Purinergic P2X7 receptor expression increases in leukocytes from intra-abdominal septic patients.

Inflammation is a tightly coordinated response of the host immune system to bacterial and viral infections, triggered by the production of inflammatory cytokines. Sepsis is defined as a systemic inflammatory response followed by immunosuppression of the host and organ dysfunction. This imbalance of the immune response increases the risk of mortality of patients with sepsis, making it a major problem for critical care units worldwide. The P2X7 receptor plays a crucial role in activating the immune system by inducing the activation of peripheral blood mononuclear cells. In this study, we analyzed a cohort of abdominal origin septic patients and found that the expression of the P2X7 receptor in the plasma membrane is elevated in the different subsets of lymphocytes. We observed a direct relationship between the percentage of P2X7-expressing lymphocytes and the early inflammatory response in sepsis. Additionally, in patients whose lymphocytes presented a higher percentage of P2X7 surface expression, the total lymphocytes populations proportionally decreased. Furthermore, we found a correlation between elevated soluble P2X7 receptors in plasma and inflammasome-dependent cytokine IL-18. In summary, our work demonstrates that P2X7 expression is highly induced in lymphocytes during sepsis, and this correlates with IL-18, along with other inflammatory mediators such as IL-6, IL-8, and procalcitonin.

Comparison of 20% mannitol and 3% hypertonic saline for intraoperative brain relaxation during supratentorial brain tumour craniotomy in patients with a midline shift / Comparación entre manitol 20% y salino hipertónico 3% para la relajación cerebral intraoperatoria durante craneotomía por tumor cerebral supratentorial en pacientes con desviación de la línea media

Purpose of the study A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 20% mannitol and 3% hypertonic saline (HS) during elective supratentorial brain tumour surgery in patients with midline shift. Material and methods Sixty patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 5mL/kg of 20% mannitol (n=30) or 3% HS (n=30) administered at skin incision. PCO2 in arterial blood was maintained within 35–40mmHg and arterial blood pressure was controlled within baseline values ±20%. The primary outcome was the proportion of satisfactory brain relaxation. The surgeon assessed brain relaxation on a four-point scale (1=excellent with no swelling, 2=minimal swelling, 3=serious swelling not requiring treatment, 4=severe swelling requiring treatment). Postsurgical intracranial changes determined by imaging techniques, postoperative complications, PACU and hospital stay, and mortality at 30 days were also recorded. Appropriate statistical tests were used for comparison; P<0.05 was considered as significant. This trial was registered in Eudract.ema.europa.eu (#2021-006290-40). Results There was no difference in brain relaxation: 2.00 [1.00–2.00] and 2.00 [1.75–3.00] for patients in mannitol and HS groups, respectively (P=0.804). Tumour size (OR: 0.99, 95% CI: 0.99–1.01; P=0.371), peritumoral oedema classification (OR: 0.57, 95% CI: 0.11–2.84; P=0.493), mass effect (OR: 0.86, 95% CI: 0.16–4.87; P=0.864), anaesthesia (OR: 4.88, 95% CI: 0.82–28.96; P=0.081) and midline shift (OR: 5.00, 95% CI: 0.84–29.70; P=0.077) did not have a significant influence on brain swelling in patients treated with either mannitol or HS. No significant differences in perioperative outcomes, mortality and length of PACU and hospital stay were observed (AU)

Objetivos del estudio Estudio prospectivo, aleatorizado y doble ciego diseñado para evaluar diferencias en la relajación cerebral entre manitol 20% y salino hipertónico (SH) 3% durante cirugía supratentorial electiva por tumor cerebral en pacientes con desviación de línea media. Material y métodos Sesenta pacientes sometidos a craneotomía supratentorial para resección tumoral se estudiaron para recibir 5ml/kg de manitol 20% (n=30) o SH 3% (n=30) administrados durante la incisión cutánea. La pCO2 en sangre arterial se mantuvo entre 35-40mmHg y la presión arterial se controló dentro de valores basales±20%. El objetivo principal fue la proporción de relajación cerebral satisfactoria. El cirujano evaluó la relajación cerebral en una escala de 4 puntos (1=excelente sin hinchazón, 2=hinchazón mínima, 3=hinchazón grave que no requiere tratamiento, 4=hinchazón severa que requiere tratamiento). Los cambios intracraneales posquirúrgicos determinados por técnicas de imagen, complicaciones postoperatorias, estancia en reanimación y hospitalaria, así como mortalidad a 30 días fueron registrados. Se usaron test estadísticos para la comparación, siendo considerado p<0,05 como significativo. El ensayo fue registrado en Eudract.ema.europa.eu (#2021-006290-40). Resultados No hubo diferencias en la relajación cerebral: 2,00 [1,00-2,00] y 2,00 [1,75-3,00] en los pacientes del grupo manitol y SH respectivamente (p=0,804). El tamaño tumoral (OR: 0,99: IC 95%:0,99-1,01; p=0,371), nivel de edema peritumoral (OR: 0,57; IC 95%:0,11-2,84; p=0,493), efecto masa (OR: 0,86; IC 95%: 0,16-4,87; p=0,864), anestesia empleada (OR: 4,88; 95% IC: 0,82-28,96; p=0,081) y desviación de la línea media (OR: 5,00; IC 95%: 0,84-29,70; p=0,077) no tuvieron influencia significativa sobre la hinchazón cerebral en los pacientes de ambos grupos. No hubo diferencias significativas en los resultados perioperatorios, mortalidad ni en estancia en reanimación ni hospitalaria (AU)

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1ß release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1ß release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers.

The prognostic impact of SIGLEC5-induced impairment of CD8+ T cell activation in sepsis.

BACKGROUND: Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis. METHODS: In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100). FINDINGS: SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8+ T-cell proliferation. Administration of sSIGLEC5r (0.8 mg/kg) had adverse effects in mouse endotoxemia models. Additionally, plasma sSIGLEC5 levels of septic patients were higher than HVs and ROC analysis revealed it as a mortality marker with an AUC of 0.713 (95% CI, 0.656-0.769; p < 0.0001). Kaplan-Meier survival curve showed a significant decrease in survival above the calculated cut-off (HR of 3.418, 95% CI, 2.380-4.907, p < 0.0001 by log-rank test) estimated by Youden Index (523.6 ng/mL). INTERPRETATION: SIGLEC5 displays the hallmarks of an IC ligand, and plasma levels of sSIGLEC5 have been linked with increased mortality in septic patients. FUNDING: Instituto de Salud Carlos III (ISCIII) and "Fondos FEDER" to ELC (PIE15/00065, PI18/00148, PI14/01234, PI21/00869), CDF (PI21/01178), RLR (FI19/00334) and JAO (CD21/00059).

Comparison of 20% mannitol and 3% hypertonic saline for intraoperative brain relaxation during supratentorial brain tumour craniotomy in patients with a midline shift.

PURPOSE OF THE STUDY: A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 20% mannitol and 3% hypertonic saline (HS) during elective supratentorial brain tumour surgery in patients with midline shift. MATERIAL AND METHODS: Sixty patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 5mL/kg of 20% mannitol (n=30) or 3% HS (n=30) administered at skin incision. PCO2 in arterial blood was maintained within 35-40mmHg and arterial blood pressure was controlled within baseline values ±20%. The primary outcome was the proportion of satisfactory brain relaxation. The surgeon assessed brain relaxation on a four-point scale (1=excellent with no swelling, 2=minimal swelling, 3=serious swelling not requiring treatment, 4=severe swelling requiring treatment). Postsurgical intracranial changes determined by imaging techniques, postoperative complications, PACU and hospital stay, and mortality at 30 days were also recorded. Appropriate statistical tests were used for comparison; P<0.05 was considered as significant. This trial was registered in Eudract.ema.europa.eu (#2021-006290-40). RESULTS: There was no difference in brain relaxation: 2.00 [1.00-2.00] and 2.00 [1.75-3.00] for patients in mannitol and HS groups, respectively (P=0.804). Tumour size (OR: 0.99, 95% CI: 0.99-1.01; P=0.371), peritumoral oedema classification (OR: 0.57, 95% CI: 0.11-2.84; P=0.493), mass effect (OR: 0.86, 95% CI: 0.16-4.87; P=0.864), anaesthesia (OR: 4.88, 95% CI: 0.82-28.96; P=0.081) and midline shift (OR: 5.00, 95% CI: 0.84-29.70; P=0.077) did not have a significant influence on brain swelling in patients treated with either mannitol or HS. No significant differences in perioperative outcomes, mortality and length of PACU and hospital stay were observed. CONCLUSIONS: 5mL/kg of 20% mannitol or 3% HS result in similar brain relaxation scores in patients undergoing craniotomy for supratentorial brain tumour with midline shift.

Extreme In Situ Liver Surgery Under Total Vascular Exclusion with Right Hepatic Vein and Inferior Vena Cava Grafts for an Intrahepatic Cholangiocarcinoma.

In this multimedia article, we demonstrate an extreme in situ liver surgery under total vascular exclusion with right hepatic vein and inferior vena cava grafts for an intrahepatic cholangiocarcinoma in a centre with experience in highly complex hepatobiliary surgery and liver transplantation. This surgical approach after neoadjuvant chemotherapy provides an opportunity for surgical salvage in patients with large tumors invading the hepatocaval confluence. This patient was considered unresectable at another hospital and referred to our unit. We performed an accurate preoperative assessment with new generation 3D modelling to plan the type of vascular reconstruction that would allow adequate hepatic venous outflow and the volume of the future liver remnant sufficient to avoid postoperative liver failure. For hemodynamic management of the patient, we performed a total hepatic vascular exclusion with veno-venous bypass without intraoperative adverse events. We used a cryopreserved carotid artery graft after previously planning the most appropriate diameter and length for right hepatic vein reconstruction. The inferior vena cava was reconstructed with gore-tex graft. During the hospital stay there were no postoperative complications. The patient is free of disease. We conclude that patients with advanced malignant liver disease should always be referred to highly specialized liver surgery centers to assess the most appropriate oncological management and the possibility of surgical resectability.

Acute renal disease in patients with ovarian peritoneal carcinomatosis treated with cytoreduction and HIPEC: the influence of surgery and the cytostatic agent used.

BACKGROUND: The main objective of this study was to evaluate the differences between cisplatin and paclitaxel in the development of postoperative renal toxicity, using as a reference the RIFLE (Risk, Injury, Insufficiency, Loss, and End-stage renal function) and AKIN (Acute Kidney Injury Network) criteria in patients with primary or recurrent ovarian cancer with peritoneal dissemination treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: One hundred fifty-two patients who were treated between December 2007 and June 2017 were analyzed. RESULTS: Patients who received previous platinum-based chemotherapy had higher baseline creatinine levels than those who had not (p = 0.05). A total of 11 (7.2%) and 4 (2.6%) patients developed an acute renal dysfunction (ARD) during the postoperative period of cytoreduction and HIPEC according to the RIFLE and AKI criteria respectively. RIFLE detects a higher rate of ARD due to different parameters such as GFR (7.2% versus 2.6%, p = 0.016). Performing ostomy (p = 0.007; OR: 39.320; 95% CI = 2.74-56.13) and using of cisplatin during HIPEC treatment (p = 0.017; OR = 13.619; 95% IC = 1.600-25.95) were factors independently related to a higher rate of ARD. CONCLUSION: ARD has a multifactorial origin. Cisplatin was associated with the development of a higher rate of ARD than paclitaxel. Diagnosis of ARD did not correlate with worse survival figures.

Grado de percepción sobre el conocimiento, las habilidades y la seguridad antes y después de un programa de entrenamiento con videolaringoscopia y mecanismo de protección Intubox® en el manejo de la vía aérea de pacientes con COVID-19 / Perception of level of knowledge, skills, and safety before and after training to perform videolaryngoscopy with the Intubox barrier system for airway management in patients with COVID-19

Objetivos. El objetivo principal fue describir el grado de percepción sobre el conocimiento, las habilidades y la seguridad antes y después de un programa de entrenamiento con videolaringoscopia y mecanismo de protección Intubox® en el manejo de la vía aérea de pacientes con COVID-19. El objetivo secundario fue evaluar la seguridad de los dispositivos de barrera en la intubación a través de un análisis visual de dispersión de partículas.Método. Ensayo clínico de un solo brazo basado en simulación. Los participantes fueron médicos que realizaron un programa de formación mediante simulación clínica de baja y alta fidelidad. Se usó un instrumento diseñado y valida-do específico para evaluar la percepción sobre el conocimiento, las habilidades y la seguridad antes y después del programa. Se realizó un análisis visual de la contaminación por gotas.Resultados. La muestra final estuvo compuesta por 27 médicos, con una edad media de 40 (DE 10,8) años y el 63% mujeres. Se obtuvo un incremento estadísticamente significativo en las dimensiones conocimiento, habilidad y seguridad tras el entrenamiento. Se observó una menor contaminación cuando se realizaron las técnicas de manejo de vía aérea con urna protectora.Conclusiones. Los urgenciólogos incrementaron su percepción sobre los conocimientos, habilidades y seguridad en el manejo de la vía aérea en pacientes con COVID-19 tras un programa de formación con simulación. El uso combinado de laringoscopia y dispositivo de barrera Intubox® causó menor dispersión de partículas durante la intubación. (AU)

Objectives. The main objective was to describe physicians’ perception of their knowledge, skill, and safety before and after training to perform videolaryngoscopy while using the Intubox barrier system when managing the airway of a patient with the coronavirus 2019 disease (COVID-19). The secondary objective was to assess the safety afforded by the barrier by means of visually evaluating particle dispersion during intubation.Methods. Single-arm clinical simulation trial. The participants were physicians who received training in both a low-fidelity and a high-fidelity simulation zone. The participants assessed their knowledge, skill, and safety when using the Intubox before and after training using a specially designed and validated questionnaire. Droplet contamination was estimated visually.Results. Twenty-seven physicians with a mean (SD) age of 40 (10.8) years participated; 63% were women. They perceived their knowledge, skill, and safety to be significantly higher after training. Droplet contamination was seen to decrease when airway management maneuvers were done with the barrier in place.Conclusions. After simulation training the emergency physicians judged their knowledge, skill, and safety to be greater when they used the barrier during airway management in patients with COVID-19. The combined use of a laryngoscope and the Intubox barrier resulted in less particle dispersion during intubation. (AU)

Perception of level of knowledge, skills, and safety before and after training to perform videolaryngoscopy with the Intubox barrier system for airway management in patients with COVID-19. / Grado de percepción sobre el conocimiento, las habilidades y la seguridad antes y después de un programa de entrenamiento con videolaringoscopia y mecanismo de protección Intubox® en el manejo de la vía aérea de pacientes con COVID-19.

OBJECTIVES: The main objective was to describe physicians' perception of their knowledge, skill, and safety before and after training to perform videolaryngoscopy while using the Intubox barrier system when managing the airway of a patient with the coronavirus 2019 disease (COVID-19). The secondary objective was to assess the safety afforded by the barrier by means of visually evaluating particle dispersion during intubation. MATERIAL AND METHODS: Single-arm clinical simulation trial. The participants were physicians who received training in both a lowfidelity and a high-fidelity simulation zone. The participants assessed their knowledge, skill, and safety when using the Intubox before and after training using a specially designed and validated questionnaire. Droplet contamination was estimated visually. RESULTS: Twenty-seven physicians with a mean (SD) age of 40 (10.8) years participated; 63% were women. They perceived their knowledge, skill, and safety to be significantly higher after training. Droplet contamination was seen to decrease when airway management maneuvers were done with the barrier in place. CONCLUSION: After simulation training the emergency physicians judged their knowledge, skill, and safety to be greater when they used the barrier during airway management in patients with COVID-19. The combined use of a laryngoscope and the Intubox barrier resulted in less particle dispersion during intubation.

OBJETIVO: El objetivo principal fue describir el grado de percepción sobre el conocimiento, las habilidades y la seguridad antes y después de un programa de entrenamiento con videolaringoscopia y mecanismo de protección Intubox® en el manejo de la vía aérea de pacientes con COVID-19. El objetivo secundario fue evaluar la seguridad de los dispositivos de barrera en la intubación a través de un análisis visual de dispersión de partículas. METODO: Ensayo clínico de un solo brazo basado en simulación. Los participantes fueron médicos que realizaron un programa de formación mediante simulación clínica de baja y alta fidelidad. Se usó un instrumento diseñado y validado específico para evaluar la percepción sobre el conocimiento, las habilidades y la seguridad antes y después del programa. Se realizó un análisis visual de la contaminación por gotas. RESULTADOS: La muestra final estuvo compuesta por 27 médicos, con una edad media de 40 (DE 10,8) años y el 63% mujeres. Se obtuvo un incremento estadísticamente significativo en las dimensiones conocimiento, habilidad y seguridad tras el entrenamiento. Se observó una menor contaminación cuando se realizaron las técnicas de manejo de vía aérea con urna protectora. CONCLUSIONES: Los urgenciólogos incrementaron su percepción sobre los conocimientos, habilidades y seguridad en el manejo de la vía aérea en pacientes con COVID-19 tras un programa de formación con simulación. El uso combinado de laringoscopia y dispositivo de barrera Intubox® causó menor dispersión de partículas durante la intubación.

CD14 release induced by P2X7 receptor restricts inflammation and increases survival during sepsis.

P2X7 receptor activation induces the release of different cellular proteins, such as CD14, a glycosylphosphatidylinositol (GPI)-anchored protein to the plasma membrane important for LPS signaling via TLR4. Circulating CD14 has been found at elevated levels in sepsis, but the exact mechanism of CD14 release in sepsis has not been established. Here, we show for first time that P2X7 receptor induces the release of CD14 in extracellular vesicles, resulting in a net reduction in macrophage plasma membrane CD14 that functionally affects LPS, but not monophosphoryl lipid A, pro-inflammatory cytokine production. Also, we found that during a murine model of sepsis, P2X7 receptor activity is important for maintaining elevated levels of CD14 in biological fluids and a decrease in its activity results in higher bacterial load and exacerbated organ damage, ultimately leading to premature deaths. Our data reveal that P2X7 is a key receptor for helping to clear sepsis because it maintains elevated concentrations of circulating CD14 during infection.

When the immune system detects an infection, it often launches an inflammatory response to fight off the disease. This defense mechanism is activated by a cascade of signaling molecules that can aggravate inflammation, causing it to damage the body's own tissues and organs. This life-threatening reaction is referred to as sepsis, and kills around 11 million people each year. New approaches are therefore needed to help alleviate the damage caused by this condition. The inflammatory response is often triggered by proteins called receptors, which sit on the surface of immune cells. When these receptors are activated, they induce cells to secrete proteins that travel around the body and activate immune cells that can eliminate the infection. In 2016, a group of researchers showed that a receptor called P2X7 stimulates the release of a signaling molecule called CD14. Patients with sepsis often have elevated amounts of CD14 in their bloodstream. Yet, it remained unclear what causes this rise in CD14 and what role this molecule plays in the development of sepsis. Now, Alarcón-Vila et al. ­ including some of the researchers involved in the 2016 study ­ have investigated the role of P2X7 in mice undergoing sepsis. This was done by puncturing the mice's intestines, causing bacteria to leak out and initiate an over-active immune response. Alarcón-Vila et al. found that mice lacking the P2X7 receptor had less CD14 and struggled to eliminate the bacterial infection from their system. This increase in bacteria caused excessive damage to the mice's organs, ultimately leading to premature death. These findings suggest that P2X7 plays an important role in preventing the onset of sepsis by helping maintain high levels of CD14 following infection. This result could help to identify new therapies that reduce the mortality rates of septic infections.

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.

Estudio hemodinámico, metabólico e histopatológico de un modelo porcino de trasplante auxiliar heterotópico hepático con arterialización portal / A hemodynamic, metabolic and histopathological study of a heterotopic auxiliary swine liver graft with portal vein arterialization

INTRODUCCIÓN: El trasplante auxiliar heterotópico hepático con arterialización de la vena porta (TAHH-AVP) es un modelo poco estudiado a pesar de su potencial terapéutico. El objetivo del estudio es valorar la respuesta hemodinámica y bioquímica durante el implante y analizar la repercusión de la arterialización portal en la funcionalidad y morfología hepática. MÉTODOS: Se realizó un estudio hemodinámico y bioquímico durante el implante auxiliar en un modelo porcino (n = 15 TAHH-AVP). Además, se analizaron las consecuencias de la arterialización portal sobre la arquitectura hepática mediante un estudio ultraestructural. RESULTADOS: La reperfusión del injerto arterializado aumentó la frecuencia cardiaca (FC) respecto a los valores basales (p = 0,004) y a la fase del pinzamiento de la vena cava (p = 0,004) y disminuyó las resistencias vasculares sistémicas respecto a la fase del pinzamiento de la vena cava (p = 0,021). Al final del implante, el gasto cardiaco permaneció elevado (p = 0,001), al igual que la FC respecto a la fase basal (p = 0,002). La presión arterial media disminuyó con el pinzamiento venoso, pero no se vio afectada ni por la reperfusión del injerto ni por el cierre de la piel. Todas las muestras histológicas obtenidas a los 3, 10 y 21 días conservaron su morfología y arquitectura hepáticas. Si bien se observaron algunos focos de necrosis perilobular el día 3 (p = 0,049) y proliferación conectiva perilobular el día 10 (p = 0,007), respecto al hígado nativo. CONCLUSIONES: El trasplante del injerto hepático arterializado descrito minimiza el número de anastomosis vasculares respecto a los modelos previamente publicados, presenta una buena tolerancia hemodinámica y metabólica, y la arterialización portal del injerto no produce cambios significativos en la histología hepática

BACKGROUND: Auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA) is a model that has been hardly studied, despite its therapeutic potential. METHODS: Hemodynamic and biochemical characterization was carried out during graft implantation, in a pig-to-pig model (n = 15 AHLT-PVA). Furthermore a histopathological study was performed to establish microscopic alterations due to PVA. RESULTS: Reperfusion of the arterialized graft produced an increase in heart rate (HR) vs. baseline (P=.004) and vs. inferior vena cava clamping phase (P=.004); and a decrease in systemic vascular resistance vs. cava clamping phase (P=.021). At the end of implantation, cardiac output remained elevated (P=.001), likewise HR remained increased vs. baseline phase (P=.002). Mean arterial pressure decreased with cava clamping, but was not affected by the reperfusion of the graft, nor the skin closure. The histopathological study at 3, 10, and 21 days post-PVA revealed that functional liver structure was maintained although it is common to find foci of perilobular necrosis on day 3 (P=.049), and perilobular connective tissue proliferation at day 10 (P=.007), vs. native liver. CONCLUSIONS: The described arterialized liver graft model minimizes the number of vascular anastomoses vs. previously described models. It is hemodynamically and metabolically well tolerated and the double arterial vascularization of the graft does not cause significant changes in liver histology

A hemodynamic, metabolic and histopathological study of a heterotopic auxiliary swine liver graft with portal vein arterialization.

BACKGROUND: Auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA) is a model that has been hardly studied, despite its therapeutic potential. METHODS: Hemodynamic and biochemical characterization was carried out during graft implantation, in a pig-to-pig model (n=15 AHLT-PVA). Furthermore a histopathological study was performed to establish microscopic alterations due to PVA. RESULTS: Reperfusion of the arterialized graft produced an increase in heart rate (HR) vs. baseline (P=.004) and vs. inferior vena cava clamping phase (P=.004); and a decrease in systemic vascular resistance vs. cava clamping phase (P=.021). At the end of implantation, cardiac output remained elevated (P=.001), likewise HR remained increased vs. baseline phase (P=.002). Mean arterial pressure decreased with cava clamping, but was not affected by the reperfusion of the graft, nor the skin closure. The histopathological study at 3, 10, and 21 days post-PVA revealed that functional liver structure was maintained although it is common to find foci of perilobular necrosis on day 3 (P=.049), and perilobular connective tissue proliferation at day 10 (P=.007), vs. native liver. CONCLUSIONS: The described arterialized liver graft model minimizes the number of vascular anastomoses vs. previously described models. It is hemodynamically and metabolically well tolerated and the double arterial vascularization of the graft does not cause significant changes in liver histology.

Effect on oximetry of dyes used for sentinel lymph node biopsy.

HYPOTHESIS: There are differences between readings of peripheral blood oxygen saturation when the effect on saturation values of methylene blue is compared with that of isosulfan blue when used in sentinel lymph node biopsy in patients with breast cancer. DESIGN: Prospective randomized study. SETTING: University tertiary care center. PATIENTS: Thirty-two women undergoing surgery for breast cancer using sentinel lymph node biopsy. INTERVENTIONS: Sentinel lymph node biopsy using methylene blue (16 patients) and isosulfan blue (16 patients); there was also a control group of 6 surgical patients in whom dyes were not used. MAIN OUTCOME MEASURES: Peripheral saturation of blood using pulse oximetry, oxygen saturation by blood-gas analysis, partial oxygen pressure by blood-gas analysis, and plasma dye levels, recorded before dye injection and 15, 30, and 60 minutes afterward. RESULTS: The 2 dyes interfered with the peripheral saturation reading, but only isosulfan blue showed significant differences. The differences in blood-gas analysis values between the 2 groups and with regard to the controls were not significant. CONCLUSIONS: Methylene blue interferes less than isosulfan blue in the peripheral saturation reading. Desaturation is factitious in both cases, and does not correspond to alterations in blood-gas analysis values.

Estudio clínico e inmunólogico del xenorrechazo en el xenotrasplante ortotópico de hígado de cerdo a babuino / Clinical and immunological study of xenorejection in orthotopic liver xenotransplantation from pig to baboon

Introducción. La experiencia de xenotrasplante hepático (Xtoh) de cerdo a primate no humano es muy limitada. Nuestros objetivos han sido: a) comprobar si el hígado de un cerdo transgénico h-DAF evita el rechazo hiperagudo; b) estudiar las funciones metabólicas del hígado porcino tras el Xtoh; y c) analizar el perfil clínico, bioquímico e inmunológico del rechazo vascular agudo retardado. Animales y métodos. Se realizaron 6 Xtoh de cerdo a babuino, 4 de cerdos no modificados y dos de cerdos transgénicos para h-DAF. Se llevaron a cabo determinaciones hematológicas, de coagulación, de xenoanticuerpos y del complemento. En el babuino que sobrevivió 8 días, se estudiaron durante los mismos las poblaciones linfocitarias y la actividad lítica de los linfocitos. Resultados. Los valores de xIgG e IgM descendieron drásticamente a los 3 min de la reperfusión, sobre todo del CH50, C3 y C4. En los hígados no modificados genéticamente apareció una coagulación intravascular diseminada por rechazo hiperagudo, con una supervivencia inferior a 12 h. Con los hígados h-DAF, la coagulación se normalizó, con una supervivencia de 8 y 4 días, falleciendo ambos por insuficiencia respiratoria, sin rechazo hiperagudo. El babuino que sobrevivió 8 días presentó a las 36 h un rechazo vascular agudo retardado, detectándose una estimulación de las HLA clase I sobre los linfocitos CD3+ y CD19+, que respondió al tratamiento. Conclusiones. El hígado transgénico h-DAAF previene el rechazo hiperagudo y mantiene la coagulación en rangos normales en el babuino. El rechazo vascular agudo provoca el cese en la producción de bilis y un patrón mixto de citólisis y colostasis. Los valores de expresión de HLA clase I en los linfocitos podrían ser útiles para diagnosticarlo (AU)