Effect of kinetic therapy on pulmonary complications.

BACKGROUND: Optimal turning of critically ill patients is not well established. Kinetic therapy (systematic mechanical rotation of patients with 40 degree turns) may improve pulmonary function more than the improvement in function achieved via the standard of care (turning patients every 2 hours). OBJECTIVE: To determine (1) if patients receiving mechanical ventilation who tolerate kinetic therapy have better pulmonary function than do patients treated with standard turning and (2) the cost-effectiveness of kinetic therapy. METHODS: A prospective, randomized, multicenter study including 234 medical, surgical, and trauma patients (137 control patients, 97 patients receiving kinetic therapy). RESULTS: Kinetic therapy significantly decreased the occurrence of ventilator-associated pneumonia and lobar atelectasis. The risk of pneumonia developing was lower (P = .002) in patients receiving kinetic therapy than in the control patients. The risk of lobar atelectasis developing was decreased (P = .02) for the patients receiving kinetic therapy. Lengths of stay in the intensive care unit and in the hospital did not differ between the groups. Charges for intensive care were less in the kinetic therapy group (81,700 dollars) than in the control group (84,958 dollars), but not significantly less. Twenty-one patients did not tolerate kinetic therapy and were not included in the analysis. CONCLUSION: Kinetic therapy helps prevent ventilator-associated pneumonia and lobar atelectasis in critically ill patients. Costs to rent the bed may be offset by the potential cost reduction associated with kinetic therapy.     

Deep vein thrombosis during prolonged mechanical ventilation despite prophylaxis

OBJECTIVE: To determine the prevalence of deep vein thrombosis (DVT) among patients requiring prolonged mechanical ventilation in the intensive care unit. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit of a university-affiliated urban teaching hospital. PATIENTS: Patients requiring mechanical ventilation for >7 days. INTERVENTIONS: All patients admitted to the medical intensive care unit requiring prolonged mechanical ventilation underwent duplex ultrasonography of their lower extremities and upper extremities every 7 days. The main outcome identified was the presence of DVT. Secondary outcomes included hospital mortality, hospital and intensive care unit lengths of stay, and the occurrence of pulmonary embolism. MEASUREMENTS AND MAIN RESULTS: A total of 110 patients requiring mechanical ventilation for >7 days were enrolled. Prophylaxis against DVT was employed in 110 of the patients (100%). A total of 26 patients (23.6%) developed DVT. Patients with DVT were statistically more likely to have underlying malignancy (30.8% vs. 8.3%; p =.004) and longer durations of central venous catheterization (26.9 +/- 22.2 days vs. 14.5 +/- 12.1 days; p =.024) compared with patients without DVT. There were no statistically significant differences in hospital mortality or lengths of stay in the hospital and intensive care unit for patients with and without DVT. Patients documented to have DVT by using duplex ultrasonography had a statistically greater frequency of subsequent pulmonary embolism during their hospitalization (11.5% vs. 0.0%; p =.012). CONCLUSION: The occurrence of DVT is common among patients requiring prolonged mechanical ventilation in the intensive care unit setting despite the use of prophylaxis measures. These data suggest that alternative strategies for the prevention of DVT should be evaluated. Additionally, early detection methods should be considered to reduce the potential morbidity associated with untreated DVT in this high-risk population.     

A phase I study of sequential versus concurrent interleukin-3 and granulocyte-macrophage colony-stimulating factor in advanced breast cancer patients treated with FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy

Cumulative thrombocytopenia is a dose-limiting toxicity of dose- intensive chemotherapy for advanced breast cancer. In this phase I study, we have studied the hematologic toxicity associated with sequential interleukin-3 (IL-3) and granulocyte-macrophage colony- stimulating factor (GM-CSF; molgramostim) administration after multiple cycles of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy compared with that after concurrent cytokine administration or to each cytokine administered alone. Ninety- three patients with advanced breast cancer were treated with five cycles of FLAC chemotherapy and either IL-3 alone, GM-CSF alone, sequential IL-3 and GM-CSF administered by schedule A (5 days of IL-3 followed by 10 days of GM-CSF) or schedule B (9 days of IL-3 followed by 6 days of GM-CSF), or concurrent administration of IL-3 and GM-CSF for 15 days. Cohorts of patients were treated with one of four dose levels of IL-3 (1,2.5, 5, and 10 micrograms/kg) administered subcutaneously for each schedule of cytokine administration. The GM-CSF dose in all schedules was 5 micrograms/kg/day. Sequential IL-3 and GM- CSF (schedule B) was associated with higher platelet nadirs, shorter durations of platelet counts less than 50,000/microL, and the need for fewer platelet transfusions over five cycles of FLAC chemotherapy compared with concurrent cytokines, sequential IL-3 and GM-CSF schedule A, and GM-CSF alone. Concurrent IL-3 and GM-CSF was associated with unexpected platelet toxicity. The duration of granulocytopenia after FLAC chemotherapy was significantly worse with IL-3 alone compared with each of the GM-CSF-containing cytokine regimens. Although no cycle 1 maximum tolerated dose for IL-3 was defined in this study, 5 micrograms/kg was well tolerated over multiple cycles of therapy and is recommended for future studies. The data from this phase I study suggest that sequential IL-3 and GM-CSF with IL-3 administered for 9 days before beginning GM-CSF may be superior to shorter durations of IL- 3 administered sequentially with GM-CSF, to concurrent IL-3 and GM-CSF, and to either colony-stimulating factor alone in ameliorating the cumulative hematologic toxicity associated with multiple cycles of FLAC chemotherapy. Additional studies of sequential IL-3 and GM-CSF are warranted.     

Diamond-Blackfan syndrome: evidence against cell-mediated erythropoietic suppression

The profound anemia of Diamond-Blackfan syndrome (DBS) is due to marrow red cell failure, but the pathogenesis is not understood. Studies by others indicated cell-mediated erythropoietic suppression in this condition. To explore this mechanism further, Ficoll-Hypaque--separated peripheral blood lymphocytes (PBL) from four anemic untreated patients with DBS, or from normals were cocultured with control marrow in vitro and the growth of erythropoietin-responsive stem cell colonies (CFU-E) was dermined. CFU-E numbers obtained from cultures with added normal PBL were not significantly different from the number without PBL. Similarly, CFU-E from cultures with added DBS PBL were not significantly different from the number without PBL (215 versus 220, 229 versus 220 and 84 versus 60, 74 versus 94/10(5) cells, respectively). Mixing marrows from a control and one DBS patient in ratios of 2:1, 1:1, or 1:2 prior to culture failed to disclose a decrease of colony growth. We could not show cellular inhibition of erythropoiesis in these patients with DBS. The mechanism of anemia in this disorder remains an open question.     

Prevention of pneumonia in the hospital setting

Although the optimal approach to reducing ventilator-associated pneumonia (VAP) is unclear, recent studies indicate that mandatory education of health care workers caring for mechanically ventilated patients can decrease overall VAP rates. Among the available interventions, shortening the duration of mechanical ventilation and providing measures to prevent the aspiration of contaminated secretions are most important. Given the evidence supporting greater morbidity, hospital mortality, and medical care costs among patients who have VAP, the prevention of this nosocomial infection should be an important priority in the hospital setting.     

Invasion of erythrocytes by Plasmodium falciparum malaria parasites: evidence for receptor heterogeneity and two receptors

Plasmodium falciparum malaria parasites with different capabilities of invading sialic acid-deficient erythrocytes were identified. Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase-treated and Tn erythrocytes twice as efficiently as Thai-2 parasites cultured in normal erythrocytes and seven to ten times more efficiently than a cloned line of Camp parasites cultured in normal erythrocytes. All three parasite lines required sialic acid for optimal invasion, but Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase- treated erythrocytes with 45% efficiency whereas Camp parasites invaded neuraminidase-treated erythrocytes with less than 10% efficiency. P falciparum malaria parasites probably possess two receptors: one that binds to a sialic acid-dependent ligand and another that binds to a sialic acid-independent ligand. Parasites may differ in the quantity or affinity of their receptors for the sialic acid-independent ligand.     

Epidemiology,Co-Infections,and Outcomes of Viral Pneumonia in Adults: An Observational Cohort Study

Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described.This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48 h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model.Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk.     

Modified LSA2-L2 treatment in 53 children with E-rosette-positive T- cell leukemia: results and prognostic factors (a Pediatric Oncology Group Study)

In an attempt to improve the poor outlook for children with T-cell leukemia (T-ALL), the Southwest Oncology Group, Pediatric Division, used a modified LSA2-L2 multidrug regimen to treat 53 patients with E- rosette-positive T-ALL. This regimen was chosen because of its demonstrated efficacy in T-cell (mediastinal) non-Hodgkin's lymphoma. Complete remission (CR) rate was 88%. Range of follow-up for those patients remaining in CR is 24-49 mo (median 39 mo). Life table analysis estimates that 40% (SE 8.3%) of all patients who started induction therapy will remain failure-free at 3 yr. For patients achieving CR, 46% (SE 9%) are projected to remain in both marrow and extramedullary CR at 3 yr. Median failure-free duration was 13 mo, but only 1 patient has relapsed beyond 16 mo. Twenty-nine percent of initial relapses were isolated CNS relapses. The following presenting factors did not relate significantly to outcome: hemoglobin, platelet count, uric acid, race, and mediastinal mass. Age greater than 10 yr was a poor prognosis indicator only in the less than 50,000/microliter WBC group. Sex was not a significant factor after adjusting for WBC. WBC was the most important prognostic factor: 19% (SE 8%) of patients with WBC greater than 50,000/microliter are projected to remain failure- free at 3 yr as compared to 67% (SE 11%) of patients with WBC less than 50,000/microliter. Although the overall results are better than those previously reported for pediatric patients with T-ALL, the long-term failure-free rate remains low for patients presenting with greater than 50,000/microliter WBC.