Endogenous IgG hypogammaglobulinaemia in critically ill adults with sepsis: systematic review and meta-analysis.

PURPOSE: Plasma immunoglobulin concentrations are acutely altered in critically ill patients with sepsis. However, the association between immunoglobulin levels on the day of sepsis diagnosis and subsequent mortality is inconsistent. METHODS: Systematic review of studies that report immunoglobulin measurements and mortality among adults with sepsis managed in a critical care setting. Fixed and random effect meta-analyses were conducted using low IgG levels as primary exposure and acute mortality as the primary outcome. Both variables were used as defined in individual studies. RESULTS: The prevalence of a low immunoglobulin G (IgG) concentration on the day of sepsis diagnosis was variable [58.3% (IQR 38.4-65.5%)]. Three cut-off points (6.1, 6.5 and 8.7 g/L) were used to define the lower limit of IgG concentrations in the included studies. A subnormal IgG level on the day of sepsis diagnosis was not associated with an increased risk of death in adult patients with severe sepsis and/or septic shock by both fixed and random effect meta-analysis (OR [95% CI] 1.32 [0.93-1.87] and 1.48 [0.78-2.81], respectively). CONCLUSIONS: This systematic review identifies studies of limited quality reporting heterogeneous sepsis cohorts with varying lower limits of normal for IgG. Although our data suggest that a subnormal IgG measurement on the day of sepsis diagnosis does not identify a subgroup of patients with a higher risk of death, further studies are needed to confirm or refute this finding, and whether optimal cut-offs and time windows can be defined for IgG measurement. This would determine whether patients receiving intravenous immunoglobulin therapy for sepsis could be stratified using IgG levels.

Mechanisms of infective endocarditis: pathogen-host interaction and risk states.

Patients with infective endocarditis (IE) form a heterogeneous group, ranging from those who are successfully treated with no adverse events, to those with severe complications and a high mortality. In this Review, we highlight pathogen-host interactions and the mechanisms underlying various risk factors for patients with IE. A temporal trend in the pattern of IE has been observed in high-income countries within the past 5 decades, with patients contracting IE at an increasingly old age, and a growing incidence of health-care-associated staphylococcal IE. Consequently, prevention strategies should no longer focus on prophylaxis of streptococcal bacteraemia during dental procedures, but instead encourage a more-general approach to reduce the incidence of health-care-associated IE. Much knowledge has been gained about the mechanisms of vegetation formation, growth, and embolization on damaged or inflamed cardiac valves, and on cardiac devices. Improved understanding of these mechanisms will help to combat the increasing problem of antimicrobial resistance. Two mechanisms of IE should increasingly be the focus of future research: the role of immunosenescence in elderly patients with IE, particularly after transcatheter aortic valve implantation, and the mechanisms that trigger septic shock, a condition that leads to a substantial increase in the risk of death in patients with IE.

Evidence-based Management of Cardiogenic Shock After Acute Myocardial Infarction.

Guidelines for evidence-based management of patients with cardiogenic shock after acute myocardial infarction focuses on early revascularisation of the occluded coronary artery as well as on support of cardiac failure and improvement of impaired organ perfusion. Also of great importance is effective treatment of shock complications, especially acute respiratory failure and other forms of multiple organ dysfunction syndrome (MODS). Cardiovascular therapy has to be accompanied by best general intensive care of these critically ill patients with high mortality. Most lives can be saved by early revascularisation, and this class I recommendation has a high level of evidence. So far, most of the other guideline recommendations are of low evidence level, in most cases based on expert opinions. Recently, the Intra-aortic Balloon Pump in Cardiogenic Shock II (IABP SHOCK II) trial with 600 patients has shown that adjunctive IABP therapy - for long a class I recommendation - does not reduce 30-day and six-month motality.

Intra-aortic balloon counterpulsation in the treatment of infarction-related cardiogenic shock--review of the current evidence.

The European ST-elevated myocardial infarction (STEMI) guideline suggested the intra-aortic balloon pump (IABP) with a recommendation level I and a level of evidence C as an effective measure in combination with balloon angioplasty in patients with cardiogenic shock (CS), stent implantation, and inotropic and vasopressor support. Similarly, upon mechanical complication due to myocardial infarction (MI), the guideline suggests that in patients with a ventricular septal defect or in most patients with acute mitral regurgitation, preoperative IABP implantation is indicated for circulatory support. The American College of Cardiology/American Heart Association STEMI guideline recommends the use of the IABP with a recommendation level I and a level of evidence B if CS does not respond rapidly to pharmacological treatment. The guideline notes that the IABP is a stabilizing measure for angiography and early revascularization. Even in MI complications, the use of preoperative IABP is recommended before surgery. Within this overview, we summarize the current evidence on IABP use in patients with CS complicated by MI. From our Cochrane data analysis, we conclude that in CS due to acute MI (AMI) treated with adjuvant systemic fibrinolysis, the IABP should be implanted. In patients with CS following AMI, treated with primary percutaneous coronary intervention (PCI), the IABP can be implanted, although data are not distinctive (i.e., indicating positive and negative effects). In the future, randomized controlled trials are needed to determine the use of IABP in CS patients treated with PCI. When patients with CS are transferred to a PCI center with or without thrombolysis, patients should receive mechanical support with an IABP. To treat mechanical MI complications-in particular ventricular septal defect-patients should be treated with an IABP to stabilize their hemodynamic situation prior to cardiac surgery. Similar recommendations are given in the German Austrian guidelines on treatment of infarction-related CS patients (http://www.awmf.org/leitlinien/detail/ll/019-013.html).

Interleukin-6, -7, -8 and -10 predict outcome in acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: The IABP-SHOCK-trial was a morbidity-based randomized controlled trial in patients with infarction-related cardiogenic shock (CS), which used the change of the quantified degree of multiorgan failure as determined by APACHE II score over a 4-day period as primary outcome measure. The prospective hypothesis was that adding IABP therapy to "standard care" would improve CS-triggered multi organ dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with IABP support. In an inflammatory marker substudy, we analysed the prognostic value of interleukin (IL)-1ß, -6, -7, -8, and -10 in patients with acute myocardial infarction complicated by cardiogenic shock. DESIGN: Inflammatory marker substudy of the prospective, randomized, controlled, open label IABP-SHOCK-trial (ClinicalTrials.gov ID-NCT00469248). SETTING AND METHODS: A single-center study was performed in a 12-bed Intensive-Care-Unit in an university hospital in which 40 consecutive patients were enrolled with an observational period of 96 h. RESULTS: The pro- and anti-inflammatory markers IL-6, -7, -8 and -10 showed a predictive power for mortality of infarct-related CS patients, while IL-1ß did not discriminate. The maximal values during the observational period, in case of IL-7 the minimal value, showed the best power to predict mortality. Both, ROC and multivariate analyses confirmed these suggestions (area under the curve: IL-8, 0.80 ± 0.08; IL-6, 0.79 ± 0.08; IL-10, 0.76 ± 0.08; IL-7, 0.69 ± 0.08). Inflammatory markers were not affected by the presence of IABP support. CONCLUSION: The inflammatory response in patients with myocardial infarction complicated by cardiogenic shock, as reflected by the inflammatory markers IL-6, IL-7, IL-8 and IL-10, demonstrates a clinically relevant prognostic contribution to clinical outcome.

Differential regulation of transcription and induction of programmed cell death by human p53-family members p63 and p73.

The p53 tumor suppressor acts as a transcription factor and has a central function in controlling apoptosis. With p63 and p73 two genes coding for proteins homologous to p53 have been identified. We describe the properties of seven human p63 and p73 proteins as transcriptional activators of p21WAF1/CIP1 expression and apoptotic inducers in direct comparison to p53 in the same assay systems employing DLD-1-tet-off colon cells. Programmed cell death is detected in cells expressing high levels of p53 and p73alpha. Cells overexpressing TAp63alpha, TAp63gamma, TA*p63alpha, TA*p63gamma, DeltaNp63alpha, and DeltaNp63gamma display low or no detectable apoptosis.