Lethal Influenza in Two Related Adults with Inherited GATA2 Deficiency.

The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.

Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection.

INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains. METHODS: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection. RESULTS: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO2 ratio (P = 0.001). CONCLUSIONS: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics.

Protección cardiocerebral post paro cardiaco / Post-cardiac arrest cardiocerebral protection

Introducción: Hasta ahora los cuidados post paro cardiaco constituyen el quinto eslabón de la cadena de supervivencia. Es el más débil y no se han desarrollado en la práctica clínica guías de tratamiento para esta entidad. Objetivo: Reunir los avances recientes en la protección cardiocerebral del síndrome post paro cardiaco. Desarrollo: El desarrollo de las estrategias de protección cardiocerebral post paro cardiaco, se basa en el conocimiento de los mecanismos fisiopatológicos que acontecen tras el retorno a la circulación espontanea. Luego de la valoración inicial se debe decidir la realización de hipotermia o de revascularización coronaria medidas terapéuticas que por su aplicación precoz logran un incremento de la supervivencia. Conclusiones: La protección cardiocerebral post paro cardiaco es compleja y aun queda mucho por investigar.

Introduction: Until now the post-cardiac arrest cares are the fifth link in the survival chain. It is the most weak without development of treatment guidelines in the clinical practice for this entity. Objective: To bring together the recent advances in cardiocerebral protection in the post-cardiac arrest syndrome. Development: The creation of post-cardiac arrest cardiocerebral protection strategies is based in the knowledge of pathophysiology mechanisms present after the spontaneous circulation. After the initial assessment it is necessary to decide the carrying-out of hypothermia or of coronary revascularization therapeutical measures that due to its early application achieve a survival increase. Conclusions: The post-cardiac arrest cardiocerebral protection is complex and thus it is necessary more researches.

Anestesia para colecistectomía laparoscópica: nuestra experiencia / Anesthesia for laparoscopic cholecystectomy: our experience

La cirugía de mínimo acceso se acompaña de variados cambios fisiopatológicos, por lo que requiere una adecuada monitorización y una atención anestésicas con características especiales. Realizamos un estudio prospectivo analítico con el objetivo de determinar el comportamiento transoperatorio, hemodinámico y respiratorio en este tipo de cirugía, determinar la correlación existente entre la presión arterial de dióxido de carbono (PaCO2) y el dióxido de carbono teleespiratorio (ETCO2) en los pacientes con y sin patologías cardiorrespiratorias previas, así como la morbilidad y la mortalidad asociadas al procedimiento. Observamos un aumento significativo de la presión pico en la vía aérea (f = 32,53; p = 0,0) y de la PaCO2 a los 5 min y a los 30 min después del neumoperitoneo. Existió una fuerte correlación lineal entre la PaCO2 y el ETCO2 en los pacientes sanos, pero no así en los enfermos. La tensión arterial diastólica experimentó un aumento significativo del 12 por ciento y la frecuencia cardíaca una disminución de 7,1 por ciento. Las náuseas y vómitos posoperatorios fueron las complicaciones más frecuentes (10 por ciento). La colecistectomía laparoscópica, en nuestra experiencia, se acompañó de excelente estabilidad cardiorrespiratoria y una reducida morbilidad(AU)

The surgery of minimum access is accompanied of varied changes fisiopatológicos, for what requires an appropriate monitorización and an anesthetic attention with characteristic special. We carry out an analytic prospective study with the objective of determining the behavior transoperatorio, hemodynamic and breathing in this surgery type, to determine the existent correlation among the arterial pressure of dioxide of carbon (PaCO2) and the dioxide of carbon teleespiratorio (ETCO2) in the patients with and without pathologies previous cardiorrespiratorias, as well as the morbilidad and the mortality associated to the procedure. We observe a significant increase of the pressure pick in the air road (f = 32,53; p = 0,0) and of the PaCO2 to the 5 min and the 30 min after the neumoperitoneo. A strong lineal correlation existed between the PaCO2 and the ETCO2 in the healthy patients, but I didn't seize in the sick persons. The tension arterial diastólica experienced a significant increase of 12 percent and the heart frequency a decrease of 7,1 percent. The nauseas and vomits posoperatorios were the most frequent complications (10 percent). The colecistectomía laparoscópica, in our experience, was accompanied of excellent stability cardiorrespiratoria and a reduced morbilidad(AU)

Shock, ¿qué hay de nuevo? / Shock: What is new about?

El shock es un síndrome común de diversas causas que se inicia por una disminución de la perfusión hística, donde la microcirculación tiene una función crítica. En estudios recientes se profundiza en la terapéutica que debe ser inmediata, pues amenaza la vida e incluye: soporte respiratorio, soporte circulatorio, monitoreo metabólico, hemodinámica y tratamiento específico. El uso de cristaloides versus coloides es controversial y depende del criterio del médico. Se evidencia la utilidad de la amrinona (ionotropo), sobre todo en pacientes en shock séptico, y como vasopresor la vasopresina. El monitoreo de la concentración plasmática del ácido láctico es necesario por su relación con la mortalidad por shock. La mortalidad del shock séptico, a pesar de múltiples investigaciones, continúa elevada. Los inhibidores de la óxido-nítrico sintasa (S metil-isiotiourea) de reciente utilización, parece alentador al inhibir la isoforma inducible (iNOS) y de igual forma la inmunoterapia, pero se necesitan de nuevos estudios para evaluar su eficacia clínica(AU)

Shock is a commom syndrome originated by different causes that starts with a decrease of histic perfusion, where macrocirculation has a critical function. In recent studies, emphasis has been made on the fact that therapeutics should be immediate in the face of this life menace and should include respiratory support, circulatory support, metabolic monitoring, hemodynamics and specific treatment. The use of crystalloids versus colloids is controversial and depends on the medical criterion. The usefulness of amrinone (ionotrope), mainly in patients with septic shock, and of vasopressin as a vasopressor is proved. The monitoring of the plasmatic concentration of the lactic acid is necessary due to its relation with mortality from shock. The mortality from septic shock is still high, in spite of the multiple investigations made. The recent utilization of nitric oxide synthase (S methyl-isothiourea) inhibitors seems to be encouraging on inhibiting the inductible isoform (iNOS), the same as immunotherapy, but new studies are necessary to evaluate its clinical efficiency(AU)