Phototoxic action of light emitting diode in the in vitro viability of Trichophyton rubrum Ação fototóxica do diodo emissor de luz na viabilidade de Trichophyton rubrum in vitro

BACKGROUND: Trichophyton rubrum is the most common agent of superficial mycosis of the skin and nails causing long lasting infections and high recurrence rates. Current treatment drawbacks involve topical medications not being able to reach the nail bed at therapeutic concentrations, systemic antifungal drugs failing to eradicate the fungus before the nails are renewed, severe side effects and selection of resistant fungal isolates. Photodynamic therapy (PDT) has been a promising alternative to conventional treatments. OBJECTIVES: This study evaluated the in vitro effectiveness of toluidine blue O (TBO) irradiated by Light emitting diode (LED) in the reduction of T. rubrum viability. METHODS: The fungal inoculums' was prepared and exposed to different TBO concentrations and energy densities of Light emitting diode for evaluate the T. rubrum sensibility to PDT and production effect fungicidal after photodynamic treatment. In addition, the profiles of the area and volume of the irradiated fungal suspensions were also investigated. RESULTS: A small reduction, in vitro, of fungal cells was observed after exposition to 100 µM toluidine blue O irradiated by 18 J/cm² Light emitting diode. Fungicidal effect occurred after 25 µM toluidine blue O irradiation by Light emitting diode with energy density of 72 J/cm². The analysis showed that the area and volume irradiated by the Light emitting diode were 52.2 mm² and 413.70 mm³, respectively. CONCLUSION: The results allowed to conclude that Photodynamic therapy using Light emitting diode under these experimental conditions is a possible alternative approach to inhibit in vitro T. rubrum and may be a promising new treatment for dermatophytosis caused by this fungus.<br>FUNDAMENTOS: Trichophyton rubrum é o agente mais comum das micoses superficiais de pele e unhas causando infecções de longa duração e altas taxas de recidiva. As desvantagens do tratamento atual envolvem medicações tópicas as quais não são capazes de alcançar o leito ungueal em concentrações terapêuticas, antifúngicos sistêmicos que não erradicam o fungo antes das unhas serem renovadas, efeitos colaterais graves e seleção de isolados fúngicos resistentes. A terapia fotodinâmica tem sido uma alternativa promissora aos tratamentos convencionais. OBJETIVOS: Este estudo avaliou a eficácia, in vitro, de azul de orto-toluidina irradiado por diodo emissor de luz na redução da viabilidade de T. rubrum. MÉTODOS: O inóculo fúngico foi preparado e exposto a diferentes concentrações de azul de orto-toluidina e densidades de energia do diodo emissor de luz, para avaliar a sensibilidade de T. rubrum e o efeito fungicida, após terapia fotodinâmica. Além disso, os perfis da área e volume das suspensões fúngicas irradiados também foram investigados. RESULTADOS: Uma pequena redução, in vitro, de células fúngicas foi observada após a exposição a 100 mM azul de orto-toluidina irradiados por diodo emissor de luz a 18 J/cm². Efeito fungicida ocorreu após irradiação 25 µM orto-toluidina por diodo emissor de luz com densidade de energia de 72 J/cm². A análise mostrou que a área e o volume irradiados pelo diodo emissor de luz foram 52,2 mm² e 413,70 mm³, respectivamente. CONCLUSÕES: Os resultados permitiram concluir que a terapia fotodinâmica com diodo emissor de luz, nas condições experimentais é uma abordagem alternativa para inibir, in vitro, T. rubrum e pode ser um tratamento promissor para as dermatofitoses causadas por este fungo

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p&lt;0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p&lt;0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status