Differences in pulmonary arterial flow hemodynamics between children and adults with pulmonary arterial hypertension as assessed by 4D-flow CMR studies.

Despite different developmental and pathological processes affecting lung vascular remodeling in both patient populations, differences in 4D MRI findings between children and adults with PAH have not been studied. The purpose of this study was to compare flow hemodynamic state, including flow-mediated shear forces, between pediatric and adult patients with PAH matched by severity of pulmonary vascular resistance index (PVRi). Adults (n = 10) and children (n = 10) with PAH matched by pulmonary vascular resistance index (PVRi) and healthy adult (n = 10) and pediatric (n = 10) subjects underwent comprehensive 4D-flow MRI to assess peak systolic wall shear stress (WSSmax) measured in the main (MPA), right (RPA), and left pulmonary arteries (LPA), viscous energy loss (EL) along the MPA-RPA and MPA-LPA tract, and qualitative analysis of secondary flow hemodynamics. WSSmax was decreased in all pulmonary vessels in children with PAH when compared with the same age group (all P < 0.05). Similarly, WSSmax was decreased in all pulmonary vessels in adult PAH patients when compared with healthy adult subjects (all P < 0.01). Average EL was increased in adult patients with PAH when compared with the same age group along both MPA-RPA (P = 0.020) and MPA-LPA (P = 0.025) tracts. There were no differences in EL indices between adults and pediatric patients. Children and adult patients with PAH have decreased shear hemodynamic forces. However, pathological flow hemodynamic formations appear to be more consistent in adult patients, whereas flow hemodynamic abnormalities appear to be more variable in children with PAH for comparable severity of PVRi. NEW & NOTEWORTHY Both children and adult patients with PAH have decreased shear hemodynamic forces inside the pulmonary arteries associated with the degree of vessel dilation and stiffness. These differences also exist between healthy normotensive children and adults. However, pathological flow hemodynamic formations appear to more uniform in adult patients, whereas in children with PAH flow, hemodynamic abnormalities appear to be more variable. Pathological flow formations appear not to have a major effect on viscous energy loss associated with the flow conduction through proximal pulmonary arteries.

Loss of follow-up in transition to adult CHD: a single-centre experience.

Lapses in care during transition in adult CHD patients lead to increased morbidity and mortality. Previous studies have investigated predictors of poor follow-up in universal healthcare paradigms and select American populations. We studied patients with a wide spectrum of CHD severity within a single American centre to identify factors associated with successful internal transition and maintenance of care. Loss of follow-up was defined as no documented cardiac follow-up for ⩾3 years. Ambulatory cardiology patients aged 16-17 years with CHD were retrospectively enrolled and contacted. A survey assessing demographics, patients' understanding of their CHD, medical status, and barriers to care was administered. On the basis of chart review of 197 enrolled patients, 74 demonstrated loss of follow-up (37.6%). Of 78 successfully contacted patients, 58 were surveyed, of whom a minority had loss of follow-up (n=16). The status of most patients with loss of follow-up was not known. Maintenance of care was associated with greater complexity of CHD (p<0.01), establishment of care with an adult CHD provider (p<0.001), use of prescription medications (p<0.001), and receipt of education emphasising the importance of long-term cardiac care (p<0.003). Insurance lapses were not associated with loss of follow-up (p=0.08). Transition and maintenance of care was suboptimal even within a single centre. Over one-third of patients did not maintain care. Patients with greater-complexity CHD, need for medications, receipt of transition education, and care provided by adult CHD providers had superior follow-up.

Visceral adipose inflammation in obesity is associated with critical alterations in tregulatory cell numbers.

BACKGROUND: The development of insulin resistance (IR) in mouse models of obesity and type 2 diabetes mellitus (DM) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue inflammation via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose inflammation and investigated the role of Tregs in IR/obesity through coordinated studies in mice and humans. METHODS AND FINDINGS: Foxp3-green fluorescent protein (GFP) "knock-in" mice were randomized to a high-fat diet intervention for a duration of 12 weeks to induce DIO/IR. Morbidly obese humans without overt type 2 DM (n = 13) and lean controls (n = 7) were recruited prospectively for assessment of visceral adipose inflammation. DIO resulted in increased CD3(+)CD4(+), and CD3(+)CD8(+) cells in visceral adipose with a striking decrease in visceral adipose Tregs. Treg numbers in visceral adipose inversely correlated with CD11b(+)CD11c(+) adipose tissue macrophages (ATMs). Splenic Treg numbers were increased with up-regulation of homing receptors CXCR3 and CCR7 and marker of activation CD44. In-vitro differentiation assays showed an inhibition of Treg differentiation in response to conditioned media from inflammatory macrophages. Human visceral adipose in morbid obesity was characterized by an increase in CD11c(+) ATMs and a decrease in foxp3 expression. CONCLUSIONS: Our experiments indicate that obesity in mice and humans results in adipose Treg depletion. These changes appear to occur via reduced local differentiation rather than impaired homing. Our findings implicate a role for Tregs as determinants of adipose inflammation.