Early experiences using bromelain-based enzymatic debridement in a tertiary burns centre in the United Kingdom: A retrospective case series review.

BACKGROUND: The modern ethos of burn care requires a holistic approach that helps patients to not only survive but also maintain a good quality of life. Bromelain-based enzymatic debridement with Nexobrid™ (NXB) has been shown to selectively debride burnt tissue and allow dermal preservation, which has the potential to reduce surgical burden and improve scarring. In this study, early experience with the use of Nexobrid™ at a tertiary burns centre between July 2016 and December 2019 is presented. In particular, the study assessed whether NXB had changed the acute care delivered to this cohort. METHODS: A retrospective analysis of the patients' records was performed. Results were analysed and presented in the context of current literature. RESULTS: Twenty adult patients (17 male, 3 female) underwent enzymatic debridement with NXB. Median age was 42.5 years. Mean total burn surface area (TBSA) on admission was 20%. Twelve patients were admitted to the intensive care unit, and eight were admitted to the adult burns ward. Mean TBSA treated with NXB was 8.2%, usually within 24 h of admission (mean). All patients had anaesthetist-led analgesia. NXB debridement was successful in 55% of patients, obviating the need for escharotomy in some patients. Sixty percent of all patients required further surgery, and 80% of facial burns treated with NXB required further surgery. Inotrope support was associated with NXB failure (p = 0.015). Mean length of stay was 29 days. DISCUSSION: Current evidence, including our own findings, cannot justify replacing the current surgical standard of care with NXB, but it certainly solidifies enzymatic debridement as a useful adjunct that should form part of the modern burn surgeon's armamentarium.

Enzyme/Nanocopper Hybrid Nanozymes: Modulating Enzyme-like Activity by the Protein Structure for Biosensing and Tumor Catalytic Therapy.

Artificial enzymes with modulated enzyme-mimicking activities of natural systems represent a challenge in catalytic applications. Here, we show the creation of artificial Cu metalloenzymes based on the generation of Cu nanoparticles in an enzyme matrix. Different enzymes were used, and the structural differences between the enzymes especially influenced the controlled the size of the nanoparticles and the environment that surrounds them. Herein, we demonstrated that the oxidase-like catalytic activity of these copper nanozymes was rationally modulated by enzyme used as a scaffold, with a special role in the nanoparticle size and their environment. In this sense, these nanocopper hybrids have confirmed the ability to mimic a unique enzymatic activity completely different from the natural activity of the enzyme used as a scaffold, such as tyrosinase-like activity or as Fenton catalyst, which has extremely higher stability than natural mushroom tyrosinase. More interestingly, the oxidoreductase-like activity of nanocopper hybrids was cooperatively modulated with the synergistic effect between the enzyme and the nanoparticles improving the catalase activity (no peroxidase activity). Additionally, a novel dual (metallic and enzymatic activity) of the nanozyme made the highly improved catechol-like activity interesting for the design of 3,4-dihydroxy-l-phenylalanine (l-DOPA) biosensor for detection of tyrosinase. These hybrids also showed cytotoxic activity against different tumor cells, interesting in biocatalytic tumor therapy.

A Retrospective Review of an Off-label Bromelain-based Selective Enzymatic Debridement (Nexobrid®) in the Treatment of Deep, Partial, and Full Thickness Burns and Hard to Heal Wounds.

BACKGROUND: Rapid and selective bromelain-based enzymatic debridement provides a non-surgical alternative for the eschar removal in deep burns, which allows for early debridement of large surface areas, accurate evaluation of burn and wound depth, and the need for skin grafting. OBJECTIVES: To evaluate the efficacy of application of a bromelain-based selective enzymatic debridement (Nexobrid®) beyond the manufacturer's guidelines for use in burns > 48 hours as well as chemical, electrical, and pediatric burns, and chronic wounds. METHODS: This retrospective review included records collected between January 2017 and April 2019, from male and female patients aged 8 months to 99 years with deep burns or wounds treated with bromelain-based selective enzymatic debridement. RESULTS: Of the 33 patients who received the bromelain-based selective enzymatic debridement agent beyond the manufacturer's guidelines, 25 (76%) were observed to have successful debridement of the eschar, 8 (24%) were observed to have little effect on the burn eschar. Sixteen required further surgery after debridement. Clinical data on the use of bromelain-based selective enzymatic debridement agents are limited, but these results suggest the capacity to effectively debride burns > 48 hours (late presentation burns), use for pediatrics and for chemical and electrical burns, and apply to hard to heal full thickness chronic wounds. CONCLUSIONS: Bromelain-based selective enzymatic debridement was found to be an effective treatment modality beyond the recommended guidelines including late presentation burns and chronic wounds. This debridement method warrants further consideration when making clinical decisions concerning burn and wound care.

Experiencia en el desbridamiento con Nexobrid(R) y cura húmeda con Prontosan(R) wound gel en el paciente quemado / Experience with Nexobrid(R) debridement and Prontosan(R) wound healling gel moist in the treatment of burn patients

Introducción y Objetivo. El desbridamiento tangencial y autoinjerto ha sido el tratamiento de elección de las quemaduras profundas. Actualmente, la disponibilidad de técnicas no quirúrgicas, como el desbridamiento enzimático con Nexobrid(R), introduce un cambio de concepto permitiendo mayor selectividad en la eliminación de la escara y optimizar la preservación de la dermis sana, menor cicatrización patológica, mejor resultado estético, y sobre todo menor agresión al paciente. Prontosan(R)Wound Gel es un hidrogel con propiedades antibacterianas para mantener cura húmeda, y no interfiere en la epitelización. Presentamos nuestra experiencia en desbridamiento enzimático y aplicación de cura húmeda con estos productos en quemaduras de segundo grado profundo y/o tercer grado faciales, en manos, extremidades inferiores y tronco. Material y Método. Incluimos todos los pacientes quemados de segundo grado profundo y/o tercer grado de cualquier extensión tratados con Nexobrid(R) para Unidad de Quemados entre diciembre de 2015 y febrero de 2017. Realizamos desbridamiento enzimático en las primeras 24 horas aplicándolo en un máximo del 15% de superficie corporal, seguido de cura con Prontosán(R) y oclusión con apósito hidrocoloide. Cobertura de quemaduras profundas que no curaron espontáneamente en quirófano, con injertos laminares. Las variables recogidas fueron: edad, sexo, agente causal, extensión, localización y profundidad, tiempo de hospitalización, localización, superficie corporal y profundidad de la quemadura en la zona en la que se aplicó Nexobrid®, eficacia del desbridamiento enzimático, necesidad de desbridamiento quirúrgico, necesidad de injerto, tiempo hasta epitelización y complicaciones. Resultados.Analizamos 17 pacientes con SCQ del 3 al 55%. Valoramos visualmente el desbridamiento enzimático inicial como completo en todos ellos. Solo 5 pacientes precisaron injertos laminares. En los que no precisaron desbridamiento quirúrgico, la epitelización se produjo a los 15 días como promedio. Estudio histopatológico en 3 pacientes: desbridamiento completo de la quemadura en 1 y parcial en 2, con abundante infiltrado inflamatorio linfocítico perivascular postratamiento. Los hallazgos histopatológicos se correlacionaron con la eficacia del desbridamiento valorado clínicamente en 1 de los 3 casos, y con el diagnóstico clínico de la quemadura en los 3 casos. Ningún caso precisó cirugía de secuelas tras un seguimiento medio de 7 meses. Conclusiones. Nexobrid(R) en combinación con Prontosan(R) Wound Gel en nuestra experiencia preliminar parece una alternativa viable en el tratamiento de quemaduras en cara, extremidad superior, extremidad inferior y tronco

Background and Objective. Tangential debridement and autograft have been the gold standard surgical treatment of deep burns. Nowadays, the availability of non surgical enzymatic debridement techniques, such as Nexobrid(R) has introduced a new concept in the treatment of burn patients, allowing an increase in the selectivity for the scar removal leading to the preservation of healthy dermis, reducing scarring, improving cosmetic outcome, and even more, minimizing aggression to the patient. Prontosan(R) Wound Gel is a hydrogel with antibacterial properties that can be used to keep wound bed moist, without interfering epithelialization. We present our experience with these combined products in deep dermal and/or subdermal burns affecting face, upper and lower extremities, perineal and trunk. Methods. All patients with deep dermal and/or subdermal burns treated with Nexobrid(R) in our Burn Unit between December 2015 and February 2017 were included. Enzymatic debridement was performed within the first 24 hours, applied up to 15% of body surface. After that, Prontosan(R) was applied and Varihesive(R) was used as a sealed dressing. Whenever grafting was necessary, it was performed in operating room adding split thickness grafts. Variables collected were: age, sex, agent, extension, location and depth of the burn, period of hospitalization, location, extension and depth of the burn in the area where Nexobrid ® was applied, efficacy of enzymatic debridement, needing for surgical debridement, needing of grafting, time to epithelialization and complications. Results. Seventeen patients with 3 to 55% burn body surface were included. Initial enzymatic debridement was complete in all patients. Only 5 patients needed split thickness grafting. Complete epithelialization was achieved on an average of 15 days. Histopathology studies were performed on 3 patients. Histopathology findings correlated to the clinical efficacy of the debridement in 1 out of the 3 cases, and to the clinical diagnosis of the burn in the 3 cases. After 7 months follow up, no patients required surgery for correction of sequelae. Conclusions. In our preliminary experience, combines use of Nexobrid(R) and Prontosan (R)Wound Gel seems a feasible alternative in the treatment of facial, upper and lower extremities and trunk burns

Time to start putting down the knife: A systematic review of burns excision tools of randomised and non-randomised trials.

AIMS: Dermal preservation during acute burn excision is key to obtaining superior healing/scar outcomes, however, determining the most appropriate excision tool is an ongoing challenge. Novel tool development means the knife is no longer our only option, yet for the majority it remains the gold standard. This systematic review aims to evaluate evidence for burns excision approaches (knife/hydrosurgery/enzymatic). METHODS: CENTRAL, EMBASE, MEDLINE (1946-2017) were searched with MeSH terms: 'debridement', 'burns', 'sharp', 'enzymatic', 'hydrosurgery'. Relevant randomised control trials (RCTs)/non-randomised controlled case series/trials were extracted/analysed. In vitro/burn non-specific studies were excluded. Main methodological parameters were intervention/excision efficacy. RESULTS: Eighteen articles met inclusion criteria (n=7148): three were RCTs, involving comparator enzymatic (NexoBrid™ (EDNX)) or hydrosurgical (Versajet™) excision to surgical Standard of Care. Both showed statistically significant decreased need for excisional excision and auto-grafting by viable tissue preservation allowing spontaneous healing by epithelialisation. CONCLUSION: Level 1 Evidence comparing excision modalities for acute burns is sparse. Although early excision with a knife is still often considered best practice, there is no tool choice consensus or robust comparison with alternate, possibly superior, tools. EDNX or Versajet™ should be considered alternatively. Further RCTs are indicated, with regards final scar outcomes and to allow consensus within current evidence.

Molecular basis and current strategies of therapeutic arginine depletion for cancer.

Renewed interest in the use of therapeutic enzymes combined with an improved knowledge of cancer cell metabolism, has led to the translation of several arginine depletion strategies into early phase clinical trials. Arginine auxotrophic tumors are reliant on extracellular arginine, due to the downregulation of arginosuccinate synthetase or ornithine transcarbamylase-key enzymes for intracellular arginine recycling. Engineered arginine catabolic enzymes such as recombinant human arginase (rh-Arg1-PEG) and arginine deiminase (ADI-PEG) have demonstrated cytotoxicity against arginine auxotrophic tumors. In this review, we discuss the molecular events triggered by extracellular arginine depletion that contribute to tumor cell death.

A prospective, randomized, double-blind, placebo-controlled clinical trial comparing the efficacy of systemic enzyme therapy for edema control in orthognathic surgery using ultrasound scan to measure facial swelling.

PURPOSE: To evaluate the effectiveness of systemic enzyme therapy for the control of edema in patients who undergo bimaxillary orthognathic surgery. MATERIALS AND METHODS: Thirty patients were included in this double-blinded, randomized, control trial. Before surgery, each patient was allotted a code (study or control group). Nine anthropometric points were selected. Thickness of the soft tissue at each of these points was measured using an ultrasound device. These measurements were performed on the day before surgery and 1, 5, and 15 days after surgery. The study group was given a twice-daily dose of systemic enzyme therapy from the first postoperative day for 5 days; the control group was given placebo. The percentage of difference in the thickness of the soft tissue was calculated at each of the 9 points on postoperative days 1, 5, and 15. These data were analyzed and compared using the Mann-Whitney test. RESULTS: The statistical evaluation showed a significant difference in soft tissue thickness between the 2 groups, especially on days 5 and 15, at most assessed points. CONCLUSION: The results of this study suggest that systemic enzyme therapy significantly decreases postoperative edema in orthognathic surgery, precluding long-term corticosteroid use.

Celiac disease: advances in treatment via gluten modification.

Celiac disease (CD) is an autoimmune enteropathy that occurs in genetically susceptible individuals carrying the prerequisite genetic markers HLA DQ2 or DQ8. These genetic markers are present in approximately 30% of the population, and the worldwide prevalence of CD is estimated to be approximately 1%-2%. Currently a gluten-free diet is the only treatment for CD, but novel therapies aimed at gluten modification are underway. This review will discuss gluten-based therapies including wheat alternatives and wheat selection, enzymatic alteration of wheat, oral enzyme supplements, and polymeric binders as exciting new therapies for treatment of CD.

Nutrición en los errores innatos del metabolismo en adultos / Nutritional support in adult patients with inborn errors of metabolism

Los Errores Innatos del Metabolismo (EIM) son trastornos genéticos caracterizados por disfunción de una proteína involucrada en el metabolismo celular, lo que provoca una alteración en el funcionamiento fisiológico de la célula. Dependiendo de la función de la proteína y de cuál sea la vía metabólica afectada, puede producirse una toxicidad por acúmulo del sustrato no metabolizado, o por la aparición de sustancias producidas por el metabolismo de dicho sustrato a través de vías alternativas, o bien fenómenos derivados del déficit del producto final de la vía metabólica. Las EIM son un grupo de enfermedades genéticas muy numeroso y complejo, con un elevado grado de heterogeneidad genética y, en consecuencia, clínica y bioquímica. En los pacientes adultos, podemos encontrar dos situaciones clínicas: pacientes con EIM diagnosticados en la edad pediátrica que alcanzan la edad adulta, o formas de inicio tardío diagnosticadas ya en la edad adulta, a menudo formas atípicas. El tratamiento nutricional es uno de los pilares fundamentales del tratamiento de muchos EIM, en ocasiones el único eficaz. En el paciente adulto, una vez alcanzada la talla final, el tratamiento tendrá como objetivo cubrir los requerimientos nutricionales del paciente y evitar descompensaciones. Dentro del tratamiento nutricional de los EIM tiene especial relevancia el uso de suplementos nutricionales específicos que ayudarán a cubrir los requerimientos nutricionales de los pacientes afectos de EIM, en muchas ocasiones difíciles de conseguir con alimentos convencionales. El uso de algunas vitaminas que actúan como cofactores enzimáticos también adquiere especial relevancia en algunos de los EIM del adulto (AU)

The Inborn Errors of Metabolism (IEM) are genetic disorders characterized by dysfunction of a protein involved in cell metabolism, causing an alteration in the physiological functioning of the cell. Depending on the protein function and the metabolic pathway which is affected, toxicity may occur because of accumulation of unmetabolized substrate, or the development of substances produced by the metabolism of the substrate through alternative pathways, or deficit of the final product of the metabolic pathway. EIM are a group of genetic diseases too numerous and complex, with a high degree of genetic heterogeneity and, consequently, clinical and biochemical. In adult patients, we can find two clinical situations: patients with IEM diagnosed in children reaching adulthood, or late-onset forms diagnosed in adulthood and often atypical. Nutritional therapy is one of the mainstays of treatment of many IEM, sometimes the only effective. In the adult patient, after reaching final height, the treatment will aim to meet the nutritional requirements of the patient and avoid worsening. Within the nutritional management of EIM is especially relevant the use of specific nutritional supplements that will help meet the nutritional requirements of patients with IEM, often difficult to achieve with conventional foods. The use of some vitamins that acts as enzyme cofactors is also especially relevant in some of the adult EIM (AU)