P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis.

Sepsis is characterized by a systemic inflammatory response followed by immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.

Alteraciones de la hemostasia durante la cirugía con quimioterapia intraperitoneal hipertérmica en pacientes con carcinomatosis peritoneal / Alterations in hemostasis during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis

INTRODUCCIÓN: La cirugía citorreductora seguida de quimioterapia intraperitoneal hipertérmica (HIPEC) se asocia frecuentemente a alteraciones de la hemostasia y a elevados requerimientos transfusionales perioperatorios. El propósito de este estudio fue analizar los trastornos hemostáticos asociados a cada una de las fases de este procedimiento terapéutico mediante tromboelastometría rotacional (ROTEM), niveles de fibrinógeno y recuento plaquetario, así como su posible relación con las necesidades transfusionales. MÉTODOS: Se efectuó un estudio prospectivo longitudinal. Se registraron niveles de hemoglobina, recuento plaquetario, niveles de fibrinógeno y parámetros tromboelastométricos: tiempo de coagulación (CT), tiempo de formación del coágulo (CFT), firmeza máxima del coágulo (MCF), y ángulo α (EXTEM, INTEM, FIBTEM). Las mencionadas determinaciones se realizaron: antes del inicio de la cirugía; al finalizar la cirugía citorreductora y al concluir la HIPEC. Se utilizaron los test estadísticos apropiados. Los valores de p < 0,05 se consideraron estadísticamente significativos. RESULTADOS: Se incluyó en el estudio a 41 mujeres con una mediana de edad de 54 años (rango: 34-76). Tras la cirugía citorreductora se observó una caída de la tasa de hemoglobina desde 11,4 ± 1,5 a 10,6 ± 1,6 g/dl; un descenso del fibrinógeno sérico desde 269 ± 69 hasta 230 ± 48 mg/dl (p < 0,01) y una reducción de MCF en FIBTEM desde 20 ± 10 hasta 16 ± 8 mm (p < 0,01). La HIPEC no se asoció a alteraciones hemostáticas. Se observó una moderada relación negativa entre el número de concentrados de hematíes administrados y los niveles de fibrinógeno (ρ = −0,5; p = 0,002) y los valores de MCF EXTEM (ρ = −0,43; p = 0,006) registrados tras la HIPEC. CONCLUSIONES: Las alteraciones hemostáticas observadas aparecen tras la cirugía citorreductora, probablemente a consecuencia de la hemorragia quirúrgica. Se requieren más estudios para confirmar una correlación entre las necesidades transfusionales y las pruebas de coagulación postoperatorias

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently associated with coagulation impairment and perioperative blood transfusion. Our aim was to investigate the impact of each procedure step on hemostasis, as measured by rotational thromboelastometry™ (ROTEM), fibrinogen level and platelet count as a primary outcome, along with its relationship with transfusion needs. METHODS: A prospective longitudinal study was performed. Hemoglobin level, fibrinogen level, platelet count and ROTEM parameters: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), α-angle (EXTEM, INTEM, FIBTEM) were measured before the procedure, at the end of cytoreductive surgery and after HIPEC. Appropriate statistical tests were used for comparison. A P<.05 was considered as significant. RESULTS: Forty-one women, with median age 54 (range 34-76) were recruited. Cytoreductive surgery was followed by a reduction of hemoglobin level from 11,4 ± 1,5 g/dl to 10,6 ± 1,6 g/dl, a reduction of serum fibrinogen level from 269 ± 69 mg/dl to 230 ± 48 mg/dl (P<.01) and MCF decline from 20 ± 10 to 16 ± 8 mm (P<.01), in the FIBTEM test. HIPEC was followed by no hemostatic impairment. The number of packed red blood cells administered during patients stay kept a mild significant relationship with both fibrinogen level (ρ = −0.5, P=.002), and MCF EXTEM values (ρ= -0.43, P=0.006), recorded after HIPEC. CONCLUSIONS: The mild observed hemostatic impairment appeared after cytoreductive surgery instead of HIPEC, involving surgical hemorrhage as the most likely responsible factor. Further studies are required to confirm a correlation between transfusion needs and postoperative hemostatic tests

Alterations in hemostasis during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently associated with coagulation impairment and perioperative blood transfusion. Our aim was to investigate the impact of each procedure step on hemostasis, as measured by rotational thromboelastometry™ (ROTEM), fibrinogen level and platelet count as a primary outcome, along with its relationship with transfusion needs. METHODS: A prospective longitudinal study was performed. Hemoglobin level, fibrinogen level, platelet count and ROTEM parameters: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), α-angle (EXTEM, INTEM, FIBTEM) were measured before the procedure, at the end of cytoreductive surgery and after HIPEC. Appropriate statistical tests were used for comparison. A P<.05 was considered as significant. RESULTS: Forty-one women, with median age 54 (range 34-76) were recruited. Cytoreductive surgery was followed by a reduction of hemoglobin level from 11,4±1,5g/dl to 10,6±1,6g/dl, a reduction of serum fibrinogen level from 269±69mg/dl to 230±48mg/dl (P<.01) and MCF decline from 20±10 to 16±8mm (P<.01), in the FIBTEM test. HIPEC was followed by no hemostatic impairment. The number of packed red blood cells administered during patients stay kept a mild significant relationship with both fibrinogen level (ρ = -0.5, P=.002), and MCF EXTEM values (ρ= -0.43, P=0.006), recorded after HIPEC. CONCLUSIONS: The mild observed hemostatic impairment appeared after cytoreductive surgery instead of HIPEC, involving surgical hemorrhage as the most likely responsible factor. Further studies are required to confirm a correlation between transfusion needs and postoperative hemostatic tests.

Manejo de las náuseas y vómitos postoperatorios / Management of postoperative nausea and vomiting

Las nauseas y vómitos postoperatorios no han recibido el suficiente interés hasta la fecha. Se han considerado molestias inherentes e inevitables tras muchas intervenciones quirúrgicas. Sin embargo, esta desagradable complicación tiene un manejo que puede resultar eficaz. Para ello hay que valorar adecuadamente el riesgo y actuar en consecuencia. Existe una amplia variedad de opciones profilácticas disponibles relacionadas con la técnica anestésica, además del oportuno tratamiento antiemético. En este artículo se revisan los factores de riesgo y se efectúan una serie de recomendaciones operatorias y postoperatorias (AU)

There still appears to be insufficient interest in the management of postoperative nausea and vomiting. They are considered as inherent and inevitable discomforts after surgical operation. However, this disagreeable complication can be effectively managed. To do this, the risk must be suitably assessed and acted on accordingly. There are a wide variety of prophylactic options available associated with the anaesthetic technique, as well as appropriate anti-emetic treatment. In this article, the risk factors are reviewed and series of operative and postoperative recommendations are made (AU)

[Management of postoperative nausea and vomiting]. / Manejo de las náuseas y vómitos postoperatorios.

There still appears to be insufficient interest in the management of postoperative nausea and vomiting. They are considered as inherent and inevitable discomforts after surgical operation. However, this disagreeable complication can be effectively managed. To do this, the risk must be suitably assessed and acted on accordingly. There are a wide variety of prophylactic options available associated with the anaesthetic technique, as well as appropriate anti-emetic treatment. In this article, the risk factors are reviewed and series of operative and postoperative recommendations are made.

Relación entre las principales alteraciones metabólicas con las cardiovasculares durante el trasplante hepático / Relationship between the main metabolic and cardiovascular alterations during liver transplantation

El principal objetivo fue describir la evolución de las concentraciones de calcio iónico sanguíneo (Ca2+), potasio sanguíneo (K+) y magnesio iónico sérico (Mg2+); y su relación con las alteraciones cardiovasculares durante el trasplante ortotópico de hígado (TOH). Se estudiaron 92 pacientes adultos tratados con TOH. Se encontró una correlación inversa entre las concentraciones Mg2+ y citrato para todos los pacientes. El Mg2+ al igual que el Ca2+, es quelado por el citrato y su evolución es una imagen especular a la del citrato. En estos pacientes, no se observó ninguna disritmia que pueda ser atribuida directamente a la hipomagnesemia iónica. En conclusión, los bajos niveles preoperatorios, junto con las trasfusiones masivas de hemoderivados y el incremento de las pérdidas renales, provocan una progresiva hipomagnesemia iónica en los pacientes tratados con TOH. Se propone que la concentración de Mg2+ sea monitorizada y eventualmente tratada, al igual como se realiza con el Ca2+ y el K= (AU)

Relación entre las principales alteraciones metabólicas con las cardiovasculares durante el trasplante hepático / Relationship between the main metabolic and cardiovascular alterations during liver transplantation

El principal objetivo fue describir la evolución de las concentraciones de calcio iónico sanguíneo (Ca2+), potasio sanguíneo (K+) y magnesio iónico sérico (Mg2+); y su relación con las alteraciones cardiovasculares durante el trasplante ortotópico de hígado (TOH). Se estudiaron 92 pacientes adultos tratados con TOH. Se encontró una correlación inversa entre las concentraciones Mg2+ y citrato para todos los pacientes. El Mg2+ al igual que el Ca2+, es quelado por el citrato y su evolución es una imagen especular a la del citrato. En estos pacientes, no se observó ninguna disritmia que pueda ser atribuida directamente a la hipomagnesemia iónica. En conclusión, los bajos niveles preoperatorios, junto con las trasfusiones masivas de hemoderivados y el incremento de las pérdidas renales, provocan una progresiva hipomagnesemia iónica en los pacientes tratados con TOH. Se propone que la concentración de Mg2+ sea monitorizada y eventualmente tratada, al igual como se realiza con el Ca2+ y el K=