Dataset Information

Complement depletion deteriorates clinical outcomes of severe abdominal sepsis: a conspirator of infection and coagulopathy in crime?

ABSTRACT: The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction.This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored.Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups.Within the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845-0.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications.Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care.ClinicalTrials.gov NCT01568853.

SUBMITTER: Ren J

PROVIDER: S-EPMC3473032 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Complement depletion deteriorates clinical outcomes of severe abdominal sepsis: a conspirator of infection and coagulopathy in crime?

Ren Jianan J Zhao Yunzhao Y Yuan Yujie Y Han Gang G Li Weiqin W Huang Qian Q Tong Zhihui Z Li Jieshou J

PloS one 20121016 10

<h4>Background</h4>The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction.<h4>Objective</h4>This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored.<h4>Methods</h4>Forty-five p ...[more]

PMID: 23091606

Similar Datasets

Project description:Background:Severe complicated intra-abdominal sepsis (SCIAS) has high mortality, thought due in part to progressive bio-mediator generation, systemic inflammation, and multiple organ failure. Treatment includes early antibiotics and operative source control. At surgery, open abdomen management with negative-peritoneal-pressure therapy (NPPT) has been hypothesized to mitigate MOF and death, although clinical equipoise for this operative approach exists. The Closed or Open after Laparotomy (COOL) study (https://clinicaltrials.gov/ct2/show/NCT03163095) will prospectively randomize eligible patients intra-operatively to formal abdominal closure or OA with NPTT. We review the ethical basis for conducting research in SCIAS. Main body:Research in critically ill incapacitated patients is important to advance care. Conducting research among SCIAS is complicated due to the severity of illness including delirium, need for emergent interventions, diagnostic criteria confirmed only at laparotomy, and obtundation from anaesthesia. In other circumstances involving critically ill patients, clinical experts have worked closely with ethicists to apply principles that balance the rights of patients whilst simultaneously permitting inclusion in research. In Canada, the Tri-Council Policy Statement-2 (TCPS-2) describes six criteria that permit study enrollment and randomization in such situations: (a) serious threat to the prospective participant requires immediate intervention; (b) either no standard efficacious care exists or the research offers realistic possibility of direct benefit; (c) risks are not greater than that involved in standard care or are clearly justified by prospect for direct benefits; (d) prospective participant is unconscious or lacks capacity to understand the complexities of the research; (e) third-party authorization cannot be secured in sufficient time; and (f) no relevant prior directives are known to exist that preclude participation. TCPS-2 criteria are in principle not dissimilar to other (inter)national criteria. The COOL study will use waiver of consent to initiate enrollment and randomization, followed by surrogate or proxy consent, and finally delayed informed consent in subjects that survive and regain capacity. Conclusions:A delayed consent mechanism is a practical and ethical solution to challenges in research in SCIAS. The ultimate goal of consent is to balance respect for patient participants and to permit participation in new trials with a reasonable opportunity for improved outcome and minimal risk of harm.

Project description:BACKGROUNDAbdominal aortic aneurysms (AAAs) are a deadly pathology with strong sexual dimorphism. Similar to humans, female mice exhibit far lower incidences of angiotensin II-induced AAAs than males. In addition to sex hormones, the X and Y sex chromosomes, and their unique complements of genes, may contribute to sexually dimorphic AAA pathology. Here, we defined the effect of female (XX) versus male (XY) sex chromosome complement on angiotensin II-induced AAA formation and rupture in phenotypically female mice.METHODSFemale low-density lipoprotein receptor (Ldlr) deficient mice with an XX or XY sex chromosome complement were infused with angiotensin II for 28 days to induce AAAs. Abdominal aortic lumen diameters were quantified by ultrasound, whereas AAA diameters were quantified at study end point. DNA microarrays were performed on abdominal aortas. To mimic males, female mice were administered a single dose of testosterone as neonates or as adults before angiotensin II infusions.RESULTSFemale Ldlr-/- deficient mice with an XX and XY sex chromosome complement had similar sex organ weights and low serum testosterone concentrations. Abdominal aortas from female XY mice selectively expressed Y chromosome genes, whereas genes known to escape X inactivation were higher in XX females. The majority of aortic gene differences in XY versus XX females fell within inflammatory pathways. AAA incidences doubled and aneurysms ruptured in XY females. AAAs from XY females exhibited inflammation, and plasma interleukin-1? concentrations were increased in XY females. Moreover, aortas from XY females had augmented matrix metalloproteinase activity and increased oxidative stress. Last, testosterone exposure applied chronically, or as a single bolus at postnatal day 1, markedly worsened AAA outcomes in XY in comparison with XX adult females.CONCLUSIONSAn XY sex chromosome complement in phenotypic females profoundly influenced aortic gene expression profiles and promoted AAA severity. When XY females were exposed to testosterone, aneurysm rupture rates were striking. Mechanisms for augmented AAA severity in XY females include increased inflammation, augmented matrix metalloproteineases, and oxidative stress. Our results demonstrate that genes on the sex chromosomes regulate aortic vascular biology and contribute to sexual dimorphism of AAAs. Sex chromosome genes may serve as novel targets for sex-specific AAA therapeutics.

Project description:Although critical care physicians view obesity as an independent poor prognostic marker, growing evidence suggests that obesity is, instead, associated with improved mortality following ICU admission. However, this prior empirical work may be biased by preferential admission of obese patients to ICUs, and little is known about other patient-centered outcomes following critical illness. We sought to determine whether 1-year mortality, healthcare utilization, and functional outcomes following a severe sepsis hospitalization differ by body mass index.Observational cohort study.U.S. hospitals.We analyzed 1,404 severe sepsis hospitalizations (1999-2005) among Medicare beneficiaries enrolled in the nationally representative Health and Retirement Study, of which 597 (42.5%) were normal weight, 473 (33.7%) were overweight, and 334 (23.8%) were obese or severely obese, as assessed at their survey prior to acute illness. Underweight patients were excluded a priori.None.Using Medicare claims, we identified severe sepsis hospitalizations and measured inpatient healthcare facility use and calculated total and itemized Medicare spending in the year following hospital discharge. Using the National Death Index, we determined mortality. We ascertained pre- and postmorbid functional status from survey data. Patients with greater body mass indexes experienced lower 1-year mortality compared with nonobese patients, and there was a dose-response relationship such that obese (odds ratio = 0.59; 95% CI, 0.39-0.88) and severely obese patients (odds ratio = 0.46; 95% CI, 0.26-0.80) had the lowest mortality. Total days in a healthcare facility and Medicare expenditures were greater for obese patients (p < 0.01 for both comparisons), but average daily utilization (p = 0.44) and Medicare spending were similar (p = 0.65) among normal, overweight, and obese survivors. Total function limitations following severe sepsis did not differ by body mass index category (p = 0.64).Obesity is associated with improved mortality among severe sepsis patients. Due to longer survival, obese sepsis survivors use more healthcare and result in higher Medicare spending in the year following hospitalization. Median daily healthcare utilization was similar across body mass index categories.

Dataset Information

Complement depletion deteriorates clinical outcomes of severe abdominal sepsis: a conspirator of infection and coagulopathy in crime?

Publications

Complement depletion deteriorates clinical outcomes of severe abdominal sepsis: a conspirator of infection and coagulopathy in crime?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure