Severe sepsis and septic shock are associated with significant mortality. Effective management of this clinical syndrome includes early resuscitation with fluids and vasoactive drugs to maintain ...vital organ perfusion and oxygen delivery. Understanding the different approach to the management of sepsis during the resuscitation and ongoing management phases is essential to initiate context- and time-specific interventions. Manipulation of hemodynamic variables to achieve a balance between oxygen delivery and consumption forms the cornerstone of hemodynamic optimisation. Minimally invasive and completely non-invasive cardiac output monitors have been developed, but require validation in this specific cohort of patients. The trend in hemodynamic parameters is particularly important when any intervention to augment cardiac output is carried out (functional hemodynamic monitoring). Cardiac output monitors and surrogates of tissue oxygenation are only able to guide management, as patient outcome is determined by acquisition and interpretation of accurate data, and suitable management decisions.
Multiple organ dysfunction after trauma Cole, E.; Gillespie, S.; Vulliamy, P. ...
British journal of surgery,
March 2020, Letnik:
107, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background
The nature of multiple organ dysfunction syndrome (MODS) after traumatic injury is evolving as resuscitation practices advance and more patients survive their injuries to reach critical ...care. The aim of this study was to characterize contemporary MODS subtypes in trauma critical care at a population level.
Methods
Adult patients admitted to major trauma centre critical care units were enrolled in this 4‐week point‐prevalence study. MODS was defined by a daily total Sequential Organ Failure Assessment (SOFA) score of more than 5. Hierarchical clustering of SOFA scores over time was used to identify MODS subtypes.
Results
Some 440 patients were enrolled, of whom 245 (55·7 per cent) developed MODS. MODS carried a high mortality rate (22·0 per cent versus 0·5 per cent in those without MODS; P < 0·001) and 24·0 per cent of deaths occurred within the first 48 h after injury. Three patterns of MODS were identified, all present on admission. Cluster 1 MODS resolved early with a median time to recovery of 4 days and a mortality rate of 14·4 per cent. Cluster 2 had a delayed recovery (median 13 days) and a mortality rate of 35 per cent. Cluster 3 had a prolonged recovery (median 25 days) and high associated mortality rate of 46 per cent. Multivariable analysis revealed distinct clinical associations for each form of MODS; 24‐hour crystalloid administration was associated strongly with cluster 1 (P = 0·009), traumatic brain injury with cluster 2 (P = 0·002) and admission shock severity with cluster 3 (P = 0·003).
Conclusion
Contemporary MODS has at least three distinct types based on patterns of severity and recovery. Further characterization of MODS subtypes and their underlying pathophysiology may lead to future opportunities for early stratification and targeted interventions.
Antecedentes
La naturaleza del síndrome de disfunción orgánica múltiple (Multiple Organ Dysfunction Syndrome, MODS) resultante de un traumatismo está evolucionando a medida que avanzan las prácticas de reanimación y más pacientes sobrevive a las lesiones y pueden recibir cuidados críticos. El objetivo de este estudio fue caracterizar los subtipos actuales MODS en atención crítica de trauma a nivel poblacional.
Métodos
Los pacientes adultos ingresados en unidades de cuidados intensivos de trauma se incluyeron en este estudio de prevalencia puntual de 4 semanas. MODS se definió como una puntuación total diaria de la escala de Evaluación de Fallo Orgánico Secuencial (Sequential Organ Failure Assessment, SOFA) > 5. Se utilizó el agrupamiento jerárquico de las puntuaciones SOFA a lo largo del tiempo para determinar los subtipos MODS.
Resultados
Se incluyeron 440 pacientes, de los cuales 245 (56%) presentaron MODS. MODS conllevó una alta mortalidad (22% versus 1%, P < 0,001) y 24% de las muertes fueron precoces, durante las primeras 48 horas tras el traumatismo. Se identificaron tres patrones de MODS, estando todos presentes al ingreso. En el tipo 1, MODS se resolvió de forma temprana, con una mediana de tiempo de recuperación de 4 días y una mortalidad del 14%. El tipo 2 presentaba un tiempo de recuperación retardado (mediana 13 días) y una mortalidad del 35%. El tipo 3 presentaba un tiempo de recuperación prolongado (mediana 25 días) y una mortalidad asociada alta del 46%. El análisis multivariable reveló asociaciones clínicas diferentes para cada tipo de MODS, con la administración de cristaloides durante 24 horas fuertemente asociada al tipo 1 (P < 0,001); el traumatismo craneal al tipo 2 (P < 0,01); y la gravedad del shock al ingreso al tipo 3 (P < 0,01).
Conclusión
Los MODS actuales presentan al menos tres tipos distintos basados en patrones de gravedad y recuperación. La caracterización de los subtipos de MODS y su fisiopatología subyacente puede contribuir a futuras oportunidades de estratificación temprana e intervenciones dirigidas.
As trauma practice advances, postinjury multiple organ dysfunction syndrome (MODS) is changing. The aim of this study was to characterize contemporary MODS in trauma critical care. Three patterns of MODS were identified, all present on admission, with distinct clinical associations. SOFA, Sequential Organ Failure Assessment.
Present from admission with subtypes having different patterns of recovery
Aims: Lactobacilli are widely distributed in food and the environment, and some colonize the human body as commensal bacteria. The aim of this study was to determine the species of lactobacilli that ...colonize the vagina and compare them with those found in food and the environment.
Methods and Results: Thirty‐five Lactobacillus strains from women from seven countries were isolated, and sequences from 16S rRNA genes were determined and compared with existing data in GenBank. A phylogenetic tree was achieved using the Neighbour‐Joining method based on the analysis of 1465 nucleotides. The results showed that most vaginal isolates were L. crispatus, L. jensenii and L. gasseri. Some were L. vaginalis, L. fermentum, L. mucosae, L. paracasei and L. rhamnosus. Two isolates from a native American woman displayed distinct branches, indicating novel phylotypes. Few vaginal isolates matched food or environmental Lactobacillus species.
Conclusions: Most women worldwide were colonized by three common Lactobacillus species: L. crispatus, L. jensenii and L. gasseri.
Significance and Impact of Study: Knowledge of vaginal Lactobacillus species richness and distribution in women worldwide may lead to the design of better probiotic products as bacterial replacement therapy.
Recent evidence suggests that neural stem/precursor cells (NPCs) promote recovery in animal models with delayed neuronal death via a number of indirect bystander effects. A comprehensive knowledge of ...how transplanted NPCs exert their therapeutic effects is still lacking. Here, we investigated the effects of a delayed transplantation of adult syngenic NPCs—injected intravenously 72 h after transient middle cerebral artery occlusion—on neurological recovery, histopathology and gene expression. NPC-transplanted mice showed a significantly improved recovery from 18 days post-transplantation (dpt) onwards, which persisted throughout the study. A small percentage of injected NPCs accumulated in the brain, integrating mainly in the infarct boundary zone, where most of the NPCs remained undifferentiated up to 30 dpt. Histopathological analysis revealed a hitherto unreported very delayed neuroprotective effect of NPCs, becoming evident at 10 and 30 dpt. Tissue survival was associated with downregulation of markers of inflammation, glial scar formation and neuronal apoptotic death at both mRNA and protein levels. Our data highlight the relevance of very delayed degenerative processes in the stroke brain that are intimately associated with inflammatory and glial responses. These processes may efficaciously be antagonized by (stem) cell-based strategies at time-points far beyond established therapeutic windows for pharmacological neuroprotection.
ABSTRACTApart from its hematopoietic function, erythropoietin (Epo) exerts neuroprotective functions in brain hypoxia and ischemia. To examine the mechanisms mediating Epo's neuroprotective activity ...in vivo, we made use of our transgenic mouse line tg21 that constitutively expresses human Epo in brain without inducing excessive erythrocytosis. We show that human Epo is expressed in tg21 brains and that cortical and striatal neurons carry the Epo receptor. After middle cerebral artery occlusion, human Epo potently protected brains of tg21 mice against ischemic injury, both when severe (90 min) and mild (30 min) ischemia was imposed. Histochemical studies revealed that Epo induced an activation of JAK‐2, ERK‐1/‐2, and Akt pathways in the ischemic brain. This activation was associated with elevated Bcl‐XL and decreased NO synthase‐1 and ‐2 levels in neurons. Intracerebroventricular injections of selective inhibitors of ERK‐1/‐2 (PD98059) or Akt (wortmannin) pathways revealed that both ERK‐1/‐2 and Akt were required for Epo's neuroprotective function, antagonization of either pathway completely abolishing tissue protection. On the other hand, ERK‐1/‐2 and Akt blockade did not reverse the neuronal NO synthase‐1/‐2 inhibition, indicating that Epo down‐regulates these NO synthases in an ERK‐1/‐2 and Akt independent manner. On the basis of our data, the dual activation of ERK‐1/‐2 and Akt is crucial for Epo's neuroprotective activity.
ABSTRACT
Apart from its hematopoietic function, erythropoietin (Epo) exerts neuroprotective activity upon reduced oxygenation or ischemia of brain, retina, and spinal cord. To examine whether Epo has ...an impact on the retrograde degeneration of retinal ganglion cells (RGCs) following optic nerve transection in vivo, we made use of our transgenic mouse line tg21 that constitutively expresses human Epo preferentially in neuronal cells without inducing polycythemia. We show that the tg21 retina expresses human Epo and that RGCs in this mouse line carry the Epo receptor. Upon axotomy, the RGCs of Epo transgenic tg21 mice were protected against degeneration, as compared with wild‐type control animals. Western blot analysis revealed decreased phosphorylation levels of STAT‐5 and reduced expression of Bcl‐XL in RGCs of axotomized tg21 animals, suggesting that the corresponding pathways are not crucial for Epo's neuroprotective activity. Increased phosphorylation levels of ERK‐1/‐2 and Akt, as well as decreased caspase‐3 activity, however, were observed in injured tg21 retinae. Injection of selective inhibitors of ERK‐1/‐2 (PD98059) or Akt (Wortmannin) pathways into the vitreous space revealed that transgenic Epo protected the RGCs by a pathway involving ERK‐1/‐2 but not Akt. In view that axotomy‐induced degeneration of RGC occurs slowly, and considering the earlier data on the safety and efficacy of Epo in human stroke patients, we predict the clinical implementation of recombinant human Epo not only in patients with acute ischemic stroke, but also with more delayed degenerative neurological diseases.
In this study we derive and validate a composite risk index termed the Assessment of Thoracic Endografting Operative Mortality, or ATOM, risk score.
All thoracic endovascular aortic repairs (TEVAR) ...in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) between 2005 and 2012 were identified. The primary outcome was operative mortality. After evaluating the association of over 60 preoperative variables and operative mortality in univariate analysis, a multivariable model was developed. Significant risk factors were assigned points equivalent to their odds ratio rounded to the nearest whole integer in the final multivariable model.
Overall, 1,981 patients comprised the study population, including 1,486 (75.0%) in the derivation and 495 (25.0%) in the validation cohort. There were 173 (8.7%) operative mortalities. A 30-point risk score incorporating 10 risk factors was generated and found to be highly predictive of operative mortality in the derivation (odds ratio OR 1.36, p < 0.001) and validation cohorts (OR 1.24, p < 0.001). The models used to create and validate the ATOM score were robust (C indices 0.84 and 0.83, respectively). There was strong correlation between predicted mortality rates based on the derivation cohort and actual mortality rates in the validation cohort (r = 0.75, p < 0.001). Operative mortality based on low (ATOM < 5), moderate (ATOM 5 to 9), and high risk (ATOM ≥ 10) was 1.3%, 6.6%, and 24.0%, respectively (p < 0.001). Higher ATOM scores also correlated with higher complication rates and longer hospital stays.
The ATOM score is a significant predictor of operative mortality in TEVAR and can be used for preoperative risk stratification.
This study evaluated trends and outcomes of tricuspid valve surgery (TVS) in North America over the past decade.
Adults undergoing TVS between 2000 and 2010 were identified in The Society of Thoracic ...Surgeons (STS) National Database. Trends were evaluated using linear regression. Multivariable logistic regression analysis was conducted using covariates from the STS valve risk model to identify significant predictors of operative mortality.
A total of 54,375 patients underwent TVS during the study period. The majority of cases were repairs (89%; n = 48,322) and were performed concomitant with another major procedure (86%; n = 46,593). The proportion of TVS that were repairs increased from 84.6% in 2000 to 89.8% in 2010 (p = 0.01). Trend analysis revealed significant changes in patient characteristics with time, including increasing age, a higher comorbidity burden, and a higher proportion of emergency cases. Despite worsening risk factors, unadjusted operative mortality for TVS declined from 10.6% in 2000 to 8.2% in 2010 (p < 0.001), and this trend persisted after risk adjustment. In the multivariable model, concomitant procedures involving multiple valves or coronary artery bypass grafting were associated with an increased risk of mortality compared with isolated TVS, although other factors including renal failure, congestive heart failure, nonelective presentation, reoperation, and tricuspid valve replacement exerted equal or stronger effects.
During the past decade, repair rates for TVS have increased significantly. Although patients undergoing TVS have demonstrated worsening risk factors, unadjusted and adjusted operative mortalities have declined. Finally, the data suggest that tricuspid valve repair when technically feasible, together with early elective surgical intervention, should be emphasized as potential candidates for continued outcome improvement.
Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. ...They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.
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