RESUMEN
Antimicrobial blue light (aBL) is an attractive option for managing biofilm burden at the skin-implant interface of percutaneous osseointegrated (OI) implants. However, marketed aBL devices have both structural and optical limitations that prevent them from being used in an OI implant environment. They must be handheld, preventing even irradiation of the entire skin-implant interface, and the devices do not offer sufficient optical power outputs required to kill biofilms. We present the developmental process of a unique aBL device that overcomes these limitations. Four prototypes are detailed, each being a progressive improvement from the previous iteration as we move from proof-of-concept to in vivo application. Design features focused on a cooling system, LED orientation, modularity, and "sheep-proofing". The final prototype was tested in an in vivo OI implant sheep model, demonstrating that it was structurally and optically adequate to address biofilm burdens at the skin-implant of percutaneous OI implants. The device made it possible to test aBL in the unique OI implant environment and compare its efficacy to clinical antibiotics-data which had not before been achievable. It has provided insight into whether or not continued pursual of light therapy research for OI implants, and other percutaneous devices, is worthwhile. However, the device has drawbacks concerning the cooling system, complexity, and size if it is to be translated to human clinical trials. Overall, we successfully developed a device to test aBL therapy for patients with OI implants and helped progress understanding in the field of infection management strategies.
Asunto(s)
Antiinfecciosos , Prótesis Anclada al Hueso , Humanos , Animales , Ovinos , Prótesis e Implantes , Luz , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
Importance: Preclinical studies have shown that transcranial near-infrared low-level light therapy (LLLT) administered after traumatic brain injury (TBI) confers a neuroprotective response. Objectives: To assess the feasibility and safety of LLLT administered acutely after a moderate TBI and the neuroreactivity to LLLT through quantitative magnetic resonance imaging metrics and neurocognitive assessment. Design, Setting, and Participants: A randomized, single-center, prospective, double-blind, placebo-controlled parallel-group trial was conducted from November 27, 2015, through July 11, 2019. Participants included 68 men and women with acute, nonpenetrating, moderate TBI who were randomized to LLLT or sham treatment. Analysis of the response-evaluable population was conducted. Interventions: Transcranial LLLT was administered using a custom-built helmet starting within 72 hours after the trauma. Magnetic resonance imaging was performed in the acute (within 72 hours), early subacute (2-3 weeks), and late subacute (approximately 3 months) stages of recovery. Clinical assessments were performed concomitantly and at 6 months via the Rivermead Post-Concussion Questionnaire (RPQ), a 16-item questionnaire with each item assessed on a 5-point scale ranging from 0 (no problem) to 4 (severe problem). Main Outcomes and Measures: The number of participants to successfully and safely complete LLLT without any adverse events within the first 7 days after the therapy was the primary outcome measure. Secondary outcomes were the differential effect of LLLT on MR brain diffusion parameters and RPQ scores compared with the sham group. Results: Of the 68 patients who were randomized (33 to LLLT and 35 to sham therapy), 28 completed at least 1 LLLT session. No adverse events referable to LLLT were reported. Forty-three patients (22 men [51.2%]; mean [SD] age, 50.49 [17.44] years]) completed the study with at least 1 magnetic resonance imaging scan: 19 individuals in the LLLT group and 24 in the sham treatment group. Radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) showed significant time and treatment interaction at 3-month time point (RD: 0.013; 95% CI, 0.006 to 0.019; P < .001; MD: 0.008; 95% CI, 0.001 to 0.015; P = .03; FA: -0.018; 95% CI, -0.026 to -0.010; P < .001).The LLLT group had lower RPQ scores, but this effect did not reach statistical significance (time effect P = .39, treatment effect P = .61, and time × treatment effect P = .91). Conclusions and Relevance: In this randomized clinical trial, LLLT was feasible in all patients and did not exhibit any adverse events. Light therapy altered multiple diffusion tensor parameters in a statistically significant manner in the late subacute stage. This study provides the first human evidence to date that light therapy engages neural substrates that play a role in the pathophysiologic factors of moderate TBI and also suggests diffusion imaging as the biomarker of therapeutic response. Trial Registration: ClinicalTrials.gov Identifier: NCT02233413.
Asunto(s)
Lesiones Traumáticas del Encéfalo/radioterapia , Terapia por Luz de Baja Intensidad/métodos , Síndrome Posconmocional/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Adulto , Anciano , Anisotropía , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/fisiopatología , Imagen de Difusión Tensora , Método Doble Ciego , Estudios de Factibilidad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Placebos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Alopecia encompasses a broad range of hair loss disorders, generally categorized into scarring and non-scarring forms. Depending on the specific pathogenesis of hair loss and geographic location, a number of psychiatric and medical comorbidities, including but not limited to thyroid disease, lupus erythematosus, diabetes mellitus, atopic dermatitis, sinusitis, coronary artery disease, anxiety, depression, and suicidality, have been identified in association with alopecia. In addition to the numerous associated comorbid conditions, patients with alopecia report decreased quality-of-life measures across symptomatic, functional, and global domains. While alopecia can affect patients of all ages, genders, and ethnicities, hair loss may more significantly impact women as hair represents an essential element of femininity, fertility, and female attractiveness in society. Individuals of lower socioeconomic status may also face health disparities in the context of alopecia as a majority of hair loss treatments are considered cosmetic in nature and accordingly are not covered by third-party insurance providers. Although traditionally thought of as a merely aesthetic concern, alopecia encompasses a significant burden of disease with well-defined comorbid associations and genuine psychosocial implications, and thus should be assessed and managed within a proper medical paradigm.
Asunto(s)
Alopecia/patología , Disparidades en el Estado de Salud , Calidad de Vida , Alopecia/psicología , Alopecia/terapia , Cicatriz/etiología , Comorbilidad , Femenino , Humanos , Masculino , Factores SocioeconómicosRESUMEN
Hair loss is both a common chief complaint by patients and a clinical challenge for physicians, especially general practitioners, yet few dermatological problems yield as much patient satisfaction when resolved as hair loss. The diagnosis is often attributed to androgen-related hair loss, while other causes, some of which are life-threatening but treatable, are overlooked. We searched for relevant literature on hair loss and supported these findings with our clinical experience to identify seven major systemic etiologies of hair loss, ranging from infectious agents to consumption of unsafe supplements. Many causes are only described in the literature through case studies, though some original articles and meta-analyses are available. Careful history taking, proper examination techniques, and judicious use of laboratory tests are essential to reach at the correct diagnosis in a cost-effective manner when performing patient work-up. Such methodical evaluation of hair loss can result in the appropriate treatment plan and provide significant patient satisfaction. Key messages Hair loss is a common chief complaint and a difficult challenge for both general practitioners and dermatology consultants. We identified seven major categories of systemic hair loss etiology and present a framework for their clinical evaluation. A methodical approach to hair loss can result in the appropriate treatment plan and provide significant patient satisfaction.