brown adipose tissue (BAT) and have been implicated in dermal temperature regulation. Nevertheless, persistent cold-intolerance exists among a substantial proportion of hypothyroid patients on adequate levothyroxine (LT4) substitution. Materials and Methods To assess if skin temperature and activation of BAT during treatment with liothyronine (LT3) differs from that of LT4 treatment, fifty-nine female hypothyroid patients with residual symptoms on LT4 or LT4/LT3 combination therapy were randomly assigned in a non-blinded crossover study to receive monotherapy with LT4 or LT3 for 12 weeks each. Change in supraclavicular (SCV) skin temperature overlying BAT, and sternal skin temperature not overlying BAT, during rest and cold stimulation were assessed by infrared thermography (IRT). In addition, abundance of exosomal miR-92a, a biomarker of BAT activation, was estimated as a secondary outcome. Results Cold stimulated skin temperatures decreased less with LT3 vs . LT4 in both SCV (mean 0.009°C/min [95% CI: 0.004, 0.014]; P &amp;lt;0.001) and sternal areas (mean 0.014°C/min [95% CI: 0.008, 0.020]; P &amp;lt;0.001). No difference in serum exosomal miR-92a abundance was observed between the two treatment groups Conclusion LT3 may reduce dermal heat loss. Thermography data suggested increased BAT activation in hypothyroid patients with cold-intolerance. However, this finding was not corroborated by assessment of the microRNA biomarker of BAT activation. Clinical Trial Registration ClinicalTrials.gov , identifier NCT0362761