Myeloid angiogenic cells exhibit impaired migration, reduced expression of endothelial markers and increased apoptosis in idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and devastating condition. There is no known cure for IPAH, and current treatment options are not always effective. Autologous myeloid angiogenic cells (MACs) have been explored as a novel therapy for IPAH but preliminary data from clinical trials show limited beneficial effects. A complete understanding of IPAH MAC function remains elusive. This study was designed to comprehensively compare cell function between IPAH MACs and healthy control MACs. MACs were procured through the culture of peripheral blood mononuclear cells in endothelial selective medium for 7 days. Compared with healthy MACs, IPAH MACs exhibited 1) significantly lower levels of endothelial markers as shown by fluorescence microscopy; 2) a markedly higher rate of apoptosis under both normal culture condition and serum starvation as shown by the TUNEL assay; 3) significantly decreased migration towards VEGF as shown by a modified Boyden chamber migration assay; and 4) similar VEGF and eNOS mRNA levels as shown by RT-qPCR. In conclusion, various aspects of IPAH MAC function are impaired. In order to achieve greater therapeutic benefits, pharmacologic and/or genetic manipulations to improve IPAH MAC function, particularly to promote cell survival and migration, are warranted.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Obstetric services in the UK during the COVID-19 pandemic: A national survey

Background: The management of obstetric patients with coronavirus disease 2019 (COVID-19) due to human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires unique considerations. Many aspects of labour and delivery practice required adaptation in response to the global pandemic and were supported by guidelines from the Royal College of Obstetrics and Gynaecologists. The adoption and adherence to these guidelines is unknown. / Methods: Participating centres in “Quality of Recovery in Obstetric Anaesthesia study - a multicentre study” (ObsQoR) completed an electronic survey based on the provision of services and care related to COVID-19 in October 2021. The survey was designed against the Royal College of Obstetricians and Gynaecologists COVID-19 guidelines. / Results: One hundred and five of the 107 participating centres completed the survey (98% response rate representing 54% of all UK obstetric units). The median [IQR] annual number of deliveries among the included sites was 4389 [3000-5325]. Ninety-nine of the 103 (94.3%) sites had guidelines for the management of peripartum women with COVID-19. Sixty-one of 105 (58.1%) had specific guidance for venous thromboembolism (VTE) prophylaxis. Thirty-seven of 104 (35.6%) centres restricted parturient birthing plans if a positive diagnosis of COVID-19 was made. A COVID-19 vaccination referral pathway encouraging full vaccination for all pregnant women was present in 63/103 centres (61.2%). / Conclusion: We found variability in care delivered and adherence to guidelines related to COVID-19. The clinical implications for this related to quality of peripartum care is unclear, however there remains scope to improve pathways for immunisation, birth plans and VTE prophylaxis

Increased CD34+ cells in PBMNCs isolated from HHT patients.

<p>Flow cytometric analysis showed that PBMNCs consisted of cells with different size and granularity (a), monocytic/lymphocytic population stained by fluorescent dye 7-AAD indicated over 99% cell viability (b). Manually gated cells for CD34 staining analysis were performed. A representative dot plot of CD34 analysis for a healthy volunteers and a HHT patient was shown in c and d, respectively. About 0.3% CD34+ cells were identified in PBMNCs from HHT patients, which was significantly higher than that in the control samples (e). *<i>p</i><0.05, compared with healthy controls.</p

Elevated basal cell apoptosis levels in CACs from HHT patients.

<p>Basal cell apoptosis in CACs after a 7-day culture was analyzed by Annexin V staining and flow cytometry. A representative dot plot of flow cytometric analysis for healthy and HHT CAC apoptosis was shown in panels a and b, respectively. Statistic analysis demonstrated that the levels of basal cell apoptosis in CACs from HHT patients were significantly higher than those in CACs of healthy individuals (c). *<i>p</i><0.05, compared with healthy controls.</p

Suppressed cell migration towards VEGF and SDF1 in CACs from patients with HHT.

<p>Cell migration towards VEGF and SDF1 in healthy CACs increased by 4-folds and 3-folds, respectively, over the non-treated cells (a and b). In contrast, both VEGF and SDF1 induced HHT CAC migration was barely increased over the non-treated cells (a and b). *<i>p</i><0.05, compared with cells without VEGF or SDF1 treatment.</p

Summary of Patient Demographics.

<p>Summary of Patient Demographics.</p