Thiosulfinate-Enriched Allium sativum Extract Exhibits Differential Effects between Healthy and Sepsis Patients: The Implication of HIF-1α.

Garlic (Allium sativum) has historically been associated with antioxidant, immunomodulatory, and microbiocidal properties, mainly due to its richness in thiosulfates and sulfur-containing phytoconstituents. Sepsis patients could benefit from these properties because it involves both inflammatory and refractory processes. We evaluated the effects of thiosulfinate-enriched Allium sativum extract (TASE) on the immune response to bacterial lipopolysaccharide (LPS) by monocytes from healthy volunteers (HVs) and patients with sepsis. We also explored the TASE effects in HIF-1α, described as the key transcription factor leading to endotoxin tolerance in sepsis monocytes through IRAK-M expression. Our results showed TASE reduced the LPS-triggered reactive oxygen species (ROS) production in monocytes from both patients with sepsis and HVs. Moreover, this extract significantly reduced tumor necrosis factor (TNF)-α, interleukin-1ß, and interleukin-6 production in LPS-stimulated monocytes from HVs. However, TASE enhanced the inflammatory response in monocytes from patients with sepsis along with increased expression of human leukocyte antigen-DR. Curiously, these dual effects of TASE on immune response were also found when the HV cohort was divided into low- and high-LPS responders. Although TASE enhanced TNFα production in the LPS-low responders, it decreased the inflammatory response in the LPS-high responders. Furthermore, TASE decreased the HIF-1α pathway-associated genes IRAK-M, VEGFA and PD-L1 in sepsis cells, suggesting HIF-1α inhibition by TASE leads to higher cytokine production in these cells as a consequence of IRAK-M downregulation. The suppression of this pathway by TASE was confirmed in vitro with the prolyl hydroxylase inhibitor dimethyloxalylglycine. Our data revealed TASE's dual effect on monocyte response according to status/phenotype and suggested the HIF-1α suppression as the possible underlying mechanism.

Black Garlic and Thiosulfinate-Enriched Extracts as Adjuvants to Ceftriaxone Treatment in a Rat Peritonitis Model of Sepsis.

To date, there have been no new drugs or adjuvants able to decrease both morbidity and mortality in the context of sepsis and septic shock. Our objective was to evaluate the use of thiosulfinate-enriched Allium sativum and black garlic extracts as adjuvants in the management of sepsis. An experimental in vivo study was carried out with male Sprague-Dawley® rats. Animals were randomized in four treatment groups: antibiotic (ceftriaxone) treatment (group I), ceftriaxone plus thiosulfinate-enriched extract (TASE, group II), ceftriaxone plus thiosulfinate-enriched extract and black garlic extracts (TASE + BGE, group III), and ceftriaxone plus black garlic extract (BGE, group IV). All animals were housed and inoculated with 1 × 1010 CFU/15 mL of intraperitoneal Escherichia coli ATCC 25922. Subsequently, they received a daily treatment according to each group for 7 days. Clinical, analytical, microbiological, and histopathological parameters were evaluated. Statistically significant clinical improvement was observed in rats receiving garlic extracts in weight (groups II and III), ocular secretions, and piloerection (group IV). Moreover, less liver edema, vacuolization, and inflammation were observed in groups receiving adjuvant support (groups II, III, and IV). When comparing interleukins 24 h after bacteria inoculum, we found statistically significant differences in TNF-alpha levels in groups receiving BGE (groups III and IV, p ≤ 0.05). Blood and peritoneal liquid cultures were also analyzed, and we detected a certain level of Enterococcus faecalis in peritoneal cultures from all treatment groups and less bacteria presence in blood cultures in rats receiving garlic extracts (groups II, III, and IV). In conclusion, TASE and BGE could be promising nutraceutical or medicinal agents as coadjuvants in the treatment of sepsis because of its effects in modulating the inflammatory response.

Optic neuritis as sign presentation of acute disseminated encephalomyelitis following Mycoplasma pneumoniae infection

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Aprotinin treatment against SARS-CoV-2: A randomized phase III study to evaluate the safety and efficacy of a pan-protease inhibitor for moderate COVID-19.

BACKGROUND: SARS-CoV-2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two-step furin-mediated entry mechanism. Aprotinin is a broad-spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti-inflammatory properties for inhibiting the innate immunity contact system. METHODS: This was a multicentre, double-blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID-19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length of hospital stay and ICU admission. The secondary endpoints were each of the primary efficacy outcomes and a composite of oxygen therapy, analytical parameters and death. Safety outcomes included adverse reactions to treatment during a 30-day follow-up period. Treatment was given for 11 days or till discharge. RESULTS: With almost identical analytical profiles, significant differences were observed in treatment time, which was 2 days lower in the aprotinin group (p = .002), and length of hospital admission, which was 5 days shorter in the aprotinin group (p = .003). The incidence of discharge was 2.19 times higher (HR: 2.188 [1.182-4.047]) in the aprotinin group than in the placebo group (p = .013). In addition, the aprotinin-treated group required less oxygen therapy and had no adverse reactions or side effects. CONCLUSION: Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID-19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe.

Análisis de los pacientes menores de edad con sospecha de COVID-19 en un servicio de urgencias y su impacto en el estudio de contactos / Pediatric patients with suspected COVID-19 in an emergency department: analysis of characteristics and transmission to contacts

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Complicaciones asociadas a niñas con síndrome de Turner / Complications related to Turner syndrome

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La elevación del índice de agua pulmonar extravascular como factor predictivo del fracaso de la presión continua en la vía aérea con casco (CPAP-Helmet) en pacientes con insuficiencia respiratoria aguda tras intervención quirúrgica mayor / Elevated Extravascular Lung Water Index (ELWI) as a Predictor of Failure of Continuous Positive Airway Pressure Via Helmet (Helmet-CPAP) in Patients With Acute Respiratory Failure After Major Surgery

Introducción: La ventilación no invasiva (VNI) se utiliza cada vez más para la prevención y el tratamiento de las complicaciones y la insuficiencia respiratorias. Algunos pacientes ingresan en las unidades de reanimación postanestésica portando monitores hemodinámicos avanzados que permiten cuantificar el agua pulmonar extravascular (EVLW) mediante la técnica de termodilución transpulmonar y la permeabilidad vascular pulmonar (PVP), parámetros que permiten obtener información sobre el edema pulmonar. Objetivo: El objetivo de este estudio fue determinar si el índice de EVLW y el índice de la PVP pueden pronosticar el fracaso (intubación) o el éxito (no intubación) en pacientes que desarrollan insuficiencia respiratoria aguda (IRA) durante el período postoperatorio de una intervención quirúrgica mayor abdominal y cuyo tratamiento de primera línea es la presión positiva continua en la vía aérea (CPAP) administrada mediante casco (CPAP-Helmet). Métodos: Se monitorizaron las variables hemodinámicas, el índice de agua pulmonar extravascular (EVLWI) y el índice de permeabilidad vascular pulmonar (PVPI) mediante un dispositivo de monitorización hemodinámica de termodilución transpulmonar (PiCCO(TM)), antes y después de la aplicación de la CPAP. Resultados: En un 66% de los pacientes con CPAP-Helmet se evitó la intubación. En dichos pacientes, el cociente PaO2/FiO2 aumentó de forma significativa (303,33 ± 65,2 vs. 141,6 ± 14,6, p < 0,01) tras la primera hora de aplicación de la CPAP. Antes de iniciar la CPAP-Helmet los valores de EVLWI y PVPI eran significativamente inferiores en los pacientes no intubados (EVLWI 8,6 ± 1,08 vs. 11,8 ± 0,99 ml/kg de peso corporal ideal (PCI), p < 0,01 y PVPI 1,7 ± 0,56 vs. 3,0 ± 0,88, p < 0,01). Se establecieron unos valores de corte óptimos de 9,5 para el EVLWI y de 2,45 para el PVPI (sensibilidad de 0,7; especificidad de 0,9, p < 0,01). Conclusión: En este tipo de pacientes, los parámetros fisiológicos que pronosticaron el fracaso de la CPAP-Helmet con mayor precisión fueron el EVLWI y el PVPI previos al inicio de la CPAP-Helmet, el cociente PaO2/FiO2 y la frecuencia respiratoria tras una hora de CPAP

Introduction: NIV is increasingly used for prevention and treatment of respiratory complications and failure. Some of them are admitted to the PACU with advanced hemodynamic monitors which allow quantification of Extravascular Lung Water (EVLW) by transpulmonary thermodilution technique (TPTD) and Pulmonary Vascular Permeability (PVP) providing information on lung edema. Aim: The objective of this study was to ascertain if EVLW Index and PVP Index may predict failure (intubation) or success (non-intubation) in patients developing acute respiratory failure (ARF) in the postoperative period following major abdominal surgery, where the first line of treatment was non-invasive continuous positive airway pressure via a helmet. Methods: Hemodynamic variables, EVLWI and PVPI were monitored with a transpulmonary thermodilution hemodynamic monitor device (PiCCO(TM)) before and after the application of CPAP. Results: Avoidance of intubation was observed in 66% of patients with Helmet-CPAP. In these patients after the first hour of application of CPAP, PaO2/FiO2 ratio significantly increased (303.33 ± 65.2 vs. 141.6 ± 14.6, P < .01). Before starting Helmet-CPAP values of EVLWI and PVPI were significantly lower in non-intubated patients (EVLWI 8.6 ± 1.08 vs. 11.8 ± 0.99 ml/kg IBW, P < .01 and PVPI 1.7 ± 0.56 vs. 3.0 ± 0.88, P < .01). An optimal cut-off value for EVLWI was established at 9.5, and at 2.45 for PVPI (sensitivity of 0.7; specificity of 0.9, P < .01). Conclusion: In this type of patient the physiological parameters that predict the failure of Helmet-CPAP with the greatest accuracy were the value of the EVLWI and PVPI before Helmet-CPAP institution and the PaO2/FiO2 ratio and the respiratory rate after one hour of CPAP

Elevated Extravascular Lung Water Index (ELWI) as a Predictor of Failure of Continuous Positive Airway Pressure Via Helmet (Helmet-CPAP) in Patients With Acute Respiratory Failure After Major Surgery.

INTRODUCTION: NIV is increasingly used for prevention and treatment of respiratory complications and failure. Some of them are admitted to the PACU with advanced hemodynamic monitors which allow quantification of Extravascular Lung Water (EVLW) by transpulmonary thermodilution technique (TPTD) and Pulmonary Vascular Permeability (PVP) providing information on lung edema. AIM: The objective of this study was to ascertain if EVLW Index and PVP Index may predict failure (intubation) or success (non-intubation) in patients developing acute respiratory failure (ARF) in the postoperative period following major abdominal surgery, where the first line of treatment was non-invasive continuous positive airway pressure via a helmet. METHODS: Hemodynamic variables, EVLWI and PVPI were monitored with a transpulmonary thermodilution hemodynamic monitor device (PiCCO™) before and after the application of CPAP. RESULTS: Avoidance of intubation was observed in 66% of patients with Helmet-CPAP. In these patients after the first hour of application of CPAP, PaO2/FiO2 ratio significantly increased (303.33±65.2 vs. 141.6±14.6, P<.01). Before starting Helmet-CPAP values of EVLWI and PVPI were significantly lower in non-intubated patients (EVLWI 8.6±1.08 vs. 11.8±0.99ml/kg IBW, P<.01 and PVPI 1.7±0.56 vs. 3.0±0.88, P<.01). An optimal cut-off value for EVLWI was established at 9.5, and at 2.45 for PVPI (sensitivity of 0.7; specificity of 0.9, P<.01). CONCLUSION: In this type of patient the physiological parameters that predict the failure of Helmet-CPAP with the greatest accuracy were the value of the EVLWI and PVPI before Helmet-CPAP institution and the PaO2/FiO2 ratio and the respiratory rate after one hour of CPAP.