Markers Of Organ Dysfunction Research Articles

Decreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis

PurposeWe sought to determine whether an early high-density lipoprotein cholesterol (HDL-C) measurement at emergency department (ED) admission is prognostic of multiorgan dysfunction syndrome (MODS) and death in a suspected sepsis cohort. Materials and MethodsTwo hundred patients with clinically suspected sepsis were recruited at admission to our tertiary care hospital's ED. Lipids were measured at the time of first ED blood draw. Clinical data were collected via chart review. Primary outcomes of interest were development of MODS and 28-day mortality. Secondary outcomes included need for critical care, single-organ failures, days alive and free of vasopressor and ventilator support, and 90-day mortality. ResultsHigh-density lipoprotein cholesterol was greatly decreased in patients who developed MODS and/or died and remained stable over the first week of admission. Receiver operator characteristic analysis demonstrated that HDL-C had superior predictive ability compared with all routine clinical markers for both development of MODS and 28-day mortality, and identified an HDL-C cutoff of 25.1 mg/dL below which patients were at significantly greater risk for development of all adverse outcomes. ConclusionsPlasma HDL-C level was characterized by early decrease and high stability, and was the best prognostic marker for adverse outcomes in a suspected sepsis cohort.

Prognosis and Biomarkers in Acute-on-Chronic Liver Failure.

As formal definitions of acute-on-chronic liver failure (ACLF) have now been established, and given an increased recognition of the dynamic nature of this condition, there is a growing clinical need to assess prognosis and response to interventions. Conventional scoring systems such as Model for End-Stage Liver Disease (MELD) fail to capture the two key prognostic elements in ACLF-namely, extrahepatic organ failure and measures of systemic inflammation-and as such are limited in their prognostic accuracy. Even the best available scoring systems such as the recently described CLIF (Chronic Liver Failure) Consortium ACLF (CLIF-C ACLF) score, are at best 75% accurate and need to be applicable to all etiologies of liver disease. Thus, in the absence of "gold standard" markers of prognosis that render one scoring system superior to another, there is a need to explore other markers of pathophysiology that may better define outcome. This review addresses the evidence for markers of oxidative stress, including those reflecting the inflammasome; elements of cell death such as cytokeratins M30 and M65; and indicators of immune dysfunction, innate immune failure and gut dysbiosis. Finally, evidence for relevance of markers of organ dysfunction, including hemodynamic response, are explored along with associated mediators such as copeptin, dimethylarginines, and renin. It is anticipated that further critique and validation of emerging and relevant biomarkers will facilitate a composite score which, either alone or in combination with existing scoring systems such as CLIF-C, will enable improved prognostication and targeting of therapy in ACLF.

Validation of test performance and clinical time zero for an electronic health record embedded severe sepsis alert

Increasing use of EHRs has generated interest in the potential of computerized clinical decision support to improve treatment of sepsis. Electronic sepsis alerts have had mixed results due to poor test characteristics, the inability to detect sepsis in a timely fashion and the use of outside software limiting widespread adoption. We describe the development, evaluation and validation of an accurate and timely severe sepsis alert with the potential to impact sepsis management. To develop, evaluate, and validate an accurate and timely severe sepsis alert embedded in a commercial EHR. The sepsis alert was developed by identifying the most common severe sepsis criteria among a cohort of patients with ICD 9 codes indicating a diagnosis of sepsis. This alert requires criteria in three categories: indicators of a systemic inflammatory response, evidence of suspected infection from physician orders, and markers of organ dysfunction. Chart review was used to evaluate test performance and the ability to detect clinical time zero, the point in time when a patient develops severe sepsis. Two physicians reviewed 100 positive cases and 75 negative cases. Based on this review, sensitivity was 74.5%, specificity was 86.0%, the positive predictive value was 50.3%, and the negative predictive value was 94.7%. The most common source of end-organ dysfunction was MAP less than 70 mm/Hg (59%). The alert was triggered at clinical time zero in 41% of cases and within three hours in 53.6% of cases. 96% of alerts triggered before a manual nurse screen. We are the first to report the time between a sepsis alert and physician chart-review clinical time zero. Incorporating physician orders in the alert criteria improves specificity while maintaining sensitivity, which is important to reduce alert fatigue. By leveraging standard EHR functionality, this alert could be implemented by other healthcare systems.

Characteristics of neonatal near miss in hospitals in Benin, Burkina Faso and Morocco in 2012-2013.

The objective of this study is to explore the usefulness of neonatal near miss in low- and middle-income countries by examining the incidence of neonatal near miss and pre-discharge neonatal deaths across various obstetric risk categories in 17 hospitals in Benin, Burkina Faso and Morocco. Data were collected on all maternal deaths, maternal near miss, neonatal near miss (based on organ-dysfunction markers), Caesarean sections, stillbirths, neonatal deaths before discharge and non-cephalic presentations, and on a sample of births not falling in any of the above categories. The burden of stillbirth, pre-discharge neonatal death or neonatal near miss ranged from 23 to 129 per 1000 births in Moroccan and Beninese hospitals, respectively. Perinatal deaths (range 17-89 per 1000 births) were more common than neonatal near miss (range 6-43 per 1000 live births), and between a fifth and a third of women who had suffered a maternal near miss lost their baby. Pre-discharge neonatal deaths and neonatal near miss had a similar distribution of markers of organ dysfunction, but unlike pre-discharge neonatal deaths most neonatal near miss (63%, 81% and 71% in Benin, Burkina Faso and Morocco, respectively) occurred among babies who were not considered premature, low birthweight or with a low 5-min Apgar score as defined by WHO's pragmatic markers of severe neonatal morbidity. Whether the measurement of neonatal near miss adds useful insights into the quality of perinatal or newborn care in settings where facility-based intrapartum and early newborn mortality is very high is uncertain. Perhaps the greatest advantage of adding near miss is the shift in focus from failure to success so that lessons can be learned on how to save lives even when clinical conditions are life-threatening.

Circulating levels of plasma lipids and cardiovascular risk in Nigerian women with severe preeclampsia

Background and Objectives: Preeclampsia has been associated with disorders of lipid metabolism. In the general population, dyslipidemia has been identified as a cause of endothelial damage and cardiovascular disease. Few studies have evaluated these relationships in Nigerian women with preeclampsia. This study aims to determine the level of plasma lipids in severe preeclampsia and assess the relationship between dyslipidemia, organ damage, and C-reactive protein (CRP) in Nigerian women with severe preeclampsia. Materials and Methods: This was a case-control study conducted on 50 women with severe preeclampsia and 50 with normal pregnancy matched for gestational age. The women were included from the antenatal clinic of the Lagos University Teaching Hospital, Lagos, Lagos State, Nigeria. Informed consent was obtained and sociodemographic and clinical data were obtained using a questionnaire. Blood was collected from the women after an overnight (10-12 h) fast for biochemical analysis. Employing the IBM SPSS statistical software, comparisons of the continuous variables and categorical variables were done using the Student's t-test and Chi-square test, respectively. Correlation analysis was used to determine the associations between the variables. Statistical significance was set at P < 0.05. Results: The levels of high-density lipoprotein (HDL) cholesterol were significantly lower (P < 0.0003) and the levels of triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and total cholesterol (TC) were significantly higher in women with severe preeclampsia compared to the controls (P < 0.0005, P < 0.007, P < 0.009, respectively). The HDL/LDL ratio was significantly lower and CRP was significantly higher in severe preeclampsia (P < 0.0001 and P ˂ 0.0002, respectively). The lipid profile parameters showed a significant association with the markers of organ dysfunction. TG showed a statistically significant correlation with uric acid, creatinine, alkaline phosphatase (ALP), systolic blood pressure (SBP), and diastolic blood pressure (DBP). HDL showed a statistically significant correlation with uric acid, ALP, aspartate aminotransferase (AST), SBP, and DBP. While TC showed a statistically significant correlation with SBP and DBP, TG, in addition, had a statistically significant correlation with CRP in women with severe preeclampsia. Conclusion: Severe preeclampsia is associated with dyslipidemia, which has been linked to organ damage and an increased cardiovascular risk in Nigerian women. Although dyslipidemia resolves with each pregnancy, risk of cardiovascular disease in the future remains. Thus, continuous monitoring of Nigerian women with a history of severe preeclampsia is suggested.

The potential utility of urinary biomarkers for risk prediction in combat casualties: a prospective observational cohort study.

IntroductionTraditional risk scoring prediction models for trauma use either anatomically based estimations of injury or presenting vital signs. Markers of organ dysfunction may provide additional prognostic capability to these models. The objective of this study was to evaluate if urinary biomarkers are associated with poor outcomes, including death and the need for renal replacement therapy.MethodsWe conducted a prospective, observational study in United States Military personnel with traumatic injury admitted to the intensive care unit at a combat support hospital in Afghanistan.ResultsEighty nine patients with urine samples drawn at admission to the intensive care unit were studied. Twelve patients subsequently died or needed renal replacement therapy. Median admission levels of urinary cystatin C (CyC), interleukin 18 (IL-18), L-type fatty acid binding protein (LFABP) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly higher in patients that developed the combined outcome of death or need for renal replacement therapy. Median admission levels of kidney injury molecule-1 were not associated with the combined outcome. The area under the receiver operating characteristic curves for the combined outcome were 0.815, 0.682, 0.842 and 0.820 for CyC, IL-18, LFABP and NGAL, respectively. Multivariable regression adjusted for injury severity score, revealed CyC (OR 1.97, 95 % confidence interval 1.26-3.10, p = 0.003), LFABP (OR 1.92, 95 % confidence interval 1.24-2.99, p = 0.004) and NGAL (OR 1.80, 95 % confidence interval 1.21-2.66, p = 0.004) to be significantly associated with the composite outcome.ConclusionsUrinary biomarker levels at the time of admission are associated with death or need for renal replacement therapy. Larger multicenter studies will be required to determine how urinary biomarkers can best be used in future prediction models.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0965-y) contains supplementary material, which is available to authorized users.

Mesenteric near-infrared spectroscopy and risk of gastrointestinal complications in infants undergoing surgery for congenital heart disease.

We hypothesised that lower mesenteric near-infrared spectroscopy values would be associated with a greater incidence of gastrointestinal complications in children weighing <10 kg who were recovering from cardiac surgery. We evaluated mesenteric near-infrared spectroscopy, central venous oxygen saturation, and arterial blood gases for 48 hours post-operatively. Enteral feeding intake, gastrointestinal complications, and markers of organ dysfunction were monitored for 7 days. A total of 50 children, with median age of 16.7 (3.2-31.6) weeks, were studied. On admission, the average mesenteric near-infrared spectroscopy value was 71±18%, and the systemic oxygen saturation was 93±7.5%. Lower admission mesenteric near-infrared spectroscopy correlated with longer time to establish enteral feeds (r=-0.58, p<0.01) and shorter duration of feeds at 7 days (r=0.48, p<0.01). Children with gastrointestinal complications had significantly lower admission mesenteric near-infrared spectroscopy (58±18% versus 73±17%, p=0.01) and higher mesenteric arteriovenous difference of oxygen at admission [39 (23-47) % versus 19 (4-27) %, p=0.02]. Based on multiple logistic regression, admission mesenteric near-infrared spectroscopy was independently associated with gastrointestinal complications (Odds ratio, 0.95; 95% confidence interval, 0.93-0.97; p=0.03). Admission mesenteric near-infrared spectroscopy showed an area under the receiver operating characteristic curve of 0.76 to identify children who developed gastrointestinal complications, with a suggested cut-off value of 72% (78% sensitivity, 68% specificity). In this pilot study, we conclude that admission mesenteric near-infrared spectroscopy is associated with gastrointestinal complications and enteral feeding tolerance in children after cardiac surgery.

Inhibition of glycogen synthase kinase-3β attenuates organ injury and dysfunction associated with liver ischemia-reperfusion and thermal injury in the rat.

Glycogen synthase kinase 3 (GSK-3) is a serine-threonine kinase discovered decades ago to have an important role in glycogen metabolism. Today, we know that this kinase is involved in the regulation of many cell functions, including insulin signaling, specification of cell fate during embryonic development, and the control of cell division and apoptosis. Insulin and TDZD-8 (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione) are inhibitors of GSK-3β that have been shown to possess organ-protective effects in inflammatory-mediated organ injury models. We aimed to evaluate the cytoprotective effect of GSK-3β inhibition on rat models of liver ischemia-reperfusion and thermal injury. In the liver ischemia-reperfusion model, TDZD-8 and insulin were administered at 5 mg/kg (i.v.) and 1.4 IU/kg (i.v.), respectively, 30 min before induction of ischemia and led to the significant reduction of the serum concentration of aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, and lactate dehydrogenase. Beneficial effects were found to be independent from blood glucose levels. In the thermal injury model, TDZD-8 was administered at 5 mg/kg (i.v.) 5 min before induction of injury and significantly reduced multiple organ dysfunction markers (liver, neuromuscular, and lung). In the lung, TDZD-8 reduced the histological signs of tissue injury, inflammatory markers (cytokines), and neutrophil chemotaxis/infiltration; reduced GSK-3β, nuclear factor-κB, and Akt activation; reduced caspase-3 and metalloproteinase-9 activation. Our study provides a new insight on the beneficial effects of GSK-3β inhibition on systemic inflammation and further elucidates the mechanism and pathway crosstalks by which TDZD-8 reduces the multiple organ injury elicited by thermal injury.

Neutrophil to Lymphocyte Ratio in Sickle Cell Anaemia Patients with Nephropathy

Background: Sickle cell anaemia (SCA) is associated with a chronic inflammatory component; blood neutrophil to lymphocyte ratio (NLR) has been described as a marker of organ dysfunction and clinical outcome in diseases associated with systemic inflammation. Objective: To evaluate NLR in Nigerian SCA patients with nephropathy. Methods: Seventy-nine (79) SCA patients in steady state and 50 aged-matched controls were prospectively enrolled for this study. Full blood count and dip-stick macro-albuminuria were done for each participant and data was analyzed using descriptive and inferential statistics. The level of statistical significance was defined as p ≤ 0.05. Original Research Article John et al.; BJMMR, 10(11): 1-6, 2015; Article no.BJMMR.20404 2 Results: The NLR was significantly higher in cases compared with controls (1.49±0.76 vs. 1.20±0.34, P=0.01) and the ANC was significantly higher in those with NLR ≥ 3.0 compared with those with NLR <3.0 (12.22±5.26x10/L vs. 6.10±2.96x10/L, respectively, P<0.001). Between cases with and without macro-albuminuria and controls, the means of NLR was significantly different (P=0.024). Macro-albuminuria was present in 16 (21.9%) of cases (all of which had NLR <3.0), this was not significantly correlated with NLR (r=-0.99, P=0.71). Conclusion: No significant relationship was observed between NLR and SCA nephropathy.

Moving Beyond Essential Interventions for Reduction of Maternal Mortality (the WHO Multicountry Survey on Maternal and Newborn Health)

Summary Background We report the main findings of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS), which aimed to assess the burden of complications related to pregnancy, the coverage of key maternal health interventions, and use of the maternal severity index (MSI) in a global network of health facilities. Methods In our cross-sectional study, we included women attending health facilities in Africa, Asia, Latin America, and the Middle East that dealt with at least 1000 childbirths per year and had the capacity to provide caesarean section. We obtained data from analysis of hospital records for all women giving birth and all women who had a severe maternal outcome (SMO; ie, maternal death or maternal near miss). We regarded coverage of key maternal health interventions as the proportion of the target population who received an indicated intervention (eg, the proportion of women with eclampsia who received magnesium sulphate). We used areas under the receiver operator characteristic curves (AUROC) with 95% CI to externally validate a previously reported MSI as an indicator of severity. We assessed the overall performance of care (ie, the ability to produce a positive effect on health outcomes) through standardised mortality ratios. Results From May 1, 2010, to Dec 31, 2011, we included 314 623 women attending 357 health facilities in 29 countries (2538 had a maternal near miss and 486 maternal deaths occurred). The mean period of data collection in each health facility was 89 days (SD 21). 23 015 (7·3%) women had potentially life-threatening disorders and 3024 (1·0%) developed an SMO. 808 (26·7%) women with an SMO had post-partum haemorrhage and 784 (25·9%) had pre-eclampsia or eclampsia. Cardiovascular, respiratory, and coagulation dysfunctions were the most frequent organ dysfunctions in women who had an SMO. Reported mortality in countries with a high or very high maternal mortality ratio was two-to-three-times higher than that expected for the assessed severity despite a high coverage of essential interventions. The MSI had good accuracy for maternal death prediction in women with markers of organ dysfunction (AUROC 0·826 [95% CI 0·802–0·851]). Interpretation High coverage of essential interventions did not imply reduced maternal mortality in the health-care facilities we studied. If substantial reductions in maternal mortality are to be achieved, universal coverage of life-saving interventions need to be matched with comprehensive emergency care and overall improvements in the quality of maternal health care. The MSI could be used to assess the performance of health facilities providing care to women with complications related to pregnancy. Funding UNDP–UNFPA–UNICEF–WHO–World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects.

Maternal near-miss audits to improve quality of care.

Department of SocialMedicine, Ribeir~ao Preto Medical School, University of S ~ao Paulo, Ribeir ~ao Preto, SP, BrazilCorrespondence: O Tunc€ alp, HRP—UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and ResearchTraining in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, 20 Avenue Appia, Geneva,Switzerland. Email tuncalpo@who.intAccepted 11 March 2014.

Anti-RAGE antibody ameliorates severe thermal injury in rats through regulating cellular immune function.

The receptor of advanced glycation end products (RAGE) participates in a variety of pathophysiological processes and inflammatory responses. The aim of this study was to investigate the therapeutic potential of an anti-RAGE neutralizing antibody for severe thermal injury in rats, and to determine whether the treatment worked via modulating cellular immune function. Full-thickness scald injury was induced in Wistar rats, which were treated with the anti-RAGE antibody (1 mg/kg, iv) at 6 h and 24 h after the injury. The rats were sacrificed on d 1, 3, 5, and 7. Blood and spleen samples were harvested to monitor organ function and to analyze dendritic cell (DC) and T cell cytokine profiles. The survival rate was analyzed up to d 7 after the injury. Administration of the antibody significantly increased the 7 d survival rate in thermally injured rats (6.67% in the model group; 33.33% in anti-RAGE group). Treatment with the antibody also attenuated the multiple organ dysfunction syndrome (MODS) following the thermal injury, as shown by significant decreases in the organ dysfunction markers, including serum ALT, AST, blood urea nitrogen, creatinine and CK-MB. Moreover, treatment with the antibody significantly promoted DC maturation and T cell activation in the spleens of thermally injured rats. Blockade of the RAGE axis by the antibody effectively ameliorated MODS and improved the survival rate in thermally injured rats, which may be due to modulation of cellular immune function.

Evaluation of severe maternal outcomes to assess quality of maternal health care at a tertiary center.

Maternal mortality and near-miss index reflect the quality of care provided by a health facility. The World Health Organization recently published near-miss approach where strict near- miss criteria based on markers of organ dysfunction are defined. The aim of the study was to determine the frequency of severe maternal complications, maternal near-miss cases and maternal deaths, to analyze causes of near-miss and maternal mortality and to determine the values of maternal near-miss indicators. This was a prospective observational study conducted at a tertiary care centre in North India from January 2012 - March 2013. WHO's near-miss approach was implemented for evaluation of severe maternal outcomes and to assess the quality of maternal health care. The number of women attending our facility with severe maternal complications was low (205 in 6,767 live births); as a result maternal near-miss ratio (MNMR) was low; 3.98/1,000 live births; Overall Maternal near-miss mortality ratio (MNM:1MD) was also low, 3.37:1, because of strict criterion of labeling near-miss and delay in referral to the hospital. Hypertensive disorder (37.5%) was the commonest underlying cause for maternal mortality. Basic implementation of WHO near-miss approach helped in the systematic identification and evidence-based management of severe maternal complications thereby improving the quality of maternal health in a developing country.

Pentraxin 3 as a Prognostic Biomarker in Patients with Systemic Inflammation or Infection

Purpose. The long pentraxin 3 (PTX3) is a key component of the humoral arm of the innate immune system. PTX3 is produced locally in response to proinflammatory stimuli. We reviewed the usefulness of systemic levels of PTX3 in critically ill patients with systemic inflammatory response syndrome (SIRS), sepsis, and bacteremia, focusing on its diagnostic and prognostic value. Methods. A PubMed search on PTX3 was conducted. The list of papers was narrowed to original studies of critically ill patients. Eleven papers on original studies of critically ill patients that report on PTX3 in SIRS, sepsis, or bacteremia were identified. Results. Systematic levels of PTX3 have little diagnostic value in critically ill patients with SIRS, sepsis, or bacteremia. Systemic levels of PTX3, however, have superior prognostic power over other commonly used biological markers in these patients. Systemic levels of PTX3 correlate positively with markers of organ dysfunction and severity-of-disease classification system scores. Finally, systemic levels of PTX3 remain elevated in the acute phase and decreased on recovery. Notably, the age of the patients and underlying disease affect systemic levels of PTX3. Conclusions. The diagnostic value of PTX3 is low in patients with sepsis. Systemic levels of PTX3 have prognostic value and may add to prognostication of patients with SIRS or sepsis, complementing severity-of-disease classification systems and other biological markers.

Pyruvate Ringer's Solution Corrects Lactic Acidosis and Prolongs Survival during Hemorrhagic Shock in Rats

BackgroundLactic acidosis is a life-threatening complication of hemorrhagic shock. There is no ideal therapy for it in the clinical setting. ObjectiveThis study was designed to investigate whether pyruvate Ringer's solution could treat hypoxic lactic acidosis associated with lethal hemorrhagic shock in rats. MethodsA total of 54 rats were subjected to hemorrhagic shock with mean arterial pressure (MAP) of 40 mm Hg for 1 h. They were then randomly divided into three groups (n = 18 each): Group N had no fluid resuscitation; Group L received lactated Ringer's solution infusion; and Group P received pyruvate Ringer's solution infusion. The survival rate was investigated after 24 h. In addition, a second set of 54 rats was selected for blood sampling, with identical methods for shock and resuscitation being followed, to determine arterial pH, blood gas analysis, lactate, pyruvate, and organs' enzyme activities at various time points. The MAP was monitored for 6 h in both populations. ResultsPyruvate Ringer's solution significantly increased the survival rate of rats subjected to fatal shock and receiving pyruvate Ringer's solution (Group P) by 1.5 times the survival rate in Group L at 24 h after fluid resuscitation (55.6% vs. 22.2%, respectively; p < 0.05). Pyruvate infusion maintained a higher MAP and fully corrected severe acidosis 1 h after resuscitation in comparison to the lactated infusion, and markedly decreased blood lactate levels and the lactate-to-pyruvate ratio 4 h after resuscitation. It also significantly improved serum markers of organ dysfunction. ConclusionPyruvate Ringer's solution efficiently treated hypoxic lactic acidosis and significantly increased the survival rate in rats with lethal hemorrhagic shock. Pyruvate Ringer's solution is potentially applicable to clinical resuscitation in humans.

Marker der Immunantwort bei Organtransplantation

The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation.

Moving beyond essential interventions for reduction of maternal mortality (the WHO Multicountry Survey on Maternal and Newborn Health): a cross-sectional study

We report the main findings of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS), which aimed to assess the burden of complications related to pregnancy, the coverage of key maternal health interventions, and use of the maternal severity index (MSI) in a global network of health facilities. In our cross-sectional study, we included women attending health facilities in Africa, Asia, Latin America, and the Middle East that dealt with at least 1000 childbirths per year and had the capacity to provide caesarean section. We obtained data from analysis of hospital records for all women giving birth and all women who had a severe maternal outcome (SMO; ie, maternal death or maternal near miss). We regarded coverage of key maternal health interventions as the proportion of the target population who received an indicated intervention (eg, the proportion of women with eclampsia who received magnesium sulphate). We used areas under the receiver operator characteristic curves (AUROC) with 95% CI to externally validate a previously reported MSI as an indicator of severity. We assessed the overall performance of care (ie, the ability to produce a positive effect on health outcomes) through standardised mortality ratios. From May 1, 2010, to Dec 31, 2011, we included 314,623 women attending 357 health facilities in 29 countries (2538 had a maternal near miss and 486 maternal deaths occurred). The mean period of data collection in each health facility was 89 days (SD 21). 23,015 (7.3%) women had potentially life-threatening disorders and 3024 (1.0%) developed an SMO. 808 (26.7%) women with an SMO had post-partum haemorrhage and 784 (25.9%) had pre-eclampsia or eclampsia. Cardiovascular, respiratory, and coagulation dysfunctions were the most frequent organ dysfunctions in women who had an SMO. Reported mortality in countries with a high or very high maternal mortality ratio was two-to-three-times higher than that expected for the assessed severity despite a high coverage of essential interventions. The MSI had good accuracy for maternal death prediction in women with markers of organ dysfunction (AUROC 0.826 [95% CI 0.802-0.851]). High coverage of essential interventions did not imply reduced maternal mortality in the health-care facilities we studied. If substantial reductions in maternal mortality are to be achieved, universal coverage of life-saving interventions need to be matched with comprehensive emergency care and overall improvements in the quality of maternal health care. The MSI could be used to assess the performance of health facilities providing care to women with complications related to pregnancy. UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects.

Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

BackgroundSepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage.MethodsAnaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines.ResultsMitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001).ConclusionsAntioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.

Hyperlactatemia Affects the Association of Hyperglycemia with Mortality in Nondiabetic Adults With Sepsis

Admission hyperglycemia has been reported as a mortality risk factor for septic nondiabetic patients; however, hyperglycemia's known association with hyperlactatemia was not addressed in these analyses. The objective was to determine whether the association of hyperglycemia with mortality remains significant when adjusted for concurrent hyperlactatemia. This was a post hoc, nested analysis of a retrospective cohort study performed at a single center. Providers had identified study subjects during their emergency department (ED) encounters; all data were collected from the electronic medical record (EMR). Nondiabetic adult ED patients hospitalized for suspected infection, two or more systemic inflammatory response syndrome (SIRS) criteria, and simultaneous lactate and glucose testing in the ED were enrolled. The setting was the ED of an urban teaching hospital from 2007 to 2009. To evaluate the association of hyperglycemia (glucose > 200 mg/dL) with hyperlactatemia (lactate ≥ 4.0 mmol/L), a logistic regression model was created. The outcome was a diagnosis of hyperlactatemia, and the primary variable of interest was hyperglycemia. A second model was created to determine if coexisting hyperlactatemia affects hyperglycemia's association with mortality; the main outcome was 28-day mortality, and the primary risk variable was hyperglycemia with an interaction term for simultaneous hyperlactatemia. Both models were adjusted for demographics; comorbidities; presenting infectious source; and objective evidence of renal, respiratory, hematologic, or cardiovascular dysfunction. A total of 1,236 ED patients were included, and the median age was 77 years (interquartile range [IQR] = 60 to 87 years). A total of 115 (9.3%) subjects were hyperglycemic, 162 (13%) were hyperlactatemic, and 214 (17%) died within 28 days of their initial ED visits. After adjustment, hyperglycemia was significantly associated with simultaneous hyperlactatemia (odds ratio [OR] = 4.14, 95% confidence interval [CI] = 2.65 to 6.45). Hyperglycemia and concurrent hyperlactatemia were associated with increased mortality risk (OR = 3.96, 95% CI = 2.01 to 7.79), but hyperglycemia in the absence of simultaneous hyperlactatemia was not (OR = 0.78, 95% CI = 0.39 to 1.57). In this cohort of septic adult nondiabetic patients, mortality risk did not increase with hyperglycemia unless associated with simultaneous hyperlactatemia. The previously reported association of hyperglycemia with mortality in nondiabetic sepsis may be due to the association of hyperglycemia with hyperlactatemia.

Advanced oxidation protein products as marker of organ dysfunction in severe acute pancreatitis

Advanced oxidation protein products as marker of organ dysfunction in severe acute pancreatitis