The Volume Ratio of Ground Glass Opacity in Early Lung CT Predicts Mortality in Acute Paraquat Poisoning

Background

Pulmonary injury is the main cause of death in acute paraquat (PQ) poisoning. However, whether quantitative lung computed tomography (CT) can be useful in predicting the outcome of PQ poisoning remains unknown. We aimed to identify early findings of quantitative lung CT as predictors of outcome in acute PQ poisoning.

Methods

Lung CT scanning (64-slide) and quantitative CT lesions were prospectively measured for patients after PQ intoxication within 5 days. The study outcome was mortality during 90 days follow-up. Survival curves were derived by the Kaplan-Meier method, and mortality risk factors were analyzed by the forward stepwise Cox regression analysis.

Results

Of 97 patients, 41 (42.3%) died. Among the eight different types of lung CT findings which appeared in the first 5-day of PQ intoxication, four ones discriminated between survivors and non-survivors including ground glass opacity (GGO), consolidation, pneumomediastinum and “no obvious lesion”. With a cutoff value of 10.8%, sensitivity of 85.4% and specificity of 89.3%, GGO volume ratio is better than adopted outcome indicators in predicting mortality, such as estimated amount of PQ ingestion, plasma or urine PQ concentration, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores. GGO volume ratios above 10.8% were associated with increased mortality (hazard ratio, 5.82; 95% confidence interval, 4.77-7.09; P < 0.001).

Conclusions

The volume ratio of GGO exceeding 10.8% is a novel, reliable and independent predictors of outcome in acute PQ poisoning.     

Psychiatric Comorbidity and Its Impact on Mortality in Patients Who Attempted Suicide by Paraquat Poisoning during 2000–2010

Background

Paraquat poisoning is a lethal method of suicide used around the world. Although restricting its accessibility had been widely discussed, the underlying psychopathological mechanism of paraquat self-poisoning and its association with mortality have not yet been explicitly evaluated.

Methods

We included all patients admitted to a tertiary general hospital in Taiwan between 2000 and 2010 following a suicide attempt by paraquat self-administration. Diagnoses were made upon psychiatric consultation based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The risk of mortality was calculated by logistic regression with various psychiatric or medical covariates.

Results

The consultation-liaison psychiatry team assessed 157 patients who attempted suicide by paraquat poisoning. Mood disorders (54.0%), including dysthymic (26.7%) and major depressive disorders (24.7%), were the most common psychiatric diagnoses among the self-poisoning patients. Among those who attempted suicide, 87 patients (58.0%) died and dysthymic disorder (OR = 5.58, 95% CI: 1.13–27.69; p<0.05) significantly increased the mortality risk after adjustment for relevant medical variables, including age, gender, severity index of paraquat poisoning (SIPP), and risk for respiratory failure.

Conclusions

Awareness of comorbid psychiatric illnesses, especially dysthymic disorder, is vital in the prevention and treatment of suicide by paraquat poisoning.     

Using Bosentan to Treat Paraquat Poisoning-Induced Acute Lung Injury in Rats

Background

Paraquat poisoning is well known for causing multiple organ function failure (MODS) and high mortality. Acute lung injury and advanced pulmonary fibrosis are the most serious complications. Bosentan is a dual endothelin receptor antagonist. It plays an important role in treating PF. There is no related literature on the use of bosentan therapy for paraquat poisoning.

Objective

To study the use of bosentan to treat acute lung injury and pulmonary fibrosis as induced by paraquat.

Method

A total of 120 adult Wister male rats were randomly assigned to three groups: the paraquat poisoning group (rats were intragastrically administered with paraquat at 50 mg/kg body weight once at the beginning); the bosentan therapy group (rats were administered bosentan at 100 mg/kg body weight by intragastric administration half an hour after paraquat was administered, then the same dose was administered once a day); and a control group (rats were administered intragastric physiological saline). On the 3rd, 7th, 14th, and 21st days following paraquat exposure, rats were sacrificed, and samples of lung tissue and venous blood were collected. The levels of transforming growth factor-β1 (TGF-β1), endothelin-1 (ET-1), and hydroxyproline (HYP) in the plasma and lung homogenate were determined. Optical and electronic microscopes were used to examine pathological changes.

Result

The TGF-β1, ET-1, and HYP of the paraquat poisoning group were significantly higher than in the control group, and they were significantly lower in the 21st day therapy group than in the paraquat poisoning group on the same day. Under the optical and electronic microscopes, lung tissue damage was observed to be more severe but was then reduced after bosentan was administered.

Conclusion

Bosentan can reduce inflammation factor release. It has a therapeutic effect on acute lung injury as induced by paraquat.     

Sequential Organ Failure Assessment Score Can Predict Mortality in Patients with Paraquat Intoxication

Introduction

Paraquat poisoning is characterized by multi-organ failure and pulmonary fibrosis with respiratory failure, resulting in high mortality and morbidity. The objective of this study was to identify predictors of mortality in cases of paraquat poisoning. Furthermore, we sought to determine the association between these parameters.

Methods

A total of 187 patients were referred for management of intentional paraquat ingestion between January 2000 and December 2010. Demographic, clinical, and laboratory data were recorded. Sequential organ failure assessment (SOFA) and acute kidney injury network (AKIN) scores were collected, and predictors of mortality were analyzed.

Results

Overall hospital mortality for the entire population was 54% (101/187). Using a multivariate logistic regression model, it was found that age, time to hospitalization, blood paraquat level, estimated glomerular filtration rate at admission (eGFR _{first day}), and the SOFA_48-h score, but not the AKIN_48-h score, were significant predictors of mortality. For predicting the in-hospital mortality, SOFA_48-h scores displayed a good area under the receiver operating characteristic curve (AUROC) (0.795±0.033, P<0.001). The cumulative survival rate differed significantly between patients with SOFA_48-h scores <3 and those ≥3 (P<0.001). A modified SOFA (mSOFA) score was further developed by using the blood paraquat level, and this new score also demonstrated a better AUROC (0.848±0.029, P<0.001) than the original SOFA score. Finally, the cumulative survival rate also differed significantly between patients with mSOFA scores <4 and ≥4 (P<0.001).

Conclusion

The analytical data demonstrate that SOFA and mSOFA scores, which are based on the extent of organ function or rate of organ failure, help to predict mortality after intentional paraquat poisoning.     

The value of plasma paraquat concentration in predicting therapeutic effects of haemoperfusion in patients with acute paraquat poisoning

Objective

This study was aimed to analyze the scavenging effect of haemoperfusion on plasma paraquat (PQ) and to evaluate the clinical significance of PQ examination in the treatment of patients with acute paraquat poisoning.

Methods

85 patients with acute paraquat intoxication by oral ingestion were admitted in West China Hospital from Jun, 2010 to Mar, 2011. A standardized therapeutic regimen including emergency haemoperfusion was given on all subjects. A total of 91 whole blood samples were taken before (0h), underway (1h after haemoperfusion beginning) and at the end (2h) of the haemoperfusion therapy. The clearance rate was calculated and related factors were analyzed.

Results

As heamoperfusion was going on, the plasma paraquat concentration of the patients kept falling down. After 1 hour of haemoperfusion, the average clearance rate (R₁) was 37.06±21.81%. After 2 hours of haemoperfusion, the average clearance rate (R₂) was 45.99±23.13%. The average of R₁/R₂ ratio was 76.61±22.80%. In the high paraquat concentration group (plasma paraquat concentration (C₀) >300 ng/mL), both the averages of R₁ and R₂ were significantly higher than those of the low paraquat concentration group (C₀≤200 ng/mL) (p<0.05), and there was no significant difference of R₁/R₂ between these two groups (p>0.05).

Conclusions

The dynamic monitoring of plasma PQ concentration was not only critical in the clinical evaluation but also helpful in guiding the treatment of patients with acute PQ intoxication. Haemoperfusion can effectively eliminate paraquat from the plasma in patients with high initial plasma PQ concentration, while in patients with low initial plasma PQ concentration (<200 ng/ml), the clearance effect of harmoperfusion was very limited. Increasing HP time might improve the overall clearance rate of HP on plasma PQ yet decrease the elimination efficiency of HP, while repeated HP treatment was helpful against the rebound phenomena.     

Routine Laboratory Results and Thirty Day and One-Year Mortality Risk Following Hospitalization with Acute Decompensated Heart Failure

Introduction

Several blood tests are performed uniformly in patients hospitalized with acute decompensated heart failure and are predictive of the outcomes: complete blood count, electrolytes, renal function, glucose, albumin and uric acid. We sought to evaluate the relationship between routine admission laboratory tests results, patient characteristics and 30-day and one-year mortality of patients admitted for decompensated heart failure and to construct a simple mortality prediction tool.

Methods

A retrospective population based study. Data from seven tertiary hospitals on all admissions with a principal diagnosis of heart failure during the years 2002–2005 throughout Israel were captured.

Results

8,246 patients were included in the study cohort. Thirty day mortality rate was 8.5% (701 patients) and one-year mortality rate was 28.7% (2,365 patients). Addition of five routine laboratory tests results (albumin, sodium, blood urea, uric acid and WBC) to a set of clinical and demographic characteristics improved c-statistics from 0.76 to 0.81 for 30-days and from 0.72 to 0.76 for one-year mortality prediction (both p-values <0.0001). Three dichotomized abnormal laboratory results with highest odds ratio for one-year mortality (hypoalbuminaemia, hyponatremia and elevated blood urea) were used to construct a simple prediction score, capable of discriminating from 1.1% to 21.4% in 30-day and from 11.6% to 55.6% in one-year mortality rates between patients with a score of 0 (1,477 patients) vs. score of 3 (544 patients).

Discussion

A small set of abnormal routine laboratory results upon admission can risk-stratify and independently predict 30-day and one-year mortality in patients hospitalized with acute decompensated heart failure.     

Early Hemoperfusion May Improve Survival of Severely Paraquat-Poisoned Patients

Background

Thousands of paraquat (PQ)-poisoned patients continue to die, particularly in developing countries. Although animal studies indicate that hemoperfusion (HP) within 2−4 h after intoxication effectively reduces mortality, the effect of early HP in humans remains unknown.

Methods

We analyzed the records of all PQ-poisoned patients admitted to 2 hospitals between 2000 and 2009. Patients were grouped according to early or late HP and high-dose (oral cyclophosphamide [CP] and intravenous dexamethasone [DX]) or repeated pulse (intravenous methylprednisolone [MP] and CP, followed by DX and repeated MP and/or CP) PQ therapy. Early HP was defined as HP <4 h, and late HP, as HP ≥4 h after PQ ingestion. We evaluated the associations between HP <4 h, <5 h, <6 h, and <7 h after PQ ingestion and the outcomes. Demographic, clinical, laboratory, and mortality data were analyzed.

Results

The study included 207 severely PQ-poisoned patients. Forward stepwise multivariate Cox hazard regression analysis showed that early HP <4 h (hazard ratio [HR] = 0.38, 95% confidence interval (CI) 0.16–0.86; P = 0.020) or HP <5 h (HR = 0.60, 95% CI: 0.39–0.92; P = 0.019) significantly decreased the mortality risk. Further analysis showed that early HP reduced the mortality risk only in patients treated with repeated pulse therapy (n = 136), but not high-dose therapy (n = 71). Forward stepwise multivariate Cox hazard regression analysis showed that HP <4.0 h (HR = 0.19, 95% CI: 0.05–0.79; P = 0.022) or <5.0 h (HR = 0.49, 95% CI: 0.24–0.98; P = 0.043) after PQ ingestion significantly decreased the mortality risk in repeated pulse therapy patients, after adjustment for relevant variables.

Conclusion

The results showed that early HP after PQ exposure might be effective in reducing mortality in severely poisoned patients, particularly in those treated with repeated pulse therapy.     

Hematoma Shape,Hematoma Size,Glasgow Coma Scale Score and ICH Score: Which Predicts the 30-Day Mortality Better for Intracerebral Hematoma?

Purpose

To investigate the performance of hematoma shape, hematoma size, Glasgow coma scale (GCS) score, and intracerebral hematoma (ICH) score in predicting the 30-day mortality for ICH patients. To examine the influence of the estimation error of hematoma size on the prediction of 30-day mortality.

Materials and Methods

This retrospective study, approved by a local institutional review board with written informed consent waived, recruited 106 patients diagnosed as ICH by non-enhanced computed tomography study. The hemorrhagic shape, hematoma size measured by computer-assisted volumetric analysis (CAVA) and estimated by ABC/2 formula, ICH score and GCS score was examined. The predicting performance of 30-day mortality of the aforementioned variables was evaluated. Statistical analysis was performed using Kolmogorov-Smirnov tests, paired t test, nonparametric test, linear regression analysis, and binary logistic regression. The receiver operating characteristics curves were plotted and areas under curve (AUC) were calculated for 30-day mortality. A P value less than 0.05 was considered as statistically significant.

Results

The overall 30-day mortality rate was 15.1% of ICH patients. The hematoma shape, hematoma size, ICH score, and GCS score all significantly predict the 30-day mortality for ICH patients, with an AUC of 0.692 (P = 0.0018), 0.715 (P = 0.0008) (by ABC/2) to 0.738 (P = 0.0002) (by CAVA), 0.877 (P<0.0001) (by ABC/2) to 0.882 (P<0.0001) (by CAVA), and 0.912 (P<0.0001), respectively.

Conclusion

Our study shows that hematoma shape, hematoma size, ICH scores and GCS score all significantly predict the 30-day mortality in an increasing order of AUC. The effect of overestimation of hematoma size by ABC/2 formula in predicting the 30-day mortality could be remedied by using ICH score.     

Use of the Delta Neutrophil Index as a Prognostic Factor of Mortality in Patients with Spontaneous Bacterial Peritonitis: Implications of a Simple and Useful Marker

Background

Spontaneous bacterial peritonitis (SBP) is a common and life-threatening infection in patients with advanced cirrhosis. The prognostic value of a novel marker, the delta neutrophil index (DNI), was investigated relative to mortality in patients with SBP.

Materials & Methods

Seventy-five patients with SBP were studied from April 2010 to May 2012. DNI at initial diagnosis of SBP was determined and compared with 30-day mortality rates.

Results

Of the patients, 87.7% were men, and the median age of all patients was 59.0 yrs. The area under the receiver-operating characteristic (ROC) curve of DNI for 30-day mortality was 0.701 (95% confidence interval [CI], 0.553–0.849; p = 0.009), which was higher than that of C-reactive protein (0.640, 95% CI, 0.494–0.786; p = 0.076) or the model for end-stage liver disease score (0.592, 95% CI, 0.436–0.748; p = 0.235). From the ROC curve, with the sum of sensitivity and specificity, the cutoff value of DNI was determined to be 5.7%. In the high-DNI group (DNI ≥5.7%), septic shock and 30-day mortality were more prevalent compared with the low-DNI group (84.2% vs. 48.2%, p = 0.007; 57.9% vs. 14.3%, p<0.001, respectively). Patients with an elevated DNI had a higher risk of 30-day mortality compared with those with a low DNI (4.225, 95% CI, 1.631–10.949; p = 0.003).

Conclusion

A higher DNI at the time of SBP diagnosis is an independent predictor of 30-day mortality in patients with SBP.     

Postmortem Analyses Unveil the Poor Efficacy of Decontamination,Anti-Inflammatory and Immunosuppressive Therapies in Paraquat Human Intoxications

Background

Fatalities resulting from paraquat (PQ) self-poisonings represent a major burden of this herbicide. Specific therapeutic approaches have been followed to interrupt its toxic pathway, namely decontamination measures to prevent PQ absorption and to increase its excretion from organism, as well as the administration of anti-inflammatory and immunosuppressive drugs. Until now, none of the postmortem studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study.

Methodology/Principal Findings

For that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NF-κB) activation and excessive collagen deposition.

Conclusions/Significance

Considering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process.     

Hospitalization Rates and Post-Operative Mortality for Abdominal Aortic Aneurysm in Italy over the Period 2000–2011

Background

Recent studies have reported declines in incidence, prevalence and mortality for abdominal aortic aneurysms (AAAs) in various countries, but evidence from Mediterranean countries is lacking. The aim of this study is to examine the trend of hospitalization and post-operative mortality rates for AAAs in Italy during the period 2000–2011, taking into account the introduction of endovascular aneurysm repair (EVAR) in 1990s.

Methods

This retrospective cohort study was carried out in Emilia-Romagna, an Italian region with 4.5 million inhabitants. A total of 19,673 patients hospitalized for AAAs between 2000 and 2011, were identified from the hospital discharge records (HDR) database. Hospitalization rates, percentage of OSR and EVAR and 30-day mortality rates were calculated for unruptured (uAAAs) and ruptured AAAs (rAAAs).

Results

Adjusted hospitalization rates decreased on average by 2.9% per year for uAAAs and 3.2% for rAAAs (p<0.001). The temporal trend of 30-day mortality rates remained stable for both groups. The percentage of EVAR for uAAAs increased significantly from 2006 to 2011 (42.7 versus 60.9% respectively, mean change of 3.9% per year, p<0.001). No significant difference in mortality was found between OSR and EVAR for uAAAs and rAAAs.

Conclusions

The incidence and trend of hospitalization rates for rAAAs and uAAAs decreased significantly in the last decade, while 30-day mortality rates in operated patients remained stable. OSR continued to be the most common surgery in rAAAs, although the gap between OSR and EVAR recently declined. The EVAR technique became the preferred surgery for uAAAs since 2008.     

Risk and Prognostic Factors of Inpatient Mortality Associated with Unintentional Insecticide and Herbicide Poisonings: A Retrospective Cohort Study

Introduction

Pesticide poisoning is an important public health problem worldwide. The study aimed to determine the risk of all-cause and cause-specific inpatient mortality and to identify prognostic factors for inpatient mortality associated with unintentional insecticide and herbicide pesticide poisonings.

Methods

We performed a retrospective cohort study of 3,986 inpatients recruited at hospitalization between 1999 and 2008 in Taiwan. We used the International Classification of Disease, 9th ed., Clinical Modification external causes of injury codes to classify poisoning agents into accidental poisoning by insecticides and herbicides. Comparisons in mortality rates were made between insecticide poisoning patients and herbicide poisoning patients by using the Cox proportional hazards models to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs).

Results

There were 168 deaths during 21,583 person-days of follow-up evaluation (7.8 per 1,000 person-days). The major causes of mortality for insecticide poisonings were the toxic effect of organophosphate and coma, and the major causes of mortality for herbicide poisonings were the toxic effect of other pesticides and the toxic effect of organophosphate. The mortality for herbicide exposure was fourfold higher than that for insecticide exposure. The factors associated with inpatient mortality were herbicide poisonings (HR = 4.58, 95% CI 3.29 to 6.37) and receiving mechanical ventilation treatment (HR = 3.85, 95% CI 2.73 to 5.42).

Conclusions

We demonstrated that herbicides stand out as the dominant agent for poisoning-related fatalities. The control of and limiting access to herbicide agents and developing appropriate therapeutic regimens, including emergency care, should be priorities.     

Hypoalbuminemia Is a Strong Predictor of 30-Day All-Cause Mortality in Acutely Admitted Medical Patients: A Prospective,Observational, Cohort Study

Objective

Emergency patients with hypoalbuminemia are known to have increased mortality. No previous studies have, however, assessed the predictive value of low albumin on mortality in unselected acutely admitted medical patients. We aimed at assessing the predictive power of hypoalbuminemia on 30-day all-cause mortality in a cohort of acutely admitted medical patients.

Methods

We included all acutely admitted adult medical patients from the medical admission unit at a regional teaching hospital in Denmark. Data on mortality was extracted from the Danish Civil Register to ensure complete follow-up. Patients were divided into three groups according to their plasma albumin levels (0–34, 35–44 and ≥45 g/L) and mortality was identified for each group using Kaplan-Meier survival plot. Discriminatory power (ability to discriminate patients at increased risk of mortality) and calibration (precision of predictions) for hypoalbuminemia was determined.

Results

We included 5,894 patients and albumin was available in 5,451 (92.5%). A total of 332 (5.6%) patients died within 30 days of admission. Median plasma albumin was 40 g/L (IQR 37–43). Crude 30-day mortality in patients with low albumin was 16.3% compared to 4.3% among patients with normal albumin (p<0.0001). Patients with low albumin were older and admitted for a longer period of time than patients with a normal albumin, while patients with high albumin had a lower 30-day mortality, were younger and were admitted for a shorter period. Multivariable logistic regression analyses confirmed the association of hypoalbuminemia with mortality (OR: 1.95 (95% CI: 1.31–2.90)). Discriminatory power was good (AUROC 0.73 (95% CI, 0.70–0.77)) and calibration acceptable.

Conclusion

We found hypoalbuminemia to be associated with 30-day all-cause mortality in acutely admitted medical patients. Used as predictive tool for mortality, plasma albumin had acceptable discriminatory power and good calibration.     

Metabonomics Analysis of Plasma Reveals the Lactate to Cholesterol Ratio as an Independent Prognostic Factor of Short-Term Mortality in Acute Heart Failure

Objective

Mortality in heart failure (AHF) remains high, especially during the first days of hospitalization. New prognostic biomarkers may help to optimize treatment. The aim of the study was to determine metabolites that have a high prognostic value.

Methods

We conducted a prospective study on a training cohort of AHF patients (n = 126) admitted in the cardiac intensive care unit and assessed survival at 30 days. Venous plasmas collected at admission were used for ¹H NMR – based metabonomics analysis. Differences between plasma metabolite profiles allow determination of discriminating metabolites. A cohort of AHF patients was subsequently constituted (n = 74) to validate the findings.

Results

Lactate and cholesterol were the major discriminating metabolites predicting 30-day mortality. Mortality was increased in patients with high lactate and low total cholesterol concentrations at admission. Accuracies of lactate, cholesterol concentration and lactate to cholesterol (Lact/Chol) ratio to predict 30-day mortality were evaluated using ROC analysis. The Lact/Chol ratio provided the best accuracy with an AUC of 0.82 (P < 0.0001). The acute physiology and chronic health evaluation (APACHE) II scoring system provided an AUC of 0.76 for predicting 30-day mortality. APACHE II score, Cardiogenic shock (CS) state and Lact/Chol ratio ≥ 0.4 (cutoff value with 82% sensitivity and 64% specificity) were significant independent predictors of 30-day mortality with hazard ratios (HR) of 1.11, 4.77 and 3.59, respectively. In CS patients, the HR of 30-day mortality risk for plasma Lact/Chol ratio ≥ 0.4 was 3.26 compared to a Lact/Chol ratio of < 0.4 (P  =  0.018). The predictive power of the Lact/Chol ratio for 30-day mortality outcome was confirmed with the independent validation cohort.

Conclusion

This study identifies the plasma Lact/Chol ratio as a useful objective and simple parameter to evaluate short term prognostic and could be integrated into quantitative guidance for decision making in heart failure care.     

Incidence and Outcome of Early Acute Kidney Injury in Critically-Ill Trauma Patients

Objective

To determine the incidence and effect on mortality of early acute kidney injury in severely injured trauma patients using the Acute Kidney Injury Network creatinine criteria.

Design

A retrospective cohort study of severely injured trauma patients admitted to the shock trauma intensive care unit.

Setting

Texas Trauma Institute, a state designated level I trauma unit certified by the American College of Surgeons Committee on Trauma.

Patients

901 severely injured trauma patients admitted over a 15 month period to the shock trauma intensive care unit.

Interventions

Retrospective analysis of prospectively collected data abstracted from an electronic trauma database.

Measurements and Main Results

Of 901 eligible patients admitted to the shock trauma intensive care unit after traumatic injury, 54 patients (6%) developed acute kidney injury, of whom 10 (19%) required renal replacement therapy. The 30-day mortality rate for the entire cohort was 83/901 (9.2%). Patients with early acute kidney injury had a mortality rate of 16/54 (29.6%). When corrected for multiple covariates including injury severity scores, the development of early acute kidney injury was associated with a significantly higher risk of death at 30 days with an OR of 3.4 (95% CI 1.6-7.4).

Conclusions

Applying the Acute Kidney Injury Network creatinine criteria in severely injured trauma patients, the incidence of early acute kidney injury was 6%. After correction for injury severity, development of early acute kidney injury was independently associated with significantly higher 30-day mortality.     

Prognostic Value of Acute Kidney Injury after Cardiac Surgery according to Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) Criteria

Objectives

The definition of acute renal failure has been recently reviewed, and the term acute kidney injury (AKI) was proposed to cover the entire spectrum of the syndrome, ranging from small changes in renal function markers to dialysis needs. This study was aimed to evaluate the incidence, morbidity and mortality associated with AKI (based on KDIGO criteria) in patients after cardiac surgery (coronary artery bypass grafting or cardiac valve surgery) and to determine the value of this feature as a predictor of hospital mortality (30 days).

Methods

From January 2003 to June 2013, a total of 2,804 patients underwent cardiac surgery in our service. Cox proportional hazard models were used to determine the association between the development of AKI and 30-day mortality.

Results

A total of 1,175 (42%) patients met the diagnostic criteria for AKI based on KDIGO classification during the first 7 postoperative days: 978 (35%) patients met the diagnostic criteria for stage 1 while 100 (4%) patients met the diagnostic criteria for stage 2 and 97 (3%) patients met the diagnostic criteria for stage 3. A total of 63 (2%) patients required dialysis treatment. Overall, the 30-day mortality was 7.1% (2.2%) for patients without AKI and 8.2%, 31% and 55% for patients with AKI at stages 1, 2 and 3, respectively. The KDIGO stage 3 patients who did not require dialysis had a mortality rate of 41%, while the mortality of dialysis patients was 62%. The adjusted Cox regression analysis revealed that AKI based on KDIGO criteria (stages 1–3) was an independent predictor of 30-day mortality (P<0.001 for all. Hazard ratio = 3.35, 11.94 and 24.85).

Conclusion

In the population evaluated in the present study, even slight changes in the renal function based on KDIGO criteria were considered as independent predictors of 30-day mortality after cardiac surgery.     

Post-Stroke Mortality,Stroke Severity,and Preadmission Antipsychotic Medicine Use – A Population-Based Cohort Study

Background and Purpose

It has been suggested that antipsychotic medication may be neuroprotective and may reduce post-stroke mortality, but studies are few and ambiguous. We aimed to investigate the post-stroke effects of preadmission antipsychotic use.

Methods

We conducted a nationwide, population-based cohort study of 81,143 persons admitted with stroke in Denmark from 2003–2010. Using Danish health care databases, we extracted data on preadmission use of antipsychotics and confounding factors. We examined the association between current, former, and never use of antipsychotics and stroke severity, length of hospital stay, and 30-day post-stroke mortality using logistic regression analysis, survival analysis, and propensity score matching.

Results

Current users of antipsychotics had a higher risk of severe or very severe stroke on The Scandinavian Stroke Scale than never users of antipsychotics (adjusted odds ratios, 1.43; 95% CI, 1.29–1.58). Current users were less likely to be discharged from hospital within 30 days of admission than never users (probability of non-discharge, 27.0% vs. 21.9%). Antipsychotics was associated with an increased 30-day post-stroke mortality among current users (adjusted mortality rate ratios, 1.42; 95% CI, 1.29–1.55), but not among former users (adjusted mortality rate ratios, 1.05; 95% CI, 0.98–1.14).

Conclusions

Preadmission use of antipsychotics was associated with a higher risk of severe stroke, a longer duration of hospital stay, and a higher post-stroke mortality, even after adjustment for known confounders. Antipsychotics play an important role in the treatment of many psychiatric conditions, but our findings do not support the hypothesis that they reduce stroke severity or post-stroke mortality.     

A Novel Approach to Accounting for Loss to Follow-Up when Estimating the Relationship between CD4 Count at ART Initiation and Mortality

Background

While CD4 strongly predicts mortality on antiretroviral therapy (ART), estimates from programmatic data suffer from incomplete patient outcomes.

Methods

We conducted a pooled analysis of one-year mortality data on ART accounting for lost patients. We identified articles reporting one-year mortality by ART initiation CD4 count. We estimated the average mortality among those lost as the value that maximizes the fit of a regression of the natural log of mortality on the natural log of the imputed mean CD4 count in each band.

Results

We found 20 studies representing 64,426 subjects and 51 CD4 observations. Without correcting for losses, one-year mortality was >4.8% for all CD4 counts <200 cells/mm³. When searching over different values for mortality among those lost, the best fitting model occurs at 60% mortality. In this model, those with a CD4≤200 had a one-year mortality above 8.7, while those with a CD4>500 had a one-year mortality <6.8%. Comparing those starting ART at 500 vs. 50, one-year mortality risk was reduced by 54% (6.8 vs. 12.5%). Regardless of CD4 count, mortality was substantially higher than when assuming no mortality among those lost, ranging from a 23–94% increase.

Conclusions

Our best fitting regression estimates that every 10% increase in CD4 count at initiation is associated with a 2.8% decline in one-year mortality, including those lost. Our study supports the health benefits of higher thresholds for CD4 count initiation and suggests that reports of programmatic ART outcomes can and should adjust results for mortality among those lost.     

Metabolomic Derangements Are Associated with Mortality in Critically Ill Adult Patients

Objective

To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU) mortality in adults.

Rationale

Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasible.

Methods

We performed metabolomic profiling of plasma from 90 ICU subjects enrolled in the BWH Registry of Critical Illness (RoCI). We tested individual metabolites and a Bayesian Network of metabolites for association with 28-day mortality, using logistic regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites and the network were tested for replication in an independent cohort of 149 adults enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD) study.

Results

We tested variable metabolites for association with 28-day mortality. In RoCI, nearly one third of metabolites differed among ICU survivors versus those who died by day 28 (N = 57 metabolites, p<.05). Associations with 28-day mortality replicated for 31 of these metabolites (with p<.05) in the CAPSOD population. Replicating metabolites included lipids (N = 14), amino acids or amino acid breakdown products (N = 12), carbohydrates (N = 1), nucleotides (N = 3), and 1 peptide. Among 31 replicated metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine, 1-arachidonoylGPC(20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine). This network achieved a 91% AUC predicting 28-day mortality in RoCI, and 74% of the AUC in CAPSOD (p<.001 in both populations).

Conclusion

Both individual metabolites and a metabolomic network were associated with 28-day mortality in two independent cohorts. Metabolomic profiling represents a valuable new approach for identifying novel biomarkers in critically ill patients.     

Safety and Feasibility of Coronary Stenting in Unprotected Left Main Coronary Artery Disease in the Real World Clinical Practice—A Single Center Experience

Background

This study evaluated the feasibility, safety, and prognostic outcome in patients with significant unprotected left main coronary artery (ULMCA) disease undergoing stenting.

Method and Results

Between January 2010 and December 2012, totally 309 patients, including those with stable angina [13.9% (43/309)], unstable angina [59.2% (183/309)], acute non-ST-segment elevation myocardial infarction (NSTEMI) [24.3% (75/309)], and post-STEMI angina (i.e., onset of STEMI<7 days) [2.6% (8/309)] with significant ULMCA disease (>50%) undergoing stenting using transradial arterial approach, were consecutively enrolled. The patients’ mean age was 68.9±10.8 yrs. Incidences of advance congestive heart failure (CHF) (defined as ≥ NYHA Fc 3) and multi-vessel disease were 16.5% (51/309) and 80.6% (249/309), respectively. Mechanical supports, including IABP for critical patients (defined as LVEF <35%, advanced CHF, or hemodynamically unstable) and extra-corporeal membrane oxygenator (ECMO) for hemodynamically collapsed patients, were utilized in 17.2% (53/309) and 2.6% (8/409) patients, respectively. Stent implantation was successfully performed in all patients. Thirty-day mortality rate was 4.5% (14/309) [cardiac death: 2.9% (9/309) vs. non-cardiac death: 1.6% (5/309)] without significant difference among four groups [2.3% (1) vs. 2.7% (5) vs. 9.3% (7) vs. 12.5% (1), p = 0.071]. Multivariate analysis identified acute kidney injury (AKI) as the strongest independent predictor of 30-day mortality (p<0.0001), while body mass index (BMI) and white blood cell (WBC) count were independently predictive of 30-day mortality (p = 0.003 and 0.012, respectively).

Conclusion

Catheter-based LM stenting demonstrated high rates of procedural success and excellent 30-day clinical outcomes. AKI, BMI, and WBC count were significantly and independently predictive of 30-day mortality.