Intensive care unit support and Acute Physiology and Chronic Health Evaluation III performance in hematopoietic stem cell transplant recipients

OBJECTIVE: Hematopoietic stem cell transplant (HSCT) recipients admitted to the intensive care unit (ICU) have high mortality. The prognostic importance of peripheral blood stem cell source in critically ill HSCT recipients and the performance of Acute Physiology and Chronic Health Evaluation (APACHE) III have not been well studied. In a previous study, the hospital mortality rate of HSCT recipients admitted to our ICU was 77%. The objectives of this study were to describe the clinical course of HSCT recipients admitted to the ICU and to determine the performance of APACHE III in predicting their mortality. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: HSCT recipients admitted to the ICU. MEASUREMENTS: Demographics, transplant type, stem cell source, APACHE II and III predicted mortality, development of sepsis and organ failure, use of mechanical ventilation, duration of hospital stay, and mortality. RESULTS: Ninety-four percent of the 112 HSCT recipients were white and 64% male. The mean APACHE II and III scores were 25 and 44, respectively. The APACHE II and III hospital predicted mortality rates were 44% and 42%, respectively. Mechanical ventilation was provided to 63%. Organ failure developed in 94% and sepsis in 62%. The ICU, hospital, and 30-day mortality rates were 33%, 46%, and 52%, respectively. Allogeneic transplant and higher APACHE III scores, but not bone marrow stem cell source, were associated with increased mortality. Invasive mechanical ventilation, vasoactive medication use, sepsis, and organ failure during patients' ICU course were also associated with increased mortality. The area under the receiver operating characteristic curve for APACHE III hospital mortality prediction was 0.704 (95% confidence interval, 0.610-0.786). For APACHE III hospital mortality prediction, the value of the Hosmer-Lemeshow statistic showed good model fit. CONCLUSIONS: Current mortality figures of HSCT recipients admitted to the ICU are better than previously reported. The APACHE III prognostic model has moderate discrimination and good calibration in predicting hospital mortality in these patients.     

Transfusion from male-only versus female donors in critically ill recipients of high plasma volume components

OBJECTIVE: To reduce the incidence of transfusion-related acute lung injury (ALI), the American Association of Blood Banks recently recommended rapid implementation of strategies to minimize transfusion of high plasma volume components, fresh frozen plasma and apheresis platelets, from potentially alloimmunized donors, especially females. The objective of this study was to evaluate the effect of transfusing components from male-only vs. female donors on development of ALI, gas exchange, and outcome in critically ill patients. DESIGN: In this retrospective case-control study, we identified patients who received high plasma volume components from male-only donors and compared them with patients matched by severity of illness, postoperative state, and number of transfusions but who received high plasma volume components from female donors. SETTING: Four intensive care units at a tertiary medical center. PATIENTS: Critically ill patients who received >2 units of fresh frozen plasma or apheresis platelets. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From a database of 3,567 patients who received a total of 46,101 units of fresh frozen plasma and 6,251 units of apheresis platelets, we identified 112 patients who received three or more male-only donor components and 112 matched controls. Baseline characteristics, ALI risk factors, and development of ALI were similar between the two groups. Arterial oxygenation (PaO2/FIO2) worsened after the female (mean difference -52, 95% confidence interval -14 to -91, p = .008) but not after male-only donor product transfusion (mean difference 22, 95% confidence interval -23 to 67, p = .325). Male-only component recipients had more ventilator-free days (median 28 vs. 27, p = .006) and a trend toward lower hospital mortality rates (14% vs. 24%, p = .054). CONCLUSIONS: In critically ill recipients of high plasma volume components, gas exchange worsened significantly after transfusion of female but not male donor components. Prospective studies are needed to evaluate the effect of recommendations by the American Association of Blood Banks on outcome of transfused critically ill patients.     

Epidemiology of treatment-associated mucosal injury after treatment with newer regimens for lymphoma, breast, lung, or colorectal cancer

Goals of work: Oral and gastrointestinal (GI) mucositis are frequent complications of chemotherapy and radiotherapy for cancer, contributing to not only the morbidity of treatment but its cost as well. The risk associated with specific chemotherapeutic agents, alone and in combination, has been characterized previously. In the current study, we sought to estimate the risk associated with newer regimens for the treatment of non-Hodgkin’s lymphoma (NHL) and common solid tumors. Methods: We reviewed published studies reporting phase II and III clinical trials of dose-dense regimens for breast cancer and NHL, TAC (docetaxel, adriamycin, cyclophosphamide) chemotherapy for breast cancer, and infusional 5-fluorouracil-based regimens for colorectal cancer. Platinum-, gemcitabine-, and taxane-based regimens for lung cancer, either alone or in combination with radiotherapy, were also considered. Using modified meta-analysis methods, we calculated quality-adjusted estimates of the risk for oral and GI mucositis by tumor type and regimen. Case reports are used to emphasize the relevance of the findings for patient care. Main results: Our findings demonstrate that mucosal toxicity remains an important complication of cancer treatment. Moreover, innovations in drug combinations, scheduling, or mode of administration significantly modulate the risk for both oral and GI mucositis. Conclusions: Ongoing review of the clinical trial experience will remain important as newer, targeted agents enter standard clinical practice.     

Systemic inflammatory response syndrome in patients hospitalized for gastrointestinal bleeding

OBJECTIVE: To describe the incidence and causes of systemic inflammatory response syndrome (SIRS), to determine the risk factors for its development, and to assess its impact on the outcome of patients hospitalized for gastrointestinal bleeding. DESIGN: Prospective, observational study. SETTING: A 528-bed, university-affiliated, teaching hospital. PATIENTS: The study included 411 adults hospitalized for gastrointestinal bleeding from January 1, 1995, through June 30, 1996. MEASUREMENTS: We obtained the demographic data, selected clinical findings, laboratory values, length of hospital stay, presence and cause of SIRS, presence of organ failure, and in-hospital mortality for each patient. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score was calculated. Univariate and multivariate logistic regression analyses were used to determine differences between groups. RESULTS: Patients' ages (mean +/- SD) were 55.9 +/- 17.3 yr; 227 (55%) were male; 247 (60%) were African-American. SIRS developed in 112 patients (27%). Sepsis was the cause of SIRS in 63% of patients (70/112). Severe sepsis developed in 20 patients and septic shock in 5 patients. The most common cause of sepsis was pneumonia (19). There were no significant differences in age, gender, race, and the presence of liver disease between patients with and without SIRS. Upper gastrointestinal bleeding (76/211 vs. 36/ 200; p = .0196), intensive care unit admission (73/152 vs. 391259; p < .0001), and higher APACHE II scores (median, 17 vs. 11; p< .0001) were associated with the development of SIRS. The length of hospital stay was longer (median, 9.5 vs. 3 days; p < .0001), and the number of organ failures (median, 1 vs. 0; p < .0001) and in-hospital mortality rates (23 vs. 4%; p < .0001) were higher in patients with SIRS than in those without SIRS. CONCLUSIONS: SIRS occurs in 27% of patients admitted for gastrointestinal bleeding and is associated with a poor prognosis. Intensive care unit admission, upper gastrointestinal bleeding, and high APACHE II scores are risk factors for the development of SIRS in patients hospitalized for gastrointestinal bleeding.     

Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients

BACKGROUND: Transfusion has long been identified as a risk factor for acute lung injury (ALI)/ARDS. No study has formally evaluated the transfusion of specific blood products as a risk factor for ALI/ARDS in critically ill medical patients. METHOD: In this single-center retrospective cohort study, 841 consecutive critically ill patients were studied for the development of ALI/ARDS. Patients who received blood product transfusions were compared with those who did not, in univariate and multivariate propensity analyses. RESULTS: Two hundred ninety-eight patients (35%) received blood transfusions. Transfused patients were older (mean [+/- SD] age, 67 +/- 17 years vs 62 +/- 19 years; p < 0.001) and had higher acute physiologic and chronic health evaluation (APACHE) III scores (74 +/- 32 vs 58 +/- 23; p < 0.001) than those who had not received transfusions. ALI/ARDS developed more commonly (25% vs 18%; p = 0.025) in patients exposed to transfusion. Seventeen patients received massive RBC transfusions (ie, > 10 U of blood transfused within 24 h), of whom 13 also received fresh-frozen plasma (FFP) and 11 received platelet transfusions. When adjusted for the probability of transfusion and other ALI/ARDS risk factors, any transfusion was associated with the development of ALI/ARDS (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.24 to 3.75). Among those patients receiving individual blood products, ALI/ARDS was more likely to develop in patients who received FFP transfusions (OR, 2.48; 95% CI, 1.29 to 4.74) and platelet transfusions (OR, 3.89; 95% CI, 1.36 to 11.52) than in those who received only RBC transfusions (OR, 1.39; 95% CI, 0.79 to 2.43). CONCLUSION: Transfusion is associated with an increased risk of the development of ALI/ARDS in critically ill medical patients. The risk is higher with transfusions of plasma-rich blood products, FFP, and platelets, than with RBCs.     

Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model

Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to localize to gliomas and deliver therapeutic agents. However, the clinical translation of MSCs remains poorly defined because previous studies relied on glioma models with uncertain relevance to human disease, typically xenograft models in immunocompromised mice. To address this shortcoming, we used the RCAS/Ntv-a system, in which endogenous gliomas that recapitulate the tumor and stromal features of human gliomas develop in immunocompetent mice. MSCs were harvested from bonemarrowof Ntv-a mice and injected into the carotid artery of Ntv-a mice previously inoculated with RCAS-PDGF-B and RCAS-IGFBP2 to induce malignant gliomas (n = 9). MSCs were labeled with luciferase for in vivo bioluminescence imaging (BLI). After intra-arterial injection, BLI revealed MSCs in the right frontal lobe in seven of nine mice. At necropsy, gliomas were detected within the right frontal lobe in all these mice, correlating with the location of the MSCs. In the twomice without MSCs based on BLI, no tumor was found, indicating thatMSC localization was tumor specific. In another cohort of mice (n = 9), MSCs were labeled with SP-DiI, a fluorescent vital dye. After intra-arterial injection, fluorescence microscopy revealed SP-DiI-labeled MSCs throughout tumors 1 to 7 days after injection but not in nontumoral areas of the brain. MSCs injected intravenously did not localize to tumors (n = 12). We conclude that syngeneic MSCs are capable of homing to endogenous gliomas in immunocompetent mice. These findings support the use of MSCs as tumor-specific delivery vehicles for treating gliomas.