Acute Organ Failure Research Articles

Organ Failure Associated with Acute Pancreatitis in African American and Hispanic Patients

Background and purpose Severe acute pancreatitis occurs in about 10% of cases of acute pancreatitis, and is associated with high mortality. Many studies have been published about acute pancreatitis and organ failure, but few address this issue among African Americans and Hispanics. As most of our patients belong to these two ethnic groups, we studied the relationship between acute pancreatitis and organ failure in this population. Methods Our study included all patients diagnosed with acute pancreatitis over 15 years. Medical records of 760 (417 African American & 343 Hispanic) patients, ages 19–85 years were reviewed retrospectively. We abstracted and analyzed data related to demographics, etiology and type of pancreatitis, organ failure, and mortality. Results Of the 760 patient, 47% were male, 42% had biliary stones, 18% had necrotizing pancreatitis, and 24% had organ failure. Of the 182 patients with organ failure, 125 patients (69%) had multiple organ failure, whereas 57 patients (31%) had dysfunction of a single organ system. Cardiovascular system failure was the most common organ dysfunction (26%) among patients with single organ failure. The occurrence of organ failure varied significantly by age and type of pancreatitis (P 0.05). Of the 760 patients, 109 patients (14.3%) died. Patients with organ failure had a higher mortality (34%) compared with those without organ failure (6%) (OR = 23.7, 95% CI = 13.7–41.2) Mortality was higher among those with multiple organ failure (38%) compared with those with single organ failure type (25%). Mortality varied significantly by type of organ failure, being highest among those with pulmonary dysfunction (60%), followed by central nervous system dysfunction (36%) (P = 0.003). Conclusion Organ failure is a serious complication in patients with acute pancreatitis. Patients with multiple organ failure and those with pulmonary failure have higher mortality relative to other groups. Prevention and active treatment of organ failure may improve the outcome of patients with acute pancreatitis.

Prognostic Value of Cytochrome C and Cytokines in Acute Viral Encephalopathy

Serum cytochrome c and cytokines were evaluated as prognostic predictors in 29 children (ages 9 mos to 9 yrs 11 mos) with viral acute encephalopathies and multiple organ failure at Fukushima Medical University School of Medicine, Japan.

Heme oxygenase‐1: a new drug target in oxidative tissue injuries in critically ill conditions

AbstractOxidative stresses associated with ischemia/reperfusion, neutrophil activation, and anesthesia with certain volatile agents, etc., are thought to play an important role in the development of acute organ failure in critical illnesses, such as acute lung injury, acute coronary artery insufficiency, acute liver failure, acute renal failure, and multiple organ dysfunction syndrome. Such oxidative stressors provoke a set of cellular responses, particularly those that participate in the defense against tissue injuries. Free heme, which can be rapidly released from hemeproteins, may constitute a major threat in the oxidant stress because it catalyzes the formation of reactive oxygen species. To counteract such insults, cells respond by inducing the 33‐kDa heat shock protein, heme oxygenase (HO)‐1, the rate‐limiting enzyme in heme degradation. Induced HO‐1 as such removes free heme by an enzymatic process. In addition, HO‐1 induction itself confers protection to tissues from further oxidative injuries. In contrast, the abrogation of HO‐1 induction, or chemical ablation of HO activity abolishes the beneficial effect of HO‐1, and results in the aggravation of tissue injuries. In this article, we review recent advances in the essential role of HO‐1 in tissue protection in various models of experimental oxidative tissue injuries as well as in human disorders, which is related to critically ill conditions, with special emphasis on the role of its induction in tissue defense and its potential therapeutic implications. Drug Dev. Res. 67:130–153, 2006. © 2006 Wiley‐Liss, Inc.

The role of body mass index and diabetes in the development of acute organ failure and subsequent mortality in an observational cohort

IntroductionSeveral studies have shown a correlation between body mass index (BMI) and both the development of critical illness and adverse outcomes in critically ill patients. The goal of our study was to examine this relationship prospectively with particular attention to the influence of concomitant diabetes mellitus (DM).MethodsWe analyzed data from 15,408 participants in the Atherosclerosis Risk in Communities (ARIC) study for this analysis. BMI and the presence of DM were defined at baseline. We defined 'acute organ failure' as those subjects who met a standard definition with diagnostic codes abstracted from hospitalization records. Outcomes assessed included the following: risk of the development of acute organ failure within three years of the baseline examination; in-hospital death while ill with acute organ failure; and death at three years among all subjects and among those with acute organ failure.ResultsAt baseline, participants with a BMI of at least 30 were more likely than those in lower BMI categories to have DM (22.4% versus 7.9%, p < 0.01). Overall, BMI was not a significant predictor of developing acute organ failure. The risk for developing acute organ failure was increased among subjects with DM in comparison with those without DM (2.4% versus 0.7%, p < 0.01). Among subjects with organ failure, both in-hospital mortality (46.5% versus 12.2%, p < 0.01) and 3-year mortality (51.2% versus 21.1%, p < 0.01) was higher in subjects with DM.ConclusionOur findings suggest that obesity by itself is not a significant predictor of either acute organ failure or death during or after acute organ failure in this cohort. However, the presence of DM, which is related to obesity, is a strong predictor of both acute organ failure and death after acute organ failure.

Prognostic Factors for Neutropenic Patients Admitted to Intensive Care.

The admission of neutropenic patients (pts) to intensive care units (ICU) is controversial, especially when mechanical ventilation is required. Knowledge of the relative prognostic impact of factors related to the underlying disease and to the severity of acute organ failures might help avoiding futile admissions. We retrospectively assessed predictors of 30-day mortality in neutropenic (<1000/ul) pts referred from a single Hematology unit to the 2 ICUs of the institution over a 10-year period. Of 66 consecutive pts, median age 48 (15–73), 82% had acute leukemia (AL) and 21% were in complete remission (CR). On ICU admission 62% of the pts had a neutrophil count ≤500/ul; microbiologically documented infection was found in 42%. The main reason for ICU referral was severe sepsis or septic shock in 62% of the cases and respiratory failure in 38%. Seventy per cent of the pts were already on vasopressor agents. At ICU entry the median Simplified Acute Physiology Score (SAPS) II was 63 and 26% of pts had ≥ 2 acute organ system failures (OSF). Coma was present in 23%. Mechanical ventilation was eventually needed in 89% and dialysis in 9% of the pts. Mortality at 30 days was 73%. By univariate logistic regression analysis mortality was not significantly related to age, to status of underlying disease (CR vs no CR/not yet known) to duration of neutropenia nor to depth of neutropenia at entry (≤ 500 vs >500/ul). Pts who died were more likely to have non-M3 AL subtype vs M3 (p=0.037), to have ≥ 2 acute OSF vs < 2 (p=0.012) and a higher SAPS II score (p< 0.001). In multivariate analysis only the latter 2 variables remained significant. In conclusion, our data show that 27% of neutropenic pts admitted to ICUs are alive at 30 days; that selection for admission should not be based on the characteristics of the underlying malignancy; and that the 30-day mortality is highly predictable by initial acute illness severity scores.

Dringlichkeit, Erfolgsaussicht, Chancengleichheit

One of the most important aspects in the treatment of patients with chronic or acute organ failure is the regulatory framework for allocating organs donated after death. The existing framework is transparent and fulfills the primary ethical requirements of fairness and equality of chances. The Continual Organ Transplantation Commission of the Federal Medical Council has been assigned to adapt the regulatory framework for organ allocation to the latest findings of scientific research. Thus, the regulations can be implemented by the contractually responsible organ allocation organization, Eurotransplant. Transplantation centers have to make sure that they can decide on an organ offer at any time with respect to organization and staff so that an accepted organ can be transplanted immediately and the ischemia phase minimized. Improvements of the precarious allocation situation will, however, only be possible, if the number of post-mortem donated organs can be increased significantly.

Organ failure associated with acute pancreatitis in African American and Hispanic patients

Background and purpose Severe acute pancreatitis occurs in about 10% of cases of acute pancreatitis, and is associated with high mortality. Many studies have been published about acute pancreatitis and organ failure, but few address this issue among African Americans and Hispanics. As most of our patients belong to these two ethnic groups, we studied the relationship between acute pancreatitis and organ failure in this population. Methods Our study included all patients diagnosed with acute pancreatitis over 15 years. Medical records of 760 (417 African American & 343 Hispanic) patients, ages 19–85 years were reviewed retrospectively. We abstracted and analyzed data related to demographics, etiology and type of pancreatitis, organ failure, and mortality. Results Of the 760 patient, 47% were male, 42% had biliary stones, 18% had necrotizing pancreatitis, and 24% had organ failure. Of the 182 patients with organ failure, 125 patients (69%) had multiple organ failure, whereas 57 patients (31%) had dysfunction of a single organ system. Cardiovascular system failure was the most common organ dysfunction (26%) among patients with single organ failure. The occurrence of organ failure varied significantly by age and type of pancreatitis (P 0.05). Of the 760 patients, 109 patients (14.3%) died. Patients with organ failure had a higher mortality (34%) compared with those without organ failure (6%) (OR = 23.7, 95% CI = 13.7–41.2) Mortality was higher among those with multiple organ failure (38%) compared with those with single organ failure type (25%). Mortality varied significantly by type of organ failure, being highest among those with pulmonary dysfunction (60%), followed by central nervous system dysfunction (36%) (P = 0.003). Conclusion Organ failure is a serious complication in patients with acute pancreatitis. Patients with multiple organ failure and those with pulmonary failure have higher mortality relative to other groups. Prevention and active treatment of organ failure may improve the outcome of patients with acute pancreatitis.

New Strategies in Immunosuppression

New immunosuppressive strategies that can prevent both acute and chronic rejection are being investigated to achieve graft tolerance and to minimize side effects and toxicity that may lead to graft loss. Drug pharmacokinetics and pharmacodynamics, as well as pharmacogenetics, all play a role in customizing treatment to the individual patient. To improve patient compliance, new drug formulations are on trial, such as the modified- release oral form of tacrolimus MR4 for once daily administration, which seems to be equivalent to bid administration in terms of steady-state exposure. Monoclonal/polyclonal antibodies are increasingly used in the induction phase in protocols where steroids are discontinued early. However, discontinuing steroids carries a high risk of acute rejection or organ failure in some subgroups of patients. The supposed benefit of steroid discontinuation may not be enjoyed by all patients. Minimizing anticalcineurin agents may prove to be similarly or even more advantageous. The use of new drugs and new combinations has greatly improved short-term transplant outcomes. The new goal is, therefore, to improve long-term results and particularly to prevent chronic rejection, thus increasing patient and organ survival.

Fracture Hematoma Is a Potent Proinflammatory Mediator of Neutrophil Function

Patients with multiple skeletal injuries are susceptible to acute respiratory distress syndrome and multiple organ failure, which result from hyperactivation of the immune system. This study was designed to evaluate in vitro the proinflammatory properties of fracture hematoma (FH). FH was isolated from patients undergoing emergent open reduction and internal fixation for isolated closed fractures. Neutrophils (PMNs), isolated from healthy volunteers, were exposed to the FH supernatant and activation was examined (CD11b and CD18 adhesion receptor expression and respiratory burst). PMN phagocytosis, apoptosis, and transmigration across an endothelial barrier were also assessed. FH increased PMN respiratory burst (control, 100; FH-treated, 186) and phagocytosis (control, 100; FH-treated, 172) but had no effect on adhesion receptor expression. Transendothelial migration of PMNs was unaffected, although FH was toxic to endothelial cells. In contrast, apoptosis of FH-treated PMNs was delayed (control, 46; FH-treated, 8). These effects, although beneficial at the site of injury in the context of antibactericidal function, may cause PMN-mediated tissue injury systemically.

Outcomes of critically ill cancer patients aged ≥ 70 years

6075 Background: Information about outcome predictors for older patients requiring critical care is limited. Our objective was to identify characteristics associated with increased six-month mortality. Methods: From May 2000 and May 2004, every cancer patient aged ≥70 years admitted to our medical-surgical intensive care unit (ICU) because of a severe illness was prospectively evaluated. Patients with acute coronary syndromes and those who had been considered cured from their cancer for > 5 years were excluded. Data were collected at admission and during ICU stay. Patients were categorized according to their age in three groups: 70–74 (n=114), 75–79 (n=60) and ≥ 80 (n=46) years old. Variables selected in the univariate analysis (p<0.25) were entered into a multivariable Cox proportional hazards regression model having as the dependent variable the six-month mortality. Results: A total of 220 patients were included and the mean age was 76±5 (range: 70–98) years. There were 185 (84%) patients with solid tumors and 35 (14%) patients had hematologic malignancies. The main reasons for ICU admission were sepsis (46%) and acute respiratory failure (11%). During ICU stay, 155 (70%) patients received mechanical ventilation and 26 (12%), hemodialysis. The hospital and six-month mortality rates were respectively, 59% and 64%. End-of-life decisions were taken in 37 (17%) patients. Baseline characteristics were similar for the three groups. The following variables were selected in the Cox model: performance status (PS) 3–4 [hazard ratio (HR)=1.67(95% confidence interval (CI)=1.1–2.54)]; uncontrolled newly-diagnosed cancer [HR=1.92(95% CI=1.22–3.02)]; cancer recurrence/progression [HR=1.90(95% CI=1.24–2.90)]; number of organ failures (OF) [HR=2.78(95% CI=1.60–4.82), for patients with 1–2 OF and HR=7.19(4.05–12.78), for patients with >2 OF]; and age ≥ 80 years [HR=1.91(1.25–1.93)]. Conclusions: The severity of acute organ failures, poor PS and uncontrolled cancer were the main determinants of increased six-month mortality. Among older critically ill cancer patients, those aged ≥ 80 years had a worse prognosis. Older patients should not be denied ICU care on the basis of age alone. No significant financial relationships to disclose.

Oxidative stress in organ preservation: a multifaceted approach to cardioplegia

Every transplant is a reperfused organ and, therefore, undergoes some degree of oxidative damage. Postischemic reperfusion injury results in non-specific free radical-mediated acute endothelial damage, cell death and organ failure. The endothelium is a key site of injury from reactive oxygen species (ROS), and the endothelial cell dysfunction is central to the pathogenesis of arteriosclerosis. Accelerated arteriosclerosis, secondary to chronic allograft rejection, is a major long-term complication of heart transplantation. Therefore, preservation methods that would decrease injury during reperfusion are very important. We have developed a unique preservation solution, with a multifaceted approach, which best preserves the organ from ROS for an extended period of time before transplantation. The advantages of extending this period of preservation include an expansion of the donor pool, by permitting more distant procurement, the ability to perform detailed tissue typing, therefore, improves histocompatibility match and a reduction in emergency surgery as a result of graft rejection.

The Effects of Surgical Fracture Fixation on the Systemic Inflammatory Response to Major Trauma

Early stabilization of major long bone fractures is beneficial in reducing the incidence of acute respiratory distress syndrome and multiple organ failure, both of which are caused by activation of the systemic inflammatory response. This activation results in tissue recruitment of and injury by circulating polymorphonuclear leukocytes. The reasons for clinical benefits of early fracture stabilization in major trauma are unknown. Published studies indicate that fracture surgery increases the posttraumatic inflammatory response. Major surgery to stabilize fractures carries a higher complication rate when performed on patients whose hypovolemic shock is not fully corrected. Thus, fracture care should be tailored to the patient, not dictated by the injured bone. Understanding the impact of fracture surgery on the systemic inflammatory response to major trauma is necessary to refine treatment and to apply it optimally to all patients.

Characteristics and outcomes of cancer patients requiring mechanical ventilatory support for &gt;24 hrs*

To describe the characteristics of a large cohort of cancer patients receiving mechanical ventilation for >24 hrs and to identify clinical features predictive of in-hospital death. Prospective cohort study. Ten-bed oncologic medical-surgical intensive care unit. A total of 463 consecutive patients were included over a 45-month period. None. Data were collected on the day of admission to the intensive care unit. The intensive care unit and hospital mortality rates were 50% and 64%, respectively. There were 359 (78%) patients with solid tumors and 104 (22%) with hematologic malignancies; 35 (8%) patients had leukopenia. Sepsis (63%), coma (15%), invasion or compression by tumor (11%), pulmonary embolism (7%), and cardiopulmonary arrest (6%) were the main reasons for mechanical ventilation. The independent unfavorable risk factors for mortality were older age (odds ratio, 3.09; 95% confidence interval, 1.61-5.93, for patients 40-70 yrs old, and odds ratio, 9.26; 95% confidence interval, 4.16-20.58, for patients >70 yrs old); performance status 3-4 (odds ratio, 2.51; 95% confidence interval, 1.40-4.51); cancer recurrence/progression (odds ratio, 3.43; 95% confidence interval, 1.81-6.53); Pao2/Fio2 ratio <150 (odds ratio, 2.64; 95% confidence interval, 1.40-4.99); Sequential Organ Failure Assessment score (excluding respiratory domain, each 4 points; odds ratio, 2.34; 95% confidence interval, 1.70-3.24); and airway/pulmonary invasion or compression by tumor as a reason for mechanical ventilation (odds ratio, 5.73; 95% confidence interval, 1.92-17.08). Severity of acute organ failures, poor performance status, cancer status, and older age were the main determinants of mortality. The appropriate use of such easily available clinical characteristics may avoid forgoing intensive care for patients with a chance of survival.

Damage Control Orthopaedics

In some groups of polytrauma patients, particularly those with chest injuries, head injuries, and those with mangled extremities, early total care of major bone fractures may be potentially harmful. Delaying all orthopaedic surgery, however, is also not always the best approach. In these situations, damage control orthopaedics, which emphasizes the stabilization and control of the injury rather than repair will add little additional physiologic insult to the patient and is a treatment option that should be considered.

Impact of two different comorbidity measures on the 6-month mortality of critically ill cancer patients

To evaluate the impact of two different comorbidity measures on the 6-month mortality of severely ill cancer patients. Prospective cohort study in a ten-bed oncological medical-surgical intensive care unit (ICU). A total of 772 consecutive patients were included over a 45-month period. The mean age was 57.6+/-16.4 years, and 642 (83%) patients had solid tumors. Data were collected on admission and during ICU stay. Comorbidities were evaluated using the Charlson Comorbidity Index (CCI) and the Adult Comorbidity Evaluation (ACE-27). The ICU, hospital, and 6-month mortality rates were 34%, 47%, and 58%, respectively. The most frequent comorbidities were hypertension (33%), diabetes mellitus (8%), and chronic pulmonary disease (7%). There were important differences between the two indices regarding the comorbidity evaluation. Using the ACE-27, 389 patients (50%) had comorbid ailments that were classified as mild (31%), moderate (14%), and severe (5%) according to the comorbidity severity. According to the CCI, 212 patients (27%) had a comorbidity, and their median score was 1 (1-2). In the multivariable Cox proportional hazard models only the presence of a severe comorbidity by the ACE-27 was associated with increased mortality. The CCI was not independently associated with the outcome. Other outcome predictors were older age, poor performance status, active cancer, need of mechanical ventilation, and severity of acute organ failures. Severe comorbidities must be considered in the outcome evaluation of ICU cancer patients. The ACE-27 seems to be a useful instrument for prognostic assessment in this population.

Risk factors of mortality for nosocomial pneumonia: importance of initial anti-microbial therapy

Nosocomial pneumonia is a common nosocomial infection and has high mortality rate. Risk factors of mortality of nosocomial pneumonia were studied in 132 hospitalised patients who developed nosocomial pneumonia. The overall mortality rate was 64/132, 48.5%. Of the 11 risk factors univariately associated with mortality due to nosocomial pneumonia, only the inappropriate initial anti-microbial therapy, high simplified acute physiology score and multiple organ failures remained significant after stepwise logistic regression. Gram-negative bacilli were still the most pre-dominant causative microbiologic agents of nosocomial pneumonia with Pseudomonas aeruginosa (20.3%), Acinetobacter baumannii (18.6%) and Escherichia coli (5.9%) being the three most predominant pathogens. A. baumannii were significantly more predominant among non-survivors than survivors (13.56 vs. 5.08%, p=0.0418). The incidence rate of methicillin-resistant Staphylococcus aureus was 19.5% higher than previous reports. We conclude that inappropriate initial anti-microbial therapy for nosocomial pneumonia is associated with the mortality rate of nosocomial pneumonia, and appropriate anti-microbial therapy improves outcome of nosocomial pneumonia.

Hemoconcentration is a poor predictor of severity in acute pancreatitis

To determine whether the hematocrit (Hct) at admission or at 24 h after admission was associated with severe acute pancreatitis (AP), organ failure (OF), and pancreatic necrosis. A total of 336 consecutive patients with a first AP episode were studied. Etiology, Hct values at admission and at 24 h, development of severe AP according to Atlanta's criteria, pancreatic necrosis, OF and mortality were recorded. Hemoconcentration was defined as Hct level >44% for males and >40% for females. The t-test and chi2 test were used to assess the association of hemoconcentration to the severity, necrosis and OF. Diagnostic accuracy was also determined. Biliary disease was the most frequent etiology (n = 148). Mean Hct levels at admission were 41+/-6% for females and 46+/-7% for males (P<0.01). Seventy-eight (23%) patients had severe AP, and OF developed in 45 (13%) patients. According to contrast-enhanced computed tomography scan, 36% (54/150) patients showed pancreatic necrosis. Hct levels were elevated in 58% (55/96) and 61% (33/54) patients with interstitial and necrotizing pancreatitis, respectively. Neither Hct levels at admission nor hemoconcentration at 24 h were associated with the severity, necrosis or OF. Sensitivity, specificity and positive predictive values for both determinations were very low; and negative predictive values were between 61% and 86%, being the highest value for OF. Hct is not a useful marker to predict a worse outcome in acute pancreatitis. In spite of the high negative predictive value of hemoconcentration, the prognosis gain is limited due to an already high incidence of mild disease.

Usefulness of Troponin-I, Lactate, C-reactive protein as a Prognostic Markers in Critically Ill Non-cardiac Patients

Background : The severity scoring system is useful for predicting the outcome of critically ill patients. However, the system is quite complicated and cost-ineffective. Simple serologic markers have been proposed to predict the outcome, which include troponin-I, lactate and C-reactive protein(CRP). The aim of this study was to evaluate the prognostic values of troponin-I, lactate and CRP in critically ill non-cardiac patients. Methods : From September 2003 to June 2004, 139 patients(Age: , M:F = 88:51), who were admitted to the MICU with non-cardiac critical illness at Gyeongsang National University Hospital, were enrolled in this study. This study evaluated the severity of the illness and the multi-organ failure score (Acute Physiologic and Chronic Health EvaluationII, Simplified Acute Physiologic ScoreII and Sequential Organ Failure Assessment) and measured the troponin-I, lactate and CRP within 24 hours after admission in the MICU. Each value in the survivors and non-survivors was compared at the 10th and 30th day after ICU admission. The mortality rate was compared at 10th and 30th day in normal and abnormal group. In addition, the correlations between each value and the severity score were assessed. Results : There were significantly higher troponin-I and CRP levels, not lactate, in the non-survivors than in the survivors at 10th day(, vs. , ) (p, , vs. , , ) (p, 0.365, p

Characteristics and Outcomes of Critically Ill Patients with Hematologic Malignancies.

The outcome of patients with hematologic malignancies (HM) requiring admission to the intensive care unit (ICU) seems to be improving as a consequence of recent advances in oncology and intensive care. However, their mortality remains exceedingly high, and a reappraisal of their outcome predictors might provide useful clinical insights. During 45 months, every consecutive patient with HM admitted to an exclusively oncologic ICU because of a severe illness was studied. Patients with an ICU stay <8h or with acute coronary syndromes were excluded. Bone marrow transplant patients were not studied because they are treated at a separate unit. The following variables were collected at admission and during ICU stay: age, gender, performance status, type and clinical status of HM, neutropenia (neutrophil count<500/mm3), infection at admission, use of invasive or non-invasive ventilation (NIV), the Simplified Acute Physiology Score (SAPS) II, the Sequential Organ Failure Assessment (SOFA), the Charlson Comorbidity Index (CI) and individual acute organ failures developing during the ICU stay. Variables selected in the univariate analysis (p<0.25) were entered in a Cox proportional-hazard regression model. In multivariate analysis, results were expressed as hazard-ratios (HR) (confidence interval 95%). Mortality at six months was the end-point of interest. A total of 156 patients with HM were admitted to the ICU. Three patients were lost for follow-up after hospital discharge and 153 patients were studied. Mean age was 51±18 years and 56% were males. SAPS II was 59±19 points and SOFA was 9±4 points. The median CI was 0 (interquartile range: 0–2) and 58 (40%) patients had a comorbid condition. Diagnoses of HM were non-Hodgkin's lymphoma (52%), multiple myeloma (14%), acute leukemia (12%), chronic leukemia (12%), Hodgkin's disease (7%) and other (3%). Thirty-six (24%) patients had leukopenia. The most frequent reason for ICU admission was acute respiratory failure (80%) and 111(73%) patients had sepsis. During ICU stay, 125 (82%) patients received mechanical ventilation (NIV=11), 104 (68%), vasopressors and 24 (16%), dialysis. Decisions to withhold or withdraw treatment were implemented in 40 (26%) patients and all of them died at the ICU. Among all patients, the ICU, in-hospital and 6-month mortality rates were 53%, 65% and 78%, respectively. Six-month mortality rates were lower for Hodgkin's disease (62%) and higher for high-grade non-Hodgkin lymphoma (84%). Unfavorable variables selected in the multivariate analysis were: active newly diagnosed HM [HR=1.71(1.03–2.85)], recurrence/progression [HR=2.60(1.58–4.29)], vasopressors need [HR=2.38(1.49–3.79)] and hematologic dysfunction [1.69(1.15–2.48)]. Acute organ failure (cardiovascular and hematologic dysfunctions) and cancer status were the main determinants of six-month mortality. Age, neutropenia and type of HM had no impact in the outcome. The appropriate use of such easily available clinical characteristics may avoid forgoing intensive care for patients with a chance of survival.

Pro-apoptotic effect of curcumin on human polymorphonuclear leukocytes (PMNS): Decreased nuclear NF-KB activity

Phytochemical curcumin (Cur), a promising dietary supplement for cancer prevention and liver protection, has been shown to induce tumor cell apoptosis (Ao). However, the effect of Cur on PMN Ao and the underlying mechanisms remain unknown. Methods. PMNs (10 6 cells/ml) freshly isolated from normal volunteers were incubated in vitro in the presence or absence of Cur (10–50 μM). Ao was examined by morphology and TUNEL analyses. The effect of Cur on LPS (100 ng/ml)-induced Ao inhibition was also studied. Myeloidperoxidase (MPO) activity was analyzed to determine the effect of Cur on PMN degranulation. To elucidate the potential mechanism, nuclear NF-kB activity was examined by EMSA. Statistical analysis was performed by ANOVA and Tukey’s test. Results. The data demonstrated that Cur increased PMN Ao from 7.17 ± 0.29 at 0 μM to 28.0 ± 2.0% at 40 μM after 6 h incubation ( P < 0.05). LPS-induced Ao suppression was also reversed by Cur (Fig. 1). PMN degranulation was inhibited by Cur as measured by a significant decrease in MPO activities (Table). The inhibition of nuclear NF-kB activity (58% at 1 h and 54% at 2 h) induced by LPS appears to contribute to the pro-apoptotic effect of Cur (Fig. 2). Conclusions. Since the delayed PMN Ao exacerbates acute respiratory distress syndrome and multiple organ failure, the characteristics of curcumin, including pro-apoptotic effects and anti-degranulation potential, make it a potential candidate for prevention and treatment of lung inflammation and injury. TABLE—ABSTRACT 13 Group MPO activity (absorbance ± SD) Medium 0.012 ± 0.002 LPS 0.101 ± 0.021 ∗ LPS + Cur (10 μ M) 0.103 ± 0.006 ∗ LPS + Cur (30 μ M) 0.018 ± 0.003 # LPS + Cur (50 μ M) 0.014 ± 0.002 # (6 h incubation, n = 6, ∗ P < 0.05 versus medium. # P < 0.05 versus LPS alone)