RESUMEN
OBJECTIVE: To identify genetic biomarkers predisposing individuals with spinal cord injury (SCI) to recurrent pressure injuries (PIs). METHODS: Repeated measures of the transcriptome profile of veterans with SCI at three Veterans Spinal Cord Injuries and Disorders Centers. Exclusion criteria included having significant active systemic disease at time of enrollment. Researchers obtained comprehensive profiles of clinical and health factors and demographic information relevant to PI history at enrollment and at each follow-up visit by reviewing patients' medical charts. Whole blood samples were collected at 6- to 12-month intervals for 2 to 4 years. In addition to DNA profiling with whole genome sequencing of the patients, RNA sequencing was performed to assess pathways associated with PI risk. RESULTS: Whole genome sequencing analysis identified 260 genes that showed increased prevalence of single-nucleotide variations in exonic regions with high (>20) combined annotation-dependent depletion scores between persons with high versus low intramuscular adipose tissue levels when cross-referenced with persons who had recurrent PIs. Gene set enrichment analysis using Hallmark and KEGG (Kyoto Encyclopedia of Genes and Genomes) gene sets of these candidate genes revealed enrichment in genes encoding proteins involved in fatty acid metabolism (P < .01). Further, RNA sequencing revealed upregulated activity in biological senescence pathways and downregulated activity in antimicrobial protection pathways. CONCLUSIONS: Genomic biomarkers may complement electronic health records to support management of complex interactive health issues such as risk of recurrent PIs in people with SCI. These findings may also be leveraged for homogeneous phenotypic grouping of higher-risk individuals.
Asunto(s)
Lesiones por Aplastamiento , Úlcera por Presión , Humanos , Úlcera por Presión/genética , Tejido Adiposo , Biomarcadores , GenómicaRESUMEN
CONTEXT/OBJECTIVE: Multiple medical specialties are often involved in the management of patients with both spinal cord injuries (SCI) and pressure injuries (PIs), sometimes leading to inadequate communication. Our Veterans Affairs (VA) hospital has an interdisciplinary team for PI patients in the SCI unit. This team conducts monthly bedside rounds and journal clubs; there is no similar team for patients with PIs outside the SCI unit. This pilot study aims to determine whether such an interdisciplinary team improves care coordination among practitioners. DESIGN: Survey-based study. SETTING: VA hospital. PARTICIPANTS: Healthcare providers who participate in interdisciplinary SCI rounds and who also care for patients with PIs outside the SCI unit. INTERVENTIONS: Interdisciplinary rounds, including monthly bedside rounds and journal clubs with variety of specialists take place within the SCI unit. There are no similar interdisciplinary rounds for patients with PIs outside of the SCI unit. OUTCOME MEASURES: The Relational Coordination (RC) survey is a validated tool for gauging team performance. Survey results quantified relational dynamics inside and outside the SCI unit across four communication domains (frequent communication, timely communication, accurate communication, and problem-solving communication) and three relationship domains (shared knowledge, mutual respect, and shared goals). RESULTS: Interdisciplinary rounds in the SCI unit was associated with significantly better RC with hospitalists, surgical specialists, infectious diseases, nursing, and pharmacy. This effect was primarily due to improvements in communication domains, without significant difference in relationship domains. CONCLUSIONS: Interdisciplinary rounds in the SCI unit significantly improves RC in the care of PI patients.
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Comunicación , Departamentos de Hospitales , Relaciones Interprofesionales , Grupo de Atención al Paciente , Úlcera por Presión/terapia , Evaluación de Procesos, Atención de Salud , Traumatismos de la Médula Espinal/terapia , Rondas de Enseñanza , Rendimiento Laboral/normas , Adulto , Femenino , Encuestas de Atención de la Salud , Departamentos de Hospitales/organización & administración , Departamentos de Hospitales/normas , Hospitales de Veteranos , Humanos , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente/organización & administración , Grupo de Atención al Paciente/normas , Proyectos Piloto , Rondas de Enseñanza/organización & administración , Rondas de Enseñanza/normas , Estados Unidos , United States Department of Veterans AffairsRESUMEN
Reference genes are often used in RT-quantitative PCR (qPCR) analysis to normalize gene expression levels to a gene that is expressed stably across study groups. They ultimately serve as a control in RT-qPCR analysis, producing more accurate interpretation of results. Whereas many reference genes have been used in various wound-healing studies, the most stable reference gene for ischemic wound-healing analysis has yet to be identified. The goal of this study was to determine systematically the most stable reference gene for studying gene expression in a rat ischemic wound-healing model using RT-qPCR. Twelve commonly used reference genes were analyzed using RT-qPCR and geNorm data analysis to determine stability across normal and ischemic skin tissue. It was ultimately determined that Ubiquitin C (UBC) and ß-2 Microglobulin (B2M) are the most stably conserved reference genes across normal and ischemic skin tissue. UBC and B2M represent reliable reference genes for RT-qPCR studies in the rat ischemic wound model and are unaffected by sustained tissue ischemia. The geometric mean of these two stable genes provides an accurate normalization factor. These results provide insight on dependence of reference-gene stability on experimental parameters and the importance of such reference-gene investigations.
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Isquemia/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Ubiquitina C/genética , Cicatrización de Heridas/genética , Microglobulina beta-2/genética , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Endogámicas F344 , Estándares de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , Piel/irrigación sanguíneaRESUMEN
The clinical efficacy of electro-therapy in the treatment of chronic wounds is currently debated, and a in-vivo evaluation of stimulation parameters will provide the statistical evidence needed to direct clinical guidelines. A low-cost, wearable electrical stimulation bandage has been developed for use with an established rat ischemic wound model. The bandage consists of a user-programmable stimulator PCB and a plastic bandage with two hydrogel electrodes. The battery-powered bandage may be used for up to seven days between dressing changes, and the stimulator may be reused. The microcontroller-based stimulator uses a boost converter circuit to generate pulses up to 90 V from a 3 V coin cell battery. Consistent operation of the boost converter over the wide input and output voltage ranges is achieved using voltage feedforward and soft-start techniques implemented in firmware. The bandages are laser-cut to shape, and electrical traces are applied using stencils and conductive nickel paint. Both the PCB and electrical traces are encapsulated to protect the animal. The device has been successfully demonstrated using the rat ischemic wound model for a period of seven days, and clinical experiments are ongoing.