The Immunoregulatory and Regenerative Potential of Activated Human Stem Cell Secretome Mitigates Acute-on-Chronic Liver Failure in a Rat Model.

Acute-on-chronic liver failure (ACLF) is a syndrome marked by sudden liver function decline and multiorgan failure, predominantly acute kidney injury (AKY), in patients with chronic liver disease. Unregulated inflammation is a hallmark of ACLF; however, the key drivers of ACLF are not fully understood. This study explores the therapeutic properties of human mesenchymal stem cell (MSC) secretome, particularly focusing on its enhanced anti-inflammatory and pro-regenerative properties after the in vitro preconditioning of the cells. We evaluated the efficacy of the systemic administration of MSC secretome in preventing liver failure and AKI in a rat ACLF model where chronic liver disease was induced using by the administration of porcine serum, followed by D-galN/LPS administration to induce acute failure. After ACLF induction, animals were treated with saline (ACLF group) or MSC-derived secretome (ACLF-secretome group). The study revealed that MSC-secretome administration strongly reduced liver histological damage in the ACLF group, which was correlated with higher hepatocyte proliferation, increased hepatic and systemic anti-inflammatory molecule levels, and reduced neutrophil and macrophage infiltration. Additionally, renal examination revealed that MSC-secretome treatment mitigated tubular injuries, reduced apoptosis, and downregulated injury markers. These improvements were linked to increased survival rates in the ACLF-secretome group, endorsing MSC secretomes as a promising therapy for multiorgan failure in ACLF.

Septic shock, hyperferritinemic syndrome, and multiple organ dysfunction without respiratory failure in a patient with disseminated histoplasmosis and advanced HIV disease

ABSTRACT AIDS-related disseminated histoplasmosis (DH) can cause septic shock and multiorgan dysfunction with mortality rates of up to 80%. A 41-year-old male presented with fever, fatigue, weight loss, disseminated skin lesions, low urine output, and mental confusion. Three weeks before admission, the patient was diagnosed with HIV infection, but antiretroviral therapy (ART) was not initiated. On day 1 of admission, sepsis with multiorgan dysfunction (acute renal failure, metabolic acidosis, hepatic failure, and coagulopathy) was identified. A chest computed tomography showed unspecific findings. Yeasts suggestive of Histoplasma spp. were observed in a routine peripheral blood smear. On day 2, the patient was transferred to the ICU, where his clinical condition progressed with reduced level of consciousness, hyperferritinemia, and refractory septic shock, requiring high doses of vasopressors, corticosteroids, mechanical ventilation, and hemodialysis. Amphotericin B deoxycholate was initiated. On day 3, yeasts suggestive of Histoplasma spp. were observed in the bone marrow. On day 10, ART was initiated. On day 28, samples of peripheral blood and bone marrow cultures revealed Histoplasma spp. The patient stayed in the ICU for 32 days, completing three weeks of intravenous antifungal therapy. After progressive clinical and laboratory improvement, the patient was discharged from the hospital on oral itraconazole, trimethoprim-sulfamethoxazole, and ART. This case highlights the inclusion of DH in the differential diagnosis of patients with advanced HIV disease, septic shock and multiorgan dysfunction but without respiratory failure. In addition, it provides early in-hospital diagnosis and treatment and comprehensive management in the ICU as determining factors for a good outcome.

Intoxicação aguda pela ingestão de Samanea tubulosa em bovino / Acute intoxication by ingestion of Samanea tubulosa in bovine

As intoxicações em animais de produção causadas por plantas são bastante relatadas, resultando em perdas econômicas diretas causadas pela morte dos animais, diminuição dos índices produtivos e reprodutivos, além de aumentar a ocorrência e susceptibilidade a outras doenças. Já as perdas indiretas, incluem os custos para o controle das plantas tóxicas nas pastagens, além das medidas de manejo como a utilização de cercas e o pastoreio alternativo para evitar as intoxicações, assim como também os gastos associados ao diagnóstico e tratamento. No presente trabalho relatou-se a intoxicação de um bovino de raça Girolando de 11 anos pelo consumo da planta conhecida como bordão-de-velho (Samanea tubulosa). As alterações pós-mortem macro e microscópicas demonstraram que a causa provável de morte foi a síndrome de disfunção de múltiplos órgãos. Estudos in vivo são necessários para conhecer mais a fundo o potencial tóxico desta planta.(AU)

Intoxications in production animals caused by plants are well reported, resulting direct losses caused by the death of animals, by the reduction of productive and reproductive indexes, as well as increase in the frequence and susceptibility to other diseases. Indirect losses can be attributed to control plants in pastures, in addition to manipulation measures, such as use of fences and alternative grazing to avoid intoxication. The present work reported the intoxication of an 11-year-old female breed of cattle by the consumption of the plant known as bordão-develho (Samanea tubulosa). Macro and microscopic finds demonstrate that the probable cause is multiple organ dysfunction syndrome. In vivo studies are needed to know more about the toxic potential of this plant.(AU)

Intoxicação aguda pela ingestão de Samanea tubulosa em bovino / Acute intoxication by ingestion of Samanea tubulosa in bovine

As intoxicações em animais de produção causadas por plantas são bastante relatadas, resultando em perdas econômicas diretas causadas pela morte dos animais, diminuição dos índices produtivos e reprodutivos, além de aumentar a ocorrência e susceptibilidade a outras doenças. Já as perdas indiretas, incluem os custos para o controle das plantas tóxicas nas pastagens, além das medidas de manejo como a utilização de cercas e o pastoreio alternativo para evitar as intoxicações, assim como também os gastos associados ao diagnóstico e tratamento. No presente trabalho relatou-se a intoxicação de um bovino de raça Girolando de 11 anos pelo consumo da planta conhecida como bordão-de-velho (Samanea tubulosa). As alterações pós-mortem macro e microscópicas demonstraram que a causa provável de morte foi a síndrome de disfunção de múltiplos órgãos. Estudos in vivo são necessários para conhecer mais a fundo o potencial tóxico desta planta.

Intoxications in production animals caused by plants are well reported, resulting direct losses caused by the death of animals, by the reduction of productive and reproductive indexes, as well as increase in the frequence and susceptibility to other diseases. Indirect losses can be attributed to control plants in pastures, in addition to manipulation measures, such as use of fences and alternative grazing to avoid intoxication. The present work reported the intoxication of an 11-year-old female breed of cattle by the consumption of the plant known as bordão-develho (Samanea tubulosa). Macro and microscopic finds demonstrate that the probable cause is multiple organ dysfunction syndrome. In vivo studies are needed to know more about the toxic potential of this plant.

Catastrophic antiphospholipid syndrome. Case report and literature review / Síndrome antifosfolípidos catastrófico. Reporte de caso y revisión bibliográfica.

The present document is the report of a case of a very rare clinical entity, which presents with acute multiorganic failure after a thrombotic storm related to antiphospholipid antibodies, the so-called catastrophic antiphospholipid syndrome, which began as a recurrent picture of mesenteric thrombosis, with a previous history of venous insufficiency and distal ulcers probably associated with an unidentified antiphospholipid; deserving management in intensive care and the consultation by the world expert, Dr. Ricard Cervera who confirmed the diagnosis and recommend treating as such entity, the patient's evolution was satisfactory so far. Final recommendations for diagnosis and current treatment options such as rituximab or eculizumab are made. The present case was added to the international registry that currently houses around 500 cases worldwide (International CAPS Registry).

Se reporta un caso de una condición clínica sumamente rara, la cual cursa con falla multiorgánica aguda posterior a una tormenta trombótica relacionada con anticuerpos antifosfolípidos, el denominado síndrome antifosfolípidos (SAF) catastrófico, el cual comenzó como un cuadro recurrente de trombosis mesentérica, con antecedentes de insuficiencia venosa y úlceras distales probablemente asociadas a un SAF no identificado, ameritando manejo en terapia intensiva y la consulta por el experto mundial Dr. Ricard Cervera, quien confirmó el diagnóstico y recomendó tratar como tal. La evolución del paciente fue satisfactoria hasta el momento. Se hacen recomendaciones finales de diagnóstico y se comentan las opciones de tratamiento actuales, como rituximab o eculizumab. El presente caso fue agregado al registro internacional de SAF catastrófico (International CAPS Registry), que actualmente alberga alrededor de 500 casos en todo el mundo.

Falla multiorgánica y desenlaces clínicos en pacientes sépticos con síndrome eutiroideo enfermo / Multiorgan failure and clinical outcomes in septic patients with euthyroid sick syndrome / Insuficiência de múltiplos órgãos e resultados clínicos em pacientes sépticos com síndrome do doente eutireoidiano

Resumen: Introducción: La prevalencia del síndrome eutiroideo enfermo en pacientes con sepsis es aproximadamente de 60%; existe poca información sobre su correlación con falla multiorgánica. Objetivo: Estimar la prevalencia del síndrome eutiroideo enfermo (SEE) y correlacionar con la presencia de fallas orgánicas específicas y puntajes de gravedad y desenlaces clínicos. Métodos: Se incluyeron pacientes con diagnóstico de sepsis en una unidad de cuidados críticos durante el periodo comprendido de marzo de 2014 a febrero de 2016; se tomaron variables clínicas y estudios de laboratorio que incluían perfil tiroideo en todos los pacientes. Análisis estadístico: Estadística descriptiva con medidas de frecuencia, tendencia central y dispersión. Se realizaron análisis de supervivencia con modelos de regresión de Cox y curvas de Kaplan-Meier para mortalidad; razones de riesgo e intervalos de confianza de 95%. Un error alfa ajustado menor de 5% a dos colas fue considerado significativo. Se usó la paquetería estadística STATA SE versión 11.1. Resultados: Se incluyó un total de 90 pacientes, 51.1% de sexo femenino, con edad de 71 ± 14.15 años, IMC al ingreso a la UCI de 24.94 ± 5.07 kg/m2. La prevalencia global de SEE es de 61.1%. Los pacientes con SEE presentaron en mayor proporción falla hemodinámica, renal y hematológica, sin alcanzar significancia estadística. En la fases combinadas 2 y 3 de SEE, sí se observó mayor proporción de falla renal: 88 versus 63.3%, RR = 1.8 (IC 95% 1.1-2.6, p = 0.037), así como altas dosis de vasopresores (norepinefrina > 0.1 µg/kg/min) RR = 2.3 (IC 95% 1.063-5.18, p = 0.024) y menor supervivencia, con una mediana en días de 28 (RIQ 19-39) versus 26 (RIQ 13-36), p = 0.7; PCT igual o mayor a 6 en un 65.5 versus 40%, RR = 1.87 (IC 95% 1.1-3.1, p = 0.18), mayor puntaje de SOFA con mediana de 12 (RIQ 8-4) versus 9 (RIQ 7-13) puntos, p = 0.09. Además, peores desenlaces durante la estancia hospitalaria, evaluados por un índice compuesto que incluye mortalidad, necesidad de ventilación mecánica invasiva (VMI), SOFA ≥ 9 con un RR = 1.713 (IC 95% 1.036-2.83, p = 0.05). El análisis de curva ROC detectó el mejor punto de corte de SOFA como predictor de SEE ≥ 11 con sensibilidad 60.0, especificidad 62 LR + 1.6, LR - 0.63, AUC = 0.6. RR = 1.7 (IC 95% 1.024-3.05, p = 0.034). Conclusiones: Los pacientes con SEE presentan mayor elevación de marcadores de inflamación, requerimiento de vasopresores y soporte ventilatorio, compromiso multiorgánico y mortalidad.

Abstract: Introduction: The prevalence of euthyroid sick syndrome in patients with sepsis is approximately 60%; there is little information on its correlation with multiorgan failure. Objective: To estimate the prevalence of euthyroid sick syndrome (ESS) and correlate it with the presence of specific organ failures, severity scores and clinical outcomes. Methods: Patients with diagnosis of sepsis in a critical care unit during the period from March 2014 to February 2016; we registered the clinical variables and laboratory studies, including thyroid function, in all patients. Statistical analysis: Descriptive statistics with frequency measures of central tendency and dispersion. Mortality-survival analysis with Cox regression models and Kaplan-Meier were made, as well as risk ratios and confidence intervals of 95%. A two-tailed adjusted alpha error of less than 5% was considered significant. The statistical package STATA SE version 11.1 was used. Results: Ninety patients were included, 51.1% female, aged 71 ± 14.15 years; the BMI at admission to the ICU was 24.94 ± 5.07 kg/m2. The overall prevalence of ESS was 61.1%. ESS patients presented in greater proportion with hemodynamic, renal and hematologic failure, without reaching statistical significance. In the combined phases 2 and 3 of SEE, a higher proportion of renal failure was observed: 88 vs. 63.3 %, RR = 1.8 (95% CI 1.1-2.6, p = 0.037). High doses of vasopressors (norepinephrine > 0.1 µg/kg/min) RR = 2.3 (95% CI 1.063-5.18, p = 0.024). Lower survival with a median of 28 days (IQR 19-39) versus 26 (IQR 13-36), p = 0.7. PCT greater than or equal to 6 in 65.5 versus 40%, RR = 1.87 (95% CI 1.1-3.1, p = 0.18); higher SOFA score with a median of 12 (IQR 8-4) versus 9 (IQR 7-13) points, p = 0.09. In addition to worse outcomes during hospital stay evaluated by a composite index that included mortality, need for invasive mechanical ventilation (IMV), SOFA ≥ 9 with a RR = 1.713 (95% CI 1.036-2.83, p = 0.05). ROC curve analysis detected the best cut of SOFA as a predictor of ESS ≥11, sensitivity 60.0, specificity 62 LR + 1.6, LR-0.63, AUC = 0.6. RR = 1.7 (95% CI 1.024-3.05, p = 0.034). Conclusions: Patients with ESS have higher markers of inflammation, increased requirement for vasopressors and ventilatory support, as well as elevated multiorgan failure and mortality.

Resumo: Introdução: A prevalência da síndrome do doente eutireoidiano em pacientes com sepse é de aproximadamente 60%, além disso há pouca informação sobre sua correlação com a insuficiência de múltiplos órgãos. Objetivo: Estimar a prevalência da síndrome do doente eutireoidiano (ESS) e correlacionar com a presença de insuficiência orgânica específica, pontuações de gravidade e desenlaces clínicos. Foram incluídos pacientes diagnosticados com sepse em uma unidade de terapia intensiva durante o período de março de 2014 a fevereiro de 2016, se tomaram variáveis clínicas e estudos laboratoriais que incluiam perfil tireoidiano em todos os pacientes. Análise estatística: Estatística descritiva com medidas de frequência, tendência central e dispersão. Realizaram-se análises de sobrevivência com modelos de regressão de Cox e curvas de Kaplan-Meier para mortalidade. Taxas de risco e intervalos de confiança de 95%. O erro alfa ajustado menor a 5% bicaudal, serão considerados significativos. O programa estatístico STATA versão 11.1. Resultados: Incluiram-se um total de 90 pacientes, 51.1% do sexo feminino, com idades entre 71 ± 14.15 anos, IMC na admissão na UTI foi de 24.94 ± 5.07 kg/m2. A prevalência global de ESS foi de 61.1%. Os pacientes com ESS apresentaram maior proporção de alteração hemodinâmica, renal e hematológica sem alcançar significância estatística. Nas fases 2 e 3 combinadas de ESS se observou maior proporção de insuficiência renal 88 versus 63.3%, RR = 1.8 (IC 95%1.1-2.6, p = 0.037). Altas doses de vasopressores (norepinefrina > 0.1 µg/kg/min) RR = 2.3 (IC 95% 1.063-5.18, p = 0.024). Menor sobrevida com uma média em dias de 28 (IQR 19-39) vs 26 (RIQ 13-36), p = 0.7. PCT igual ou maior a 6 em um 65.5 vs 40%, RR = 1.87 (IC de 95% 1.1-3.1, p = 0.18) maior pontuação SOFA com uma média de 12 (RIQ 8-4) vs 9 (RIQ 7-13) pontos, p = 0.09. Ademais com piores desenlaces durante a estadia hospitalar avaliada por um índice de composto que inclui a mortalidade, a necessidade de VMI, SOFA ≥ 9 com um RR = 1.713 (IC 95% 1.036-2.83, p = 0.05). A análise da curva ROC detectou o melhor ponto de corte de SOFA como um preditor de ESS ≥ 11 sensibilidade 60.0, especificidade 62 LR + 1.6, LR-0.63, AUC = 0.6. RR = 1.7 (IC de 95% 1.024-3.05, p = 0.034). Conclusões: Os pacientes com ESS apresentam maior elevação dos marcadores inflamatórios, maior necessidade de vasopressores, suporte ventilatório, compromisso múltiplo de órgãos e mortalidade.