Anti-Inflammatory Effects of Nutritionally Relevant Concentrations of Oleuropein and Hydroxytyrosol on Peripheral Blood Mononuclear Cells: An Age-Related Analysis.

Immunosenescence and inflammaging facilitate the insurgence of chronic diseases. The Mediterranean diet is a non-invasive intervention to improve the chronic low-grade inflammatory status associated with aging. Olive oil oleuropein (OLE) and hydroxytyrosol (HT) demonstrated a controversial modulatory action on inflammation in vitro when tested at concentrations exceeding those detectable in human plasma. We studied the potential anti-inflammatory effects of OLE and HT at nutritionally relevant concentrations on peripheral blood mononuclear cells (PBMCs) as regards cell viability, frequency of leukocyte subsets, and cytokine release, performing an age-focused analysis on two groups of subjects: Adult (age 18-64 years) and Senior (age ≥ 65 years). OLE and HT were used alone or as a pre-treatment before challenging PBMCs with lipopolysaccharide (LPS). Both polyphenols had no effect on cell viability irrespective of LPS, but 5 µM HT had an LPS-like effect on monocytes, reducing the intermediate subset in Adult subjects. OLE and HT had no effect on LPS-triggered release of TNF-α, IL-6 and IL-8, but 5 µM HT reduced IL-10 secretion by PBMCs from Adult vs. Senior group. In summary, nutritionally relevant concentrations of OLE and HT elicit no anti-inflammatory effect and influence the frequency of immune cell subsets with age-related different outcomes.

Hybrid Palliation for Hypoplastic Borderline Left Ventricle: One More Chance to Biventricular Repair.

Treatment options for hypoplastic borderline left ventricle (LV) are critically dependent on the development of the LV itself and include different types of univentricular palliation or biventricular repair performed at birth. Since hybrid palliation allows deferring major surgery to 4-6 months, in borderline cases, the decision can be postponed until the LV has expressed its growth potential. We aimed to evaluate anatomic modifications of borderline LV after hybrid palliation. We retrospectively reviewed data from 45 consecutive patients with hypoplastic LV who underwent hybrid palliation at birth between 2011 and 2015. Sixteen patients (mean weight 3.15 Kg) exhibited borderline LV and were considered for potential LV growth. After 5 months, five patients underwent univentricular palliation (Group 1), eight biventricular repairs (Group 2) and three died before surgery. Echocardiograms of Groups 1 and 2 were reviewed, comparing LV structures at birth and after 5 months. Although, at birth, all LV measurements were far below the normal limits, after 5 months, LV mass in Group 2 was almost normal, while in Group 1, no growth was evident. However, aortic root diameter and long axis ratio were significantly higher in Group 2 already at birth. Hybrid palliation can be positively considered as a "bridge-to-decision" for borderline LV. Echocardiography plays a key role in monitoring the growth of borderline LV.

Anomalous aortic origin of the pulmonary arteries: Case series and literature review.

Anomalous origin of the pulmonary arteries from the ascending aorta is a rare, but severe clinical entity necessitating a scrupulous evaluation. Either the right or the left pulmonary arteries can arise directly from the ascending aorta while the other pulmonary artery retains its origin from the right ventricular outflow tract. Such a finding can be isolated or can coexist with several congenital heart lesions. Direct intrapericardial aortic origin, however, must be distinguished with origin through a persistently patent arterial duct. In the current era, clinical manifestations usually become evident in the newborn rather than during infancy, as used to be the case. They include respiratory distress or congestive heart failure due to increased pulmonary flow and poor feeding. The rate of survival has now increased due to early diagnosis and prompt surgical repair, should now be expected to be at least 95%. We have treated four neonates with this lesion over the past 7 years, all of whom survived surgical repair. Right ventricular systolic pressure was significantly decreased at follow-up. Our choice of treatment was to translocate the anomalous pulmonary artery in end-to-side fashion to the pulmonary trunk. Our aim in this report is to update an Italian experience in the diagnosis and treatment of anomalous direct origin of one pulmonary artery from the aorta, adding considerations on the lessons learned from our most recent review of the salient literature.

Changes in left and right ventricular two-dimensional echocardiographic speckle-tracking indices in pediatric LVAD population: A retrospective clinical study.

Echocardiographic strain and strain-rate imaging is a promising tool for the evaluation of myocardial segmental function, for the early detection of myocardial dysfunction, and for the prediction of reverse remodeling. We aimed at studying the changes in left and right ventricular function in pulsatile left ventricular assist device pediatric patients by two-dimensional echocardiography and two-dimensional speckle-tracking echocardiography. Echocardiographic and clinical data of patients implanted with a pulsatile-flow left ventricular assist device from 2011 to 2018 were retrospectively reviewed before and after implantation at 1, 3, and 6 months. A total of 18 patients were enrolled. Median age and weight at implantation were 9 months (5-23 months) and 5.85 kg (4.85-8.75 kg), respectively; median left ventricular assist device support was 181 (114.5-289.5) days. 13 patients (73%) were transplanted and 5 patients (27%) died. At follow-up: left ventricular ejection fraction increase at 1 month (p = 0.001) and 3 months (p = 0.01), left ventricular global longitudinal strain improvement at 1 month (p = 0.0008) and 3 months (p = 0.02), and right ventricular free-wall longitudinal strain increase at 1 month (p = 0.01). At short term after left ventricular assist device implantation, both left ventricular and right ventricular mechanics improved. The temporary benefit seems to decrease over time. The worsening of left ventricular function has been followed by a worsening of right ventricular function probably due to the ventricular interdependence.

Assessment of cardiac function in infants with transposition of the great arteries after surgery: comparison of two methods.

BACKGROUND: Assessment of cardiac function is crucial in pediatric patients undergoing cardiovascular surgery, monitoring cardiac output and changing hemodynamic conditions during surgery accordingly is important to improve post-surgical outcome. We aimed to measure cardiac index (CI) and maximal rate of the increase of left ventricular pressure dp/dt(max) with the pressure recording analytic method (PRAM, MostCare®) and compared it with transthoracic echocardiographic cardiac index estimation in infants with transposition of the great arteries (TGA) undergoing surgical correction. METHODS: We enrolled 74 infants with TGA consecutively into this study. CI and dp/dt(max) were measured with PRAM and echocardiography at 0, 4, 8, 12, 24 and 48 h postoperatively. Blood brain natriuretic peptide (BNP) and blood lactate (Lac) were measured at baseline and after operation. RESULTS: The median age at surgery was 13 days (range 1-25 days) with an average weight of 3.24 kg (range 2.31-4.17 kg). CI estimated by PRAM was 1.11 ± 0.12 L/min/m2 (range 0.69-1.36) and by Doppler echocardiography was 1.13 ± 0.13 L/min/m2 (range 0.76-1.40). dp/dt(max) estimated by PRAM was 1.31 ± 0.03 mmHg/s (range 1.23-1.43) and by Doppler echocardiography was 1.31 ± 0.04 L/min/m2 (range 1.25-1.47). CI (r = 0.817, P < 0.001) and dp/dt(max) (r = 0.794, P < 0.001) measured by two methods were highly correlated with a linear relation. Blood BNP and lactate increased to the highest level at 8-12 h post-operatively. CONCLUSIONS: In the early post-operative period, PRAM provides reliable estimates of cardiac index and dp/dt(max) value compared with echocardiographic measurements. PRAM through mostcare® is a reliable continuous monitoring method for peri-operative management in children with congenital heart disease.

Long-term survival and phenotypic spectrum in heterotaxy syndrome: A 25-year follow-up experience.

BACKGROUND: Heterotaxy syndrome (HS) is a group of congenital disorders characterized by abnormal arrangement of thoraco-abdominal organs across the left-right axis of the body, classified as right (RAI) and left atrial isomerism (LAI)·We investigated the long-term survival and phenotypic spectrum in our HS cohort. Results are compared to literature data. METHODS: This is a single centre, observational, both retro and prospective study. Cardiac features, surgical management and abdominal ultrasound (US) of all HS patients were reviewed or investigated if missing. We evaluated all anatomical data and their clinical impact on survival, arrhythmias, infections, and heart transplant (HT). RESULTS: 136 patients were classified as RAI (81) and LAI (55). Long-term survival and freedom from HT reached 69.8% and 87.8% at 40 years in RAI and LAI, respectively. Multivariate analysis showed that LAI is an independent predictor for pacemaker implantation (p = 0.019). Splenic status varied in both groups: in RAI, abdominal US showed asplenia, polysplenia and normal spleen in 48%, 4% and 32% of patients, respectively, whereas in LAI polysplenia, asplenia and normal spleen occurred in 64%, 4% and 16% of cases, respectively. CONCLUSIONS: Mortality was significantly lower (9%) compared to literature (50%). Although patients with RAI experienced a higher mortality, no independent predictors were found. We demonstrated that the obsolete cardiac definition of "asplenia" and "polysplenia" instead of RAI and LAI is misleading, because of the high variability of the splenic phenotype among patients of both groups.

Bradyarrhythmias in Repaired Atrioventricular Septal Defects: Single-Center Experience Based on 34 Years of Follow-Up of 522 Patients.

Atrioventricular Septal Defect (AVSD) is a rare congenital heart defect (CHD) often associated with genetic syndromes, most commonly Down syndrome (DS). Over the last four decades, surgical repair has increased survival and improved quality of life in these patients. The prevalence of bradyarrhythmias namely, atrioventricular block (AVB) and sinus node dysfunction (SND) in AVSD is partially known. 522 cases with both partial and complete AVSD (38.7% with DS), undergoing intracardiac repair from 1982 to 2016 at our institution, were reviewed from our system database. 38 (7.3%) patients received permanent PM implantation for AVB (early or late) or SND. On one hand, AVB requiring PM was found in 26 (4.98%). This was further subdivided into early-onset 14 (2.6%) and late-onset AVB 12 (2.2%) (median 4 [IQR 1-7] years). On the other hand, 12 (2.3%) experienced late SND requiring PM (median 11 [IQR 3.5-15.2] years). Early and late AVB were independent from the type of AVSD (partial or complete), whereas the late SND was remarkably observed in complete AVSD compared to partial AVSD (p = 0.017). We classified the cohort into two main categories: DS (202, 38.7%) and non-DS (320, 61.3%). At Kaplan-Meier survival analysis, DS was significantly associated with late-onset bradyarrhythmias (p = 0.024). At Cox regression analysis, we identified DS as an independent predictor of PM implantation (HR 2.17). In conclusion, about 7% of repaired AVSD patients need PM implantation during follow-up. There are no differences in early and late AVB occurrence according to the type of AVSD. There is a higher incidence of late SND in repaired complete AVSD, with a later timing onset in patients with associated DS. Moreover, DS seems to be an independent predictor of PM implantation.

Addendum: Measurement of charged particle yields from PMMA irradiated by a 220 MeV/u 12C beam.

In this paper we report the re-analysis of the data published in (Piersanti et al. 2014) documenting the charged secondary particles production induced by the interaction of a 220 MeV/u 12C ion beam impinging on a polymethyl methacrylate (PMMA) target, measured in 2012 at the GSI facility in Darmstadt (Germany). This re-analysis takes into account the inhomogeneous light response of the LYSO crystal in the experimental setup measured in a subsequent experiment (2014) performed in the Heidelberg Ion- Beam Therapy Center. A better description of the detector and re-calculation of the geometrical efficiencies have been implemented as well, based on an improved approach that accounts also for the energy dependence of the emission spectrum. The new analysis has small effect on the total secondary charged flux, but has an impact on the production yield and emission velocity distributions of the different particle species (protons, deuterons and tritons) at different angles with respect to the beam direction (60° and 90°). All these observables indeed depend on the particle identification algorithms and hence on the LYSO detector energy response. The results of the data re-analysis presented here are intended to supersede and replace the results published in (Piersanti et al. 2014).

Benchmarking Geant4 hadronic models for prompt-γ monitoring in carbon ion therapy.

PURPOSE: The real-time monitoring of the spread-out Bragg peak would allow the planned dose delivered during treatment to be directly verified, but this poses a major challenge in modern ion beam therapy. A possible method to achieve this goal is to exploit the production of secondary particles by the nuclear reactions of the beam with the patient and correlate their emission profile to the planned target volume position. In this study, we present both the production rate and energy spectra of the prompt-γ produced by the interactions of the 12 C ion beam with a polymethyl methacrylate (PMMA) target. We also assess three different Monte Carlo models for prompt-γ simulation based on our experimental data. METHODS: The experiment was carried out at the GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany with a 220 MeV/u 12 C ions beam impinging on a 5× 5× 20 cm3 polymethyl methacrylate beam stopping target, with the prompt-γ being detected by a hexagonally-shaped barium fluoride scintillator with a circumscribed radius of 5.4 cm and a length of 14 cm, placed at 60° and 90° with respect to the beam direction. Monte Carlo simulations were carried out with three different hadronic models from the Geant4 code: binary ion cascade (BIC), quantum molecular dynamics (QMD), and Liege intranuclear cascade (INCL++ ). RESULTS: An experimental prompt-γ yield of 1.06 × 10-2  sr-1 was measured at 90°. A good agreement was observed between the shapes of the experimental and simulated energy spectra, especially with the INCL++ physics list. The prompt-γ yield obtained with this physics list was compatible with the measurement within 2σ, with a relative difference of 26% on average. BIC and QMD physics lists proved to be less accurate than INCL++ , with the difference between the measured and simulated yields exceeding 100%. The differences between the three physics lists were ascribed to important discrepancies between the models of the physical processes producing prompt-γ emissions. CONCLUSION: In conclusion, this study provides prompt-γ yield values in agreement with previously published results for different carbon ions energies. This work demonstrates that the INCL++ physics list from Geant4 is more accurate than BIC and QMD to reproduce prompt-γ emission properties.

Monitoring of Hadrontherapy Treatments by Means of Charged Particle Detection.

The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages.