Clinical Presentation and Outcomes of Kawasaki Disease in Children from Latin America: A Multicenter Observational Study from the REKAMLATINA Network.

OBJECTIVES: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). STUDY DESIGN: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). RESULTS: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). CONCLUSION: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD.

Kawasaki disease presenting with hoarseness: A multinational study of the REKAMLATINA network.

BACKGROUND: Recently, hoarseness affecting the supraglottic structure has been reported in Kawasaki disease (KD). The objective of this study was to characterize the frequency of hoarseness in acute KD patients in Latin America. METHODS: We used prospective data from the multinational Red de Enfermedad de Kawasaki en America Latina (REKAMLATINA) network. A total of 865 patients from 20 countries were enrolled during the 3 year study period. Data on hoarseness were available in 858 (99.2%) patients. The clinical and laboratory characteristics between hoarse and non-hoarse KD were compared. RESULTS: Hoarseness was documented in 100 (11.6%) patients. Hoarse patients were younger than those with KD without hoarseness (median age 18 vs 26 months; P = 0.002) and presented with lower hemoglobin (10.7 g/dL vs 11.3 g/dL; P = 0.040) and hematocrit levels (32% vs 33%, P = 0.048). CONCLUSIONS: Hoarseness was found to be prevalent as a presenting sign of acute KD in younger children. Anemia may indicate the presence of active inflammation.

Glial cells in the driver seat of leukodystrophy pathogenesis.

Glia cells are often viewed as support cells in the central nervous system, but recent discoveries highlight their importance in physiological functions and in neurological diseases. Central to this are leukodystrophies, a group of progressive, neurogenetic disease affecting white matter pathology. In this review, we take a closer look at multiple leukodystrophies, classified based on the primary glial cell type that is affected. While white matter diseases involve oligodendrocyte and myelin loss, we discuss how astrocytes and microglia are affected and impinge on oligodendrocyte, myelin and axonal pathology. We provide an overview of the leukodystrophies covering their hallmark features, clinical phenotypes, diverse molecular pathways, and potential therapeutics for clinical trials. Glial cells are gaining momentum as cellular therapeutic targets for treatment of demyelinating diseases such as leukodystrophies, currently with no treatment options. Here, we bring the much needed attention to role of glia in leukodystrophies, an integral step towards furthering disease comprehension, understanding mechanisms and developing future therapeutics.

Giant coronary artery aneurysms complicating Kawasaki disease in Mexican children.

BACKGROUND: One of the most important complications of Kawasaki disease is the development of giant coronary aneurysms. Risk factors for their development are still not clear. METHODS: A retrospective analysis was conducted at the National Institute of Paediatrics in Mexico City, Mexico. It included all patients with a diagnosis of acute Kawasaki disease between August, 1995 and August, 2015. Clinical and laboratory findings, as well as echocardiographic measurements, were recorded. Patients with giant coronary aneurysms (z-score⩾10) were compared with the rest of the patients. A value of p<0.05 was considered statistically significant. Odds ratios and their 95% confidence intervals were calculated to define risk factors. RESULTS: During the study period, 416 patients were diagnosed with Kawasaki disease. Of them, 34 developed giant coronary aneurysms during the acute stage of the disease. In the multivariate analysis, patients younger than 1 year, those with a higher duration of illness at the time of diagnosis, and those who received additional intravenous immunoglobulin showed a significantly higher frequency of giant coronary aneurysms. CONCLUSIONS: One of the main factors associated with the development of giant coronary aneurysms was the delay in the diagnosis of Kawasaki disease. This finding highlights the importance of maintaining a high suspicion of the disease, which would enable an early diagnosis and prompt treatment and decrease the risk for developing giant coronary aneurysms.

Kawasaki disease in a healthcare provider: an adult case in a paediatric resident.

Kawasaki disease is a small-to-medium-vessel vasculitis of unknown origin that predominantly affects children, although the disease can occur in adults. We report the case of a 26-year-old paediatric resident with fever, exanthema, ocular changes, arthralgia, and desquamation of palms and soles. Diagnosis was established after the fever resolved, and no treatment with intravenous gammaglobulin was administered. His echocardiogram showed normal coronary arteries. Acute Kawasaki disease in adults is a rare and under-recognised condition. It is important to consider the disease in patients with prolonged fever associated with unusual clinical features.

Bio-inspired green light crosslinked alginate-heparin hydrogels support HUVEC tube formation.

Alginate is a polysaccharide which forms hydrogels via ionic and/or covalent crosslinking. The goal was to develop a material with suitable, physiologically relevant mechanical properties and biological impact for use in wound treatment. To determine if the novel material can initiate tube formation on its own, without the dependance on the addition of growth factors, heparin and/or arginyl-glycyl-aspartic acid (RGD) was covalently conjugated onto the alginate backbone. Herein, cell adhesion motifs and bioactive functional groups were incorporated covalently within alginate hydrogels to study the: 1) impact of crosslinked heparin on tubular network formation, 2) impact of RGD conjugation, and the 3) biological effect of vascular endothelial growth factor (VEGF) loading on cellular response. We investigated the structure-properties-function relationship and determined the viscoelastic and burst properties of the hydrogels most applicable for use as a healing cell and tissue adhesive material. Methacrylation of alginate and heparin hydroxyl groups respectively enabled free-radical covalent inter- and intra-molecular photo-crosslinking when exposed to visible green light in the presence of photo-initiators; the shear moduli indicate mechanical properties comparable to clinical standards. RGD was conjugated via carbodiimide chemistry at the alginate carboxyl groups. The adhesive and mechanical properties of alginate and alginate-heparin hydrogels were determined via burst pressure testing and rheology. Higher burst pressure and material failure at rupture imply physical tissue adhesion, advantageous for a tissue sealant healing material. After hydrogel formation, human umbilical vein endothelial cells (HUVECs) were seeded onto the alginate-based hydrogels; cytotoxicity, total protein content, and tubular network formation were assessed. Burst pressure results indicate that the cell responsive hydrogels adhere to collagen substrates and exhibit increased strength under high pressures. Furthermore, the results show that the green light crosslinked alginate-heparin maintained cell adhesion and promoted tubular formation.

cis-[6-(Pyridin-2-yl)-1,3,5-triazine-2,4-diamine](dichloride) Palladium(II)-Based Electrolyte Membrane Reactors for Partial Oxidation Methane to Methanol.

Methane is an abundant resource and the main constituent of natural gas. It can be converted into higher value-added products and as a subproduct of electricity co-generation. The application of polymer electrolyte reactors for the partial oxidation of methane to methanol to co-generate power and chemical products is a topic of great interest for gas and petroleum industries, especially with the use of materials with a lower amount of metals, such as palladium complex. In this study, we investigate the ideal relationship between cis-[6-(pyridin-2-yl)-1,3,5-triazine-2,4-diamine(dichloride)palladium(II)] (Pd-complex) nanostructure and carbon to obtain a stable, conductive, and functional reagent diffusion electrode. The physical and structural properties of the material were analyzed by Fourier transform infrared (FT-IR) and Raman spectroscopies, transmission electron microscopy (TEM), and X-ray powder diffraction (XRD) techniques. The electrocatalytic activity studies revealed that the most active proportion was 20% of Pd-complex supported on carbon (m/m), which was measured with lower values of open-circuit and power density but with higher efficiency in methanol production with reaction rates of r = 4.2 mol L-1·h-1 at 0.05 V.

Conversion of Methane into Methanol Using the [6,6'-(2,2'-Bipyridine-6,6'-Diyl)bis(1,3,5-Triazine-2,4-Diamine)](Nitrato-O)Copper(II) Complex in a Solid Electrolyte Reactor Fuel Cell Type.

The application of solid electrolyte reactors for methane oxidation to co-generation of power and chemicals could be interesting, mainly with the use of materials that could come from renewable sources and abundant metals, such as the [6,6'- (2, 2'-bipyridine-6, 6'-diyl)bis (1,3,5-triazine-2, 4-diamine)](nitrate-O)copper (II) complex. In this study, we investigated the optimal ratio between this complex and carbon to obtain a stable, conductive, and functional reagent diffusion electrode. The most active Cu-complex compositions were 2.5 and 5% carbon, which were measured with higher values of open circuit and electric current, in addition to the higher methanol production with reaction rates of 1.85 mol L-1 h-1 close to the short circuit potential and 1.65 mol L-1 h-1 close to the open circuit potential, respectively. This activity was attributed to the ability of these compositions to activate water due to better distribution of the Cu complex in the carbon matrix as observed in the rotating ring disk electrode experiments.

Recognition of Fungal Components by the Host Immune System.

By being the first point of contact of the fungus with the host, the cell wall plays an important role in the pathogenesis, having many molecules that participate as antigens that are recognized by immune cells, and also that help the fungus to establish infection. The main molecules reported to trigger an immune response are chitin, glucans, oligosaccharides, proteins, melanin, phospholipids, and others, being present in the principal pathogenic fungi with clinical importance worldwide, such as Histoplasma capsulatum, Paracoccidioides brasiliensis, Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, and Sporothrix schenckii. Knowledge and understanding of how the immune system recognizes and responds to fungal antigens are relevant for the future research and development of new diagnostic tools and treatments for the control of mycosis caused by these fungi.

Use of Adjunctive Therapy in Acute Kawasaki Disease in Latin America.

Objective: To characterize the use of adjunctive therapy in Kawasaki disease (KD) in Latin America. Methods: The study included 1,418 patients from the Latin American KD Network (REKAMLATINA) treated for KD between January 1, 2009, and May 31, 2017. Results: Of these patients, 1,152 received only a single dose of IVIG, and 266 received additional treatment. Age at onset was similar in both groups (median 2 vs. 2.2 years, respectively). The majority of patients were male (58 vs. 63.9%) and were hospitalized with the first 10 days of fever (85.1 vs. 84.2%). The most common adjunctive therapy administered was steroids for IVIG-resistance, followed by additional doses of IVIG. The use of biologics such as infliximab was limited. KD patients who received adjunctive therapy were more likely to have a lower platelet count and albumin level as well as a higher Z score of the coronary arteries. Conclusion: This is the first report of adjunctive therapies for KD across Latin America. IVIG continues to be the initial and resistance treatment, however, steroids are also used and to a lesser extent, biological therapy such as infliximab. Future studies should address the barriers to therapy in children with acute KD throughout Latin America.

Presentation and Outcomes of Kawasaki Disease in Latin American Infants Younger Than 6 Months of Age: A Multinational Multicenter Study of the REKAMLATINA Network.

Objective: To characterize the clinical presentation and outcomes of Kawasaki disease (KD) in infants <6 months of age as compared to those ≥6 months in Latin America. Methods: We evaluated 36 infants <6 months old and 940 infants ≥6 months old diagnosed with KD in Latin America. We compared differences in laboratory data, clinical presentation, treatment response, and coronary artery outcomes between the two cohorts. Results: The majority (78.1%) of infants and children ≥6 months of age were initially diagnosed with KD, as compared to only 38.2% of infants <6 months. Clinical features of KD were more commonly observed in the older cohort: oral changes (92 vs. 75%, P = 0.0023), extremity changes (74.6 vs. 57.1%, P = 0.029), and cervical lymphadenopathy (67.6 vs. 37.1%, P = 0.0004). Whether treated in the first 10 days of illness or after the 10th day, infants <6 months were at greater risk of developing a coronary artery aneurysm compared to KD patients ≥6 months treated at the same point in the course of illness [ ≤ 10 days (53.8 vs. 9.4%, P = 0.00012); >10 days (50 vs. 7.4%, P = 0.043)]. Conclusion: Our data show that despite treatment in the first 10 days of illness, infants <6 months of age in Latin America have a higher risk of developing a coronary artery aneurysm. Delay in the diagnosis leads to larger coronary artery aneurysms disproportionately in these infants. Thus, suspicion for KD should be high in this vulnerable population.

Design and experimental analysis of a new malleovestibulopexy prosthesis using a finite element model of the human middle ear.

INTRODUCTION AND OBJECTIVE: Many designs of prostheses are available for middle ear surgery. In this study we propose a design for a new prosthesis, which optimises mechanical performance in the human middle ear and improves some deficiencies in the prostheses currently available. Our objective was to design and assess the theoretical acoustic-mechanical behaviour of this new total ossicular replacement prosthesis. METHODS: The design of this new prosthesis was based on an animal model (an iguana). For the modelling and mechanical analysis of the new prosthesis, we used a dynamic 3D computer model of the human middle ear, based on the finite elements method (FEM). RESULTS: The new malleovestibulopexy prosthesis design demonstrates an acoustical-mechanical performance similar to that of the healthy human middle ear. This new design also has additional advantages, such as ease of implantation and stability in the middle ear. CONCLUSIONS: This study shows that computer simulation can be used to design and optimise the vibroacoustic characteristics of middle ear implants and demonstrates the effectiveness of a new malleovestibulopexy prosthesis in reconstructing the ossicular chain.

Spanish consensus on vulvar disorders in postmenopausal women.

INTRODUCTION: The consequences of vulvar disorders in terms of health, sexuality, and quality of life are usually undervalued, with disparities in the conceptual, diagnosis and treatment criteria. AIM: The objective of this guide will be to analyse the factors associated with the diagnosis and treatment of vulvar disorders and to provide recommendations for the most appropriate diagnostic and therapeutic measures. METHODOLOGY: A panel of experts from various Spanish scientific societies related to sexual health (Spanish Menopause Society [SMS] and the Asociación Española de Patología Cervical y Colposcopia [AEPCC]) met to reach a consensus on these issues and to decide the optimal timing and methods based on the best evidence available. RESULTS: We recommend a biopsy of all vulvar lesions with an uncertain diagnosis, especially with asymmetry, irregular borders, variegated and irregular colour and diameter >6mm. For vulvodynia, we recommend the use of lubricants or topical treatments with lidocaine or bupivacaine, amitriptyline, baclofen or triamcinolone. For vulvar epithelial disorders, we recommend beginning with topical corticosteroids of moderate to high potency. For sexual dysfunction, a multidisciplinary approach is the best management strategy in these patients.

Efectos de la hemodilución hipervolemica en la cirugia de aneurismas intracraneales / Effects of hipervolemic hemodilution on the surgery of intracranial aneurysms

Se describen los efectos de la administración de manitol al 20% en dosis total de 1000 ml, en los pacientes sometidos a cirugía de aneurisma intracraneales. Los efectos sobre el estado hidroelectrolítico, ácido-base y hemodinámicos son discutidos con base a lo reportado en la literatura y sobre la posibilidad de protección cerebral y reducción de complicaciones postquirúrgicas. La disminución en el microhematocrito y el aumento en la PVC a consecuencia de la administraçäo de manitol podemos definirla como hemodilución hipervolémica