Advance Care Planning Preferences and Readiness in Cirrhosis: A Prospective Assessment of Patient Perceptions and Knowledge.

Background: In 2014, the province of Alberta launched a campaign to promote public awareness of advance care planning (ACP) and its associated two-part documentation-a Goals of care designation (GCD, a medical order written by a health care practitioner detailing wishes for care) and a personal directive (PD, a document naming a surrogate decision maker). Notably, unlike the GCD, the PD can be self-initiated independent of a health practitioner. Objective: Two years after the campaign, we aimed to assess knowledge and recall of participation in ACP among cirrhosis patients. Design/Setting: Consecutive adult cirrhosis patients attending one of two specialty cirrhosis clinics in Edmonton, Alberta, were surveyed. Results: Ninety-seven patients were included. Mean model for end-stage liver disease was 12. Although 97% of patients indicated it was extremely important to know the reality of their illness, only 53% understood that cirrhosis would affect their future quality of life. Thirty-three percent of patients had completed a PD and 14% had completed a GCD. Seventy-eight percent of patients believed a GCD was important to them and 85% preferred to complete it in an outpatient clinic setting. Only a minority of patients who had taken the initiative to complete a PD in the community also had a GCD. Conclusions: Despite efforts to raise awareness of and educate Albertans about ACP, <20% of cirrhosis patients have a completed GCD. Additional strategic prioritization is required in both patients and providers to ensure that health practitioner-facilitated ACP is carried out as standard-of-care in all patients with cirrhosis.

Reduction in Regulatory T Cells in Early Pregnancy Causes Uterine Artery Dysfunction in Mice.

Preeclampsia, fetal growth restriction, and miscarriage remain important causes of maternal and perinatal morbidity and mortality. These complications are associated with reduced numbers of a specialized T lymphocyte subset called regulatory T cells (Treg cells) in the maternal circulation, decidua, and placenta. Treg cells suppress inflammation and prevent maternal immunity toward the fetus, which expresses foreign paternal alloantigens. Treg cells are demonstrated to contribute to vascular homeostasis, but whether Treg cells influence the vascular adaptations essential for a healthy pregnancy is unknown. Thus, using a mouse model of Treg-cell depletion, we investigated the hypothesis that depletion of Treg cells would cause increased inflammation and aberrant uterine artery function. Here, we show that Treg-cell depletion resulted in increased embryo resorption and increased production of proinflammatory cytokines. Mean arterial pressure exhibited greater modulation by NO in Treg cell-deficient mice because the L-NG-nitroarginine methyl ester-induced increase in mean arterial pressure was 46% greater compared with Treg cell-replete mice. Uterine artery function, which is essential for the supply of nutrients to the placenta and fetus, demonstrated dysregulated hemodynamics after Treg-cell depletion. This was evidenced by increased uterine artery resistance and pulsatility indices and enhanced conversion of bET-1 (big endothelin-1) to the active and potent vasoconstrictor, ET-1 (endothelin-1). These data demonstrate an essential role for Treg cells in modulating uterine artery function during pregnancy and implicate Treg-cell control of maternal vascular function as a key mechanism underlying normal fetal and placental development.

Effect of advanced maternal age on pregnancy outcomes and vascular function in the rat.

Advanced maternal age is becoming increasingly common in Western societies and is associated with increased maternal and fetal morbidity and mortality. We hypothesized that aging results in impaired vascular function in pregnancy because of increased vascular oxidative stress and resultant scavenging of nitric oxide in both uterine and systemic arteries, causing reduced uteroplacental perfusion and poor pregnancy outcomes. Using aged rats (9.5 months), we investigated the effect of a delayed first natural pregnancy on pregnancy outcomes and uterine and mesenteric artery function on gestational day 20. Delayed pregnancy in the rat reduced fertility by 46%, reduced litter size by 36%, caused fetal growth restriction, increased placental weight, and increased maternal systolic blood pressure (by 16 mm Hg). Uterine arteries from aged dams displayed reduced constriction to phenylephrine (young: 14.3±0.94 mN/mm versus aged: 11.4±0.5 mN/mm, P=0.02) and potassium chloride (124 mmol/L; young: 21.8±1.27 mN/mm versus aged: 14.2±1.7 mN/mm; P=0.01). Methacholine-induced vasodilation was similar in uterine arteries from young and aged dams. However, mesenteric arteries from aged dams had a greater nitric oxide and a reduced endothelial-derived hyperpolarization contribution to methacholine-mediated vasodilation compared with young dams. Both uterine and mesenteric arteries from aged dams had greater active myogenic responses, with area under the curve increased by 228% and 151%, in aged uterine and mesenteric arteries, respectively. These results demonstrate that vascular function is altered at an advanced maternal age and provides further insights into the risks of poor pregnancy outcomes observed in women who delay pregnancy.