Background The small incisions of minimally invasive surgery have the proposed benefit of less surgical trauma, less pain, and faster recovery. This study was done to compare minimally invasive techniques for aortic valve replacement, including right anterior mini-thoracotomy and mini-sternotomy, to conventional sternotomy. Methods We retrospectively reviewed 503 patients who underwent isolated aortic valve replacement at our institution from 2012 to 2015 using one of three techniques: 1) Mini-thoracotomy, 2) Mini-sternotomy, 3) Conventional sternotomy. Demographics, operative morbidity, mortality, and postoperative complications were compared. Results Of the 503 cases, 267 (53.1%) were mini-thoracotomy, 120 (23.8%) were mini-sternotomy, and 116 (23.1%) were conventional sternotomy. Mini-thoracotomy patients, compared to mini-sternotomy and conventional sternotomy, had significantly shorter bypass times [82 (IQ 67–113) minutes; vs. 117 (93.5–139.5); vs. 102.5 (85.5–132.5), respectively ( p < 0.0001)], a lower incidence of prolonged ventilator support [3.75% vs. 9.17 and 12.9%, respectively ( p = 0.0034)], and required significantly shorter ICU and postoperative stays, resulting in an overall shorter hospitalization [6 (IQ 5–9) days; vs. 7 (5–14.5); vs 9 (6–15.5), respectively ( p < 0.05)]. Incidence of other postoperative complications were lower in the mini-thoracotomy group compared to mini-sternotomy and conventional sternotomy, without significance. Minimally invasive techniques trended towards better survival [mini-thoracotomy 1.5%, mini-sternotomy 1.67%, and conventional sternotomy 5.17% ( p = 0.13)]. Conclusions Minimally invasive aortic valve replacement approaches are safe, effective alternatives to conventional sternotomy. The mini-thoracotomy approach showed decreased operative times, decreased lengths of stay, decreased incidence of prolonged ventilator time, and a trend towards lower mortality when compared to mini-sternotomy and conventional sternotomy.

The tumor suppressor phosphatase and tensin homolog (PTEN) dephosphorylates PIP3 and antagonizes the prosurvival PI3K-Akt pathway. Targeted deletion of PTEN in mice led to early embryonic lethality. To elucidate its role in embryonic epithelial morphogenesis and the underlying mechanisms, we used embryonic stem cell-derived embryoid body (EB), an epithelial cyst structurally similar to the periimplantation embryo. PTEN is upregulated during EB morphogenesis in parallel with apoptosis of core cells, which mediates EB cavitation. Genetic ablation of PTEN causes Akt overactivation, apoptosis resistance and cavitation blockade. However, rescue experiments using mutant PTEN and pharmacological inhibition of Akt suggest that the phosphatase activity of PTEN and Akt are not involved in apoptosis-mediated cavitation. Instead, hypoxia-induced upregulation of Bnip3, a proapoptotic BH3-only protein, mediates PTEN-dependent apoptosis and cavitation. PTEN inactivation inhibits hypoxia-and reactive oxygen species-induced Bnip3 elevation. Overexpression of Bnip3 in PTEN-null EBs rescues apoptosis of the core cells. Mechanistically, suppression of Bnip3 following PTEN loss is likely due to reduction of hypoxia-inducible factor-2α (HIF-2α) because forced expression of an oxygen-stable HIF-2α mutant rescues Bnip3 expression and apoptosis. Lastly, we show that HIF-2α is upregulated by PTEN at both transcriptional and posttranscriptional levels. Ablation of prolyl hydroxylase domain-containing protein 2 (PHD2) in normal EBs or inhibition of PHD activities in PTEN-null EBs stabilizes HIF-2α and induces Bnip3 and caspase-3 activation. Altogether, these results suggest that PTEN is required for apoptosis-mediated cavitation during epithelial morphogenesis by regulating the expression of HIF-2α and Bnip3.