A phosphatase gene is linked to nectar dihydroxyacetone accumulation in manuka (Leptospermum scoparium).

Floral nectar composition beyond common sugars shows great diversity but contributing genetic factors are generally unknown. Manuka (Leptospermum scoparium) is renowned for the antimicrobial compound methylglyoxal in its derived honey, which originates from the precursor, dihydroxyacetone (DHA), accumulating in the nectar. Although this nectar trait is highly variable, genetic contribution to the trait is unclear. Therefore, we investigated key gene(s) and genomic regions underpinning this trait. We used RNAseq analysis to identify nectary-associated genes differentially expressed between high and low nectar DHA genotypes. We also used a manuka high-density linkage map and quantitative trait loci (QTL) mapping population, supported by an improved genome assembly, to reveal genetic regions associated with nectar DHA content. Expression and QTL analyses both pointed to the involvement of a phosphatase gene, LsSgpp2. The expression pattern of LsSgpp2 correlated with nectar DHA accumulation, and it co-located with a QTL on chromosome 4. The identification of three QTLs, some of the first reported for a plant nectar trait, indicates polygenic control of DHA content. We have established plant genetics as a key influence on DHA accumulation. The data suggest the hypothesis of LsSGPP2 releasing DHA from DHA-phosphate and variability in LsSgpp2 gene expression contributing to the trait variability.

Efficacy and Safety of an Extravascular Implantable Cardioverter-Defibrillator.

BACKGROUND: The extravascular implantable cardioverter-defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known. METHODS: We conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system. The primary efficacy end point was successful defibrillation at implantation. The efficacy objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients with successful defibrillation was greater than 88%. The primary safety end point was freedom from major system- or procedure-related complications at 6 months. The safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%. RESULTS: A total of 356 patients were enrolled, 316 of whom had an implantation attempt. Among the 302 patients in whom ventricular arrhythmia could be induced and who completed the defibrillation testing protocol, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% confidence interval [CI], 96.6%; P<0.001 for the comparison with the performance goal of 88%); 299 of 316 patients (94.6%) were discharged with a working ICD system. The Kaplan-Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; P<0.001 for the comparison with the performance goal of 79%). No major intraprocedural complications were reported. At 6 months, 25 major complications were observed, in 23 of 316 patients (7.3%). The success rate of antitachycardia pacing, as assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). A total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes. Eight systems were explanted without extravascular ICD replacement over the 10.6-month mean follow-up period. CONCLUSIONS: In this prospective global study, we found that extravascular ICDs were implanted safely and were able to detect and terminate induced ventricular arrhythmias at the time of implantation. (Funded by Medtronic; ClinicalTrials.gov number, NCT04060680.).

Biological or mechanical prostheses for isolated aortic valve replacement in patients aged 50-65 years: the ANDALVALVE study.

OBJECTIVES: The decision about whether to use a biological or a mechanical prosthesis for aortic valve replacement remains controversial in patients between 50 and 65 years of age and has yet to be addressed in a Mediterranean population. This research aimed to analyse long-term survival and major morbidity rates (30-day mortality, stroke, any prosthetic reoperation and major bleeding) within this population. METHODS: Our multicentre observational retrospective study included all subjects aged 50-65 years who had a primary isolated aortic valve replacement due to severe aortic stenosis at 7 public hospitals from Andalusia (Spain) between 2000 and 2015. Concomitant surgery, reoperations and endocarditis were the exclusion criteria. A total of 1443 patients were enrolled in the study (272 with biological and 1171 with mechanical valves). Multivariate analyses including a 2:1 propensity score matching (506 mechanical and 257 biological prostheses) were conducted. RESULTS: Bioprostheses were implanted in 18.8% (n = 272): 35% were women; the mean EuroSCORE-I was 3%. The mean follow-up was 8.1 ± 4.9 years in a matched sample: 8.8 ± 4.9 years in those receiving a mechanical vs 7.1 ± 4.5 years in those receiving a biological prosthesis (P = 0.001). In the paired sample, the 15-year survival rate was 73% in those who had a biological vs 76% in those who had a mechanical valve [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.54-1.20; P = 0.159]. No significant differences were observed in patients ≥55 years old (74% of 15-year survival in both groups: HR 0.88, 95% CI 0.56-1.34; P = 0.527). A higher rate of major bleeding was found in patients with a mechanical prosthesis (P = 0.004), whereas reoperation was more frequent among those with a biological prosthesis (P = 0.01). CONCLUSIONS: Long-term survival was comparable in patients above 55 years of age. Mechanical prostheses were associated with more major bleeding and bioprostheses, with more reoperations. A bioprosthesis in patients above 55 years old is a reasonable choice. CLINICAL TRIAL REGISTRATION NUMBER: NCT03239509.

Endothelial vascular markers in coronary surgery.

Coronary heart disease is associated with high morbidity and mortality. Endothelial dysfunction in affected patients is linked to long-term atherosclerotic disease progression and cardiovascular event rates. The present paper reports on changes in the levels of endothelial progenitor cells (VEGFR2/CD133/CD34), essential for endothelial repair, and of endothelial microvesicles (CD31/annexin V) as indicators of endothelial lesion, in patients undergoing coronary bypass surgery with respect both to baseline levels and to counts in healthy subjects. In an observational descriptive study, 31 patients scheduled for coronary revascularization surgery were compared with those of 25 healthy controls. In a subsequent longitudinal study, patients undergoing surgery were monitored at 5 timepoints up until 48 h after surgery. Endothelial progenitor cell (VEGFR2/CD133/CD34) and endothelial microvesicle (CD31/annexin V) levels were quantified by flow cytometry. Baseline endothelial progenitor cell counts in coronary patients were significantly lower than those of healthy controls (p < 0.001); however, after surgery, levels rose steadily over all 5 timepoints to 48 h  with statistically significant differences (p < 0.001) between intra-operative and 48 h after surgery (T5). Endothelial microvesicle levels were significantly higher in coronary patients prior to surgery than in healthy controls (p < 0.001), and despite declining at 48 h remained significantly higher than those of controls (p < 0.001). Coronary surgery has had a positive impact on the endothelium in the patients, prompting a decrease in signs of endothelial dysfunction and a considerable improvement in the endothelial repair mechanisms involved in angiogenesis, playing an important role in the inflammatory response and the remodelling process of ischemic myocardium in postoperative period.

Heart transplantation in a patient with recurrent early extensive endocarditis.

Active valvular endocarditis could be considered a contraindication to heart transplantation. Nevertheless, there have been some reports of success with this form of treatment, despite the characteristics of the infection and its aggressive nature. Here, we describe the case of a patient with acute bicuspid aortic valvular endocarditis caused by Staphylococcus aureus and with a periannular abscess. Cryopreserved aortic homograft replacement of the aortic root was initially carried out, in addition to debridement and reconstruction of the interventricular septum with a pericardial patch. Early recurrence occurred, however, with extensive tissue destruction, a periaortic abscess and involvement of multiple valves, associated with severe sepsis. In view of the failure of 'conventional' surgery, an emergency heart transplantation was decided on after discussing the case with the Spanish National Transplant Organization (ONT), because of the theoretical contraindication of transplantation in this case. Transplantation was finally carried out after a waiting period of 3 days, in emergency code conditions, and the postoperative course proved uneventful, with no reinfection during the follow-up period. The present case suggests that heart transplantation may be an alternative option in patients suffering aggressive endocarditis with extensive involvement of the heart structures.

Prophylactic vitamin D in healthy infants: assessing the need.

The objective was to evaluate the need for vitamin D prophylaxis in healthy infants. This was a prospective and randomized study performed at primary care clinics. Eighty-eight full-term 1-month-old healthy infants were randomly assigned to receive (n = 41) or not (n = 47) 402 IU/d of vitamin D for 1 year. Primary outcome measures were serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations at 3, 6, and 12 months of age; secondary measures included data on feeding, habitat, season of birth, sun exposure, and physical examination. At 3 and 6 months of age, serum 25OHD levels (±SD) were significantly higher (P < .001) in the prophylaxis group. In the group without prophylaxis, serum 25OHD increased with age; and breast-fed infants aged 3 months had the lowest value (20.2 ± 9.4 ng/mL), which was significantly (P = .001) lower than that of formula-fed infants (35.0 ± 9.7 ng/mL). The PTH levels were not influenced by the prophylaxis or feeding. No influence of either the habitat or season of birth on serum 25OHD concentrations was demonstrated. No infant had clinical signs of vitamin D deficiency. Serum 25OHD and PTH concentrations were weakly but significantly correlated (r = -0.29, P = .009) at 3 months of age. Healthy infants without vitamin D prophylaxis had lower circulating concentrations of 25OHD at 3 and 6 months of age, the lowest value being found in 3-month breast-fed infants. The clinical relevance of these findings is probably negligible because serum 25OHD levels spontaneously increased with age and were not associated with high serum PTH. Clinical manifestations of rickets were not observed.

Aneurisma del septo interventricular con fistulización posterior a cavidades derechas / Interventricular septal aneurysm with fistulas developing into the right cavities

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[Incidence and clinical impact of pulmonary homograft dysfunction after the Ross procedure]. / Incidencia e impacto clínico de la estenosis del homoinjerto pulmonar tras el procedimiento de Ross.

INTRODUCTION AND OBJECTIVES: We analyzed the incidence, risk factors and clinical impact of pulmonary homograft dysfunction after the Ross procedure in our patients. PATIENTS AND METHOD: All patients were evaluated at 3, 6 and 12 months, and annually thereafter. Patients with a transhomograft pressure gradient greater than 30 mmHg were referred for cardiac magnetic resonance imaging. RESULTS: At the end of the study, 9 patients (11.8%) showed a transhomograft pressure gradient >30 mmHg after a mean period of 15.3 months post-surgery. Mean transhomograft pressure gradient was 19.8 (16.2%) (range, 2-100 mmHg). All patients were in functional class I, except 2 who were in New York Heart Association class II with severe stenosis. These 2 patients were treated percutaneously with stent placement and no reoperation. No association was found between clinical outcome and sex, age or homograft diameter. We found a trend toward greater perioperative use of plasma, platelets and red cells in the group of patients in comparison to controls, although the difference was significant only for postoperative use of plasma (1.7 [3] vs 5.5 [5.3] units; P<0.05). Cardiac magnetic resonance imaging showed stenosis predominantly in the body of the homograft, whereas the valvular component itself remained competent. Right ventricular hypertrophy was mild or very mild in 7 patients and moderate in 2. CONCLUSIONS: The incidence of some degree of pulmonary homograft dysfunction after the Ross procedure was non-negligible, but its clinical impact seems to be slight. Patients with severe stenosis were treated successfully via a percutaneous approach. The use of blood products might be a risk factor for the development of this complication.

Incidencia e impacto clínico de la estenosis del homoinjerto pulmonar tras el procedimiento de Ross / Incidence and clinical impact of pulmonary homograft dysfunction after the Ross procedure

Introducción y objetivos. Estudiamos la incidencia, los factores de riesgo y el impacto clínico de la estenosis del homoinjerto pulmonar tras la intervención de Ross en nuestra serie clínica. Pacientes y método. El seguimiento se realizó a los 3, 6 y 12 meses, y después anualmente. Los pacientes con gradiente a través del homoinjerto pulmonar > 30 mmHg fueron sometidos a una resonancia magnética cardíaca. Resultados. De los 76 pacientes intervenidos, 9 (11,8 por ciento) presentaron un homoinjerto pulmonar > 30 mmHg una media de 15,3 meses después de la intervención. El gradiente medio fue de 19,8 ñ 16,2 mmHg (rango, 2-100). Todos los pacientes se encontraban en grado funcional I de la New York Heart Association excepto 2, que estaban en grado funcional II con estenosis severa y fueron tratados percutáneamente con stents, sin necesidad de reoperación. No encontramos asociación con el sexo, la edad ni el diámetro del homoinjerto. El uso de hemoderivados (hematíes, plasma y plaquetas) fue mayor en el grupo afectado que en el de control, si bien no alcanzó significación estadística, a excepción del uso de plasma en cuidados intensivos (1,7 ñ 3 frente a 5,5 ñ 5,3 unidades; p < 0,05). El estudio con resonancia magnética cardíaca demostró afección eminentemente del cuerpo de homoinjerto, con aparato valvular competente. La repercusión en el ventrículo derecho fue muy leve-leve (n = 7) o moderada (n = 2).Conclusiones. La incidencia de disfunción del homoinjerto pulmonar no es desdeñable, si bien el impacto clínico parece ser muy discreto y los casos severos se controlan satisfactoriamente de forma percutánea. El uso de hemoderivados podría ser un factor de riesgo para el desarrollo de esta complicación (AU)

Características clínicas y pronósticas de la endocarditis infecciosa en el anciano / Clinical course and prognosis of infective endocarditis in the elderly

Introducción y objetivos. En las últimas décadas se ha producido un aumento en la edad media de los pacientes con endocarditis infecciosa. El objetivo de este estudio es conocer las características clínicas y pronósticas de esta enfermedad en pacientes ancianos (mayores de 65 años) y compararlas con las de adultos más jóvenes. Métodos. Estudio prospectivo de 125 casos en pacientes no drogadictos mayores de 14 años desde 1987 hasta 1997 realizado en una única institución. Veintiún pacientes eran mayores de 65 años. Resultados. No hubo diferencias significativas entre los dos grupos de edad en cuanto al retraso en el diagnóstico, los síntomas clínicos, la localización de la endocarditis infecciosa y la frecuencia de hemocultivos negativos. Las prótesis fueron un factor predisponente más frecuente en los ancianos (el 41 por ciento de endocarditis sobre prótesis frente al 33 por ciento en los adultos jóvenes). Los ancianos presentaron una mayor proporción de casos por Streptococcus (el 47 frente al 29 por ciento; p < 0,05). Los ancianos fueron intervenidos con menos frecuencia que los adultos (el 46 y el 56 por ciento, respectivamente) predominando en ellos la cirugía con carácter urgente (el 32 por ciento urgente y el 14 por ciento electiva). La mortalidad precoz fue mayor en los ancianos (50 por ciento) que en los adultos (15 por ciento); p < 0,05. Conclusiones. La endocarditis infecciosa en ancianos ocurre con mayor frecuencia en portadores de prótesis valvulares. Una mayor tasa de complicaciones graves en la fase activa le confiere un peor pronóstico a corto y medio plazo. La indicación de cirugía con carácter electivo podría contribuir a mejorar el pronóstico (AU)

Pronóstico a corto y largo plazo de la endocarditis sobre prótesis en pacientes no drogadictos / Short and long-Term prognosis of prosthetic valve endocarditis in non-addicts

Introducción y objetivos. La endocarditis infecciosa sobre prótesis es una enfermedad con una elevada morbimortalidad durante la fase activa y un riesgo importante de complicaciones en el seguimiento. El objetivo de nuestro estudio es conocer las características clínicas, así como la evolución a corto y largo plazo de estos enfermos. Pacientes y métodos. Estudio prospectivo de 43 casos consecutivos de endocarditis sobre prótesis en pacientes no drogadictos entre enero de 1987 y marzo de 1997.Resultados. La edad media de los pacientes era de 51 ñ 16 años. Hubo 8 casos (19 por ciento) de endocarditis sobre prótesis precoz (en los dos meses siguientes a la cirugía cardíaca), 14 (32 por ciento) de endocarditis sobre prótesis intermedia (entre los dos y doce meses poscirugía) y 21 (49 por ciento) de endocarditis sobre prótesis tardía (más allá del primer año de la cirugía). Se realizó un ecocardiograma transesofágico a 32 pacientes, con una sensibilidad del 81 por ciento. Presentaron algún tipo de complicación el 86 por ciento de los casos y fueron intervenidos en la fase activa de la enfermedad el 53 por ciento de los casos (25 por ciento con carácter urgente). La mortalidad hospitalaria fue del 23 por ciento (el 50 por ciento para la endocarditis sobre prótesis precoz). Tras un seguimiento medio de 56 meses, hubo 5 casos de recurrencia, necesitaron cirugía cuatro pacientes y fallecieron cinco.La supervivencia, excluyendo la mortalidad precoz, fue del 82 por ciento a los 5 años, no existiendo diferencias significativas entre los pacientes que recibieron tratamiento médico solo y los que fueron intervenidos en la fase activa. Conclusiones. La mortalidad precoz de la endocarditis sobre prótesis, según la experiencia de nuestro centro, está en torno al 20 por ciento. El pronóstico de los supervivientes a la fase activa de la enfermedad es favorable en la mayoría de los casos. La endocarditis sobre prótesis precoz continúa teniendo una elevada mortalidad temprana a pesar de utilizar un tratamiento combinado medicoquirúrgico (AU)

Características generales y resultados a corto y largo plazo de la endocarditis infecciosa en pacientes no drogadictos / General Features and Short and Long-Term Results of Infective Endocarditis in Non-Drug Addicts

Introducción y objetivos. La endocarditis infecciosa es una enfermedad con una morbimortalidad elevada en la fase activa y con un riesgo no despreciable de complicaciones en el seguimiento. El objetivo de este estudio es conocer las características clínicas y pronósticas de la endocarditis infecciosa a corto y a largo plazo en pacientes no drogadictos. Pacientes y métodos. Un estudio prospectivo de 138 casos de endocarditis infecciosa en pacientes no adictos a drogas por vía parenteral tratados en nuestro centro desde 1987 hasta 1997. Resultados. La edad media de los pacientes fue 44 ñ 20 años. Noventa y cinco casos (69 por ciento) fueron endocarditis sobre válvula nativa y cuarenta y tres (31 por ciento) endocarditis sobre prótesis. Los estreptococos causaron el 34 por ciento de los casos y los estafilococos el 33 por ciento. El 83 por ciento de los pacientes desarrolló algún tipo de complicación en la fase hospitalaria. Fueron intervenidos en la fase activa de la enfermedad el 51 por ciento de los pacientes, siendo en el 22 por ciento de los casos con carácter urgente. La mortalidad hospitalaria fue del 21 por ciento. En el seguimiento fueron intervenidos diez pacientes (9 por ciento) y fallecieron siete (5 por ciento del total de la serie). La supervivencia global a los 10 años es del 71 por ciento. No hubo diferencias estadísticas en la supervivencia en cuanto al tipo de tratamiento (médico o quirúrgico) recibido en la fase activa. Conclusiones. Una tasa elevada de cirugía en la fase activa se asocia con una supervivencia favorable a largo plazo sin aumentar la mortalidad precoz. El tratamiento médico ofrece también unos resultados favorables a largo plazo en los casos de endocarditis infecciosa sin factores de mal pronóstico y buena evolución (AU)

Embolia en cavidades cardiacas derechas: Aspectos diagnósticos y terapéuticos / Right heart chambers embolism. Diagnostic and therapeutic aspects

La trombosis venosa profunda puede causar embolias pulmonares. En raras ocasiones, la embolización se produce, no directamente en el árbol arterial pulmonar, sino en las cavidades cardiacas derechas. Aunque el valor de la ecocardiografía en el diagnóstico es bien reconocido, actualmente no existe consenso en cuanto al tratamiento apropiado. Presentamos seis casos de trombo flotante en aurícula derecha, diagnosticado por ecocardiografía, en pacientes con embolias pulmonares o con shock o síncope sin causa evidente. Se realizó embolectomía quirúrgica en 4 pacientes, y tratamiento fibrinolítico en 2, sin mortalidad hospitalaria. La elevada mortalidad asociada con esta patología puede reducirse con un diagnóstico ecocardiográfico rápido y un tratamiento emergente con fibrinolisis o cirugía. Nuestros datos sugieren la posible utilización de la fibrinolisis como tratamiento de primera elección en casos seleccionados