Mucoadhesive film for oral delivery of vaccines for protection of the respiratory tract.

The delivery of vaccines plays a pivotal role in influencing the strength and longevity of the immune response and controlling reactogenicity. Mucosal immunization, as compared to parenteral vaccination, could offer greater protection against respiratory infections while being less invasive. While oral vaccination has been presumed less effective and believed to target mainly the gastrointestinal tract, trans-buccal delivery using mucoadhesive films (MAF) may allow targeted delivery to the mucosa. Here we present an effective strategy for mucosal delivery of several vaccine platforms incorporated in MAF, including DNA plasmids, viral vectors, and lipid nanoparticles incorporating mRNA (mRNA/LNP). The mRNA/LNP vaccine formulation targeting SARS-CoV-2 as a proof of concept remained stable within MAF consisting of slowly releasing water-soluble polymers and an impermeable backing layer, facilitating enhanced penetration into the oral mucosa. This formulation elicited antibody and cellular responses comparable to the intramuscular injection, but also induced the production of mucosal IgAs, highlighting its efficacy, particularly for use as a booster vaccine and the potential advantage for protection against respiratory infections. The MAF vaccine preparation demonstrates significant advantages, such as efficient delivery, stability, and simple noninvasive administration with the potential to alleviate vaccine hesitancy.

Novel nanostructured lipid carriers loading Apigenin for anterior segment ocular pathologies.

Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation.

Plasmid DNA ionisable lipid nanoparticles as non-inert carriers and potent immune activators for cancer immunotherapy.

Immunotherapy is currently a standard of care in the treatment of many malignancies. However, predictable side effects caused by systemic administration of highly immunostimulatory molecules have been a serious concern within this field. Intratumoural expression or silencing of immunogenic and immunoinhibitory molecules using nucleic acid-based approaches such as plasmid DNA (pDNA) and small interfering RNA (siRNA), respectively, could represent a next generation of cancer immunotherapy. Here, we employed lipid nanoparticles (LNPs) to deliver either non-specific pDNA and siRNA, or constructs targeting two prominent immunotherapeutic targets OX40L and indoleamine 2,3-dioxygenase-1 (IDO), to tumours in vivo. In the B16F10 mouse model, intratumoural delivery of LNP-formulated non-specific pDNA and siRNA led to strong local immune activation and tumour growth inhibition even at low doses due to the pDNA immunogenic nature. Replacement of these non-specific constructs by pOX40L and siIDO resulted in more prominent immune activation as evidenced by increased immune cell infiltration in tumours and tumour-draining lymph nodes. Consistently, pOX40L alone or in combination with siIDO could prolong overall survival, resulting in complete tumour regression and the formation of immunological memory in tumour rechallenge models. Our results suggest that intratumoural administration of LNP-formulated pDNA and siRNA offers a promising approach for cancer immunotherapy.

Biosafety evaluation of etoposide lipid nanomedicines in C. elegans.

Neuroblastoma is a pediatric tumor that originates during embryonic development and progresses into aggressive tumors, primarily affecting children under two years old. Many patients are diagnosed as high-risk and undergo chemotherapy, often leading to short- and long-term toxicities. Nanomedicine offers a promising solution to enhance drug efficacy and improve physical properties. In this study, lipid-based nanomedicines were developed with an average size of 140 nm, achieving a high encapsulation efficiency of over 90% for the anticancer drug etoposide. Then, cytotoxicity and apoptosis-inducing effects of these etoposide nanomedicines were assessed in vitro using human cell lines, both cancerous and non-cancerous. The results demonstrated that etoposide nanomedicines exhibited high toxicity and selectively induced apoptosis only in cancerous cells.Next, the biosafety of these nanomedicines in C. elegans, a model organism, was evaluated by measuring survival, body size, and the effect on dividing cells. The findings showed that the nanomedicines had a safer profile than the free etoposide in this model. Notably, nanomedicines exerted etoposide's antiproliferative effect only in highly proliferative germline cells. Therefore, the developed nanomedicines hold promise as safe drug delivery systems for etoposide, potentially leading to an improved therapeutic index for neuroblastoma treatment.

Formulation and Optimization of Solid Lipid Nanoparticle-based Gel for Dermal Delivery of Linezolid using Taguchi Design.

BACKGROUND: Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved for the treatment of uncomplicated and complicated skin and soft tissue infections caused by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most cases. However, prolonged therapy is associated with various side effects and lifethreatening complications. Cutaneous application of LNZ will assist in reducing the dose, hence minimizing the unwanted side/adverse effects associated with oral administration. Dermal delivery provides an alternative route of administration, facilitating a local and sustained concentration of the antimicrobial at the site of infection. OBJECTIVE: The current research work aimed to formulate solid lipid nanoparticles (SLNs) based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft tissue infections to maximise its benefits and minimise the side effects. METHODS: SLNs were prepared by high-shear homogenisation and ultrasound method using Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration, drug-to-lipid ratio, and sonication time was investigated on particle size, zeta potential, and entrapment efficiency using the Taguchi design. The main effect plot of means and signal-to-noise ratio were generated to determine the optimized formulation. The optimized batch was formulated into a gel, and ex vivo permeation study, in vitro and in vivo antibacterial activity were conducted. RESULTS: The optimised process parameters to achieve results were 2% surfactant concentration, a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was 206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in vitro drug release. The gel showed a 5.03 ± 0.15 cm zone of inhibition while evaluated for in vitro antibacterial activity against Staphylococcus aureus. Ex vivo skin permeation studies demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results showed a significant reduction in colony-forming units in the group treated with LNZ SLN-based gel. CONCLUSION: Ex vivo studies ascertain the presence of the drug at the desired site and improve therapy. In vivo results demonstrated the ability of SLN-based gel to significantly reduce the number of bacteria in the stripped infection model. The utilization of SLN as an LNZ carrier holds significant promise in dermal delivery.

Data-driven development of an oral lipid-based nanoparticle formulation of a hydrophobic drug.

Due to its cost-effectiveness, convenience, and high patient adherence, oral drug administration normally remains the preferred approach. Yet, the effective delivery of hydrophobic drugs via the oral route is often hindered by their limited water solubility and first-pass metabolism. To mitigate these challenges, advanced delivery systems such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been developed to encapsulate hydrophobic drugs and enhance their bioavailability. However, traditional design methodologies for these complex formulations often present intricate challenges because they are restricted to a relatively narrow design space. Here, we present a data-driven approach for the accelerated design of SLNs/NLCs encapsulating a model hydrophobic drug, cannabidiol, that combines experimental automation and machine learning. A small subset of formulations, comprising 10% of all formulations in the design space, was prepared in-house, leveraging miniaturized experimental automation to improve throughput and decrease the quantity of drug and materials required. Machine learning models were then trained on the data generated from these formulations and used to predict properties of all SLNs/NLCs within this design space (i.e., 1215 formulations). Notably, formulations predicted to be high-performers via this approach were confirmed to significantly enhance the solubility of the drug by up to 3000-fold and prevented degradation of drug. Moreover, the high-performance formulations significantly enhanced the oral bioavailability of the drug compared to both its free form and an over-the-counter version. Furthermore, this bioavailability matched that of a formulation equivalent in composition to the FDA-approved product, Epidiolex®.

Robust increase in glucagon secretion after oral protein intake, but not after glucose or lipid intake in Japanese people without diabetes.

Few studies in Asian populations have analyzed how glucagon secretion is affected by ingested glucose, proteins or lipids, individually. To investigate the fluctuations of glucagon secretion after the intake of each of these nutrients, 10 healthy volunteers underwent oral loading tests using each of glucose, proteins and lipids, and blood levels of glucose, insulin and glucagon were measured every 30 min for 120 min. Whereas glucagon secretion was suppressed and minimally affected by oral glucose intake and lipid intake, respectively, oral protein intake robustly increased glucagon secretion, as well as insulin secretion. Further studies are needed to elucidate the mechanism by which protein loading increases glucagon secretion.

Injectable Lipid Emulsion and Clinical Outcomes in Patients Exclusively Receiving Parenteral Nutrition in an ICU: A Retrospective Cohort Study Using a Japanese Medical Claims Database.

Guidelines for the nutritional management of critically ill patients recommend the use of injectable lipid emulsion (ILE) as part of parenteral nutrition (PN). The ILE's impact on outcomes remains unclear. Associations between prescribed ILE and in-hospital mortality, hospital readmission, and hospital length of stay (LOS) in critically ill patients in the intensive care unit (ICU) were investigated. Patients who were ≥18 years old in an ICU from January 2010 through June 2020, receiving mechanical ventilation, and fasting for >7 days, were selected from a Japanese medical claims database and divided, based on prescribed ILE during days from 4 to 7 of ICU admission, into 2 groups, no-lipid and with-lipid. Associations between the with-lipid group and in-hospital mortality, hospital readmission, and hospital LOS were evaluated relative to the no-lipid group. Regression analyses and the Cox proportional hazards model were used to calculate the odds ratios (OR) and regression coefficients, and hazard ratios (HR) were adjusted for patient characteristics and parenteral energy and amino acid doses. A total of 20,773 patients were evaluated. Adjusted OR and HR (95% confidence interval) for in-hospital mortality were 0.66 (0.62-0.71) and 0.68 (0.64-0.72), respectively, for the with-lipid group relative to the no-lipid group. No significant differences between the two groups were observed for hospital readmission or hospital LOS. The use of ILE for days 4 to 7 in PN prescribed for critically ill patients, who were in an ICU receiving mechanical ventilation and fasting for more than 7 days, was associated with a significant reduction in in-hospital mortality.

Lipidic lyotropic liquid crystals: Insights on biomedical applications.

Liquid crystals (LCs) possess unique physicochemical properties, translatable into a wide range of applications. To date, lipidic lyotropic LCs (LLCs) have been extensively explored in drug delivery and imaging owing to the capability to encapsulate and release payloads with different characteristics. The current landscape of lipidic LLCs in biomedical applications is provided in this review. Initially, the main properties, types, methods of fabrication and applications of LCs are showcased. Then, a comprehensive discussion of the main biomedical applications of lipidic LLCs accordingly to the application (drug and biomacromolecule delivery, tissue engineering and molecular imaging) and route of administration is examined. Further discussion of the main limitations and perspectives of lipidic LLCs in biomedical applications are also provided. STATEMENT OF SIGNIFICANCE: Liquid crystals (LCs) are those systems between a solid and liquid state that possess unique morphological and physicochemical properties, translatable into a wide range of biomedical applications. A short description of the properties of LCs, their types and manufacturing procedures is given to serve as a background to the topic. Then, the latest and most innovative research in the field of biomedicine is examined, specifically the areas of drug and biomacromolecule delivery, tissue engineering and molecular imaging. Finally, prospects of LCs in biomedicine are discussed to show future trends and perspectives that might be utilized. This article is an ampliation, improvement and actualization of our previous short forum article "Bringing lipidic lyotropic liquid crystal technology into biomedicine" published in TIPS.

Effectiveness Comparison of Polysaccharides, Proteins, and Lipids as Composite Edible Coatings on the Quality of Food Products / Comparación de la Efectividad de Polisacáridos, Proteínas y Lípidos como Recubrimientos Compuestos Comestibles en la Calidad de los Productos Alimenticios

Background: This research was motivated by the complaints of tomato farmers about their crops that quickly rotted before being sold, as well as the many research results (raw materials and methods) that edible coating films could not be applied optimally. Objectives: The research was a practical recommendation by comparing the effectiveness of raw materials (polysaccharides, proteins, and lipids) with the dipping and spray methods. Materials and methods used in the comparison process were the application of Structural Equation Modeling (SEM) with the Partial Least Square (PLS) approach. Results: Dipping has a strong effect (f2 ≥ 0.35; p<0.05), while spray had a moderate effect (f2: 0.15-0.35; p<0.05). Thus, the role of dipping as a mediator was more dominant than spray. Compared to proteins and lipids, polysaccharides had the best effectiveness (ß:0.460-0.584; f2: 0.15-0.35; p<0.05). Conclusion: the three ingredients improved the quality of tomatoes, and the dipping method was easier to apply by farmers than the spray method, which had many obstacles in its application

Antecedentes: esta investigación está motivada por las quejas de los productores de tomate sobre sus cultivos que se pudren rápidamente antes de ser vendidos, así como por los muchos resultados de la investigación (materias primas y métodos) de que las películas de recubrimiento comestibles no se pudieron aplicar de manera óptima. Objetivos: La investigación consiste en recomendaciones prácticas mediante la comparación de la eficacia de las materias primas (polisacáridos, proteínas y lípidos) con los métodos de inmersión y aspersión. Métodos: El método utilizado en el proceso de comparación es la aplicación del modelo de ecuaciones estructurales (SEM) con el enfoque de mínimos cuadrados parciales (PLS). Resultados: La inmersión tiene un efecto fuerte (f2 ≥ 0,35; p<0,05), mientras que la pulverización tiene un efecto moderado (f2: 0,15-0,35; p<0,05). Por lo tanto, el papel de la inmersión como mediador es más dominante que el del rociado. Los polisacáridos tienen la mejor eficacia (ß:0,460-0,584; f2: 0,15-0,35; p<0,05) en comparación con las proteínas y los lípidos. Conclusión: es que los tres ingredientes pueden mejorar la calidad de los tomates, y el método de inmersión es más fácil de aplicar por los agricultores que el método de aspersión, que tiene muchos obstáculos en su aplicación

Eficacia y seguridad de la fórmula nutricional con bajo contenido lipídico y alto contenido de triglicéridos de cadena media para el tratamiento de pacientes menores de 18 años con linfangiectasia intestinal primaria / Efficacy and safety of nutritional formula with low lipid content and high content of medium chain triglycerides for the treatment of patients under 18 years of age with primary intestinal lymphangiectasia

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el que expone la evaluación de tecnología acerca de la eficacia y seguridad de la fórmula nutricional con bajo contenido lipídico y alto contenido de triglicéridos de cadena media (TCM) para el tratamiento de pacientes menores de 18 años con linfangiectasia intestinal primaria (LIP). Así, el Dr. Marco Morales Acosta, médico especialista en pediatría del Hospital Nacional Edgardo Rebagliati Martins perteneciente a la Red Prestacional Rebagliati, siguiendo la Directiva N° 003-IETSI-ESSALUD-2016, envía al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso, por fuera del petitorio, del producto fórmula nutricional con bajo contenido lipídico y alto contenido de TCM. ASPECTOS GENERALES: La linfangiectasia intestinal primaria (LIP) es una condición causada por una deformidad congénita del sistema linfático del intestino delgado; la cual se caracteriza por la dilatación (local o difusa) de los vasos linfáticos de la mucosa y submucosa del intestino delgado (Suresh et al., 2009; Vignes & Bellanger, 2008; Waldmann et al., 1961). Esta dilatación de vasos linfáticos conduciría a la fuga de la linfa hacia el intestino delgado (enteropatía perdedora de proteínas); ocasionando hipoproteinemia, hipogammaglobulinemia, hipoalbuminemia, linfopenia; los que, a su vez, conducen a edema, pérdida de peso, entre otros (Abramowsky et al., 1989; Vignes & Bellanger, 2008). Aunque también se ha sugerido que el paso de la linfa hacia el lumen del intestino delgado podría deberse a una ruptura directa de los vasos linfáticos a través de la mucosa (Waldmann et al., 1961). La LIP es una enfermedad infrecuente que suele presentarse en menores de 3 años; aunque también se han reportado casos en la adultez (Freeman & Nimmo, 2011; Vignes & Bellanger, 2008). A la fecha, la prevalencia e incidencia mundial de LIP sigue siendo desconocida. En el Perú, solo se ha identificado un reporte de caso publicado en el año 2019 (Usnayo et al., 2019). Los médicos especialistas en pediatría del Servicio de Nutrición Pediátrica del Hospital Nacional Edgardo Rebagliati Martins reportan que en los últimos 10 años han atendido a tres pacientes con LIP. METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia sobre la eficacia y seguridad la fórmula nutricional con bajo contenido lipídico y alto contenido de TCM para el tratamiento de pacientes menores de 18 años con LIP. La búsqueda bibliográfica se realizó en las bases de datos PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitárias y guías de práctica clínica (GPC) incluyendo el National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), Scottish Intercollegiate Guidelines Network (SIGN), Institute for Clinical and Economic Review (ICER), Instituto de Calidad y Eficiencia en la Atención de la Salud (IQWiG, por sus siglas en alemán), Agency for Healthcare Research and Quality (AHRQ), Guidelines International Network (GIN), National Health and Medical Research Council (NHMRC), Haute Autorité de Santé (HAS), International HTA Database, la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), la Organización Mundial de la Salud (OMS), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) y la Agencia de Evaluación de Tecnologías Sanitarias del País Vasco. Asimismo, se realizó una búsqueda de GPC de las principales sociedades o instituciones especializadas en enfermedades raras como la National Organization for Rare Disorders (NORD) y Orphanet. Finalmente, se realizó una búsqueda en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o que no hayan sido publicados aún. RESULTADOS: Luego de la búsqueda bibliográfica, realizada hasta el 25 de setiembre del 2021, se incluyeron tres estudios. El primero fue un estudio observacional que comparó tres dietas en pacientes con linfangiectasia intestinal (Aoyagi et al., 2005). El segundo fue un estudio observacional que realizó un análisis pre-post de una dieta alta en proteínas (1.5 ­ 3.0 g/Kg/día) y baja en lípidos (15 ­ 20 % del total de calorías); de los cuales el 60 % fueron TCM, en pacientes menores de 18 años con LIP (Prasad et al., 2019). El tercer estudio fue una revisión de evidencia científica en la cual se compararon los reportes de pacientes tratados con TCM y pacientes que recibieron otros tratamientos (Desai et al., 2009). Adicionalmente, se incluyó una ETS realizada por el Ministerio de Sanidad, Servicios Sociales e Igualdad de España (Güemes et al., 2013). CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación 9.~ aprueba el uso de la fórmula nutricional con bajo contenido lipídico (25 % del requerimiento calórico) y alto contenido de TCM (mayor o igual al 56 %) para el tratamiento de los pacientes con LIP, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud, según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.

Eficacia y seguridad de la fórmula nutricional con bajo contenido lipídico y alto en triglicéridos de cadena media en pacientes pediátricos con quilotorax / Efficacy and safety of nutritional formula with low lipid content and high medium chain triglycerides in pediatric patients with chylothorax

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el que expone la evaluación de la eficacia y seguridad de la fórmula nutricional con bajo contenido lipídico y alto en triglicéridos de cadena media (TCM) en pacientes pediátricos con quilotórax. Así, el médico Marco Morales Acosta, especialista en pediatría, del Servicio de Pediatría Clínica del Hospital Nacional Edgardo Rebagliati Martins, perteneciente a la Red Prestacional Rebagliati, siguiendo la Directiva N.° 003-IETSIESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso, por fuera del petitorio del producto: fórmula nutricional con bajo contenido lipídico y alto en TCM. ASPECTOS GENERALES: El quilotórax es la acumulación de líquido linfático en la cavidad pleural, que resulta de fugas provenientes de los vasos linfáticos (Tutor, 2014). El quilotórax se diagnostica tras la detección de concentración de triglicéridos en el líquido pleural mayor a 110 mg/dl (Rocha et al., 2006). En la población pediátrica, el quilotórax es causado, principalmente, por defectos congénitos o por daños al conducto torácico como resultado de complicaciones posquirúrgicas (Soto-Martinez & Massie, 2009). La incidencia aproximada del quilotórax congénito es de 1 por cada 10,000 nacidos vivos (Zheng et al., 2020); mientas que, la incidencia del quilotórax post-cirugía cardíaca en población pediátrica varía de 0.85 % a 9.2 % (Rocha et al., 2006). A pesar de no tener alta incidencia, los pacientes menores de 18 años con quilotórax tienen riesgo de mortalidad de hasta el 50 % cuando no reciben tratamiento, mayor morbilidad y tienen mayor tiempo de estancia hospitalaria (mediana = 38.8 días; rango intercuartil [R1Q) = 27.8 - 52.3, frente a mediana = 27.0 días, RIQ = 18.9 - 39.1 días; p < 0.001), comparado con los que no desarrollaron quilotórax luego de una cirugía cardiaca (Bai et al., 2021; Yeh et al., 2013). METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad de la fórmula con bajo contenido lipídico y alto contenido de TCM. La búsqueda bibliográfica se realizó en las bases de datos bibliográfica de PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo la World Health Organization (WHO), la National Institute for Health and Care Excellence (NICE), la Agency for Healthcare Research and Quality's (AHRQ), la Scottish Intercollegiate Guidelines Network (SIGN), la New Zealand Guidelines Group (NZGG), la National Health and Medical Research Council (NHMRC), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Institute for Quality and Efficiency in Health Care (IQWIG), el Scottish Medicines Consortium (SMC), la Comissáo Nacional de Incorporção de Tecnologias no Sistema Único de Saúde (CONITEC), el Instituto de Evaluación Tecnológica en Salud (IETS) y el Instituto de Efectividad Clínica y Sanitaria (IECS). Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o que no hayan sido publicados aún. RESULTADOS: Luego de la búsqueda bibliográfica, no se encontró alguna GPC, ETS o ECA fase III que cumpla con los primeros criterios de inclusión. Tras la ampliación de los criterios de elegibilidad, se incluyeron tres estudios observacionales (Bellini et al., 2012; Cormack et al., 2004; Zheng et al., 2020). Dos de estos estudios (Cormack 2004 & Zheng 2020), usaron el diseño de cohortes de tipo retrospectivo, y compararon el tiempo hasta la resolución del quilotórax (solo en Zheng et al 2020), duración de drenaje pleural (solo en Cormack et al 2004), tiempo de hospitalización y mortalidad en los pacientes con quilotórax posquirúrgico que usaron la fórmula con bajo contenido lipídico alto en TCM versus los que usaron la NPT. El último estudio (Bellini et al 2012), se trata de una serie de casos de neonatos con quilotórax congénito, donde se reporta la experiencia de tratamiento de estos pacientes usando la fórmula nutricional con bajo contenido lipídico y alto en TCM con o sin la octreotida. Los desenlaces de interés evaluados fueron la resolución del quilotórax y la mortalidad. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de la fórmula con bajo contenido lipídico y alto en TCM, con o sin octreotida, en pacientes menores de 18 años con diagnóstico de quilotórax debido a cualquier etiología (congénito o adquirido) que pueden recibir nutrición enteral, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud, según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.

Effectiveness of unconditional cash transfers combined with lipid-based nutrient supplement and/or behavior change communication to prevent stunting among children in Pakistan: a cluster randomized controlled trial.

BACKGROUND: In Pakistan, the prevalence of stunting among children younger than 5 y has remained above WHO critical thresholds (≥30%) over the past 2 decades. OBJECTIVES: We hypothesized that an unconditional cash transfer (UCT) combined with lipid-based nutrient supplement (LNS) and/or social and behavior change communication (SBCC) will prevent stunting among children 6-23 mo of age. METHODS: This was a 4-arm, community-based cluster randomized controlled trial conducted in the district of Rahim Yar Khan, Pakistan. A total of 1729 children (UCT, n = 434; UCT + SBCC, n = 433; UCT + LNS, n = 430; and UCT + LNS + SBCC, n = 432) were enrolled at 6 mo of age and measured monthly for 18 mo until the age of 24 mo. RESULTS: At 24 mo of age, children who received UCT + LNS [rate ratio (RR): 0.85; 95% CI: 0.74, 0.97; P = 0.015) and UCT + LNS + SBCC (RR: 0.86; 95% CI: 0.77, 0.96; P = 0.007) had a significantly lower risk of being stunted compared with the UCT arm. No significant difference was noted among children who received UCT + SBCC (RR: 1.03; 95% CI: 0.91, 1.16; P = 0.675) in the risk of being stunted compared with the UCT arm. The pooled prevalence of stunting among children aged 6-23 mo was 41.7%, 44.8%, 38.5%, and 39.3% in UCT, UCT + SBCC, UCT + LNS, and UCT + LNS + SBCC, respectively. In pairwise comparisons, a significant impact on stunting among children in UCT + LNS (P = 0.029) and UCT + LNS + SBCC (P = <0.001) was noted compared with the UCT arm. CONCLUSIONS: UCT combined with LNS and UCT + LNS + SBCC were effective in reducing the prevalence of stunting among children aged 6-23 mo in marginalized populations. UCT + SBCC was not effective in reducing the child stunting prevalence. This trial was registered at clinicaltrials.gov as NCT03299218.

The Effects of Chronic Consumption of Lipid-Rich and Delipidated Bovine Dairy Milk on Brown Adipose Tissue Volume in Wild-Type Mice.

Brown adipose tissue (BAT) activation is associated with increased energy expenditure by inducing non-shivering thermogenesis. The ingestion of a milk fat globule membrane (MFGM) supplement and a high calorie diet are reported gateways into BAT activation. However, little is known about the effect of the MFGM and high calorie diets on BAT volume. To gain insight into this, mice were maintained on a high-fat (HF) or low-fat (LF) diet in conjunction with either full-cream (FC) or skim bovine dairy milk (BDM). After being maintained on their respective diets for 13 weeks, their body composition, including BAT volume, was measured using X-ray microtomography. A high calorie diet resulted in an increase in the BAT volume and mice consuming an HF diet in conjunction with FC BDM had a significantly greater BAT volume than all the other groups. Conversely, mice consuming an HF diet in addition to skim milk had a lower BAT volume compared to the HF control. The data presented suggest that the consumption of a high calorie diet in conjunction with FC BDM increases the BAT volume in wild-type mice. This study may provide valuable insight into future studies investigating BAT volume and BAT activity in relation to environmental factors, including diet.

Effects of Periodic Religious Fasting for Decades on Nutrient Intakes and the Blood Biochemical Profile.

The aim of the present study was to examine differences and correlations in nutrient intakes and serum parameters related to nutrient intake (lipid profile, vitamins, and trace elements) in 200 lifelong Christian Orthodox Church (COC) fasters with periodic abstinence from certain foods (predominantly of animal origin) for approximately half of the year and 200 non-fasting controls, all of whom did not take dietary supplements. Nutrient intakes were assessed through three-day dietary recalls. Blood samples were drawn for the analysis of potential biomarkers of nutrient intake. Fasters had lower energy intake, due to lower fat and protein intake, compared to non-fasters (p < 0.05). Fasters also had lower intakes of vitamins A, B1, B2, B6, B12, D, folate, pantothenate, sodium, calcium, zinc, and phosphorus. Most participants (in both groups) did not meet the recommended dietary allowances of most vitamins and elements. Most serum biochemical parameters did not reflect the differences in nutrient intakes between groups, and none exhibited a correlation coefficient above 0.5 with nutrient intakes. Our findings suggest that COC fasting is associated with reduced intake of many nutrients, although this does not seem to have an impact on the blood biochemical profile.

Dietary Lipids and Dyslipidemia in Chronic Kidney Disease.

The progression of chronic kidney disease (CKD) leads to altered lipid metabolism. CKD patients exhibit high blood triglyceride (TG) levels, reduced concentrations and functionality of high-density lipoproteins (HDL), and elevated levels of atherogenic small, dense, low-density lipoproteins (sdLDL). Disorders of lipid metabolism and other metabolic disturbances place CKD patients at high risk for cardiovascular disease (CVD). Extensive evidence supports the cardioprotective effects of unsaturated fatty acids, including their beneficial effect on serum cholesterol and TG levels. Dietary lipids might therefore be especially important in the nutritional management of CKD. We review current dietary recommendations for fat intake by CKD patients and suggest potential nutritional interventions by emphasizing dietary lipids that might improve the blood lipid profile and reduce cardiovascular risk in CKD.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers. RESULTS: SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics. CONCLUSIONS: SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers.

BACKGROUND: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development. OBJECTIVES: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024). RESULTS: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11). CONCLUSIONS: Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. RESULTS: SQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation. CONCLUSIONS: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.