The COVID-19 pandemic impacted the volume and nature of pediatric primary care visits nationwide. This study aimed to identify trends in pediatric visits at our institution during the pandemic to ...reveal opportunities to improve care of children and adolescents.
We performed a retrospective chart review of all pediatric visits conducted at a single family medicine clinic within a large academic medical center in Northern California from January 1, 2019, through September 30, 2021. Data collected for each visit included age, sex, type of visit (preventive or problem-focused), reason for visit (if problem-focused), and mode of visit (in-person or telehealth). We analyzed data using descriptive statistics and χ2 tests.
A total of 4,844 pediatric visits occurred during the study period. Visit volume dropped 9% from 2019 to 2020 and recovered to prepandemic levels in 2021. During the study period from 2019 to 2021, the percentage of problem-focused visits increased from 30% to 37% (P=.008) among adolescents, driven largely by an increase in the percentage of behavioral health visits from 14% to 29% (P<.001). We found no significant changes in the age or sex of patients seen. Telemedicine visit volume decreased from 2020 to 2021 in all age categories except for adolescents, which remained stable at 43% of all visits.
A sharp increase in behavioral health concerns among adolescents stands out as the most notable impact of COVID-19 on pediatric care at our institution. Our findings raise questions about how behavioral health care can be optimized for adolescents in the postpandemic era.
The role of increased smooth muscle cell (SMC) integrin αv signaling in Marfan syndrome (MFS) aortic aneurysm remains unclear. Herein, we examine the mechanism and potential efficacy of integrin αv ...blockade as a therapeutic strategy to reduce aneurysm progression in MFS.
Induced pluripotent stem cells (iPSCs) were differentiated into aortic SMCs of the second heart field (SHF) and neural crest (NC) lineages, enabling in vitro modeling of MFS thoracic aortic aneurysms. The pathological role of integrin αv during aneurysm formation was confirmed by blockade of integrin αv with GLPG0187 in
MFS mice.
iPSC-derived MFS SHF SMCs overexpress integrin αv relative to MFS NC and healthy control SHF cells. Furthermore, integrin αv downstream targets (FAK focal adhesion kinase/Akt
/mTORC1 mechanistic target of rapamycin complex 1) were activated, especially in MFS SHF. Treatment of MFS SHF SMCs with GLPG0187 reduced p-FAK/p-Akt
/mTORC1 activity back to control SHF levels. Functionally, MFS SHF SMCs had increased proliferation and migration compared to MFS NC SMCs and control SMCs, which normalized with GLPG0187 treatment. In the
MFS mouse model, integrin αv, p-Akt
, and downstream targets of mTORC1 proteins were elevated in the aortic root/ascending segment compared to littermate wild-type control. Mice treated with GLPG0187 (age 6-14 weeks) had reduced aneurysm growth, elastin fragmentation, and reduction of the FAK/Akt
/mTORC1 pathway. GLPG0187 treatment reduced the amount and severity of SMC modulation assessed by single-cell RNA sequencing.
The integrin αv-FAK-Akt
signaling pathway is activated in iPSC SMCs from MFS patients, specifically from the SHF lineage. Mechanistically, this signaling pathway promotes SMC proliferation and migration in vitro. As biological proof of concept, GLPG0187 treatment slowed aneurysm growth and p-Akt
signaling in
mice. Integrin αv blockade via GLPG0187 may be a promising therapeutic approach to inhibit MFS aneurysmal growth.
