Estudio de los marcadores de severidad en la sepsis grave y shock séptico

La sepsis es la respuesta del organismo a la infección, y se caracteriza por la activación de distintos sistemas de proteasas, inflamación intravascular y una alteración en la extracción de oxígeno, que pueden conducir a un cuadro de disfunción multiorgánica. La complejidad de esta respuesta inmune del huésped hace poco probable que un solo biomarcador pueda describir adecuadamente y estratificar a los pacientes con sepsis. HIPÓTESIS La determinación de parámetros relacionados con la inflamación, coagulación, estrés oxidativo y perfusión tisular como pilares fundamentales de la fisiopatología de la sepsis, así como la interrelación de ellos, se considera de utilidad en la práctica clínica para llegar a un diagnóstico precoz, valorar la evolución clínica y plantear terapias futuras. MATERIAL Y MÉTODOS Se definieron dos grupos de pacientes: un grupo de enfermos y un grupo control. El grupo de enfermos presentaba sepsis grave o shock séptico de acuerdo a las definiciones establecidas por la Conferencia de Consenso de 1991 y 2003 y en el momento de inclusión todos ellos se encontraban bajo efectos de la sedación, intubados y conectados a ventilación mecánica. El grupo control estaba constituido por pacientes con patología hematológica tipo anemias o mielodisplasias que a priori no presentaban alteraciones de los parámetros a estudio. Se obtuvieron variables demográficas, función renal, función hepática, parámetros hemodinámicas, respiratorios y de perfusión tisular. Como marcadores de inflamación se estudiaron citoquinas proinflamatorias (TNF-α, IL-6 e IL-8) y antiinflamatorias (IL-10), así como el cociente IL-10/TNF-α. De los marcadores de coagulación se estudiaron anticoagulantes naturales, factores de coagulación y la homocisteína, y de los marcadores de estrés oxidativo los niveles de malondialdehído, la actividad xantina oxidasa y los niveles de glutatión en su forma oxidada (GSSG) y reducida (GSH), así como el cociente GSSG/GSH. Se obtuvieron muestras en cuatro tiempos en el grupo de enfermos, a las 24, 48 y 72 horas de ingreso en UCI, y en el momento de alta o cuando se preveía un desenlace fatal inminente. En el grupo control se obtuvieron las muestras en un único tiempo. RESULTADOS: El grupo estudio estaba formado por 23 pacientes (52% varones, edad media de 74,5 años) con criterios de sepsis grave y shock séptico. El grupo control incluyó 10 pacientes (60% varones, edad media de 72 años). El origen de la sepsis fue abdominal (17 pacientes), patología pulmonar (3 pacientes), origen urológico (1 paciente) y dos bacteriemias. La puntuación de los índices de gravedad para los diferentes scores utilizados fueron: APACHE II : 18,33 ± 6,59; SAPS 3 : 71,17 ± 14,72; SOFA score :10,79 ± 2,58. La mortalidad global del grupo fue de 37, 5% todos ellos en situación de disfunción multiorgánica. Al comparar el grupo de enfermos en el momento de su ingreso con el grupo control, se encontraron diferencias entre las variables estudiadas para la función renal, hepática, parámetros de inflamación, coagulación, y estrés oxidativo. En el grupo de enfermos, la determinación de los niveles de Proteína C, el cociente IL-10/ TNF-α, y niveles de glutatión reducido en el momento de ingreso, permitió discriminar entre aquellos que fallecían respecto a los que sobrevivían. Al estudiar la evolución de los marcadores en los diferentes tiempos, y comparar entre los pacientes que sobreviven en comparación con los que no sobreviven, observamos una evolución heterogénea de todas las variables, y que la progresiva normalización de parámetros de inflamación, coagulación y estrés oxidativo se acompañan de mejor pronóstico. Entre los marcadores de inflamación estudiados, observamos una relación con la disfunción miocárdica y la perfusión tisular, así como una relación entre los niveles de IL-8 y la función renal. Así mismo, encontramos una interrelación entre parámetros de inflamación y coagulación, en concreto con los niveles de IL-6 y proteína C y, entre los niveles de IL-8 y factor VII de la coagulación. Dentro de los marcadores de estrés oxidativo, la actividad xantina oxidasa se relaciona con las cifras de creatinina. Se valoró la relación de las diferentes variables analizadas con los scores de gravedad APACHE II y SOFA, encontrando únicamente una relación para los niveles de AT III y el cociente IL-10/ TNF-α con el SOFA score. Por último, en pacientes sometidos a técnicas de depuración renal continuas, pudimos observar cambios en los niveles de los diferentes marcadores estudiados, aunque no pudimos establecer diferencias al comparar con el grupo que no precisó de técnicas de reemplazo rena

One-year quality of life among post-hospitalization COVID-19 patients

IntroductionThe long-term effects of SARS-CoV-2 are unclear, as are the factors influencing the evolution. Objective: to assess health-related quality of life 1 year after a hospital admission due to COVID-19 and to identify factors that may influence it.Materials and methodsRetrospective observational study in a tertiary hospital from March 2021 to February 2022. Inclusion criteria: ≥18 years old and admitted for SARS-CoV-2 infection. Exclusion criteria: death, not located, refusal to participate, cognitive impairment, and language barrier. Variables: demographic data, medical history, clinical and analytical outcomes during hospital admission, treatment received, and vaccination against SARS-CoV-2 following admission. Participants were interviewed by phone 1 year after admission, using the SF-36 quality of life questionnaire.ResultsThere were 486 included patients. The domains yielding the lowest scores were general health (median 65%, interquartile range [IQR] 45–80), vitality (median 65%, IQR 45–80), and mental health (median 73.5%, IQR 60–100). Multivariable analysis showed that female sex and fibromyalgia/fatigue had a negative influence on all domains. Obesity was associated with worse outcomes in physical functioning, physical role, bodily pain, and vitality. Other factors associated with worse scores were an older age in physical functioning and high age-adjusted Charslon comorbidity in physical functioning and general health. Age was associated with better results in emotional role and High C-reactive protein at admission on vitality.ConclusionOne year after admission for COVID-19, quality of life remains affected, especially the domains of general health, vitality, and mental health. Factors associated with worse outcomes are female sex, fibromyalgia/chronic fatigue, and obesity

The Effect of Enteral Immunonutrition in the Intensive Care Unit: Does It Impact on Outcomes?

Background: The present research aimed to evaluate the effect on outcomes of immunonutrition (IMN) enteral formulas during the intensive care unit (ICU) stay. Methods: A multicenter prospective observational study was performed. Patient characteristics, disease severity, nutritional status, type of nutritional therapy and outcomes, and laboratory parameters were collected in a database. Statistical differences were analyzed according to the administration of IMN or other types of enteral formulas. Results: In total, 406 patients were included in the analysis, of whom 15.02% (61) received IMN. Univariate analysis showed that patients treated with IMN formulas received higher mean caloric and protein intake, and better 28-day survival (85.2% vs. 73.3%; p = 0.014. Unadjusted Hazard Ratio (HR): 0.15; 95% CI (Confidence Interval): 0.06-0.36; p < 0.001). Once adjusted for confounding factors, multivariate analysis showed a lower need for vasopressor support (OR: 0.49; 95% CI: 0.26-0.91; p = 0.023) and continuous renal replacement therapies (OR: 0.13; 95% CI: 0.01-0.65; p = 0.049) in those patients who received IMN formulas, independently of the severity of the disease. IMN use was also associated with higher protein intake during the administration of nutritional therapy (OR: 6.23; 95% CI: 2.59-15.54; p < 0.001), regardless of the type of patient. No differences were found in the laboratory parameters, except for a trend toward lower triglyceride levels (HR: 0.97; 95% CI: 0.95-0.99; p = 0.045). Conclusion: The use of IMN formulas may be associated with better outcomes (i.e., lower need for vasopressors and continuous renal replacement), together with a trend toward higher protein enteral delivery during the ICU stay. These findings may ultimately be related to their modulating effect on the inflammatory response in the critically ill. NCT Registry: 03634943

An extensive thermodynamic characterization of the dimerization domain of the HIV-1 capsid protein

The type 1 human immunodeficiency virus presents a conical capsid formed by several hundred units of the capsid protein, CA. Homodimerization of CA occurs via its C-terminal domain, CA-C. This self-association process, which is thought to be pH-dependent, seems to constitute a key step in virus assembly. CA-C isolated in solution is able to dimerize. An extensive thermodynamic characterization of the dimeric and monomeric species of CA-C at different pHs has been carried out by using fluorescence, circular dichroism (CD), absorbance, nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), and size-exclusion chromatography (SEC). Thermal and chemical denaturation allowed the determination of the thermodynamic parameters describing the unfolding of both CA-C species. Three reversible thermal transitions were observed, depending on the technique employed. The first one was protein concentration-dependent; it was observed by FTIR and NMR, and consisted of a broad transition occurring between 290 and 315 K; this transition involves dimer dissociation. The second transition (Tm ~ 325 K) was observed by ANS-binding experiments, fluorescence anisotropy, and near-UV CD; it involves partial unfolding of the monomeric species. Finally, absorbance, far-UV CD, and NMR revealed a third transition occurring at Tm ~ 333 K, which involves global unfolding of the monomeric species. Thus, dimer dissociation and monomer unfolding were not coupled. At low pH, CA-C underwent a conformational transition, leading to a species displaying ANS binding, a low CD signal, a red-shifted fluorescence spectrum, and a change in compactness. These features are characteristic of molten globule-like conformations, and they resemble the properties of the second species observed in thermal unfolding

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p &lt; 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p &lt; 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p &lt; 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease