The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Consenso experto sobre el uso clínico de los tratamientos por vía tópica en el manejo del dolor neuropático periférico

Objective: To propose consensus from a panel of state level that integrates clinical experience and the most current evidence, recommendations on the clinical use of topical treatments for the management of peripheral neuropathic pain (PNP). Methods: We propose, based on a literature review on topical therapeutic options in PNP, a series of professional standards and clinical recommendations for improving the use of these topical agents. We used the modified Delphi method in two rounds to contrast the views of a national panel of 52 renowned experts, selected by a "snowball" strategy among the group of anesthesiologists pain units (94 %) and other specialists (neurologist and trauma). We evaluated 61 clinical recommendations grouped into 6 areas: a) PNP systemic versus topical treatment (11 items); b) postsurgical neuropathic pain, post-traumatic and painful stumps (12 items); c) post-herpetic neuralgia, intercostal and trigeminal (9 items); d) PNP entrapment (8 items); e) CRPS (11 items); and f) diabetic neuropathy (DN) and other polyneuropathy (HIV, alcohol, toxicity, etc.) (10 items). We used a Likert-type ordinal scale of 9 points (disagree/agree) to evaluate each recommendation. After the first round of the survey, information was provided requested to reconsider the vote on items not agree. Results: After the first round the panel consensus was achieved in 37 of the 61 issues raised. At the end of the second round of the agreement amounted to 46 (75 %). In general, there was consensus among experts on whether to introduce topical treatment in first line treatment of PNP and its greater acceptance by patients compared with systemic. He was also a shared view consider in the management of various types of PNP. Also reached a high level of agreement to accept, from a physiological point of view, the indication for treatment with capsaicin patch 8 % for various types of PNP. Conclusions: Experts in the clinical management of PNP show a high level of professional agreement with various therapeutic recommendations for study. The dissemination of such recommendations can help improving the routine management of topical drugs for neuropathic pain in our health system.Objetivo: Proponer a partir del consenso de un panel de expertos de ámbito estatal que integre la experiencia clínica y la evidencia disponible más actual, recomendaciones sobre el uso clínico de los tratamientos por vía tópica para el manejo del dolor neuropático periférico (DNP). Métodos: Se proponen, a partir de una revisión bibliográfica sobre las distintas opciones terapéuticas tópicas en DNP, una serie de criterios profesionales y recomendaciones clínicas para la mejora del uso de dichos agentes tópicos. Se empleó el método Delphi modificado en dos rondas para contrastar las opiniones de un panel nacional de 52 reconocidos expertos, seleccionados mediante una estrategia en "bola de nieve" de entre el colectivo de anestesiólogos de unidades del dolor (94 %) y otros especialistas (neurólogos y traumatólogos). Se evaluaron 61 recomendaciones clínicas agrupadas en 6 áreas temáticas: a) DNP: tratamiento tópico versus sistémico (11 ítems); b) dolor neuropático postquirúrgico, postraumático y muñones dolorosos (12 ítems); c) neuralgia posherpética, intercostal y del trigémino (9 ítems); d) DNP por atrapamiento (8 ítems); e) síndrome de dolor regional complejo (11 ítems); y f) neuropatía diabética (ND) y otras polineuropatías (por VIH, alcohol, toxicidad, etc.) (10 ítems). Se empleó una escala ordinal de tipo Likert de 9 puntos (desacuerdo/acuerdo) para evaluar cada recomendación. Tras la primera ronda de encuesta, se facilitó al panel información del resultado (resultados estadísticos y opiniones libres de los panelistas) y se solicitó la reconsideración del voto sobre los ítems no consensuados. Resultados: Tras la primera ronda del panel se logró consenso en 37 de las 61 cuestiones planteadas. Al final de la segunda ronda el acuerdo ascendió hasta 46 ítems (75 %). En general, se aprecia consenso entre los expertos sobre la conveniencia de introducir los tratamientos tópicos en primera línea de tratamiento del DNP y sobre su mejor aceptación por los pacientes frente a los sistémicos. Asimismo, fue criterio compartido que la combinación de estos fármacos tópicos con los tratamientos sistémicos es una opción a considerar en el manejo de varios tipos de DNP. También se alcanzó un alto grado de acuerdo en aceptar, desde un punto de vista fisiopatológico, la indicación del tratamiento con parche de capsaicina al 8 % para varios tipos de DNP. Conclusión: Los expertos en el manejo clínico del DNP muestran un elevado nivel de acuerdo profesional con diversas recomendaciones terapéuticas analizadas en el estudio. La difusión de tales recomendaciones puede ayudar a la mejora del manejo rutinario de fármacos tópicos para el dolor neuropático en nuestro sistema sanitario