Time course and predictors for neoaortic root dilatation and neoaortic valve regurgitation during adult life after arterial switch operation

[ES] Introducción y objetivos: Hay pocos datos sobre la evolución en adultos de la dilatación de la raíz neoaórtica (RAO) y la insuficiencia valvular neoaórtica (IA) tras la cirugía de switch arterial (SA) en la transposición de grandes arterias. Métodos: Análisis retrospectivo de 152 pacientes con transposición de grandes arterias, mayores de 15 años, intervenidos mediante SA y seguidos durante 4,9 ± 3,3 años en 2 centros de referencia. Se analizaron los cambios de diámetro de la RAO ajustados a superficie corporal y la progresión a grado moderado/grave de la IA con ecocardiografías seriadas. Se realizó un modelo de regresión de Cox para identificar factores predictores de progresión de la IA. Resultados: Inicialmente, 4 pacientes (2,6%) presentaban IA grave (3 habían precisado cirugía valvular) y 9 (5,9%) moderada. La RAO basal media era 20,05 ± 2,4 mm/m2, y al final del seguimiento, 20,73 ± 2,8 mm/m2 (p < 0,001), con un crecimiento medio de 0,14 (IC95%, 0,07-0,2) mm/m2/año. La IA progresó en 20 (13,5%) y 6 (4%) fueron intervenidos. La progresión de IA se asoció con válvula bicúspide, IA inicial, dilatación de la RAO inicial y crecimiento de la RAO. La válvula bicúspide (HR = 3,3; IC95%, 1,1-15,2; p = 0,037), la IA inicial (HR = 5,9; IC95%, 1,6-59,2; p = 0,006) y el crecimiento de la RAO (HR = 4,1; IC95%, 2-13,5; p = 0,023) resultaron predictores independientes. Conclusiones: La dilatación de la RAO y la IA progresan en el adulto joven intervenido mediante SA. La válvula bicúspide, la IA basal y el crecimiento de la RAO son predictores de progresión de IA.[EN] Introduction and objectives: There are limited data on the long-term development of neoaortic root dilatation (NRD) and neoaortic valve regurgitation (AR) after arterial switch operation (ASO) for transposition of the great arteries during adult life. Methods: We performed a retrospective longitudinal analysis of 152 patients older than 15 years who underwent ASO for transposition of the great arteries and who were followed-up for 4.9 ± 3.3 years in 2 referral centers. Sequential changes in body surface-adjusted aortic root dimensions and progression to moderate/severe AR were determined in patients with 2 or more echocardiographic examinations. Risk factors for dilatation were tested by Cox regression to identify predictors of AR progression. Results: At baseline, moderate AR was present in 9 patients (5.9%) and severe AR in 4 (2.6%), of whom 3 had required aortic valve surgery. Initially, the median neoaortic root dimension was 20.05 ± 2.4 mm/m2, which increased significantly to 20.73 ± 2.8 mm/m2 (P < .001) at the end of follow-up. The mean change over time was 0.14 mm/m2/y (95%CI, 0.07-0.2). Progressive AR was observed in 20 patients (13.5%) and 6 patients (4%) required aortic valve surgery. Progressive AR was associated with bicuspid valve, AR at baseline, NRD at baseline, and neoaortic root enlargement. Independent predictors were bicuspid valve (HR, 3.3; 95%CI, 1.1-15.2; P = .037), AR at baseline (HR, 5.9; 95%CI, 1.6-59.2; P = .006) and increase in NRD (HR, 4.1 95%CI, 2-13.5; P = .023). Conclusions: In adult life, NRD and AR progress over time after ASO. Predictors of progressive AR are bicuspid valve, AR at baseline, and increase in NRD

Critically short telomeres and toxicity of chemotherapy in early breast cancer

Cumulative toxicity from weekly paclitaxel (myalgia, peripheral neuropathy, fatigue) compromises long-term administration. Preclinical data suggest that the burden of critically short telomeres ( 21.9% CSTs) had 2-fold higher number of neuropathy (P = 0.04) or fatigue (P = 0.019) episodes and >3-fold higher number of myalgia episodes (P = 0.005). The average telomere length was unrelated to the incidence of side effects.The percentage of CSTs, but not the average telomere size, is associated with weekly paclitaxel-derived toxicity.This work was supported by the Fondo de Investigación Sanitaria [FIS PI10/00288 and FIS PI13/00430]; AECC Scientific Foundation [Beca de Retorno-2010, to MQF]; Spanish Ministry of Economy and Competitiveness Projects [SAF2013-45111-R]; Madrid Regional Government Projects [S2010/BMD- 2303]; AXA Research Found; Fundación Botin; AVON Spain; and Boehringer-Ingelheim Spain.S

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Giant right atrium, what does it hide? Case presentation

[Background] Malformation of the right atrium is a rare cardiac abnormality and is usually reported as isolated malformation in the literature.[Case presentation] Prenatal giant atrial dilatation in an asymptomatic infant was treated surgically at 18 months of age, due to potential risk of thrombosis and arrhythmias. Post-surgical echocardiographic images illustrate residual atrial elevated pressure.[Conclusions] Sometimes, as seems in our case, right atrial dilatation hides an associated restrictive right ventricle.Peer reviewe

Follow-up of a simple method for aortic valve reconstruction with fixed pericardium in children.

In 2013, we published a simple method for aortic valve reconstruction in children using fixed pericardium in this journal. This was not expected to be a durable solution but a temporizing measure in the absence of other solutions, in order to buy time for growth that would allow subsequent prosthetic valve insertion. As such, this was implemented in 3 patients with excellent immediate results, as reported in our original publication. We are now writing to provide longer term information. In 2 cases, a newborn and a 12-year-old boy, the valve calcified heavily at 4 years' follow-up. By then, the valvar annulus had grown sufficiently to accept a prosthetic valve in both cases. In these 2 cases, the material used for valve reconstruction was autologous pericardium fixed in 0.6% gluteraldehyde. In the third patient, a 3-year-old girl, the valve failed by dehiscence of the suture line 6 months following surgery. In this case, fixed bovine pericardium had been used, which is more rigid than autologous pericardium, thus possibly explaining the dehiscence. However, the pericardial patch was not calcified. Thus, the described method lived up to our expectation of buying time for growth for later insertion of a prosthetic valve in 2 of the 3 cases

3-Hydroxyphenylpropionate and Phenylpropionate Are Synergistic Activators of the MhpR Transcriptional Regulator from Escherichia coli*

The degradation of the aromatic compound phenylpropionate (PP) in Escherichia coli K-12 requires the activation of two different catabolic pathways coded by the hca and the mhp gene clusters involved in the mineralization of PP and 3-hydroxyphenylpropionate (3HPP), respectively. The compound 3-(2,3-dihydroxyphenyl)propionate (DHPP) is a common intermediate of both pathways which must be cleaved by the MhpB dioxygenase before entering into the primary cell metabolism. Therefore, the degradation of PP has to be controlled by both its specific regulator (HcaR) but also by the MhpR regulator of the mhp cluster. We have demonstrated that 3HPP and DHPP are the true and best activators of MhpR, whereas PP only induces no response. However, in vivo and in vitro transcription experiments have demonstrated that PP activates the MhpR regulator synergistically with the true inducers, representing the first case of such a peculiar synergistic effect described for a bacterial regulator. The three compounds enhanced the interaction of MhpR with its DNA operator in electrophoretic mobility shift assays. Inducer binding to MhpR is detected by circular dichroism and fluorescence spectroscopies. Fluorescence quenching measurements have revealed that the true inducers (3HPP and DHPP) and PP bind with similar affinities and independently to MhpR. This type of dual-metabolite synergy provides great potential for a rapid modulation of gene expression and represents an important feature of transcriptional control. The mhp regulatory system is an example of the high complexity achievable in prokaryotes

Respiratory Muscle Function and Exercise Performance in Adult Patients with Fontan Circulation

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).At rest, a good Fontan circulation can provide a normal cardiac output (CO). However, as a consequence of its unique hemodynamic nature, the limitations of the Fontan circuit are exposed during exercise. We aimed to provide a comprehensive assessment of the pathophysiology of exercise in adult Fontan patients (FPs) and identify factors limiting their functional capacity (FC). In a single-center study conducted in 37 FPs aged ≥16 years and 19 healthy-controls (HCs) who underwent CPET on a cycle ergometer in February and March 2022, the mean peakVO2 was 21 ± 5.4 mL/kg/min, which was 55% of the predicted value. Morphologically, the left single ventricle showed a higher peakVO2% predicted value (57.4 ± 14.4% vs. 43.4 ± 8.1%, p = 0.045). The factors associated with low peakVO2 values were an early flattened or descending O2 pulse at maximal exertion (52 ± 14% vs. 62 ± 12.5, p = 0.04 and 47.6 ± 9% vs. 60 ± 14, p = 0.018, respectively) and chronotropic insufficiency (53 ± 12% vs. 69.8 ± 20%, p = 0.008). The OUES was found to be a useful parameter to assess the FC in FPs in maximal and submaximal exercise testing. A strong positive correlation was observed between the %OUES and peakVO2%predicted (r = 0.726, p > 0.001). The lung function was impaired in the FPs, mostly with a mild restrictive pattern (56.8%). The FPs showed lower inspiratory muscle strength compared to the HCs but it was not statistically associated with either the peakVO2 or VE/VCO2 slope. Regular intense physical activity improves one’s FC. Although FPs have inspiratory muscle weakness, its impact on their FC is unclear. The peakVO2% predicted grew progressively higher as the level of physical activity increased (low level 49.5 ± 14%, moderate level 55 ± 12%, intense level 69 ± 20%).Peer reviewe

De la castaña a San Juan cambia el tiempo y nosotros-as más

Este proyecto pretende crear un marco que engloba las diferentes actividades de la escuela. Los objetivos son establecer relaciones sociales en un ámbito cada vez más amplio, establecer vínculos de relación con los adultos y sus iguales, conocer y participar en fiestas, tradiciones y costumbres de su entorno con interés y observar los cambios a que están sometidos los elementos del entorno. La puesta en práctica de este proyecto se engloba en un planteamiento educativo más general, en que estas fiestas son momentos estelares dentro de una dinámica de trabajo cotidiano en la escuela. Las actividades consisten en la celebración de las fiestas más significativas como la fiesta de la castaña, la de Navidad, la de Carnaval o la de San Isidro, las cuales permiten trabajar en la escuela las características de las distintas épocas del año. La evaluación tiene en cuenta el desarrollo de las capacidades, la participación y opinión de padres y la actividad en la reunión de equipo que se celebra después de cada fiesta.Madrid (Comunidad Autónoma). Consejería de Educación y CulturaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES