Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease.

BACKGROUND: Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages. OBJECTIVES: The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease. METHODS: Phase 2, open-label trial in children (ages, 28 days to <18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis. PRIMARY ENDPOINT: a composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy. RESULTS: From 2017 to 2021, 192 participants were randomized, 129 apixaban and 63 SOC. Diagnoses included single ventricle (74%), Kawasaki disease (14%), and other heart disease (12%). One apixaban participant (0.8%) and 3 with SOC (4.8%) had major or clinically relevant nonmajor bleeding (% difference -4.0 [95% CI: -12.8 to 0.8]). Apixaban incidence rate for all bleeding events was nearly twice the rate of SOC (100.0 vs 58.2 per 100 person-years), driven by 12 participants with ≥4 minor bleeding events. No thromboembolic events or deaths occurred in either arm. Apixaban pediatric PK steady-state exposures were consistent with adult levels. CONCLUSIONS: In this pediatric multinational, randomized trial, bleeding and thromboembolism were infrequent on apixaban and SOC. Apixaban PK data correlated well with adult trials that demonstrated efficacy. These results support the use of apixaban as an alternative to SOC for thromboprophylaxis in pediatric heart disease. (A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist [VKA] or Low Molecular Weight Heparin [LMWH] in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation; NCT02981472).

Three-Dimensional Porous Scaffolds Derived from Bovine Cancellous Bone Matrix Promote Osteoinduction, Osteoconduction, and Osteogenesis.

The use of three-dimensional porous scaffolds derived from decellularized extracellular matrix (ECM) is increasing for functional repair and regeneration of injured bone tissue. Because these scaffolds retain their native structures and bioactive molecules, in addition to showing low immunogenicity and good biodegradability, they can promote tissue repair and regeneration. Nonetheless, imitating these features in synthetic materials represents a challenging task. Furthermore, due to the complexity of bone tissue, different processes are necessary to maintain these characteristics. We present a novel approach using decellularized ECM material derived from bovine cancellous bone by demineralization, decellularization, and hydrolysis of collagen to obtain a three-dimensional porous scaffold. This study demonstrates that the three-dimensional porous scaffold obtained from bovine bone retained its osteoconductive and osteoinductive properties and presented osteogenic potential when seeded with human Wharton's jelly mesenchymal stromal cells (hWJ-MSCs). Based on its characteristics, the scaffold described in this work potentially represents a therapeutic strategy for bone repair.

Low Incidence and Mortality by SARS-CoV-2 Infection Among Healthcare Workers in a Health National Center in Mexico: Successful Establishment of an Occupational Medicine Program.

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Healthcare workers (HCWs) constitute a population which is significantly affected by SARS-CoV-2 infection worldwide. In Mexico, the Instituto Nacional de Enfermedades Respiratorias (INER) is the principal national reference of respiratory diseases. Aim: To evaluate the efficiency of the INER-POL-TRAB-COVID19 program to mitigate the SARS-CoV-2 infection risk among the INER-healthcare workers (INER-HCW). Methods: Currently, the INER has 250 beds and 200 respiratory ventilators to support COVID-19 patients in critical condition. On March 1st, 2020, the INER-POL-TRAB-COVID19 program was launched to mitigate the SARS-CoV-2 infection risk among the INER-HCW. Findings: From March 1st to October 1st, 2020, 71.5% of INER-HCWs were tested for SARS-CoV-2 infection, and 77% of them were frontline workers. Among the tested INER-HCWs, 10.4% were positive for SARS-CoV-2 infection. Nonetheless, nosocomial infection represented only 3.8% of the cases and the mortality was null. Fifty-three of INER-HCWs positive to SARS-CoV-2 had a negative test 42-56 days post-diagnosis and were returned to service. Finally, although a change in the PPE implemented on May 11th, 2020, the incidence of SARS-CoV-2 infection was not affected. Conclusion: INER has a lower incidence of HCWs infected with SARS-CoV-2 as compared to the mean of the national report. The implementation of the INER-POL-TRAB-COVID19 program is efficient to decrease the risk of infection among the HCWs. Our findings suggest that the implementation of a similar program at a national level can be helpful to provide a safe environment to HCWs and to prevent the collapse of health institutions.

Importancia del rabdomioma cardiaco en población pediátrica. Experiencia de 39 años. Serie de casos / Importance of heart rabdomioma in pediatric population. A 39 year experience. Case series

Resumen Introducción: Los rabdomiomas son los tumores cardiacos benignos más prevalentes en la etapa fetal y durante la infancia. Objetivo: Nuestro objetivo es dar a conocer nuestra experiencia durante 39 años en pacientes pediátricos con rabdomioma en nuestra institución, así como enfatizar la importancia de su detección, estudio y control por la asociación que tiene con esclerosis tuberosa (ET). Material y métodos: Realizamos un estudio retrospectivo y descriptivo, de enero de 1980 a marzo del 2018. Veinticuatro cumplieron con nuestros criterios, recogimos información respecto a la clínica y estudios de gabinete, así como su evolución y el tratamiento dado. Se les llamó vía telefónica para conocer su evolución y estado actual. Resultados: Encontramos 51 pacientes con diagnóstico de tumor cardiaco, de los cuales 24 eran rabdomiomas. El diagnóstico se hizo prenatal en 8 pacientes, 5 al nacimiento y en 11 durante el primer año de vida. Las manifestaciones clínicas más frecuentes fueron la presencia de soplo, arritmias, cianosis, disnea y diaforesis. En 17 de ellos se hizo diagnóstico de ET. La mitad tuvo seguimiento por neurología, 10 por dermatología, 8 por oftalmología y 4 con genética. La mitad se dejó en vigilancia, a 7 se les dio tratamiento médico y 5 requirieron cirugía. En cuanto a la evolución, 17 pacientes se mantuvieron estables, 5 presentaron regresión espontánea y 2 fallecieron. Conclusiones: El rabdomioma es un tumor benigno poco frecuente, su evolución puede ser maligna y asociado a ET ensombrece el pronóstico.

Abstract Introduction: Rhabdomyomas are the most prevalent benign heart tumors in the fetal stage and during childhood. Objective: Our objective is to make known our experience over 39 years in pediatric patients with rhabdomyoma in our institution, as well as to emphasize the importance of its detection, study and control due to the association it has with tuberous sclerosis (TS). Material and methods: We conducted a retrospective, descriptive and cross-sectional study, from January 1980 to March 2018. Twenty-four met our criteria, we collected information regarding the clinic and cabinet studies, as well as their evolution and the treatment given. They were called by telephone to know their evolution and current status. Results: We found 51 patients with a diagnosis of cardiac tumor, of which 24 were rhabdomyomas. The diagnosis was made prenatal in 8 patients, 5 at birth and in 11 during the first year of life. The most frequent clinical manifestations were the presence of murmur, arrhythmias, cyanosis, dyspnea, and diaphoresis. In 17 of them a diagnosis of TS was made. Half had follow-up by neurology, 10 by dermatology, 8 by ophthalmology and 4 with genetics. Half were left under surveillance, 7 were given medical treatment and 5 required surgery. Regarding the clinical evolution 17 patients remained stable, 5 presented spontaneous regression and 2 died. Conclusions: Rhabdomyoma is a rare benign tumor, its evolution can be malignant and associated with TS, it darkens the prognosis.

[Importance of heart rabdomioma in pediatric population. A 39 year experience. Case series]. / Importancia del rabdomioma cardiaco en población pediátrica. Experiencia de 39 años. Serie de casos.

Introducción: Los rabdomiomas son los tumores cardiacos benignos más prevalentes en la etapa fetal y durante la infancia. Objetivo: Nuestro objetivo es dar a conocer nuestra experiencia durante 39 años en pacientes pediátricos con rabdomioma en nuestra institución, así como enfatizar la importancia de su detección, estudio y control por la asociación que tiene con esclerosis tuberosa (ET). Material y métodos: Realizamos un estudio retrospectivo y descriptivo, de enero de 1980 a marzo del 2018. Veinticuatro cumplieron con nuestros criterios, recogimos información respecto a la clínica y estudios de gabinete, así como su evolución y el tratamiento dado. Se les llamó vía telefónica para conocer su evolución y estado actual. Resultados: Encontramos 51 pacientes con diagnóstico de tumor cardiaco, de los cuales 24 eran rabdomiomas. El diagnóstico se hizo prenatal en 8 pacientes, 5 al nacimiento y en 11 durante el primer año de vida. Las manifestaciones clínicas más frecuentes fueron la presencia de soplo, arritmias, cianosis, disnea y diaforesis. En 17 de ellos se hizo diagnóstico de ET. La mitad tuvo seguimiento por neurología, 10 por dermatología, 8 por oftalmología y 4 con genética. La mitad se dejó en vigilancia, a 7 se les dio tratamiento médico y 5 requirieron cirugía. En cuanto a la evolución, 17 pacientes se mantuvieron estables, 5 presentaron regresión espontánea y 2 fallecieron. Conclusiones: El rabdomioma es un tumor benigno poco frecuente, su evolución puede ser maligna y asociado a ET ensombrece el pronóstico.

Influence of the PLGA/gelatin ratio on the physical, chemical and biological properties of electrospun scaffolds for wound dressings.

Chronic wounds are a global health problem, and their treatments are difficult and long lasting. The development of medical devices through tissue engineering has been conducted to heal this type of wound. In this study, it was demonstrated that the combination of natural and synthetic polymers, such as poly (D-L lactide-co-glycolide) (PLGA) and gelatin (Ge), were useful for constructing scaffolds for wound healing. The aim of this study was to evaluate the influence of different PLGA/gelatin ratios (9:1, 7:3 and 5:5 (v/v)) on the physical, chemical and biological properties of electrospun scaffolds for wound dressings. These PLGA/Ge scaffolds had randomly oriented fibers with smooth surfaces and exhibited distances between fibers of less than 10 µm. The 7:3 and 5:5 PLGA/Ge scaffolds showed higher swelling, hydrophilicity and degradation rates than pure PLGA and 9:1 (v/v) PLGA/Ge scaffolds. Young's moduli of the scaffolds were 72 ± 10, 48 ± 6, 58 ± 6 and 6 ± 1 MPa for the pure PLGA scaffold and the 9:1, 7:3 and 5:5 (v/v) PLGA/Ge scaffolds, respectively. Mesenchymal stem cells (MSCs) seeded on all the PLGA/Ge scaffolds were viable, and the cells were attached to the fibers at the different analyzed timepoints. The most significant proliferation rate was observed for cells on the 7:3 PLGA/Ge scaffolds. Biocompatibility analysis showed that all the scaffolds produced inflammation at the first week postimplantation; however, the 7:3 and 5:5 (v/v) PLGA/Ge scaffolds were degraded completely, and there was no inflammatory reaction observed at the fourth week after implantation. In contrast, the 9:1 PLGA/Ge scaffolds persisted in the tissue for more than four weeks; however, at the eighth week, no traces of the scaffolds were found. In conclusion, the scaffolds with the 7:3 PLGA/Ge ratio showed suitable physical, chemical and biological properties for applications in chronic wound treatments.

In vitro and in vivo assessment of lactic acid-modified chitosan scaffolds for potential treatment of full-thickness burns.

Autologous skin transplantation is today's "gold standard" treatment for full-thickness burns. However, when > 30% of total body surface area is damaged, there is an important shortage of autologous donor sites for skin grafting; then, treatment alternatives become crucial. Such alternatives can be based on polymeric scaffolds capable of functioning as protective covers and cells/factors carriers. Chitosan (CTS) is a natural-derived polymer with relevant biological-related properties but poor mechanical performance. Improved mechanical properties can be achieved through lactic acid grafting (LA-g); nevertheless, LA-g affects the biological response towards the CTS-based materials. In this work, CTS-LA scaffolds with different LA-g percentages were synthesized and evaluated to determine appropriate LA-g degrees for full-thickness burns treatment. In vitro results indicated that the higher the LA-g percentage, the lower the capability of the scaffolds to sustain fibroblasts culture. Scaffolds with LA-g around 28% (CTS-LA28) sustained cell culture and allowed normal cell functionality. Further evaluation of CTS-LA28 as acellular and cellular grafts in a full-thickness burn mouse model showed that at 28 days post-burn, macroscopic characteristic of the reparation tissue were closer to healthy skin when cellular grafts were used for treatment; histological evaluation also showed that dermis cellularity and collagenous fibers structure were similar to those in healthy skin when cellular grafts were used for burns treatment. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2875-2891, 2017.