Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Increased cytomegalovirus immune responses at disease onset are protective in the long-term prognosis of patients with multiple sclerosis.

OBJECTIVE: It remains unclear whether viral infections interfere with multiple sclerosis (MS) disease progression. We evaluated the prognostic role of antibody responses toward viruses determined at disease onset on long-term disease outcomes. METHODS: Humoral immune responses against Epstein-Barr virus (EBV)-encoded nuclear antigen EBNA1, viral capsid antigen (VCA) and early antigen, and toward cytomegalovirus (HCMV), human herpesvirus 6 and measles were investigated in a cohort of 143 patients with MS for their association with long-term disability and inflammation disease outcomes. RESULTS: Median (IQR) follow-up was 20 (17.2-22.8) years. In univariable analysis, increased HCMV levels were associated with a lower risk to Expanded Disability Status Scale 4.0 (HR 0.95; 95% CI 0.91 to 0.99; p=0.03), to develop a secondary progressive MS (HR 0.94; 95% CI 0.90 to 0.99; p=0.02) and to first-line treatment (HR 0.98; 95% CI 0.96 to 0.99; p=0.04). High HCMV IgG levels were associated with a longer time to first-line treatment (p=0.01). Increased immune responses against EBV-VCA were associated with higher risk for first-line (HR 1.45; 95% CI 1.12 to 1.88; p=0.005) and second-line treatments (HR 2.03; 95% CI 1.18 to 3.49; p=0.01), and high VCA IgG levels were associated with shorter time to first-line (p=0.004) and second-line (p=0.02) therapies. EBNA1-specific IgG levels correlated with disease severity (0.17; p=0.04) and with an increased relapse rate during follow-up (relapse rate 1.26; 95% CI 1.03 to 1.56; p=0.02) that remained stable in multivariable analysis. CONCLUSIONS: These results indicate that elevated immune responses against HCMV at disease onset have protective effects on long-term disability and inflammation disease outcomes. Our data also indicate that increased immune responses against EBV in early phases may influence long-term disease prognosis.

Aortic flow dynamics and stiffness in Loeys-Dietz syndrome patients: a comparison with healthy volunteers and Marfan syndrome patients.

AIMS: To assess aortic flow and stiffness in patients with Loeys-Dietz syndrome (LDS) by 4D flow and cine cardiovascular magnetic resonance (CMR) and compare the results with those of healthy volunteers (HV) and Marfan syndrome (MFS) patients. METHODS AND RESULTS: Twenty-one LDS and 44 MFS patients with no previous aortic dissection or surgery and 35 HV underwent non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), and aortic diameters were obtained at 20 planes from the ascending (AAo) to the proximal descending aorta (DAo). IRF and SFRR were also quantified for aortic regions (proximal and distal AAo, arch and proximal DAo). Peak-systolic wall shear stress (WSS) maps were also estimated. Aortic stiffness was quantified using pulse wave velocity (PWV) and proximal AAo longitudinal strain. Compared to HV, LDS patients had lower rotational flow at the distal AAo (P = 0.002), arch (P = 0.002), and proximal DAo (P < 0.001) even after adjustment for age, stroke volume, and local diameter. LDS patients had higher SFRR in the proximal DAo compared to both HV (P = 0.024) and MFS patients (P = 0.015), even after adjustment for age and local diameter. Axial and circumferential WSS in LDS patients were lower than in HV. AAo circumferential WSS was lower in LDS compared to MFS patients. AAo and DAo PWV and proximal AAo longitudinal strain revealed stiffer aortas in LDS patients compared to HV (P = 0.007, 0.005, and 0.029, respectively) but no differences vs. MFS patients. CONCLUSION: Greater aortic stiffness as well as impaired IRF and WSS were present in LDS patients compared to HV. Conversely, similar aortic stiffness and overlapping aortic flow features were found in Loeys-Dietz and Marfan patients.

Aortic Branch Aneurysms and Vascular Risk in Patients With Marfan Syndrome.

BACKGROUND: Aortic branch aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their prevalence and eventual prognostic significance are unknown. OBJECTIVES: The goal of this study was to assess the prevalence of aortic branch aneurysms in MFS and their relationship with aortic prognosis. METHODS: MFS patients with a pathogenic FBN1 genetic variant and at least one magnetic resonance or computed tomography angiography study assessing aortic branches were included. Aortic events and those related to aneurysm complications were recorded during follow-up. RESULTS: A total of 104 aneurysms were detected in 50 (26.7%) of the 187 patients with MFS (mean age 37.9 ± 14.4 years; 54% male) included in this study, with the iliac artery being the most common location (45 aneurysms). Thirty-one patients (62%) had >1 peripheral aneurysm, and surgery was performed in 5 (4.8%). Patients with aneurysms were older (41.9 ± 12.7 years vs. 36.7 ± 14.8 years; p = 0.040) and had more dilated aortic root (42.2 ± 6.4 mm vs. 38.8 ± 8.0 mm; p = 0.044) and dyslipidemia (31.0% vs. 9.7%; p = 0.001). In a subgroup of 95 patients with no previous aortic surgery or dissection followed up for 3.3 ± 2.6 years, the presence of arterial aneurysms was associated with a greater need for aortic surgery (hazard ratio: 3.4; 95% confidence interval: 1.1 to 10.3; p = 0.028) in a multivariable Cox analysis adjusted for age and aortic diameter. CONCLUSIONS: Aortic branch aneurysms are present in one-quarter of patients with MFS and are related to age and aortic dilation, and they independently predict the need for aortic surgery. The systematic use of whole-body vascular assessment is recommended to identify other sites of vascular involvement at risk for complications and to define the subgroup of patients with more aggressive aortic disease.

Changes in the diagnosis and management of acute aortic syndrome and associated mortality in the last 20 years.

INTRODUCTION AND OBJECTIVES: Mortality is high in acute aortic syndrome (AAS), which therefore requires early treatment. This study aimed to analyze changes in the diagnosis and treatment of AAS over 20 years at our center. METHODS: From 1999 to 2018, 451 patients diagnosed with AAS (336 men; mean age, 60.9±12.4 years) were prospectively included (270 type A and 181 type B). Clinical variables, diagnosis, treatment, and in-hospital complications were analyzed. RESULTS: The use of computed tomography (CT) as the first-line diagnostic technique increased from 62.8% to 94.2% (P <.001). Surgical treatment of type A AAS rose from 67.4% to 82.5% (P=.09). Mortality from type A AAS decreased significantly from 53.1% to 26.3% (P <.001) as a result of the fall in mortality from surgical treatment (from 45.4% to 17.0%; P <.001). The use of medical treatment alone for type B AAS decreased from 91.8% to 61.7% (P <.001) due to the greater use of endovascular treatment. Mortality from type B AAS showed no significant reduction (16.2% to 10.6%; P=.15). CONCLUSIONS: The diagnosis and treatment of AAS has changed substantially in the last 2 decades. CT has become the first-line diagnostic technique for AAS. In type A AAS, mortality has fallen significantly due to improvements in the results of surgical treatment. In type B AAS, the use of medical treatment alone has decreased due to the expansion of endovascular treatment, although in-hospital mortality has not decreased significantly.

Strongyloidiasis screening in migrants living in Spain: systematic review and meta-analysis.

OBJECTIVES: To provide information regarding the prevalence of strongyloidiasis among migrants coming from Strongyloides stercoralis-endemic areas who reside in Spain. METHODS: Systematic review of the literature and meta-analysis of studies showing prevalence of S. stercoralis infection among migrants from Latin America, Africa, Eastern Europe, Asia and Oceania who reside in Spain. We included articles published until 30 April 2019 without language restriction. The keywords used for the search included 'Strongyloides stercoralis', 'strongyloidiasis', 'Spain', 'screening' and 'migrants'. RESULTS: Twenty-four studies were included in the review and meta-analysis, comprising 12 386 screened people. Eleven studies (7020 patients) evaluated the presence of S. stercoralis infection only through investigation of larvae in faeces, showing an overall prevalence of 1% (95%CI 1-1%). Thirteen studies (5366 patients) used a serological test, showing an overall prevalence of 14% (95%CI 11-17%). Strongyloidiasis seroprevalence was 20% (95%CI 15-24%) among migrants from sub-Saharan Africa, 14% (95%CI 10-18%) among those from Latin America and 8% (95%CI 5-11%) among migrants from North Africa. CONCLUSIONS: Migrants coming from strongyloidiasis-endemic areas living in Spain had a high S. stercoralis infection prevalence, particularly those from sub-Saharan Africa and Latin America. This population should be screened using serology as the most sensitive test for S. stercoralis infection. This could be easily implemented at primary care level.

OBJECTIFS: Fournir des informations sur la prévalence de la strongyloïdose parmi les migrants résidant en Espagne et provenant de zones endémiques pour Strongyloides stercoralis. MÉTHODES: Revue systématique de la littérature et méta-analyse des études montrant la prévalence de l'infection à S. stercoralis parmi les migrants d'Amérique latine, d'Afrique, d'Europe de l'Est, d'Asie et d'Océanie qui résident en Espagne. Nous avons inclus des articles publiés jusqu'au 30 avril e 2019 sans restriction de langue. Les mots clés utilisés pour la recherche comprenaient "Strongyloides stercoralis", "strongyloïdose", "Espagne", "dépistage" et "migrants". RÉSULTATS: Vingt-quatre études ont été incluses dans la revue et la méta-analyse, comprenant 12.386 personnes dépistées. Onze études (7.020 patients) ont évalué la présence d'une infection à S. stercoralis uniquement en examinant les larves dans les selles, montrant une prévalence globale de 1% (IC95%: 1-1%). Treize études (5.366 patients) ont utilisé un test sérologique, montrant une prévalence globale de 14% (IC95%: 11-17%). La séroprévalence de la strongyloïdose était de 20% (IC95%: 15-24%) chez les migrants d'Afrique subsaharienne, 14% (IC95%: 10-18%) chez ceux d'Amérique latine et 8% (IC95%: 5-11%) chez ceux d'Afrique du Nord. CONCLUSIONS: Les migrants en provenance de zones d'endémie pour la strongyloïdose vivant en Espagne avaient une prévalence élevée d'infection à S. stercoralis, en particulier ceux d'Afrique subsaharienne et d'Amérique latine. Cette population devrait être dépistée en utilisant la sérologie comme le test le plus sensible pour l' infection à S. stercoralis. Cela pourrait être facilement mis en œuvre au niveau des soins primaires.

Myocardial protection in the arterial switch operation: Custodiol versus cold blood cardioplegia.

OBJECTIVES: The optimal myocardial protective solution in the neonatal arterial switch operation remains controversial. The aim of this study was to demonstrate that Bretschneider's histidine-tryptophan-ketoglutarate crystalloid solution (Custodiol) offers protection at least similar to that of cold blood cardioplegia. METHODS: Patients who underwent the neonatal arterial switch operation with Custodiol between January 2016 and December 2018 (n = 23) were compared with an historical cohort from August 2010 to December 2015 in which cold blood cardioplegia was used (n = 41). A linear mixed-effect model for repeated measures was performed to test the recovery of myocardial function based on inotropic and vasoactive inotropic scores, cardiac enzyme release and left ventricular ejection fraction. RESULTS: Patients in the cold blood cardioplegia group had higher inotropic scores in the first 24 h (0 h, P = 0.001 and 24 h, P = 0.006) and higher vasoactive inotropic scores in the first 72 h (0 h, 24 h and 48 h, P < 0.001; 72 h, P = 0.012). Cardiac troponin-I concentrations were higher in the cold blood cardioplegia group at postoperative hours 1-72 (1 h, 6 h, 12 h and 24 h, P < 0.001; 48 h, P = 0.001 and 72 h, P = 0.003). Creatinine-kinase-MB concentrations were higher in the cold blood cardioplegia group at postoperative hours 1-24 (1 h, 6 h and 12 h, P < 0.001; 24 h, P = 0.042). The left ventricular ejection fraction was higher in the Custodiol group just after the operation (P = 0.005), at 24 h (P = 0.001) and on the first day without inotropic support (P = 0.011). CONCLUSIONS: Neonatal myocardium protected with Custodiol during the arterial switch operation presented optimal ventricular function recovery with less inotropic support and less myocardial damage compared with cold blood cardioplegia.

Imported endemic mycoses in Spain: Evolution of hospitalized cases, clinical characteristics and correlation with migratory movements, 1997-2014.

Endemic mycoses are systemic fungal infections. Histoplasmosis is endemic in all temperate areas of the world; coccidioidomycosis and paracoccidioidomycosis are only present in the American continent. These pathogens are not present in Spain, but in the last years there has been an increase of reported cases due to migration and temporary movements. We obtained from the Spanish hospitals records clinical and demographic data of all hospitalized cases between 1997 and 2014. There were 286 cases of histoplasmosis, 94 of Coccidioidomycosis and 25 of paracoccidioidomycosis. Overall, histoplasmosis was strongly related to HIV infection, as well as with greater morbidity and mortality. For the other mycoses, we did not find any immunosuppressive condition in most of the cases. Although we were not able to obtain data about clinical presentation of all the cases, the most frequently found was pulmonary involvement. We also found a temporal correlation between the Spanish population born in endemic countries and the number of hospitalized cases along this period. This study reflects the importance of imported diseases in non-endemic countries due to migratory movements.

Anatomical and clinical predictors of valve dysfunction and aortic dilation in bicuspid aortic valve disease.

OBJECTIVE: Bicuspid aortic valve (BAV) is associated with early valvular dysfunction and proximal aorta dilation with high heterogeneity. This study aimed to assess the determinants of these complications. METHODS: Eight hundred and fifty-two consecutive adults diagnosed of BAV referred from cardiac outpatient clinics to eight echocardiographic laboratories of tertiary hospitals were prospectively recruited. Exclusion criteria were aortic coarctation, other congenital disorders or intervention. BAV morphotype, significant valve dysfunction and aorta dilation (≥2 Z-score) at sinuses and ascending aorta were established. RESULTS: Three BAV morphotypes were identified: right-left coronary cusp fusion (RL) in 72.9%, right-non-coronary (RN) in 24.1% and left-non-coronary (LN) in 3.0%. BAV without raphe was observed in 18.3%. Multivariate analysis showed aortic regurgitation (23%) to be related to male sex (OR: 2.80, p<0.0001) and valve prolapse (OR: 5.16, p<0.0001), and aortic stenosis (22%) to BAV-RN (OR: 2.09, p<0.001), the presence of raphe (OR: 2.75, p<0.001), age (OR: 1.03; p<0.001), dyslipidaemia (OR: 1.77, p<0.01) and smoking (OR: 1.63, p<0.05). Ascending aorta was dilated in 76% without differences among morphotypes and associated with significant valvular dysfunction. By contrast, aortic root was dilated in 34% and related to male sex and aortic regurgitation but was less frequent in aortic stenosis and BAV-RN. CONCLUSIONS: Normofunctional valves are more prevalent in BAV without raphe. Aortic stenosis is more frequent in BAV-RN and associated with some cardiovascular risk factors, whereas aortic regurgitation (AR) is associated with male sex and sigmoid prolapse. Although ascending aorta is the most commonly dilated segment, aortic root dilation is present in one-third of patients and associated with AR. Remarkably, BAV-RL increases the risk for dilation of the proximal aorta, whereas BAV-RN spares this area.

Evaluation of cytokine profile and HLA association in benznidazole related cutaneous reactions in patients with Chagas disease.

BACKGROUND: Benznidazole is the drug of choice for Chagas disease. The major drawback of this drug is the high adverse events rate, being cutaneous reactions the most frequent one, leading to definitive withdrawal of treatment in 15%-30% of patients. METHODS: Prospective observational study where adult Chagas disease patients accepting to receive benznidazole (100 mg/8 hours for 60 days) were included. The objective was to characterize the skin toxicity of benznidazole in patients with Chagas disease, determine the serum cytokine profile, and evaluate the potential association with specific HLA alleles and benznidazole concentration. Serum cytokine levels were measured at day 0, 15, and 60 of treatment. Class I and II HLA alleles were determined. When cutaneous reaction was detected, a skin biopsy was performed. Serum benznidazole concentration was determined at the time of cutaneous reaction, or at day 15 of treatment. RESULTS: Fifty-two patients were included, 20(38.5%) had cutaneous reaction, and median time of appearance was 9 days. Skin biopsies showed histopathological findings consistent with drug eruption. Patients with cutaneous drug-reaction had higher proportion of eosinophilia during treatment, and higher interleukin (IL)-5 and IL-10 serum concentrations at day 15 of treatment than those without cutaneous reaction. Treatment interruption (that included moderate-severe cutaneous reactions) was more frequent in patients carrying HLA-B*3505 allele (45.5% vs 15.4%, P = .033). No differences in benznidazole serum concentration were found. CONCLUSIONS: Benznidazole related cutaneous reaction rate is high, and it was produced by a delayed hypersensitivity reaction with a Th2 response. Carrying HLA-B*3505 allele could be associated with moderate-severe cutaneous reaction.

La Colaboración Cochrane en Cuba: parte VII: los metanálisis: aproximaciones útiles para su comprensión / The Colaboration Cochrane in Cuba: the meta-analysis: some useful approaches for its comprehension

Se realiza una aproximación al análisis, síntesis e integración sistémica de la información, que ocurre durante el transcurso de la investigación metanalítica desde la perspectiva de los procesos de producción de información. Se establecen los antecedentes y las formas de clasificación de los metanálisis. Se estudia cada una de las 6 etapas por las que transcurre la investigación metanalítica, a saber: formulación del problema, búsqueda de la literatura, codificación de los estudios, medida de los resultados, análisis e interpretación y publicación del informe final. Se exponen los diferentes tipos de sesgos que pueden perjudicar la calidad de la revisión metanalítica y se repasan los conceptos estadísticos necesarios para la correcta comprensión de esta clase de estudios

La Biblioteca Virtual de Salud de la provincia Holguín: un diagnóstico preliminar

Con el objetivo de iniciar el desarrollo de la Biblioteca Virtual de Salud de la provincia Holguín, se realizó un diagnóstico preliminar de las condiciones existentes en el territorio para su implementación. Se exponen los conceptos fundamentales relacionados con la biblioteca virtual, se identifican las instituciones con mayor potencial científico en el área, así como los productos y servicios de información con condiciones para trasladarse a un entorno de red. Se establece una estrategia para la implantación de la biblioteca virtual de salud, su extensión a las diferentes instituciones que componen el sistema de salud de la provinicia. Finalmente, se exponen los factores críticos del éxito para este proyecto.

Aimed at the development of the Medical Virtual Library of Holguin Province a preliminary diagnosis of existing conditions was carried out. The main concepts related to the virtual library are exposed, institutions with a higher scientific potential in health care areas are identified as well as the products and information services that can be moved to the web. The strategy to the introduction of the virtual library is provided as well as its extension to the different institutions of the Health Care System of the province. Finally, some critical aspects for the success of this project are exposed.

Elementos conceptuales básicos útiles para comprender las redes de telecomunicación / Useful basic conceptual elements for understanding telecommunication networks

Se expone un conjunto de conocimientos con el objetivo de introducir a los especialistas en información en los conceptos básicos relacionados con las redes de telecomunicación, como vía para perfeccionar la cultura bibliotecaria en el campo de las nuevas tecnologías de información. Dicha cultura contribuirá decisivamente a un uso más eficiente de las redes del Sistema Nacional de Salud, a partir del desarrollo progresivo de una infraestructura de información electrónica que permita a los profesionales del sector de la comunicación y el intercambio con la comunidad científica internacional, así como el acceso conveniente y oportuno a la información

Metanálisis si; metanálisis no

Se realiza un breve recuento del surgimiento del metanálisis, su desarrollo actual y se toma como referencia la base de datos en CD-ROM Medline. Se hace énfasis en los aspectos metodológicos y bioestadísticos, así como en sus etapas de elaboración y en los modelos estadísticos necesario para su aplicación. Se relacionan los softwares disponibles que permiten aplicar dicha técnica. Se exponen las dificultades existentes para realiazr estudios metanalíticos a partir de los trabajos publicados en nuestro país. Se incluye una lista bibliográfica sobre el tema