Incidence of contrast-associated acute kidney injury: a prospective cohort / Incidência de lesão renal aguda associada ao contraste: uma coorte prospectiva

ABSTRACT Introduction: Contrast-associated acute kidney injury (CA-AKI) is a deterioration of kidney function that occurs after the administration of a iodinated contrast medium (ICM). Most studies that defined this phenomenon used older ICMs that were more prone of causing CA-AKI. In the past decade, several articles questioned the true incidence of CA-AKI. However, there is still a paucity of a data about the safety of newer ICM. Objective: To assess the incidence of CA-AKI in hospitalized patients that were exposed to computed tomography (CT) with and without ICM. Methods: Prospective cohort study with 1003 patients who underwent CT in a tertiary hospital from December 2020 through March 2021. All inpatients aged > 18 years who had a CT scan during this period were screened for the study. CA-AKI was defined as a relative increase of serum creatinine of ≥ 50% from baseline or an absolute increase of ≥ 0.3 mg/dL within 18 to 48 hours after the CT. Chi-squared test, Kruskal-Wallis test, and linear regression model with restricted cubic splines were used for statistical analyses. Results: The incidence of CA-AKI was 10.1% in the ICM-exposed group and 12.4% in the control group when using the absolute increase criterion. The creatinine variation from baseline was not significantly different between groups. After adjusting for baseline factors, contrast use did not correlate with worse renal function. Conclusion: The rate of CA-AKI is very low, if present at all, with newer ICMs, and excessive caution regarding contrast use is probably unwarranted.

RESUMO Introdução: Lesão renal aguda associada ao contraste (LRA-AC) é uma deterioração da função renal que ocorre após a administração de meio de contraste iodado (MCI). A maioria dos estudos que definiram esse fenômeno utilizaram MCI mais antigos, mais propensos a causar LRA-AC. Na última década, diversos artigos questionaram a verdadeira incidência de LRA-AC. Entretanto, ainda há escassez de dados sobre a segurança dos MCI mais novos. Objetivo: Avaliar a incidência de LRA-AC em pacientes hospitalizados expostos à tomografia computadorizada (TC) com e sem MCI. Métodos: Estudo de coorte prospectivo com 1.003 pacientes submetidos a TC em hospital terciário, de dezembro/2020 a março/2021. Todos os pacientes internados com idade ≥ 18 anos que realizaram TC nesse período foram selecionados. A LRA-AC foi definida como aumento relativo de creatinina sérica de ≥ 50% em relação ao valor basal ou aumento absoluto de ≥ 0,3 mg/dL dentro de 18 a 48 horas após a TC. Utilizamos o teste qui-quadrado, teste de Kruskal-Wallis e modelo de regressão linear com splines cúbicos restritos para análises estatísticas. Resultados: A incidência de LRA-AC foi 10,1% no grupo exposto ao MCI e 12,4% no grupo controle ao usar o critério de aumento absoluto. A variação da creatinina em relação ao valor basal não foi significativamente diferente entre os grupos. Após ajuste para fatores basais, o uso de contraste não se correlacionou com pior função renal. Conclusão: A taxa de LRA-AC é muito baixa, caso exista, com MCIs mais novos, e a cautela excessiva quanto ao uso de contraste provavelmente não se justifica.

Risk factors for acute kidney injury in patients hospitalized with COVID-19 / Fatores de risco para lesão renal aguda em pacientes hospitalizados com COVID-19

Abstract Introduction: Acute kidney injury (AKI) occurs frequently in COVID-19 patients and is associated with greater morbidity and mortality. Knowing the risks of AKI allows for identification, prevention, and timely treatment. This study aimed to identify the risk factors associated with AKI in hospitalized patients. Methods: A descriptive, retrospective, cross-sectional, and analytical component study of adult patients hospitalized with COVID-19 from March 1 to December 31, 2020 was carried out. AKI was defined by the creatinine criteria of the KDIGO-AKI guidelines. Information, regarding risk factors, was obtained from electronic medical records. Results: Out of the 934 patients, 42.93% developed AKI, 60.59% KDIGO-1, and 9.9% required renal replacement therapy. Patients with AKI had longer hospital stay, higher mortality, and required more intensive care unit (ICU) admission, mechanical ventilation, and vasopressor support. Multivariate analysis showed that age (OR 1.03; 95% CI 1.02-1.04), male sex (OR 2.13; 95% CI 1.49-3.04), diabetes mellitus (DM) (OR 1.55; 95% CI 1.04-2.32), chronic kidney disease (CKD) (OR 2.07; 95% CI 1.06-4.04), C-reactive protein (CRP) (OR 1.02; 95% CI 1.00-1.03), ICU admission (OR 1.81; 95% CI 1.04-3.16), and vasopressor support (OR 7.46; 95% CI 3.34-16.64) were risk factors for AKI, and that bicarbonate (OR 0.89; 95% CI 0.84-0.94) and partial pressure arterial oxygen/inspired oxygen fraction index (OR 0.99; 95% CI 0.98-0.99) could be protective factors. Conclusions: A high frequency of AKI was documented in COVID-19 patients, with several predictors: age, male sex, DM, CKD, CRP, ICU admission, and vasopressor support. AKI occurred more frequently in patients with higher disease severity and was associated with higher mortality and worse outcomes.

RESUMO Introdução: Lesão renal aguda (LRA) ocorre frequentemente em pacientes com COVID-19 e associa-se a maior morbidade e mortalidade. Conhecer riscos da LRA permite a identificação, prevenção e tratamento oportuno. Este estudo teve como objetivo identificar fatores de risco associados à LRA em pacientes hospitalizados. Métodos: Realizou-se estudo descritivo, retrospectivo, transversal e de componente analítico de pacientes adultos hospitalizados com COVID-19 de 1º de março a 31 de dezembro, 2020. Definiu-se a LRA pelos critérios de creatinina das diretrizes KDIGO-LRA. Informações sobre fatores de risco foram obtidas de prontuários eletrônicos. Resultados: Dos 934 pacientes, 42,93% desenvolveram LRA, 60,59% KDIGO-1 e 9,9% necessitaram de terapia renal substitutiva. Pacientes com LRA apresentaram maior tempo de internação, maior mortalidade e necessitaram de mais internações em UTIs, ventilação mecânica e suporte vasopressor. A análise multivariada mostrou que idade (OR 1,03; IC 95% 1,02-1,04), sexo masculino (OR 2,13; IC 95% 1,49-3,04), diabetes mellitus (DM) (OR 1,55; IC 95% 1,04-2,32), doença renal crônica (DRC) (OR 2,07; IC 95% 1,06-4,04), proteína C reativa (PCR) (OR 1,02; IC 95% 1,00-1,03), admissão em UTI (OR 1,81; IC 95% 1,04-3,16) e suporte vasopressor (OR 7,46; IC 95% 3,34-16,64) foram fatores de risco para LRA, e que bicarbonato (OR 0,89; IC 95% 0,84-0,94) e índice de pressão parcial de oxigênio arterial/fração inspirada de oxigênio (OR 0,99; IC 95% 0,98-0,99) poderiam ser fatores de proteção. Conclusões: Documentou-se alta frequência de LRA em pacientes com COVID-19, com diversos preditores: idade, sexo masculino, DM, DRC, PCR, admissão em UTI e suporte vasopressor. LRA ocorreu mais frequentemente em pacientes com maior gravidade da doença e associou-se a maior mortalidade e piores desfechos.

Gerenciamento do protocolo de prevenção de lesão por pressão: construção de painel de bordo informatizado / Management of the pressure injury prevention protocol: construction of a computerized dashboard / Gestión del protocolo de prevención de lesiones por presión: construcción de panel informatizado

Objetivo: Relatar a construção e implantação de painel de bordo, desenvolvido por enfermeiros e profissionais da tecnologia da informação, para gerenciamento do Protocolo de Prevenção de Lesão por Pressão. Métodos: Trata-se de um relato de experiência sobre a construção e implantação de painel de bordo informatizado para gerenciamento de protocolo em um hospital privado universitário, localizado no interior do estado de São Paulo. Resultados: A construção do painel de bordo foi dividida nas seguintes etapas: revisão e atualização do protocolo, construção do modelo eletrônico e implementação. A divulgação foi realizada pela Comissão de Prevenção de Lesão por Pressão. Conclusão: O painel de bordo possibilitou a visualização rápida e em tempo real dos riscos dos pacientes, intervenções propostas e efetividade das medidas de prevenção, além de promover a integração e empoderamento dos profissionais na gestão do cuidado. (AU)

Objective: To report the construction and implementation of a dashboard, developed by nurses and information technology professionals, to manage the Pressure Injury Prevention Protocol. Methods: This is an experience report on the construction and implementation of a computerized dashboard for protocol management in a private university hospital, located in the interior of the state of São Paulo. Results: The construction of the dashboard was divided into the following steps: review and update of the protocol, construction of the electronic model and implementation. The Pressure Injury Prevention Commission disclosed the tool. Conclusion: The dashboard enabled the quick and real-time visualization of patient risks, proposed interventions and effectiveness of prevention measures, in addition to promoting the integration and empowerment of professionals in the management of care. (AU)

Objetivo: Informar la construcción e implementación de un panel, desarrollado por enfermeras y profesionales de tecnologías de la información, para gestionar el Protocolo de Prevención de Lesiones por Presión. Métodos: Se trata de un informe de experiencia sobre la construcción e implementación de un panel computarizado para la gestión del protocolo en un hospital universitario privado, en el interior del estado de São Paulo. Resultados: La construcción del panel se dividió en los siguientes pasos: revisión y actualización del protocolo, construcción del modelo electrónico e implementación. La divulgación fue realizada por la Comisión de Prevención de Lesiones por Presión. Conclusión: El panel permitió la visualización rápida y en tiempo real de los riesgos del paciente, las intervenciones propuestas y la efectividad de las medidas de prevención, además de promover la integración y el empoderamiento de los profesionales en la gestión del cuidado. (AU)

El humo del electrocauterio, el riesgo olvidado y minimizado de la cirugía / Smoke from electrocautery, the forgotten and minimized risk of surgery

Introducción. La nueva era de la cirugía es cada vez más dependiente de la tecnología, y un ejemplo de ello es el uso generalizado de electrocauterio como parte primordial de la práctica quirúrgica. El humo quirúrgico es un subproducto de la disección y la coagulación de los tejidos producidas por los equipos de energía, que representa múltiples riesgos potenciales para la salud del grupo quirúrgico, sin embargo, se han minimizado los peligros causados por la exposición de manera frecuente y acumulativa a este aerosol. Métodos. Se realizó un análisis crítico, desde una posición reflexiva de la información disponible, estableciendo los posibles riesgos relacionados con la exposición al humo quirúrgico. Discusión. Es visible la necesidad imperativa de establecer directrices nacionales, pautas normativas y recomendaciones estandarizadas para cumplir con las exigencias dadas por los sistemas de gestión en salud ocupacional y seguridad del trabajo, cuyo objetivo principal es hacer efectivo el uso de mascarillas quirúrgicas apropiadas, la implementación de programa de vigilancia epidemiológica ambiental en sala de cirugía, la priorización del uso constante de aspiradores y sistemas de evacuación, y la ejecución de programas educativos de sensibilización dirigidos al personal implicado. De igual manera, se abre la inquietud de la necesidad de nuevos estudios para definir con mayor precisión el peligro de este aerosol. Conclusión. Se recomienda de manera responsable utilizar todas las estrategias preventivas existentes para intervenir en salas de cirugía los riesgos minimizados y olvidados del humo quirúrgico.

Introduction. The new era of surgery is increasingly dependent on technology, and an example of this is the widespread use of electrocautery as a primary part of surgical practice. Surgical smoke is a byproduct of the dissection and coagulation of tissues produced by energy equipment, which represents multiple potential health risks for the surgical group; however, the dangers caused by cumulative exposure have been minimized. Methods. A critical analysis was carried out from a reflective position of the available information, establishing the possible risks related to exposure to surgical smoke. Discussion. The imperative need to establish national normative guidelines and standardized recommendations to comply with the demands given by the occupational health and work safety management systems, whose main objective is to make effective the use of appropriate surgical masks, implementation of environmental epidemiological surveillance program in the operating room, prioritizing the constant use of vacuum cleaners and evacuation systems, and carrying out educational awareness programs aimed at the personnel involved. Likewise, there is concern about the need for new studies to more precisely define the danger of this aerosol. Conclusion. It is recommended to responsibly use all existing preventive strategies to intervene in operating rooms to minimize the forgotten risks of surgical smoke.

Pediatric nephrologist-intensivist interaction in acute kidney injury / Interação nefro-intensivista pediátrica na lesão renal aguda

ABSTRACT Introduction: Acute Kidney Injury (AKI) in the Intensive Care Unit (ICU) have concepts of diagnosis and management have water balance as their main point of evaluation. In our ICU, from 2004 to 2012, the nephrologist's participation was on demand only; and as of 2013 their participation became continuous in meetings to case discussion. The aim of this study was to establish how an intense nephrologist/intensivist interaction influenced the frequency of dialysis indication, fluid balance and pRIFLE classification during these two observation periods. Methods: Retrospective study, longitudinal evaluation of all children with AKI undergoing dialysis (2004 to 2016). Parameters studied: frequency of indication, duration and volume of infusion in the 24 hours preceding dialysis; diuresis and water balance every 8 hours. Non-parametric statistics, p ≤ 0.05. Results: 53 patients (47 before and 6 after 2013). There were no significant differences in the number of hospitalizations or cardiac surgeries between the periods. After 2013, there was a significant decrease in the number of indications for dialysis/year (5.85 vs. 1.5; p = 0.000); infusion volume (p = 0.02), increase in the duration of dialysis (p = 0.002) and improvement in the discrimination of the pRIFLE diuresis component in the AKI development. Conclusion: Integration between the ICU and pediatric nephrology teams in the routine discussion of cases, critically approaching water balance, was decisive to improve the management of AKI in the ICU.

RESUMO Introdução: Os conceitos sobre diagnóstico e conduta da Lesão Renal Aguda (LRA) na Unidade de Terapia Intensiva (UTI) tem como ponto primordial a avaliação do balanço hídrico. Em nossa UTI, de 2004 a 2012, a participação do nefrologista era sob demanda. A partir de 2013, a participação passou a ser contínua em reunião de discussão de casos. O objetivo deste estudo foi determinar como a maior interação nefrologista/intensivista influenciou a frequência de indicação de diálise, no balanço hídrico e na classificação pRIFLE durante esses dois períodos de observação. Método: Estudo retrospectivo, avaliação longitudinal de todas as crianças com LRA em diálise (2004 a 2016). Parâmetros estudados: frequência de indicação, tempo de duração e volume de infusão nas 24 horas precedendo a diálise; diurese e balanço hídrico a cada 8 horas. Estatística não paramétrica, p ≤ 0,05. Resultado: 53 pacientes (47 antes e 6 após 2013). Sem diferença significativa no número de internações e nem de cirurgias cardíacas entre os períodos. Após 2013, houve diminuição significativa no número de indicação de diálise/ano (5,85 vs. 1,5; p = 0,000); no volume de infusão (p = 0,02), aumento do tempo de duração da diálise (p = 0,002) e melhora da discriminação do componente diurese do pRIFLE na indicação de LRA. Conclusão: Integração entre equipes de UTI e nefrologia pediátrica na discussão rotineira de casos, abordando criticamente o balanço hídrico, foi determinante para a melhora na conduta da LRA na UTI.

Case fatality rate among COVID-19 patients treated with acute kidney replacement therapy / Letalidade entre pacientes com injúria renal aguda por COVID-19 tratados com suporte renal artificial

Abstract Introduction: Acute kidney injury (AKI) is a frequent complication of severe COVID-19 and is associated with high case fatality rate (CFR). However, there is scarcity of data referring to the CFR of AKI patients that underwent kidney replacement therapy (KRT) in Brazil. The main objective of this study was to describe the CFR of critically ill COVID-19 patients treated with acute kidney replacement therapy (AKRT). Methods: Retrospective descriptive cohort study. We included all patients treated with AKRT at an intensive care unit in a single tertiary hospital over a 15-month period. We excluded patients under the age of 18 years, patients with chronic kidney disease on maintenance dialysis, and cases in which AKI preceded COVID-19 infection. Results: A total of 100 out of 1479 (6.7%) hospitalized COVID-19 patients were enrolled in this study. The median age was 74.5 years (IQR 64 - 82) and 59% were male. Hypertension (76%) and diabetes mellitus (56%) were common. At the first KRT prescription, 85% of the patients were on invasive mechanical ventilation and 71% were using vasoactive drugs. Continuous veno-venous hemodiafiltration (CVVHDF) was the preferred KRT modality (82%). CFR was 93% and 81 out of 93 deaths (87%) occurred within the first 10 days of KRT onset. Conclusion: AKRT in hospitalized COVID-19 patients resulted in a CFR of 93%. Patients treated with AKRT were typically older, critically ill, and most died within 10 days of diagnosis. Better strategies to address this issue are urgently needed.

Resumo Introdução: Injúria renal aguda (IRA) é uma complicação frequente da COVID-19 grave e está associada a alta taxa de letalidade (TL). Entretanto, há escassez de dados referentes à TL de pacientes com IRA submetidos a suporte renal artificial (SRA) no Brasil. O objetivo principal deste estudo foi descrever a TL de pacientes graves com IRA por COVID-19 tratados com SRA. Métodos: Estudo de coorte descritivo retrospectivo. Incluímos todos os pacientes tratados com SRA em unidade de terapia intensiva de um único hospital terciário por 15 meses. Excluímos pacientes menores de 18 anos, pacientes com doença renal crônica em diálise de manutenção e casos nos quais a IRA precedeu a infeção por COVID-19. Resultados: Incluímos neste estudo um total de 100 dos 1479 (6,7%) pacientes hospitalizados com COVID-19. A mediana de idade foi 74,5 anos (IIQ 64 - 82) e 59% eram homens. Hipertensão (76%) e diabetes mellitus (56%) foram comuns. Na primeira prescrição de SRA, 85% dos pacientes estavam em ventilação mecânica invasiva e 71% em uso de drogas vasoativas. A hemodiafiltração contínua foi a modalidade de SRA preferida (82%). A TL foi de 93% e 81 dos 93 óbitos (87%) ocorreram nos primeiros 10 dias do início da SRA. Conclusão: O SRA em pacientes hospi­talizados com IRA por COVID-19 resultou em TL de 93%. Os pacientes tratados com SRA eram geralmente idosos, gravemente enfermos e a maioria foi a óbito em até 10 dias após o diagnóstico. Estratégias melhores para abordar esse problema são urgentemente necessárias.

Traumatismo anorrectal contuso. Reporte de un caso y revisión bibliográfica / Blunt anorectal trauma. Case reportand literature review

Introducción: El traumatismo anorrectal es una causa poco frecuente de consulta al servicio de emergencias, con una incidencia del 1 al 3%. A menudo está asociado a lesiones potencialmente mortales, por esta razón, es fundamental conocer los principios de diagnóstico y tratamiento, así como los protocolos de atención inicial de los pacientes politraumatizados. Método: Reportamos el caso de un paciente masculino de 47 años con trauma anorrectal contuso con compromiso del esfínter anal interno y externo, tratado con reparación primaria del complejo esfinteriano con técnica de overlapping, rafia de la mucosa, submucosa y muscular del recto. A los 12 meses presenta buena evolución sin incontinencia anal. Conclusión: El tratamiento del trauma rectal, basado en el dogma de las 4 D (desbridamiento, derivación fecal, drenaje presacro, lavado distal) fue exitoso. La técnica de overlapping para la lesión esfinteriana fue simple y efectiva para la reconstrucción anatómica y funcional. (AU)

Introduction: Anorectal trauma is a rare cause of consultation to the Emergency Department, with an incidence of 1 to 3%. It is often associated with life-threatening injuries, so it is essential to know the principles of diagnosis and treatment, as well as the initial care protocols for the polytrau-matized patient. Methods: We present the case of a 47-year-old man with a blunt anorectal trauma involving the internal and external anal sphincter, treated with primary overlapping repair of the sphincter complex and suturing of the rectal wall. At 12 months the patient presents good outcome, without anal incontinence. Conclusion: The treatment of rectal trauma, based on the 4 D ́s dogma (debridement, fecal diversion, presacral drainage, distal rectal washout lavage) was successful. Repair of the overlapping sphincter injury was simple and effective for anatomical and functional reconstruction. (AU)

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Edema pulmonar por reexpansión. Reporte de Caso / Pulmonary edema due to re-expansion. Case Report

Introducción. El edema pulmonar por reexpansión es una complicación poco frecuente, secundaria a una rápida reexpansión pulmonar posterior al drenaje por toracentesis o toracostomía cerrada. Al día de hoy, se ha descrito una incidencia menor al 1 % tras toracostomía cerrada, con mayor prevalencia en la segunda y tercera década de la vida. Su mecanismo fisiopatológico exacto es desconocido; se ha planteado un proceso multifactorial de daño intersticial pulmonar asociado con un desequilibrio de las fuerzas hidrostáticas. Caso clínico. Presentamos el caso de un paciente que desarrolló edema pulmonar por reexpansión posterior a toracostomía cerrada. Se hizo una revisión de la literatura sobre esta complicación. Resultados. Aunque la clínica sugiere el diagnóstico, la secuencia de imágenes desempeña un papel fundamental. En la mayoría de los casos suele ser autolimitado, por lo que su manejo es principalmente de soporte; sin embargo, se han reportado tasas de mortalidad que alcanzan hasta el 20 %, por tanto, es importante conocer los factores de riesgo y las medidas preventivas. Conclusión. El edema pulmonar de reexpansión posterior a toracostomía es una complicación rara en los casos con neumotórax, aunque es una complicación que se puede presentar en la práctica diaria, por lo cual debe tenerse en mente para poder hacer el diagnóstico y un manejo adecuado.

Introduction. Re-expansion pulmonary edema is a rare complication secondary to rapid pulmonary re-expansion after drainage by thoracentesis and/or closed thoracostomy. As of today, an incidence of less than 1% has been described after closed thoracostomy, with a higher prevalence in the second and third decades of life. Its exact pathophysiological mechanism is unknown; a multifactorial process of lung interstitial damage associated with an imbalance of hydrostatic forces has been proposed. Clinical case. We present the case of a patient who developed pulmonary edema due to re-expansion after closed thoracostomy, conducting a review of the literature on this complication. Results. Although the clinic suggests the diagnosis, the sequence of images plays a fundamental role. In most cases, it tends to be a self-limited disease, so its management is mainly supportive. However, mortality rates of up to 20% have been recorded. Therefore, it is important to identify patients with major risk factors and initiate preventive measures in these patients. Conclusions. Re-expansion pulmonary edema after thoracostomy is a rare complication in cases with pneumothorax; however, it is a complication that can occur in daily practice. Therefore, it must be kept in mind to be able to make the diagnosis and an adequate management.

Acute kidney injury and hypercalcemia associated with veterinary supplements applications in adult man / Injúria renal aguda e hipercalcemia associadas a aplicações de suplementos veterinários em homem adulto

The compound "ADE" is an injectable oil for veterinary use which contains large amounts of vitamins A, D and E. The parenteral application in humans leads to a granuloma reaction which triggers hypercalcemia. A 42-year-old man was admitted with lower limb pain, nephrolithiasis and nephrocalcinosis. Laboratory tests revealed creatinine 4.59 mg/dl, calcium 13.3 mg/dl and parathormone 13.8 pg/ml. He underwent an ureterolithotripsy, stent placement, intravenous crystalloid fluids, and corticosteroid. He improved symptoms, kidney function and normalized serum calcium. The "ADE"-induced hypercalcemia diagnosis can be challenging. The early diagnosis may avoid negative outcomes.

O composto "ADE'' é um óleo veterinário injetável que contém grandes quantidades de vitaminas A, D e E. A aplicação parenteral causa reação granulomatosa e hipercalcemia. Um homem de 42 anos foi admitido com dor no membro inferior, nódulos musculares endurecidos, nefrolitíase e nefrocalcinose. O laboratório revelou creatinina 4,59 mg/dl, cálcio 13,3 mg/dl e paratormônio 13,8 pg/ml. Foi tratado com ureterolitotripsia, cateter duplo-J, cristaloide intravenoso e corticoterapia. Ele apresentou melhora dos sintomas, função renal e normalizou cálcio. O diagnóstico da hipercalcemia pelo "ADE'' pode ser desafiador. O diagnóstico precoce pode evitar desfechos negativos.

Effect of Long-term Peripheral Nerve Stimulation on Neuro-Muscular Complex Morphologic Recovery in Experiment / Efecto de la Estimulación del Nervio Periférico a Largo Plazo sobre la Recuperación Morfológica del Complejo Neuromuscular en Experimento

SUMMARY: Peripheral nerve injury is an extremely important medical and socio-economic problem. It is far from a solution, despite on rapid development of technologies. To study the effect of long-term electrical stimulation of peripheral nerves, we used a domestically produced electrical stimulation system, which is approved for clinical use. The study was performed on 28 rabbits. Control of regeneration was carried out after 3 month with morphologic techniques. The use of long-term electrostimulation technology leads to an improvement in the results of the recovery of the nerve trunk after an injury, both directly at the site of damage, when stimulation begins in the early period, and indirectly, after the nerve fibers reach the effector muscle.

La lesión de los nervios periféricos es un problema médico y socioeconómico extremadamente importante. Sin embargo, y a pesar del rápido desarrollo de las tecnologías, aún no tiene solución. Para estudiar el efecto de la estimulación eléctrica a largo plazo de los nervios periféricos, utilizamos un sistema de estimulación eléctrica de producción nacional, que está aprobado para uso clínico. El estudio se realizó en 28 conejos. El control de la regeneración se realizó a los 3 meses con técnicas morfológicas. El uso de tecnología de electro estimulación a largo plazo conduce a una mejora en los resultados de la recuperación del tronco nervioso después de una lesión, tanto directamente en el lugar del daño, cuando la estimulación comienza en el período temprano, como indirectamente, después de que las fibras nerviosas alcanzan el músculo efector.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Trauma cerrado de aorta torácica, desde el servicio de urgencias hasta el quirófano: revisión narrativa / Blunt trauma of the thoracic aorta, from the emergency department to the operating room: narrative review / Trauma contuso da aorta torácica: do pronto-socorro ao centro cirúrgico, uma revisão narrativa

El trauma es la principal causa de muerte de la población en edad productiva. El abordaje del trauma torácico cerrado todavía es un desafío para el médico de urgencias. Aunque no es una entidad frecuente, se asocia con una alta mortalidad y resultados adversos. El diagnóstico del trauma cerrado de aorta torácica (LCAT) requiere un alto índice de sospecha, dado que los signos y síntomas no son específicos de esta enfermedad (dolor torácico, dolor interescapular, disnea, disfagia, estridor, disfonía). Es importante resaltar que la ausencia de inestabilidad hemodinámica no debe descartar una lesión aórtica. Para su diagnóstico imagenológico se debe tener en cuenta que los rayos X de tórax no tienen el rendimiento adecuado, el patrón de referencia es la angiotomografía y el ecocardiograma transesofágico (ETE) constituye una opción diagnóstica. El manejo incluye líquidos endovenosos y antihipertensivos como medida transitoria, manejo quirúrgico definitivo y, en algunos casos, manejo expectante o diferido. Los pacientes inestables o con signos de ruptura inminente deben ser llevados de manera inmediata a cirugía. El manejo quirúrgico temprano ha impactado en la mortalidad. A pesar de los avances en las técnicas quirúrgicas, la técnica quirúrgica abierta documenta mayor tasa de mortalidad que el manejo endovascular, el cual tiene numerosas ventajas al ser poco invasivo. Esta es una revisión narrativa que destaca algunos aspectos clave sobre los mecanismos de lesión, diagnóstico y manejo inicial del trauma cerrado aorta torácica. Por último, se propone un algoritmo de abordaje de trauma de aorta.

Trauma is the leading cause of death in the productive-age population. Addressing blunt chest trauma is still a challenge for the emergency physician. Although it is not a common entity, it is associated with high mortality and adverse outcomes. The diagnosis of blunt thoracic aortic trauma (LCAT) requires a high index of suspicion, given that the signs and symptoms are not specific to this disease (chest pain, interscapular pain, dyspnea, dysphagia, stridor, dysphonia). It is important to highlight that the absence of hemodynamic instability should not rule out aortic injury. For its imaging diagnosis, it must be taken into account that chest X-rays do not have adequate performance; the reference standard is angiotomography and transesophageal echocardiography (TEE) is a diagnostic option. Management includes intravenous fluids and antihypertensives as a temporary measure, definitive surgical management and, in some cases, expectant or deferred management. Unstable patients or patients with signs of imminent ruptura should be taken immediately to surgery. Early surgical management has impacted mortality. Despite advances in surgical techniques, the open surgical technique documents a higher mortality rate than endovascular management, which has numerous advantages as it is minimally invasive. This is a narrative review that highlights some key aspects about the mechanisms of injury, diagnosis and initial management of blunt thoracic aortic trauma. Finally, an algorithm for addressing aortic trauma is proposed.

O trauma é a principal causa de morte na população em idade produtiva. Abordar o trauma torácico contuso ainda é um desafio para o médico emergencista. Embora não seja uma entidade comum, está associada a alta mortalidade e resultados adversos. O diagnóstico de trauma fechado de aorta torácica (TACE) requer alto índice de suspeição, visto que os sinais e sintomas não são específicos desta doença (dor torácica, dor interescapular, dispneia, disfagia, estridor, disfonia). É importante ressaltar que a ausência de instabilidade hemodinâmica não deve descartar lesão aórtica. Para seu diagnóstico por imagem deve-se levar em consideração que a radiografia de tórax não apresenta desempenho adequado; o padrão de referência é a angiotomografia e a ecocardiografia transesofágica (ETE) é uma opção diagnóstica. O manejo inclui fluidos intravenosos e anti-hipertensivos como medida temporária, manejo cirúrgico definitivo e, em alguns casos, manejo expectante ou diferido. Pacientes instáveis ou com sinais de ruptura iminente devem ser encaminhados imediatamente para cirurgia. O manejo cirúrgico precoce impactou a mortalidade. Apesar dos avanços nas técnicas cirúrgicas, a técnica cirúrgica aberta documenta maior taxa de mortalidade do que o manejo endovascular, que apresenta inúmeras vantagens por ser minimamente invasivo. Esta é uma revisão narrativa que destaca alguns aspectos-chave sobre os mecanismos de lesão, diagnóstico e manejo inicial do trauma contuso da aorta torácica. Finalmente, é proposto um algoritmo para tratar o trauma aórtico.

Lesão renal aguda e COVID-19 em adultos jovens na terapia intensiva / Lesión renal aguda y COVID-19 en adultos jóvenes en cuidados intensivos / Acute kidney injury and COVID-19 in young adults in intensive care

Resumo Objetivo Descrever a prevalência de lesão renal aguda em adultos jovens com diagnóstico da COVID-19 admitidos em unidade terapia intensiva. Métodos Estudo retrospectivo, quantitativo e analítico. A amostra foi de adultos jovens (20 a 40 anos) admitidos em unidades de terapia intensiva, com diagnóstico de infecção por SARS-CoV-2 entre março e dezembro de 2020. Os dados foram obtidos por meio do prontuário eletrônico, e a lesão renal aguda foi definida pelo valor da creatinina, segundo critérios das diretrizes da Kidney Disease Improving Global Outcomes. A significância estatística foi de p≤0,05. Resultados Foram internados 58 adultos jovens, sendo 63,8% do sexo masculino. A hipertensão arterial sistêmica esteve presente em 39,6%, a obesidade em 18,9% e o diabetes mellitus em 8,6%. A lesão renal aguda foi identificada em 55,1%, sendo o estágio 3 predominante em 43,1% deles. Nesses pacientes, o uso de ventilação mecânica e de drogas vasoativas foi significativo em 92%, assim como a disfunção orgânica respiratória (80%), seguida da renal (76%). Fatores de risco, como transplante renal ou doença renal crônica e obesidade, aumentaram em 12,3 e 9,0 vezes, respectivamente, a chance de desenvolver lesão renal aguda. Conclusão Este estudo demonstrou alta prevalência de lesão renal em adultos jovens e sua associação com comorbidades prévias. Obesidade, transplante renal e doença renal crônica elevaram a chance de o adulto jovem desenvolver lesão renal aguda, resultando em desfechos a favor da morbimortalidade.

Resumen Objetivo Describir la prevalencia de lesión renal aguda en adultos jóvenes con diagnóstico de COVID-19 admitidos en unidad de cuidados intensivos. Métodos Estudio retrospectivo, cuantitativo y analítico. La muestra fue de adultos jóvenes (20 a 40 años) admitidos en unidades de cuidados intensivos, con diagnóstico de infección por SARS-CoV-2 entre marzo y diciembre de 2020. Los datos se obtuvieron por medio de historias clínicas electrónicas, y la lesión renal aguda fue definida por el valor de la creatinina, de acuerdo con criterios de las directrices de la Kidney Disease Improving Global Outcomes. La significación estadística fue de p≤0,05. Resultados Hubo 58 adultos jóvenes internados, el 63,8 % de sexo masculino. La hipertensión arterial sistémica estuvo presente en el 39,6 %, la obesidad en el 18,9 % y la diabetes mellitus en el 8,6 %. Se identificó lesión renal aguda en el 55,1 %, de nivel 3 como predominante en el 43,1 % de los casos. En esos pacientes, el uso de ventilación mecánica y de drogas vasoactivas fue significativo en el 92 %, así como también la disfunción orgánica respiratoria (80 %), seguida de la renal (76 %). Los factores de riesgo, como trasplante renal o enfermedad renal crónica y obesidad, aumentaron 12,3 y 9,0 veces respectivamente la probabilidad de presentar lesión renal aguda. Conclusión Este estudio demostró alta prevalencia de lesión renal en adultos jóvenes y su asociación con comorbilidades previas. La obesidad, el trasplante renal y la enfermedad renal crónica aumentaron la probabilidad de que los adultos jóvenes presenten lesión renal aguda, lo que da como resultado desenlaces a favor de la morbimortalidad.

Abstract Objective To describe acute kidney injury prevalence in young adults diagnosed with COVID-19 admitted to the Intensive Care Unit. Methods This is a retrospective, quantitative and analytical study. The sample consisted of young adults (20 to 40 years old) admitted to Intensive Care Units, diagnosed with SARS-CoV-2 infection between March and December 2020. Data were obtained through electronic medical records, and kidney injury acute was defined by the creatinine value, according to the Kidney Disease Improving Global Outcomes guidelines criteria. Statistical significance was p≤0.05. Results A total of 58 young adults were hospitalized, 63.8% of whom were male. Hypertension was present in 39.6%, obesity in 18.9%, and diabetes mellitus in 8.6%. Acute kidney injury was identified in 55.1%, with stage 3 predominating in 43.1% of them. In these patients, the use of mechanical ventilation and vasoactive drugs was significant in 92% as well as respiratory organ dysfunction (80%), followed by renal organ dysfunction (76%). Risk factors such as kidney transplantation or chronic kidney disease and obesity increased by 12.3 and 9.0 times, respectively, the chances of developing acute kidney injury. Conclusion This study demonstrated a high kidney injury prevalence in young adults and its association with previous comorbidities. Obesity, kidney transplantation and chronic kidney disease increased the chance of young adults to develop acute kidney injury, resulting in outcomes in favor of morbidity and mortality.

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats

Purpose: To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. Methods: Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. Results: After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). Conclusions: For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

Identificación de Factores Clínicos Relacionados a una Mayor Mortalidad Asociada a Insuficiencia Renal Aguda en pacientes de Terapia Intensiva

La insuficiencia renal aguda (IRA) es una de las complicaciones más frecuentes en los pacientes hospitalizados, siendo un factor de riesgo de mortalidad. Es de suma importancia identificar la asociación de factores clínicos que empeoran la mortalidad en pacientes con IRA internados en una unidad de terapia intensiva (UTI). Se incluyeron 218 pacientes, de los cuales el 63,7% (n=139) correspondieron a hombres con un promedio de edad de 43±19 años. El análisis de correlación de variables de control, dependiente e independiente fue a través del coeficiente de Spearman y el OR fue analizado mediante regresión logística. De los 218 pacientes, falleció el 33% (n=72) de los pacientes internados en UTI. La IRA ocurrió en 28,4% (n=62) del total de pacientes y de estos, el 61,3% (n=38) fallecieron, con un OR de 4,94 (p 0,0001). La mayor proporción de fallecidos perteneció a la categoría AKIN 3. Las variables clínicas de ventilación mecánica (PR 3,57, IC 95%, 0,34-37,93), uso de drogas vasoactivas (PR 8,32, IC 95%, 3,20-21,64), puntuación APACHE III (PR 1,12, IC 95%, 1,03-1,23), edad (PR 1,01, IC 95%, 0,99-1,04) y los sometidos a cirugía (PR 0,28, IC 95%, 0,10-0,80) tuvieron asociación positiva y aumentaron la mortalidad. La presencia de variables clínicas de ventilación mecánica, la utilización de drogas vasoactivas, sepsis, el estudio APACHE III, la edad, la categoría AKIN 3, y el antecedente de cirugía previo al ingreso a UTI aumentan significativamente la mortalidad en pacientes con IRA en UTI.

Acute renal failure (ARF) is one of the most frequent complications in hospitalized patients and is a risk factor for mortality. It is extremely important to identify the association of clinical factors that worsen mortality in patients with ARF admitted to an intensive care unit (ICU). A total of 218 patients were included, of which 63.7% (n=139) were men with a mean age of 43±19 years. The correlation analysis of control, dependent, and independent variables was done through Spearman's coefficient and the OR was analyzed through logistic regression. Of the 218 patients, 33% (n=72) died in the ICU. ARF occurred in 28.4% (n=62) of all patients and of these, 61.3% (n=38) died, with an OR of 4.94 (p 0.0001). The highest proportion of deceased patients were in the AKIN 3 category. The clinical variables of mechanical ventilation (PR 3.57, 95% CI, 0.34-37.93), use of vasoactive drugs (PR 8.32, 95% CI, 3.20-21.64), APACHE III score (PR 1.12, 95% CI, 1.03-1.23), age (PR 1.01, 95% CI, 0.99-1.04) and those who underwent surgery (PR 0.28, 95% CI, 0.10-0.80) had a positive association and increased mortality. The presence of clinical variables of mechanical ventilation, the use of vasoactive drugs, sepsis, APACHE III stage, age, AKIN 3 category, and a history of surgery before admission to the ICU significantly increase mortality in patients with ARF in ICU.

Respiratory system parameters in children with low severity cystic fibrosis: is there early involvement in relation to healthy peers? / Parâmetros do sistema respiratório em crianças com fibrose cística de baixa gravidade: há acometimento precoce em relação a pares saudáveis?

ABSTRACT Objective: To compare and analyze pulmonary function and respiratory mechanics parameters between healthy children and children with cystic fibrosis. Methods: This cross-sectional analytical study included healthy children (HSG) and children with cystic fibrosis (CFG), aged 6-13 years, from teaching institutions and a reference center for cystic fibrosis in Florianópolis/SC, Brazil. The patients were paired by age and sex. Initially, an anthropometric evaluation was undertaken to pair the sample characteristics in both groups; the medical records of CFG were consulted for bacterial colonization, genotype, and disease severity (Schwachman-Doershuk Score — SDS) data. Spirometry and impulse oscillometry were used to assess pulmonary function. Results: In total, 110 children were included, 55 in each group. In the CFG group, 58.2% were classified as excellent by SDS, 49.1% showed the ΔF508 heterozygotic genotype, and 67.3% were colonized by some pathogens. Statistical analysis revealed significant differences between both groups (p<0.05) in most pulmonary function parameters and respiratory mechanics. Conclusions: Children with cystic fibrosis showed obstructive ventilatory disorders and compromised peripheral airways compared with healthy children. These findings reinforce the early changes in pulmonary function and mechanics associated with this disease.

RESUMO Objetivo: Comparar e analisar parâmetros de função pulmonar e de mecânica respiratória entre escolares saudáveis e com fibrose cística (FC). Métodos: Estudo transversal que incluiu escolares saudáveis (GES) e com FC (GFC), com idades entre seis e 13 anos, provenientes de instituições de ensino e de um centro de referência da FC em Florianópolis/SC, Brasil, pareados por idade e sexo, respectivamente. Inicialmente, conduziu-se avaliação antropométrica para pareamento e caracterização de ambos os grupos e, no GFC, consultou-se prontuário médico para registro dos dados de colonização bacteriana, genótipo e gravidade da doença (Escore de Schwachman-Doershuk — ESD). Para a avaliação da função pulmonar, realizou-se espirometria e a avaliação da mecânica respiratória foi conduzida por meio do sistema de oscilometria de impulso. Resultados: Participaram 110 escolares, 55 em cada grupo. No GFC, 58,2% foram classificados pelo ESD como excelentes, 49,1% apresentaram genótipo ∆F508 heterozigoto e 67,3% eram colonizados por alguma patógeno. Houve diferença significativa (p<0,05) na maioria dos parâmetros de função pulmonar e de mecânica respiratória entre os grupos. Conclusões: Escolares com FC apresentaram distúrbio ventilatório obstrutivo e com comprometimento de vias aéreas periféricas, em comparação aos escolares hígidos. Esse evento reforça o início precoce da alteração de função pulmonar e de mecânica respiratória nessa enfermidade, evidenciados pelos achados desta investigação.

Improvement effect and mechanism of total flavonoids from Rosa multiflora root on vascular injury in rheumatoid arthritis model rats / 中国药房

OBJECTIVE To study the improvement effect of total flavonoids from Rosa multiflora root on vascular injury in rheumatoid arthritis （RA） model rats and its potential mechanism. METHODS Female Wistar rats were randomly divided into normal control group， model group， aspirin group （positive control， 30 mg/kg）， low-dose and high-dose groups of total flavonoids from R. multiflora root （4.15， 8.30 g/kg， by crude drug）， with 10 rats in each group. Except for the normal control group， the RA model was induced in other groups by collagen induction and high-fat diet. After 14 days of modeling， they were given corresponding drug solution/0.5% sodium carboxymethyl cellulose solution intragastrically， once a day， for 36 consecutive days. The total body score， arthritis index （AI） and swollen joint count （SJC） of the rats were evaluated regularly. After the last medication， serum levels of interleukin-6 （IL-6）， intercellular adhesion molecule-1 （ICAM-1） and vascular cell adhesion molecule- 1 （VCAM-1） were determined. The pathological morphological changes in the vascular tissue of thoracic aorta were observed； the protein expression of Toll-like receptor 4 （TLR4） and the protein phosphorylation levels of Janus kinase 2 （JAK2） and signal transduction and activator of transcription 3 （STAT3） in vascular tissue of thoracic aorta were measured. RESULTS Compared with the normal control group， serum levels of IL-6， ICAM-1 and VCAM-1， protein expression of TLR4， and the protein phosphorylation levels of JAK2 and STAT3 in vascular tissue of thoracic aorta were increased significantly in model group （P＜ 0.01）. The atherosclerotic plaque （atheroma）， cholesterol crystal， lymphocyte infiltration and a small number of unbroken foam cell aggregation could be seen in the vascular tissue of thoracic aorta. Compared with the model group， total body score （except for the low-dose group）， AI and SJC were decreased significantly in groups of total flavonoids from R. multiflora root on the 28th day （P＜0.05 or P＜0.01）； total body score，AI and SJC were decreased significantly in low-dose group of total flavonoids from R. multiflora root on the 49th day （P＜0.05 or P＜0.01）； the other quantitative indicators in serum and vascular tissue were significantly reversed in groups of total flavonoids from R. multiflora root （P＜0.05 or P＜0.01）， and pathological damage of vascular tissue was significantly relieved. CONCLUSIONS Total flavonoids from R. multiflora root can significantly improve vascular injury in RA model rats， and its mechanism may be related to reducing the protein expression of TLR4 in vascular tissue and inhibiting the activation of IL-6/JAK2/ STAT3 signaling pathway.

Development of an in vitro screening method for idiosyncratic hepatotoxic components in traditional Chinese medicine: a case study with Epimedii Folium and Psoraleae Fructus / 药学学报

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

Effect of fumigation therapy of Flos Farfarae in cigarette smoke-induced lung injury mice based on metabolomics / 药学学报

This study aimed to investigate the effect of Flos Farfarae (FF) fumigation on cigarette smoke-induced lung injury mice, and analyze the metabolic profile of lung tissue by metabolomics. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shanxi University (Approval number: SXULL2019014). By using HS-GC-MS to analyze volatile components of Flos Farfarae, 23 compounds were identified. The results showed that FF fumigation improved the lung tissue morphology of cigarette smoke-induced lung injury mice, lowered the levels of interleukin 6 (IL-6) and interleukin-1β (IL-1β). The lung tissue samples were applied for metabolomic analysis based on UHPLC-QTOF MS, the results showed that 70 metabolites were changed in the lung tissue of mice after cigarette exposure, and 35 of them could be regulated, including lysophosphatidylcholine (LPC), 12-HETE, adenosine, and xanthine. These metabolites, such as LPC, 12-HETE, adenosine, and xanthine were mainly associated with the body's inflammatory response. It was observed that these metabolites are primarily involved in purine metabolism, arachidonic acid metabolism, phospholipid metabolism, and pyruvate metabolism pathways. These findings suggest that the volatile terpenoids in the FF may regulate the metabolites associated with the inflammatory response in the lung tissue, such as lysophosphatidylcholine, 12-HETE, and adenosine, which could further alleviate lung inflammation induced by cigarette smoke through the metabolic pathways of purine metabolism and others. This study proved the scientific basis of the traditional application of FF fumigation, and provided a theoretical basis for the further product development.