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1.  A decision rule to aid selection of patients with abdominal sepsis requiring a relaparotomy 
BMC Surgery  2013;13:28.
Accurate and timely identification of patients in need of a relaparotomy is challenging since there are no readily available strongholds. The aim of this study is to develop a prediction model to aid the decision-making process in whom to perform a relaparotomy.
Data from a randomized trial comparing surgical strategies for relaparotomy were used. Variables were selected based on previous reports and common clinical sense and screened in a univariable regression analysis to identify those associated with the need for relaparotomy. Variables with the strongest association were considered for the prediction model which was constructed after backward elimination in a multivariable regression analysis. The discriminatory capacity of the model was expressed with the area under the curve (AUC). A cut-off analysis was performed to illustrate the consequences in clinical practice.
One hundred and eighty-two patients were included; 46 were considered cases requiring a relaparotomy. A prediction model was build containing 6 variables. This final model had an AUC of 0.80 indicating good discriminatory capacity. However, acceptable sensitivity would require a low threshold for relaparotomy leading to an unacceptable rate of negative relaparotomies (63%). Therefore, the prediction model was incorporated in a decision rule were the interval until re-assessment and the use of Computed Tomography are related to the outcome of the model.
To construct a prediction model that will provide a definite answer whether or not to perform a relaparotomy seems a utopia. However, our prediction model can be used to stratify patients on their underlying risk and could guide further monitoring of patients with abdominal sepsis in order to identify patients with suspected ongoing peritonitis in a timely fashion.
PMCID: PMC3750491  PMID: 23870702
Secondary peritonitis; Abdominal sepsis; Relaparotomy; On-demand; Prediction model; Decision rule
2.  Costs of relaparotomy on-demand versus planned relaparotomy in patients with severe peritonitis: an economic evaluation within a randomized controlled trial 
Critical Care  2010;14(3):R97.
Results of the first randomized trial comparing on-demand versus planned-relaparotomy strategy in patients with severe peritonitis (RELAP trial) indicated no clear differences in primary outcomes. We now report the full economic evaluation for this trial, including detailed methods, nonmedical costs, further differentiated cost calculations, and robustness of different assumptions in sensitivity analyses.
An economic evaluation was conducted from a societal perspective alongside a randomized controlled trial in 229 patients with severe secondary peritonitis and an acute physiology and chronic health evaluation (APACHE)-II score ≥11 from two academic and five regional teaching hospitals in the Netherlands. After the index laparotomy, patients were randomly allocated to an on-demand or a planned-relaparotomy strategy. Primary resource-utilization data were used to estimate mean total costs per patient during the index admission and after discharge until 1 year after the index operation. Overall differences in costs between the on-demand relaparotomy strategy and the planned strategy, as well as relative differences across several clinical subgroups, were evaluated.
Costs were substantially lower in the on-demand group (mean, €65,768 versus €83,450 per patient in the planned group; mean absolute difference, €17,682; 95% CI, €5,062 to €29,004). Relative differences in mean total costs per patient (approximately 21%) were robust to various alternative assumptions. Planned relaparotomy consistently generated more costs across the whole range of different courses of disease (quick recovery and few resources used on one end of the spectrum; slow recovery and many resources used on the other end). This difference in costs between the two surgical strategies also did not vary significantly across several clinical subgroups.
The reduction in societal costs renders the on-demand strategy a more-efficient relaparotomy strategy in patients with severe peritonitis. These differences were found across the full range of healthcare resources as well as across patients with different courses of disease.
Trial Registration
PMCID: PMC2911734  PMID: 20507557
3.  Initial microbial spectrum in severe secondary peritonitis and relevance for treatment 
This study aims to determine whether abdominal microbial profiles in early severe secondary peritonitis are associated with ongoing infection or death. The study is performed within a randomized study comparing two surgical treatment strategies in patients with severe secondary peritonitis (n = 229). The microbial profiles of cultures retrieved from initial emergency laparotomy were tested with logistic regression analysis for association with ‘ongoing infection needing relaparotomy’ and in-hospital death. No microbial profile or the presence of yeast or Pseudomonas spp. was related to the risk of ongoing infection needing relaparotomy. Resistance to empiric therapy for gram positive cocci and coliforms was moderately associated with ongoing abdominal infection (OR 3.43 95%CI 0.95–12.38 and OR 7.61, 95%CI 0.75–76.94). Presence of only gram positive cocci, predominantly Enterococcus spp, was borderline independently associated with in-hospital death (OR 3.69, 95%CI 0.99–13.80). In secondary peritonitis microbial profiles do not predict ongoing abdominal infection after initial emergency laparotomy. However, the moderate association of ongoing infection with resistance to the empiric therapy compels to more attention for resistance when selecting empiric antibiotic coverage.
PMCID: PMC3319890  PMID: 21800218
4.  Diffuse postoperative peritonitis -value of diagnostic parameters and impact of early indication for relaparotomy 
Current criteria for performing relaparotomy for suspected peritonitis are non explicit and based on non-quantitative, subjective arguments or hospital practice. The aim of this study was to determine the value of routinely used clinical and diagnostic parameters in early detection of postoperative, diffuse peritonitis (PP). Furthermore, the prognosis and outcome after early indication for relaparotomy in patients with PP compared to community-aquired peritonitis (CAP) was evaluated.
Between 1999 and 2008, a total of 251 patients with diffuse secondary peritonitis either postoperative (PP) or community acquired (CAP) were analyzed retrospectively. PP (n = 114) and CAP (n = 137) were compared regarding physical examination, MPI-Score, APACHE II-Score, evidence of organ failure, laboratory parameters, diagnostic instruments and clinical course. The treatment regimen comprised surgical source control (with/without programmed lavage), abdominal closure and relaparotomy on demand, broad spectrum antibiotic therapy and intensive care support.
The APACHE II-Score (20 CAP vs. 22 PP, p = 0.012), MPI-Score (27 CAP vs. 30 PP, p = 0.001) and the number of lavages differed significantly. Positive phyiscal testing and signs of sepsis [abdominal pain (81.6% PP vs. CAP 97.1%, p = 0.03), rebound tenderness (21.9% vs. 35.8%, p = 0.02), fever (35.1% vs. 51.8%, p = 0.03)] occurred significantly less often in the PP patients than in the CAP group. Conventional radiography (66.2%) and ultrasonography (44.3%) had a lower diagnostic sensitivity than did abdominal CT-scan (97.2%). Mortality was higher in the PP group but did not differ significantly between the two groups (47.4% PP vs. 35.8% CAP, p = 0.06).
The value of physical tests and laboratory parameters in diagnosing abdominal sepsis is limited. CT-scanning revealed the highest diagnostic accuracy. A treatment regimen of early relaprotomy appears to be the most reasonable strategy for as early discovery of postoperative peritonitis as possible.
PMCID: PMC3352290  PMID: 19948445
peritonitis; abdominal sepsis; relaparotomy; diagnosis; treatment
5.  Evaluation of SOFA-based models for predicting mortality in the ICU: A systematic review 
Critical Care  2008;12(6):R161.
To systematically review studies evaluating the performance of Sequential Organ Failure Assessment (SOFA)-based models for predicting mortality in patients in the intensive care unit (ICU).
Medline, EMBASE and other databases were searched for English-language articles with the major objective of evaluating the prognostic performance of SOFA-based models in predicting mortality in surgical and/or medical ICU admissions. The quality of each study was assessed based on a quality framework for prognostic models.
Eighteen articles met all inclusion criteria. The studies differed widely in the SOFA derivatives used and in their methods of evaluation. Ten studies reported about developing a probabilistic prognostic model, only five of which used an independent validation data set. The other studies used the SOFA-based score directly to discriminate between survivors and non-survivors without fitting a probabilistic model. In five of the six studies, admission-based models (Acute Physiology and Chronic Health Evaluation (APACHE) II/III) were reported to have a slightly better discrimination ability than SOFA-based models at admission (the receiver operating characteristic curve (AUC) of SOFA-based models ranged between 0.61 and 0.88), and in one study a SOFA model had higher AUC than the Simplified Acute Physiology Score (SAPS) II model. Four of these studies used the Hosmer-Lemeshow tests for calibration, none of which reported a lack of fit for the SOFA models. Models based on sequential SOFA scores were described in 11 studies including maximum SOFA scores and maximum sum of individual components of the SOFA score (AUC range: 0.69 to 0.92) and delta SOFA (AUC range: 0.51 to 0.83). Studies comparing SOFA with other organ failure scores did not consistently show superiority of one scoring system to another. Four studies combined SOFA-based derivatives with admission severity of illness scores, and they all reported on improved predictions for the combination. Quality of studies ranged from 11.5 to 19.5 points on a 20-point scale.
Models based on SOFA scores at admission had only slightly worse performance than APACHE II/III and were competitive with SAPS II models in predicting mortality in patients in the general medical and/or surgical ICU. Models with sequential SOFA scores seem to have a comparable performance with other organ failure scores. The combination of sequential SOFA derivatives with APACHE II/III and SAPS II models clearly improved prognostic performance of either model alone. Due to the heterogeneity of the studies, it is impossible to draw general conclusions on the optimal mathematical model and optimal derivatives of SOFA scores. Future studies should use a standard evaluation methodology with a standard set of outcome measures covering discrimination, calibration and accuracy.
PMCID: PMC2646326  PMID: 19091120
6.  Scoring systems for outcome prediction in patients with perforated peptic ulcer 
Patients with perforated peptic ulcer (PPU) often present with acute, severe illness that carries a high risk for morbidity and mortality. Mortality ranges from 3-40% and several prognostic scoring systems have been suggested. The aim of this study was to review the available scoring systems for PPU patients, and to assert if there is evidence to prefer one to the other.
Material and methods
We searched PubMed for the mesh terms “perforated peptic ulcer”, “scoring systems”, “risk factors”, ”outcome prediction”, “mortality”, ”morbidity” and the combinations of these terms. In addition to relevant scores introduced in the past (e.g. Boey score), we included recent studies published between January 2000 and December 2012) that reported on scoring systems for prediction of morbidity and mortality in PPU patients.
A total of ten different scoring systems used to predict outcome in PPU patients were identified; the Boey score, the Hacettepe score, the Jabalpur score the peptic ulcer perforation (PULP) score, the ASA score, the Charlson comorbidity index, the sepsis score, the Mannheim Peritonitis Index (MPI), the Acute physiology and chronic health evaluation II (APACHE II), the simplified acute physiology score II (SAPS II), the Mortality probability models II (MPM II), the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity physical sub-score (POSSUM-phys score). Only four of the scores were specifically constructed for PPU patients. In five studies the accuracy of outcome prediction of different scoring systems was evaluated by receiver operating characteristics curve (ROC) analysis, and the corresponding area under the curve (AUC) among studies compared. Considerable variation in performance both between different scores and between different studies was found, with the lowest and highest AUC reported between 0.63 and 0.98, respectively.
While the Boey score and the ASA score are most commonly used to predict outcome for PPU patients, considerable variations in accuracy for outcome prediction were shown. Other scoring systems are hampered by a lack of validation or by their complexity that precludes routine clinical use. While the PULP score seems promising it needs external validation before widespread use.
PMCID: PMC3626602  PMID: 23574922
Perforated peptic ulcer; Scoring systems; Outcome prediction; Mortality; Morbidity
7.  Topical negative pressure in managing severe peritonitis: A positive contribution? 
AIM: To assess the use of topical negative pressure (TNP) in the management of severe peritonitis.
METHODS: This is a four-year prospective analysis from January 2005 to December 2008 of 20 patients requiring TNP following laparotomy for severe peritonitis.
RESULTS: There were 11 males with an average age of (59.3 ± 3.95) years. Nine had a perforated viscus, five had anastomotic leaks, three had iatrogenic bowel injury, and a further three had severe pelvic inflammatory disease. TNP and the VAC® Abdominal Dressing System were initially used. These were changed every two to three days. Abdominal closure was achieved in 15/20 patients within 4.53 ± 1.64 d. One patient required relaparotomy due to residual sepsis. Two patients with severe faecal peritonitis due to perforated diverticular disease received primary anastomosis at second look laparotomy, as sepsis and their general condition improved. In the remaining 5/20 cases, the abdomen was left open due to bowel oedema and or abdominal wall oedema. Dressing was switched to TNP and VAC® GranuFoam®. Three of the five patients returned a few months later for abdominal wall reconstruction and restoration of intestinal continuity. Two patients developed intestinal fistulae. All 20 patients survived.
CONCLUSION: The use of TNP is safe. Further studies are needed to assess its value in managing these difficult cases.
PMCID: PMC2712900  PMID: 19610140
Severe peritonitis; Open abdomen; Topical negative pressure; VAC® Abdominal Dressing System; VAC® GranuFoam®
8.  Abdominal negative-pressure therapy: a new method in countering abdominal compartment and peritonitis - prospective study and critical review of literature 
Annals of Intensive Care  2012;2(Suppl 1):S23.
Application of abdominal negative-pressure therapy (NPT) is lifesaving when conservative measures fail to reduce sustained increase of the intra-abdominal pressure and it is impossible to achieve source control in a single operation due to severe peritonitis. The aim of this study is to share the initial experience with abdominal NPT in Latvia and provide a review of the relevant literature.
In total, 22 patients were included. All patients were treated with KCI® ABThera™ NPT systems. Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission, daily sequential organ failure assessment score and Mannheim peritonitis index (MPI) were calculated for severity definition. The frequency of NPT system changes, daily amount of aspirated fluid effluent and the time of abdominal closure were assessed. The overall hospital and ICU stay, as well as the outcomes and the complication rate, were analysed.
A complicated intra-abdominal infection was treated in 18 patients. Abdominal compartment syndrome due to severe acute pancreatitis (SAP), secondary ileus and damage control in polytrauma were indications for NPT in four patients. The median age of the patients was 59 years (range, 28 to 81), median APACHE II score was 15 points (range, 9 to 32) and median MPI was 28 points (range, 21 to 40), indicating a prognostic mortality risk of 60%. Sepsis developed in all patients, and in 20 of them, it was severe. NPT systems were changed on a median of every 4 days, and abdominal closure was feasible on the seventh postoperative day without needing a repeated laparotomy. Two NPT systems were removed due to bleeding from the retroperitoneal space in patients with SAP. Intestinal fistulae developed in three patients that were successfully treated conservatively. Incisional hernia occurred in three patients. The overall ICU and hospital stay were 14 (range, 5 to 56) and 25 days (range, 10 to 87), respectively. Only one patient died, contributing to the overall mortality of 4.5%.
Application of abdominal NPT could be a very promising technique for the control of sustained intra-abdominal hypertension and management of severe sepsis due to purulent peritonitis. Further trials are justified for a detailed evaluation of abdominal NPT indications.
PMCID: PMC3527158  PMID: 23281649
9.  Re-laparotomy After Cesarean Section: Risk, Indications and Management Options 
Medical Archives  2014;68(1):41-43.
To identify risks, indications and outcomes for relaparotomy after cesarean delivery.
A prospective case-controlled study conducted at Mansoura University Hospital, Egypt from 2009 to 2012. Each case was matched randomly to 2 cases that had delivered by cesarean section during the same period and did not undergo repeated surgical intervention. Information's on indications were obtained to gather information's on risks factors.
relaparotomy complicated 1.04 %(n= 26) of the total number of the cesarean section (CS) (n=2500). The principal indications for relaparotomy were internal bleeding (Intra-abdominal bleeding in 41.7% (n=10); rectus sheath hematoma in 29.2% (n=7) and uncontrolled postpartum hemorrhage (PPH) in 29.2 %(n=7) of cases, followed by infections in 7.7% (n=2) of cases. Resulting in 11.5 %(n=3) maternal death. Predictors for relaparotomy after cesarean delivery from univariate logistic model, placenta previa (OR=6.898, 95% CI=1.867- 25.4, P=.004), fetal weight greater than 4 kg (OR=6.409, 95% CI=1.444-28.44,. 015). Previous cesarean section and parity were not a risk for re-laparotomy.
In this study, the incidence of relaparotomy after cesarean delivery was very high (1.04%). Associated with high maternal mortality (11.5%). The main predictors were placenta previa and fetal macrosomia.
PMCID: PMC4272472  PMID: 24783911
Cesarean section; Re-laparotomy; risk; management options
10.  Urgent Abdominal Re-Explorations 
Treatment of a number of complications that occur after abdominal surgeries may require that Urgent Abdominal Re-explorations (UARs), the life-saving and obligatory operations, are performed. The objectives of this study were to evaluate the reasons for performing UARs, outcomes of relaparotomies (RLs) and factors that affect mortality.
Demographic characteristics; initial diagnoses; information from and complications of the first surgery received; durations and outcomes of UAR(s) performed in patients who received early RLs because of complicated abdominal surgeries in our clinic between 01.01.2000 and 31.12.2004 were investigated retrospectively. Statistical analyses were done using the chi-square and Fisher exact tests.
Early UAR was performed in 81 out of 4410 cases (1.8%). Average patient age was 50.46 (13–81) years with a male-to-female ratio of 60/21. Fifty one (62.96%) patients had infection, 41 (50.61%) of them had an accompanying serious disease, 24 (29.62%) of them had various tumors and 57 (70.37%) patients were operated under emergency conditions during first operation. Causes of urgent abdominal re-explorations were as follows: leakage from intestinal repair site or from anostomosis (n:34; 41.97%); hemorrhage (n:15; 18.51%); intestinal perforation (n:8; 9.87%); intraabdominal infection or abscess (n:8; 9.87%); progressive intestinal necrosis (n:7; 8.64%); stomal complications (n:5; 6.17%); and postoperative ileus (n:4; 4.93%). Two or more UARs were performed in 18 (22.22%) cases, and overall mortality was 34.97% (n:30). Interval between the first laparotomy and UAR averaged as 6.95 (1–20) days, and average hospitalization period was 27.1 (3–78) days.
Mortality rate was found to be higher among the patients who received multiple UARs. The most common (55.5%) cause of mortality was sepsis/multiple organ failure (MOF). The rates for common mortality and sepsis/MOF-dependent mortality that occured following UAR were significantly higher in patients who received GIS surgery than in those who received other types of surgeries (p:0.000 and 0.010, respectively).
UARs that are performed following complicated abdominal surgeries have high mortality rates. In particular, UARs have higher mortality rates following GIS surgeries or when infectious complications occur. The possibility of efficiently lowering these high rates depends on the success of the first operations that the patient had received.
PMCID: PMC1475563  PMID: 16759414
11.  A Modified Sequential Organ Failure Assessment (MSOFA) Score for Critical Care Triage 
Disaster medicine and public health preparedness  2010;4(4):10.1001/dmp.2010.40.
The Sequential Organ Failure Assessment (SOFA) score has been recommended for triage during a mass influx of critically-ill patients, but requires laboratory measurement of four parameters which may be impractical with constrained resources. We hypothesized that a modified SOFA (MSOFA) score that requires only one laboratory measurement would predict patient outcome as well as the SOFA score.
After a retrospective derivation, in a prospective observational study in a 24-bed medical, surgical, and trauma intensive care unit, we determined serial SOFA and MSOFA scores on all patients admitted during calendar year 2008 and compared ability to predict mortality and need for mechanical ventilation.
1,770 patients (56% male) with a 30-day mortality of 10.5% were included in the study. Day 1 SOFA and MSOFA scores performed equally well at predicting mortality with an area under the receiver operating curve (AUC) of 0.83 (95% CI: 0.81-0.85) and 0.84 (95% CI 0.82-0.85) respectively (p=0.33 for comparison). Day 3 SOFA and MSOFA predicted mortality for the 828 patients remaining in the ICU with an AUC of 0.78 and 0.79 respectively. Day 5 scores performed less well at predicting mortality. Day 1 SOFA and MSOFA predicted need for mechanical ventilation on Day 3 with an AUC of 0.83 and 0.82 respectively. Mortality for the highest category of SOFA and MSOFA score (>11 points) was 53% and 58% respectively.
The MSOFA predicts mortality as well as the SOFA and is easier to implement in resource-constrained settings, but using either score as a triage tool would exclude many patients who would otherwise survive.
PMCID: PMC3811929  PMID: 21149228
Critical care triage; Intensive care unit; Pandemic; Disaster
12.  Analysis of the severity and prognosis assessment of aged patients with community-acquired pneumonia: a retrospective study 
Journal of Thoracic Disease  2013;5(5):626-633.
Community-acquired pneumonia (CAP) is a prevalent and potentially life-threatening infection, and has poor prognosis in aged patients. The objective of this study was to compare the potential of admission N-terminal pro B-type natriuretic peptide (proBNP) levels and scoring models [CURB-65, Pneumonia Severity Index (PSI), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores] to predict outcomes for aged patients with CAP admitted to Intensive Care Unit (ICU), and to explore the prognostic factors.
Clinical data of the patients were collected retrospectively, whose CURB-65, PSI, APACHE II scores were calculated and in whom measurements of proBNP was performed. The outcomes of interest were severity evaluation, prediction of need for mechanical ventilation and 28-day mortality. Receiver operating characteristic (ROC) curve was conducted to predict the assessment ability of proBNP and scoring models on different outcomes, and the logistic regression analysis was performed to screen factors affecting prognosis.
240 patients were enrolled, with the mean age of 75±8 years old. Admission levels of NT-proBNP, scoring models were significantly higher in SCAP patients, MV group, and non-survivors compared to non-SCAP patients, no-MV group, and 28-day survivors, respectively (P<0.001). PSI had the highest area under the curve (AUC) and specificity for the three outcomes considered (AUC: 0.868 and specificity: 0.906 for 28-day mortality, AUC: 0.864 and specificity: 0.831 for requirement of MV, and AUC: 0.888 and specificity: 0.894 for severity evaluation). NT-proBNP had the highest sensitivity of 0.987 and 0.903 on prediction of mortality and need for MV. And APACHE II scoring model with the highest sensitivity of 0.890 was used to evaluate severity. Logistic regression analysis showed that the odd ratio (OR) of systolic blood pressure, PSI, and APACHE II scores were 0.886, 1.019, and 1.249.
PSI scores was the best indicator in predicting different clinical outcomes of aged patients with CAP among the proBNP and three scoring systems. Systolic blood pressure might be as a protective factor for prognosis while PSI and APACHE II scores as risk factors for prognosis of aged patients with CAP.
PMCID: PMC3815733  PMID: 24255776
Aged; community-acquired pneumonia (CAP); severity; prognosis
13.  Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation 
PLoS Medicine  2013;10(12):e1001577.
In this paper, Choi and colleagues analyzed levels of mitochondrial DNA in two prospective observational cohort studies and found that increased mtDNA levels are associated with ICU mortality, and improve risk prediction in medical ICU patients. The data suggests that mtDNA could serve as a viable plasma biomarker in MICU patients.
Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients.
Methods and Findings
Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6–15.8, p = 1×10−7) and ME ARDS (OR 8.4, 95% CI 2.9–24.2, p = 9×10−5) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10−4) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers.
Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients.
Please see later in the article for the Editors' Summary
Editors' Summary
Intensive care units (ICUs, also known as critical care units) are specialist hospital wards that provide care for people with life-threatening injuries and illnesses. In the US alone, more than 5 million people are admitted to ICUs every year. Different types of ICUs treat different types of problems. Medical ICUs treat patients who, for example, have been poisoned or who have a serious infection such as sepsis (blood poisoning) or severe pneumonia (inflammation of the lungs); trauma ICUs treat patients who have sustained a major injury; cardiac ICUs treat patients who have heart problems; and surgical ICUs treat complications arising from operations. Patients admitted to ICUs require constant medical attention and support from a team of specially trained nurses and physicians to prevent organ injury and to keep their bodies functioning. Monitors, intravenous tubes (to supply essential fluids, nutrients, and drugs), breathing machines, catheters (to drain urine), and other equipment also help to keep ICU patients alive.
Why Was This Study Done?
Although many patients admitted to ICUs recover, others do not. ICU specialists use scoring systems (algorithms) based on clinical signs and physiological measurements to predict their patients' likely outcomes. For example, the APACHE II scoring system uses information on heart and breathing rates, temperature, levels of salts in the blood, and other signs and physiological measurements collected during the first 24 hours in the ICU to predict the patient's risk of death. Existing scoring systems are not perfect, however, and “biomarkers” (molecules in bodily fluids that provide information about a disease state) are needed to improve risk prediction for ICU patients. Here, the researchers investigate whether levels of circulating cell-free mitochondrial DNA (mtDNA) are associated with ICU deaths and whether these levels can be used as a biomarker to improve risk prediction in ICU patients. Mitochondria are cellular structures that produce energy. Levels of mtDNA in the plasma (the liquid part of blood) increase in response to trauma and infection. Moreover, mtDNA activates molecular processes that lead to inflammation and organ injury.
What Did the Researchers Do and Find?
The researchers measured mtDNA levels in the plasma of patients enrolled in two prospective observational cohort studies that monitored the outcomes of ICU patients. In the Brigham and Women's Hospital Registry of Critical Illness study, blood was taken from 200 patients within 24 hours of admission into the hospital's medical ICU. In the Molecular Epidemiology of Acute Respiratory Distress Syndrome study (acute respiratory distress syndrome is a life-threatening inflammatory reaction to lung damage or infection), blood was taken from 243 patients within 48 hours of admission into medical and non-medical ICUs at two other US hospitals. Patients admitted to medical ICUs with a raised mtDNA level (3,200 or more copies of a specific mitochondrial gene per microliter of plasma) had a 7- to 8-fold increased risk of dying within 28 days of admission compared to patients with mtDNA levels of less than 3,200 copies/µl plasma. There was no evidence of an association between raised mtDNA levels and death among patients admitted to non-medical ICUs. The addition of an elevated mtDNA level to a clinical model for risk prediction that included the APACHE II score and biomarkers that are already used to predict ICU outcomes improved the net reclassification index (an indicator of the improvement in risk prediction algorithms offered by new biomarkers) of 28-day mortality among medical ICU patients in both studies.
What Do These Findings Mean?
These findings indicate that raised mtDNA plasma levels are associated with death in medical ICUs and show that, among patients in medical ICUs, measurement of mtDNA plasma levels can improve the prediction of the risk of death from the APACHE II scoring system, even when commonly measured biomarkers are taken into account. These findings do not indicate whether circulating cell-free mtDNA increased because of the underlying severity of illness or whether mtDNA actively contributes to the disease process in medical ICU patients. Moreover, they do not provide any evidence that raised mtDNA levels are associated with an increased risk of death among non-medical (mainly surgical) ICU patients. These findings need to be confirmed in additional patients, but given the relative ease and rapidity of mtDNA measurement, the determination of circulating cell-free mtDNA levels could be a valuable addition to the assessment of patients admitted to medical ICUs.
Additional Information
Please access these websites via the online version of this summary at
The UK National Health Service Choices website provides information about intensive care
The Society of Critical Care Medicine provides information for professionals, families, and patients about all aspects of intensive care
MedlinePlus provides links to other resources about intensive care (in English and Spanish)
The UK charity ICUsteps supports patients and their families through recovery from critical illness; its booklet Intensive Care: A Guide for Patients and Families is available in English and ten other languages; its website includes patient experiences and relative experiences of treatment in ICUs
Wikipedia has a page on ICU scoring systems (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC3876981  PMID: 24391478
14.  The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation* 
Critical care medicine  2009;37(5):1649-1654.
Organ failure worsens outcome in sepsis. The Sequential Organ Failure Assessment (SOFA) score numerically quantifies the number and severity of failed organs. We examined the utility of the SOFA score for assessing outcome of patients with severe sepsis with evidence of hypoperfusion at the time of emergency department (ED) presentation.
Prospective observational study.
Urban, tertiary ED with an annual census of >110,000.
ED patients with severe sepsis with evidence of hypoperfusion. Inclusion criteria: suspected infection, two or more criteria of systemic inflammation, and either systolic blood pressure <90 mm Hg after a fluid bolus or lactate >4 mmol/L. Exclusion criteria age <18 years or need for immediate surgery.
SOFA scores were calculated at ED recognition (T0) and 72 hours after intensive care unit admission (T72). The primary outcome was in-hospital mortality. The area under the receiver operating characteristic curve was used to evaluate the predictive ability of SOFA scores at each time point. The relationship between Δ SOFA (change in SOFA from T0 to T72) was examined for linearity.
A total of 248 subjects aged 57 ± 16 years, 48% men, were enrolled over 2 years. All patients were treated with a standardized quantitative resuscitation protocol; the in-hospital mortality rate was 21%. The mean SOFA score at T0 was 7.1 ± 3.6 points and at T72 was 7.4 ± 4.9 points. The area under the receiver operating characteristic curve of SOFA for predicting in-hospital mortality at T0 was 0.75 (95% confidence interval 0.68 - 0.83) and at T72 was 0.84 (95% confidence interval 0.77-0.90). The Δ SOFA was found to have a positive relationship with in-hospital mortality.
The SOFA score provides potentially valuable prognostic information on in-hospital survival when applied to patients with severe sepsis with evidence of hypoperfusion at the time of ED presentation.
PMCID: PMC2703722  PMID: 19325482
sepsis; severe sepsis; scoring system; Sequential Organ Failure Assessment; mortality
15.  Chronic Liver Failure-Sequential Organ Failure Assessment is better than the Asia-Pacific Association for the Study of Liver criteria for defining acute-on-chronic liver failure and predicting outcome 
World Journal of Gastroenterology : WJG  2014;20(40):14934-14941.
AIM: To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF) in predicting short-term prognosis of patients with ACLF.
METHODS: Consecutive patients of cirrhosis with acute decompensation were prospectively included. They were grouped into ACLF and no ACLF groups as per CLIF-SOFA and APASL criteria. Patients were followed up for 3 mo from inclusion or mortality whichever was earlier. Mortality at 28-d and 90-d was compared between no ACLF and ACLF groups as per both criteria. Mortality was also compared between different grades of ACLF as per CLIF-SOFA criteria. Prognostic scores like CLIF-SOFA, Acute Physiology and Chronic Health Evaluation (APACHE)-II, Child-Pugh and Model for End-Stage Liver Disease (MELD) scores were evaluated for their ability to predict 28-d mortality using area under receiver operating curves (AUROC).
RESULTS: Of 50 patients, 38 had ACLF as per CLIF-SOFA and 19 as per APASL criteria. Males (86%) were predominant, alcoholic liver disease (68%) was the most common etiology of cirrhosis, sepsis (66%) was the most common cause of acute decompensation while infection (66%) was the most common precipitant of acute decompensation. The 28-d mortality in no ACLF and ACLF groups was 8.3% and 47.4% (P = 0.018) as per CLIF-SOFA and 39% and 37% (P = 0.895) as per APASL criteria. The 28-d mortality in patients with no ACLF (n = 12), ACLF grade 1 (n = 11), ACLF grade 2 (n = 14) and ACLF grade 3 (n = 13) as per CLIF-SOFA criteria was 8.3%, 18.2%, 42.9% and 76.9% (χ2 for trend, P = 0.002) and 90-d mortality was 16.7%, 27.3%, 78.6% and 100% (χ2 for trend, P < 0.0001) respectively. Patients with prior decompensation had similar 28-d and 90-d mortality (39.3% and 53.6%) as patients without prior decompensation (36.4% and 63.6%) (P = NS). AUROCs for 28-d mortality were 0.795, 0.787, 0.739 and 0.710 for CLIF-SOFA, APACHE-II, Child-Pugh and MELD scores respectively. On multivariate analysis of these scores, CLIF-SOFA was the only significant independent predictor of mortality with an odds ratio 1.538 (95%CI: 1.078-2.194).
CONCLUSION: CLIF-SOFA criteria is better than APASL criteria to classify patients into ACLF based on their prognosis. CLIF-SOFA score is the best predictor of short-term mortality.
PMCID: PMC4209557  PMID: 25356054
Cirrhosis; Acute decompensation; Mortality; Prognosis; Acute on chronic liver failure
16.  Comparison of risk prediction scoring systems for ward patients: a retrospective nested case-control study 
Critical Care  2014;18(3):R132.
The rising prevalence of rapid response teams has led to a demand for risk-stratification tools that can estimate a ward patient’s risk of clinical deterioration and subsequent need for intensive care unit (ICU) admission. Finding such a risk-stratification tool is crucial for maximizing the utility of rapid response teams. This study compares the ability of nine risk prediction scores in detecting clinical deterioration among non-ICU ward patients. We also measured each score serially to characterize how these scores changed with time.
In a retrospective nested case-control study, we calculated nine well-validated prediction scores for 328 cases and 328 matched controls. Our cohort included non-ICU ward patients admitted to the hospital with a diagnosis of infection, and cases were patients in this cohort who experienced clinical deterioration, defined as requiring a critical care consult, ICU admission, or death. We then compared each prediction score’s ability, over the course of 72 hours, to discriminate between cases and controls.
At 0 to 12 hours before clinical deterioration, seven of the nine scores performed with acceptable discrimination: Sequential Organ Failure Assessment (SOFA) score area under the curve of 0.78, Predisposition/Infection/Response/Organ Dysfunction Score of 0.76, VitalPac Early Warning Score of 0.75, Simple Clinical Score of 0.74, Mortality in Emergency Department Sepsis of 0.74, Modified Early Warning Score of 0.73, Simplified Acute Physiology Score II of 0.73, Acute Physiology and Chronic Health Evaluation II of 0.72, and Rapid Emergency Medicine Score of 0.67. By measuring scores over time, it was found that average SOFA scores of cases increased as early as 24 to 48 hours prior to deterioration (P = 0.01). Finally, a clinical prediction rule which also accounted for the change in SOFA score was constructed and found to perform with a sensitivity of 75% and a specificity of 72%, and this performance is better than that of any SOFA scoring model based on a single set of physiologic variables.
ICU- and emergency room-based prediction scores can also be used to prognosticate risk of clinical deterioration for non-ICU ward patients. In addition, scoring models that take advantage of a score’s change over time may have increased prognostic value over models that use only a single set of physiologic measurements.
PMCID: PMC4227284  PMID: 24970344
17.  Performance Assessment of the SOFA, APACHE II Scoring System, and SAPS II in Intensive Care Unit Organophosphate Poisoned Patients 
Journal of Korean Medical Science  2013;28(12):1822-1826.
This study assessed the ability of the Sequential Organ Failure Assessment (SOFA) and Acute Physiology, Chronic Health Evaluation (APACHE) II scoring systems, as well as the Simplified Acute Physiology Score (SAPS) II method to predict group mortality in intensive care unit (ICU) patients who were poisoned with organophosphate. The medical records of 149 organophosphate poisoned patients admitted to the ICU from September 2006 to December 2012 were retrospectively examined. The SOFA, APACHE II, and SAPS II were calculated based on initial laboratory data in the Emergency Department, and during the first 24 hr of ICU admission. The probability of death was calculated for each patient based on the SOFA score, APACHE II score, and SAPS II equations. The ability to predict group mortality by the SOFA score, APACHE II score, and SAPS II method was assessed using two by two decision matrices and receiver operating characteristic (ROC) curve analysis. A total of 131 patients (mean age, 61 yr) were enrolled. The sensitivities, specificities, and accuracies were 86.2%, 82.4%, and 83.2% for the SOFA score, respectively; 65.5%, 68.6%, and 67.9% for the APACHE II scoring system, respectively; and 86.2%, 77.5%, and 79.4% for the SAPS II, respectively. The areas under the curve in the ROC curve analysis for the SOFA score, APACHE II scoring system, and SAPS II were 0.896, 0.716, and 0.852, respectively. In conclusion, the SOFA, APACHE II, and SAPS II have different capability to discriminate and estimate early in-hospital mortality of organophosphate poisoned patients. The SOFA score is more useful in predicting mortality, and easier and simpler than the APACHE II and SAPS II.
PMCID: PMC3857381  PMID: 24339715
18.  Mannose-Binding Lectin Deficiency Facilitates Abdominal Candida Infections in Patients with Secondary Peritonitis▿  
Mannose-binding lectin (MBL) deficiency due to variations in the MBL gene is associated with increased susceptibility to infections. In this study, the association between MBL deficiency and the occurrence of abdominal yeast infection (AYI) in peritonitis patients was examined. Eighty-eight patients with secondary peritonitis requiring emergency laparotomy were included. MBL genotype (wild type [WT] versus patients with variant genotypes), MBL plasma concentrations, and Candida risk factors were examined in patients with and those without AYI (positive abdominal yeast cultures during [re]laparotomy). A variant MBL genotype was found in 53% of patients with AYI and 38% of those without AYI (P = 0.18). A significantly higher proportion of variant patients had an AYI during early peritonitis (during first laparotomy) than WT patients (39% versus 16%, respectively; P = 0.012). Patients with AYI had lower MBL levels than did patients without AYI (0.16 μg/ml [0.0 to 0.65 μg/ml] versus 0.65 μg/ml (0.19 to 1.95 μg/ml); P = 0.007). Intensity of colonization (odds ratio [OR], 1.1; 95% confidence interval [CI], 1.0 to 1.1), MBL plasma concentrations of <0.5 μg/ml (OR, 4.5; 95% CI, 1.2 to 16.3), and numbers of relaparotomies (OR, 1.7; 95% CI, 1.0 to 2.8) were independently associated with AYI. In summary, deficient MBL plasma levels were independently associated with the development of AYI in patients with secondary peritonitis and seemed to facilitate early infection.
PMCID: PMC2223851  PMID: 17978009
19.  Should C-reactive protein concentration at ICU discharge be used as a prognostic marker? 
BMC Anesthesiology  2010;10:17.
About one third of hospital mortality in critically ill patients occurs after Intensive Care Unit (ICU) discharge. Some authors have recently hypothesized that unresolved or latent inflammation and sepsis may be an important factor that contributes to death following successful discharge from the ICU.
The aim of our study was to determine the ability of the clinical and inflammatory markers at ICU discharge to predict post-ICU mortality.
A prospective observational cohort study was conducted during a 14-month period in an 8 bed polyvalent ICU. Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, Therapeutic Intervention Scoring System-28 (TISS-28), C-reactive protein (CRP), white cell count (WCC) and body temperature of the day of ICU discharge were collected from patients who survived their first ICU admission.
During this period 156 patients were discharged alive from the ICU. A total of 29 patients (18.6%) died after ICU discharge. There were no differences in clinical and demographic characteristics between survivors and nonsurvivors. C-reactive protein levels at ICU discharge were not significantly different between survivors and nonsurvivors. The area under receiver operating characteristics curves of APACHE II, SAPS II, SOFA, TISS-28, CRP, WCC and body temperature at ICU discharge as prognostic markers of hospital death were 0.76 (95% confidence interval (CI) 0.67-0.86); 0.75 (95% CI 0.66-0.85); 0.72 (95% CI 0.62-0.83); 0.64 (95% CI 0.52-0.77); 0.55 (95% CI 0.43-0.67); 0.55 (95% CI 0.42-0.66) and 0.54 (95% CI 0.44-0.67) respectively. The hospital mortality rate of the patients with CRP <5, 5-10, >10 mg/dL was 15.1%, 16.1% and 33.3% respectively (p = NS).
At ICU discharge serum CRP concentration was a poor marker of post-ICU prognosis. Post-ICU death appears to be unrelated to the persistent inflammatory response.
PMCID: PMC2954920  PMID: 20875120
20.  Predicting six-month mortality of patients with traumatic brain injury: usefulness of common intensive care severity scores 
Critical Care  2014;18(2):R60.
The aim of this study was to evaluate the usefulness of the APACHE II (Acute Physiology and Chronic Health Evaluation II), SAPS II (Simplified Acute Physiology Score II) and SOFA (Sequential Organ Failure Assessment) scores compared to simpler models based on age and Glasgow Coma Scale (GCS) in predicting long-term outcome of patients with moderate-to-severe traumatic brain injury (TBI) treated in the intensive care unit (ICU).
A national ICU database was screened for eligible TBI patients (age over 15 years, GCS 3–13) admitted in 2003–2012. Logistic regression was used for customization of APACHE II, SAPS II and SOFA score-based models for six-month mortality prediction. These models were compared to an adjusted SOFA-based model (including age) and a reference model (age and GCS). Internal validation was performed by a randomized split-sample technique. Prognostic performance was determined by assessing discrimination, calibration and precision.
In total, 1,625 patients were included. The overall six-month mortality was 33%. The APACHE II and SAPS II-based models showed good discrimination (area under the curve (AUC) 0.79, 95% confidence interval (CI) 0.75 to 0.82; and 0.80, 95% CI 0.77 to 0.83, respectively), calibration (P > 0.05) and precision (Brier score 0.166 to 0.167). The SOFA-based model showed poor discrimination (AUC 0.68, 95% CI 0.64 to 0.72) and precision (Brier score 0.201) but good calibration (P > 0.05). The AUC of the SOFA-based model was significantly improved after the insertion of age and GCS (∆AUC +0.11, P < 0.001). The performance of the reference model was comparable to the APACHE II and SAPS II in terms of discrimination (AUC 0.77; compared to APACHE II, ΔAUC −0.02, P = 0.425; compared to SAPS II, ΔAUC −0.03, P = 0.218), calibration (P > 0.05) and precision (Brier score 0.181).
A simple prognostic model, based only on age and GCS, displayed a fairly good prognostic performance in predicting six-month mortality of ICU-treated patients with TBI. The use of the more complex scoring systems APACHE II, SAPS II and SOFA added little to the prognostic performance.
PMCID: PMC4056363  PMID: 24708781
21.  Effect of Obesity and Decompressive Laparotomy on Mortality in Acute Pancreatitis Requiring Intensive Care Unit Admission 
World Journal of Surgery  2012;37(2):318-332.
Controversy still exists on the effect that obesity has on the morbidity and mortality in severe acute pancreatitis (SAP). The primary purpose of this study was to compare the mortality rate of obese versus nonobese patients admitted to the ICU for SAP. Secondary goals were to assess the potential risk factors for abdominal compartment syndrome (ACS) and to investigate the performance of validated scoring systems to predict ACS and in-hospital mortality.
A retrospective cohort of adults admitted to the ICU for SAP was stratified by their body mass index (BMI) as obese and nonobese. The rates of morbidity, mortality, and ACS were compared by univariate and multivariate regression analyses. Areas under the curve (AUC) were used to evaluate the discriminating performance of severity scores and other selected variables to predict mortality and the risk of ACS.
Forty-five patients satisfied the inclusion criteria and 24 (53 %) were obese with similar characteristics to nonobese patients. Among all the subjects, 11 (24 %) died and 16 (35 %) developed ACS. In-hospital mortality was significantly lower for obese patients (12.5 vs. 38 %; P = 0.046) even though they seemed to develop ACS more frequently (41 vs. 28 %; P = 0.533). At multivariable analysis, age was the most significant factor associated with in-hospital mortality (odds ratio (OR) = 1.273; 95 % confidence interval (CI) 1.052–1.541; P = 0.013) and APACHE II and Glasgow-Imrie for the development of ACS (OR = 1.143; 95 % CI 1.012–1.292; P = 0.032 and OR = 1.221; 95 % CI 1.000–1.493; P = 0.05) respectively. Good discrimination for in-hospital mortality was observed for patients’ age (AUC = 0.846) and number of comorbidities (AUC = 0.801). ACS was not adequately predicted by any of the clinical severity scores (AUC = 0.548–0.661).
Patients’ age was the most significant factor associated with mortality in patients affected by SAP. Higher APACHE II and Glasgow-Imrie scores were associated with the development of ACS, but their discrimination performance was unsatisfactory.
PMCID: PMC3553416  PMID: 23052814
22.  Predictors of Mortality in Patients Successfully Weaned from Extracorporeal Membrane Oxygenation 
PLoS ONE  2012;7(8):e42687.
Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill patients, such as those with life-threatening respiratory failure or post-cardiotomy cardiogenic shock. This study compares the predictive value of Acute Physiology, Age, and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Organ System Failure (OSF) obtained on the first day of ECMO removal, and the Acute Kidney Injury Network (AKIN) stages obtained at 48 hours post-ECMO removal (AKIN48-hour) in terms of hospital mortality for critically ill patients.
This study reviewed the medical records of 119 critically ill patients successfully weaned from ECMO at the specialized intensive care unit of a tertiary-care university hospital between July 2006 and October 2010. Demographic, clinical, and laboratory data were collected retrospectively as survival predictors.
Overall mortality rate was 26%. The most common condition requiring ECMO support was cardiogenic shock. By using the areas under the receiver operating characteristic (AUROC) curve, the Sequential Organ Failure Assessment (SOFA) score displayed good discriminative power (AUROC 0.805±0.055, p<0.001). Furthermore, multiple logistic regression analysis indicated that daily urine output on the second day of ECMO removal (UO24–48 hour), mean arterial pressure (MAP), and SOFA score on the day of ECMO removal were independent predictors of hospital mortality. Finally, cumulative survival rates at 6-month follow-up differed significantly (p<0.001) for a SOFA score≤13 relative to those for a SOFA score>13.
Following successful ECMO weaning, the SOFA score proved a reproducible evaluation tool with good prognostic abilities.
PMCID: PMC3411657  PMID: 22870340
23.  Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience 
Indian Journal of Nephrology  2012;22(1):33-38.
Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. We carried out prospective study in 2010, to describe clinical characteristics, laboratory parameters, prognostic factors, and outcome in 59 (44 males, 15 females) smear-positive malaria patients with AKI. The severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) score, Multiple Organ Dysfunction Score (MODS), and Glasgow Coma Scale (GCS) scores. All patients received artesunate and hemodialysis (HD). Mean age of patients was 33.63 ± 14 years. Plasmodium falciparum malaria was seen in 76.3% (n = 45), Plasmodium vivax in 16.9% (n = 10), and mixed infection in 6.8% (n = 4) patients. Presenting clinical features were fever (100%), nausea-vomiting (85%), oliguria (61%), abdominal pain/tenderness (50.8%), and jaundice (74.5%). Mean APACHE II, SOFA, MODS, and GCS scores were 18.1 ± 3, 10.16 ± 3.09, 9.71 ± 2.69, and 14.15 ± 1.67, respectively, all were higher among patients who died than among those who survived. APACHE II ≥20, SOFA and MODS scores ≥12 were associated with higher mortality (P < 0.05). 34% patients received blood component transfusion and exchange transfusion was done in 15%. Mean number of HD sessions required was 4.59 ± 3.03. Renal biopsies were performed in five patients (three with patchy cortical necrosis and two with acute tubular necrosis). 81.3% of patients had complete renal recovery and 11.8% succumbed to malaria. Prompt diagnosis, timely HD, and supportive therapy were associated with improved survival and recovery of kidney functions in malarial with AKI. Mortality was associated with higher APACHE II, SOFA, MODS, GCS scores, requirement of inotrope, and ventilator support.
PMCID: PMC3263060  PMID: 22279340
Acute kidney injury; hemodialysis; jaundice; malaria; outcome
24.  Utility of Procalcitonin (PCT) and Mid regional pro-Adrenomedullin (MR-proADM) in risk stratification of critically ill febrile patients in Emergency Department (ED). A comparison with APACHE II score 
BMC Infectious Diseases  2012;12:184.
The aim of our study was to evaluate the prognostic value of MR-proADM and PCT levels in febrile patients in the ED in comparison with a disease severity index score, the APACHE II score. We also evaluated the ability of MR-proADM and PCT to predict hospitalization.
This was an observational, multicentric study. We enrolled 128 patients referred to the ED with high fever and a suspicion of severe infection such as sepsis, lower respiratory tract infections, urinary tract infections, gastrointestinal infections, soft tissue infections, central nervous system infections, or osteomyelitis. The APACHE II score was calculated for each patient.
MR-proADM median values in controls were 0.5 nmol/l as compared with 0.85 nmol/l in patients (P < 0.0001), while PCT values in controls were 0.06 ng/ml versus 0.56 ng/ml in patients (P < 0.0001). In all patients there was a statistically significant stepwise increase in MR-proADM levels in accordance with PCT values (P < 0.0001). MR-proADM and PCT levels were significantly increased in accordance with the Apache II quartiles (P < 0.0001 and P = 0.0012 respectively).
In the respiratory infections, urinary infections, and sepsis-septic shock groups we found a correlation between the Apache II and MR-proADM respectively and MR-proADM and PCT respectively. We evaluated the ability of MR-proADM and PCT to predict hospitalization in patients admitted to our emergency departments complaining of fever. MR-proADM alone had an AUC of 0.694, while PCT alone had an AUC of 0.763. The combined use of PCT and MR-proADM instead showed an AUC of 0.79.
The present study highlights the way in which MR-proADM and PCT may be helpful to the febrile patient’s care in the ED. Our data support the prognostic role of MR-proADM and PCT in that setting, as demonstrated by the correlation with the APACHE II score. The combined use of the two biomarkers can predict a subsequent hospitalization of febrile patients. The rational use of these two molecules could lead to several advantages, such as faster diagnosis, more accurate risk stratification, and optimization of the treatment, with consequent benefit to the patient and considerably reduced costs.
PMCID: PMC3447640  PMID: 22874067
Procalcitonin; Mid regional pro-Adrenomedullin; Fever; APACHE II score
25.  Risk stratification and prognostic performance of the predisposition, infection, response, and organ dysfunction (PIRO) scoring system in septic patients in the emergency department: a cohort study 
Critical Care  2014;18(2):R74.
The predisposition, infection, response and organ dysfunction (PIRO) staging system was designed as a stratification tool to deal with the inherent heterogeneity of septic patients. The present study was conducted to assess the performance of PIRO in predicting multiple organ dysfunction (MOD), intensive care unit (ICU) admission, and 28-day mortality in septic patients in the emergency department (ED), and to compare this scoring system with the Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores.
Consecutive septic patients (n = 680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS, and APACHE II scores were calculated for each patient on ED arrival. Organ function was reassessed within 3 days of enrollment. All patients were followed up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU admission or death within 28 days after enrollment. The predictive ability of the four components of PIRO was analyzed separately. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess the prognostic and risk stratification value of the scoring systems.
Organ dysfunction independently predicted ICU admission, MOD, and 28-day mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816, respectively. The predictive value of predisposition, infection, and response was weaker than that of organ dysfunction. A negative correlation was found between the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II scores significantly differed between patients who did and did not meet the outcome criteria (P < 0.001). PIRO and APACHE II independently predicted ICU admission and MOD, but MEDS did not. All three systems were independent predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889 for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in predicting ICU admission and MOD.
The study indicates that PIRO is helpful for risk stratification and prognostic determinations in septic patients in the ED.
PMCID: PMC4056311  PMID: 24739219

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