Using DaSilva Cone Operation to Establish 1.5 or 2 Ventricle Circulation After Initial Single Ventricle Palliation with Starnes Procedure.

Ebstein anomaly (EA) is a congenital dysplasia of the tricuspid valve resulting in reduced right ventricular (RV) volume and tricuspid regurgitation. Severe EA in the neonatal period is associated with high mortality. The Starnes procedure (fenestrated RV exclusion) is reserved for EA patients with cardiogenic shock and has previously committed patients to single ventricle (SV) palliation. In this report, we present the results of a strategy to redirect patients utilizing the Da Silva Cone operation to achieve a 2 or 1.5 ventricle circulation. Single-center retrospective study including all consecutive cases of Da Silva Cone operation after Starnes procedure. Between 2019 and 2023, six conversions from Starnes procedure to Cone reconstruction were performed. All were critically ill before their Starnes procedure; four on extracorporeal membrane oxygenation. Two patients were successfully rerouted to a two-ventricle repair; the remainder to 1.5 ventricle circulation. RV pressure estimates showed no correlation with success. Post-Cone intensive care and hospital stays were brief, median 5 and 6 days, respectively. All are between 2.5 and 6 years old, without indications for SV palliation. There were no deaths, with follow up ranging 1 month-4 years. No repeat interventions were performed on the tricuspid valves. One subject had a surgical pulmonary valve replacement. Tricuspid regurgitation was mild in all. The Da Silva Cone operation offers successful redirection of EA patients from a SV pathway to a 1.5 or 2 ventricle pathway after Starnes procedure. The approach is feasible and durable in midterm follow-up. The decision to initially proceed with Starnes need not be an irrevocable decision to continue down a SV palliation pathway.

Impact of Circuit Size on Coagulation and Hemolysis Complications in Pediatric Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) circuit volume, patient size, and blood flow may influence coagulation and hemolysis complications. We performed a single-center retrospective analysis of ECMO patients over a 6.5 year period. In 299 ECMO runs, 13% required coagulation-associated circuit changes. Respiratory ECMO was associated with coagulation-associated circuit changes [odds ratio (O/R) 2.8, p < 0.05] and developed severe (plasma-free hemoglobin [pfHb] > 100 mg/dl) hemolysis (O/R 2.3, p < 0.05). Severe hemolysis and component changes were associated with hospital mortality (O/R 2.3 and 2.5, respectively, p < 0.05). The activated partial thromboplastin time (aPTT) to residence time (RT) ratio (aPTT/RT) was used as a surrogate for coagulation risk. We found that aPTT/RT > 2.5 more than doubled time to circuit change (3-8 days, p < 0.05), but aPTT/RT > 3 increased bleeding risks and hospital mortality (O/R 1.8; p < 0.1). Hemolysis was associated with patient weight and circuit to patient volume ratio (CPVR) (p < 0.05), but not pump type. Hemolysis slightly increased with transfusion (p = 0.08), and transfusion requirements increased for CPVR >50% (p < 0.1).Our data suggest that pediatric respiratory ECMO patients are more likely to develop coagulation and hemolysis complications, which are associated with increased mortality. This may result from higher inflammatory processes, which affect coagulation and red cell fragility. Minimizing circuit volume, inflammation, and red cell stress may help to reduce these two complications and their associated mortality.

Effect of vitamin E on tamoxifen-treated breast cancer cells.

BACKGROUND: Induction of apoptosis by tamoxifen has been postulated to involve oxidative stress. Tamoxifen (TAM) may act on estrogen receptors (ER) located in the plasma membrane. Our hypothesis that supplemental antioxidant vitamin E (alpha-tocopherol) acts at the plasma membrane to alter the effectiveness of tamoxifen was tested in ER-positive breast cancer cell lines, MCF-7 and T47D. METHODS: Cells were treated in vitro with 20-muM TAM alone and in combination with 10-muM alpha-tocopherol (AT). Estrogen growth signals were quantified by immunohistochemical staining for the mitogen-activated protein kinase p-ERK. Rapid changes in intracellular calcium were detected in TAM-treated MCF-7 and T-47D cells by fluorescence microscopy of cells loaded with the calcium-sensitive dye Fluo 4AM. Apoptosis was assayed by flow cytometry. RESULTS: Proliferating cells in normal medium exhibited strong p-ERK staining. Addition of TAM abolished p-ERK staining and caused cell rounding and death. The addition of AT led to the restoration of cell proliferation and p-ERK expression even in the presence of high-dose TAM. Intracellular calcium rapidly increased in MCF-7 and T47D cells upon exposure to TAM, followed by an increase in caspase activation and eventual apoptosis. The increase in intracellular calcium was abolished by the addition of 10muM AT to TAM, and pan-caspase staining decreased at 5 hours from 72% to 41%. CONCLUSIONS: These studies suggest that supplemental vitamin E decreases the inhibitory effect of TAM on the proliferation of ER+ breast cancer cells and eliminates the rapid rise in intracellular calcium that leads to apoptosis stimulated by TAM. The use of vitamin E acetate supplements may be inadvisable for women taking tamoxifen.