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Sacubitril/Valsartan (S/V) is used with optimal results in the therapy of heart failure (HF); reduces mortality and hospitalizations by 20% compared to ACE inhibitor therapy. There is a little data on the use of S/V in adult patients with congenital or acquired pediatric heart disease (GUCH). In these patients, HF is a real challenge for the cardiologist. HF in GUCH often has a different pathophysiology than usual, and interesting univentricular hearts in Fontan circulation, systemic right ventricle and patients undergoing multiple cardiac surgical procedures. The literature is poor in information and the guidelines do not give clear indications. We report our experience on a GUCH population. Starting from November 2019 we started S/V therapy in 13 GUCH patients with severe ventricular dysfunction, all in NYHA class III and already in optimal therapy for HF. Median age was 42.7 years (27–79 years); 8 males and 5 females. Basic heart disease: 4 patients with Fontan circulation, 3 patients with systemic right ventricle (TGA, operated according to Mustard), n. 2 complete CAV operated, n. 1 Ebstein‘s disease, n.1 Patent ductus arteriosus, n. 2 pediatric onset dilated cardiomyopathy. Median duration of follow–up 11.6 months (2–26 months). In n. 1 patient it was necessary to suspend the S/V due to skin itching, which resolved on diuscontinuation. The dosage was reduced in tree patients due to symptomatic hypotension (1 of these was taking Sildenafil). In n. In 1 patient there was a reduction in the glomerular filtration rate, which did not require discontinuation of the drug. After treatment: 6 patients are in NYHA class I, n. 3 pts in NYHA II class and 4 pts remained in NYHA III class. In the year preceding the start of S/V therapy, all patients cumulatively had n. 15 hospitalizations; in the year following the first six months of treatment, the number of hospitalizations decreased to no. 5 (4 for HF and 1 for severe anemia) The ejection fraction, evaluated by Simpson‘s method, remained stable. However, the limitations of the echocardiographic method in patients with such complex anatomy must be considered Conclusions The use of S/V is safe and effective in GUCH patients. However, larger studies and longer follow–up are needed.

<p>Automated image analysis tools for Ki67 breast cancer digital pathology images would have significant value if integrated into diagnostic pathology workflows. Such tools would reduce the workload of pathologists, while improving efficiency, and accuracy. Developing tools that are robust and reliable to multicentre data is challenging, however, differences in staining protocols, digitization equipment, staining compounds, and slide preparation can create variabilities in image quality and color across digital pathology datasets. In this work, a novel unsupervised color separation framework based on the IHC color histogram (IHCCH) is proposed for the robust analysis of Ki67 and hematoxylin stained images in multicentre datasets. An “overstaining” threshold is implemented to adjustforbackgroundoverstaining,andanautomatednucleiradiusestimatorisdesigned to improve nuclei detection. Proliferation index and F1 scores were compared between the proposed method and manually labeled ground truth data for 30 TMA cores that have ground truths for Ki67+ and Ki67− nuclei. The method accurately quantified the PI over the dataset, with an average proliferation index difference of 3.25%. To ensure the method generalizes to new, diverse datasets, 50 Ki67 TMAs from the Protein Atlas were used to test the validated approach. As the ground truth for this dataset is PI ranges, the automated result was compared to the PI range. The proposed method correctly classified 74 out of 80 TMA images, resulting in a 92.5% accuracy. In addition to these validations experiments, performance was compared to two color-deconvolution based methods, and to six machine learning classifiers. In all cases, the proposed work maintained more consistent (reproducible) results, and higher PI quantification accuracy.</p> <p><br></p>