Decision-tree model for predicting outcomes after out-of-hospital cardiac arrest in the emergency department

Introduction

Estimation of outcomes in patients after out-of-hospital cardiac arrest (OHCA) soon after arrival at the hospital may help clinicians guide in-hospital strategies, particularly in the emergency department. This study aimed to develop a simple and generally applicable bedside model for predicting outcomes after cardiac arrest.

Methods

We analyzed data for 390,226 adult patients who had undergone OHCA, from a prospectively recorded nationwide Utstein-style Japanese database for 2005 through 2009. The primary end point was survival with favorable neurologic outcome (cerebral performance category (CPC) scale, categories 1 to 2 [CPC 1 to 2]) at 1 month. The secondary end point was survival at 1 month. We developed a decision-tree prediction model by using data from a 4-year period (2005 through 2008, n = 307,896), with validation by using external data from 2009 (n = 82,330).

Results

Recursive partitioning analysis of the development cohort for 10 predictors indicated that the best single predictor for survival and CPC 1 to 2 was shockable initial rhythm. The next predictors for patients with shockable initial rhythm were age (<70 years) followed by witnessed arrest and age (>70 years) followed by arrest witnessed by emergency medical services (EMS) personnel. For patients with unshockable initial rhythm, the next best predictor was witnessed arrest. A simple decision-tree prediction mode permitted stratification into four prediction groups: good, moderately good, poor, and absolutely poor. This model identified patient groups with a range from 1.2% to 30.2% for survival and from 0.3% to 23.2% for CPC 1 to 2 probabilities. Similar results were observed when this model was applied to the validation cohort.

Conclusions

On the basis of a decision-tree prediction model using four prehospital variables (shockable initial rhythm, age, witnessed arrest, and witnessed by EMS personnel), OHCA patients can be readily stratified into the four groups (good, moderately good, poor, and absolutely poor) that help predict both survival at 1 month and survival with favorable neurologic outcome at 1 month. This simple prediction model may provide clinicians with a practical bedside tool for the OHCA patient''s stratification in the emergency department.     

Diabetic Foot Disease: Emerging Technologies: Morphological Pattern Classification System for Plantar Thermography of Patients with Diabetes

Background

A plantar temperature distribution can be obtained by thermography; however, the advantage has not been effectively utilized in the past. We previously proposed a classification method based on the angiosome concept, but the method was insufficient because it was too subjective and complicated for clinicians. In this study, we propose a new classification system of plantar forepart thermographic patterns using an image segmentation technique.

Methods

A cross-sectional observational study was conducted including 32 healthy volunteers and 129 patients with diabetes mellitus (DM). Individual thermographic variations and trends were evaluated. A comparison was conducted between the patterns obtained by our previous angiosome-based research and the patterns found by the new classification system.

Results

The system objectively found wider variations of the plantar forepart thermographic patterns in the patients with DM compared with those in the control subjects. In patients with DM, the system showed that the whole-high pattern was most frequent (46%), followed by the butterfly pattern (12%). In the control group, the butterfly pattern was most frequent (44%), followed by the whole-high pattern (19%). Both ankle and toe brachial indices were higher in feet with high temperature area in the inner side of the plantar.

Conclusions

Thermographic patterns found by the new computer-based system were similar to those obtained in our previous subjective work. The classification system found forefoot-low pattern and tiptoe-low pattern objectively. The system based on infrared thermography will be a screening tool to assess circulatory status in daily foot care of patients with DM.     

The cardio-ankle vascular index predicts chronic kidney disease in Japanese subjects

ObjectiveChronic kidney disease (CKD) is known to be associated with the incidence and mortality of cardiovascular disease. Therefore, the prevention of CKD may improve the mortality of cardiovascular disease. The risk factors of CKD are variable and multifactorial, similar to atherosclerosis. We hypothesized that the index of atherosclerosis predicts future CKD, and investigated the association between the cardio-ankle vascular index (CAVI), the index of arterial stiffness in part of atherosclerosis, and CKD occurrence in non-CKD patients.MethodsOf the 1000 patients undergoing CAVI in our hospital from 2006 to 2007 without CKD, we followed renal function for 1 or more years in 369 patients. CKD was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m².ResultsWe divided our study patients into 4 groups according to their CAVI: <8.0 (n = 85), 8.0–9.0 (n = 75), 9.0–10.0 (n = 112), and ≥10.0 (n = 97), respectively. The differences in serum creatinine between baseline and follow-up were 0.09 ± 0.04, 0.11 ± 0.05, 0.17 ± 0.04 and 0.23 ± 0.04, respectively (the P value for the lowest group versus the highest group was 0.04). The age- and sex-adjusted odds ratios (95% confidential interval, P value versus the lowest group) for the occurrence of CKD were 1.13 (0.58–2.20, P = 0.09), 1.58 (0.85–2.94, P = 0.09), and 2.38 (1.23–4.61, P = 0.02). Even after multivariate adjustment, the relationship remained.ConclusionCAVI was found to be associated with future renal dysfunction, thus suggesting that a CAVI ≥10 may therefore be a risk factor for CKD in Japanese patients.     

Three novel single nucleotide polymorphisms (SNPs) of the CYP2B6 gene in Japanese individuals

We sequenced all exons and exon-intron junctions of the CYP2B6 gene from 200 Japanese individuals. We found three novel single nucleotide polymorphisms (SNPs) (1375A>G, 1427G>A and 1454A>T) causing amino acid substitutions (Met(459)Val, Gly(476)Asp and Gln(485)Leu in exon 9), respectively. The detected SNP was as follows: 1) SNP, 031226Hiratsuka01; GENE NAME, CYP2B6; ACCESSION NUMBER, AC023172; LENGTH, 25 base; 5'-CAGAACTTCTCCA/GTGGCCAGCCCCG-3'. 2) SNP, 031226Hiratsuka02; GENE NAME, CYP2B6; ACCESSION NUMBER, AC023172; LENGTH, 25 base; 5'-CCCAGGAGTGTGG/ATGTGGGCAAAAT-3'. 3) SNP, 031226Hiratsuka03; GENE NAME, CYP2B6; ACCESSION NUMBER, AC023172; LENGTH, 25 base; 5'-CCCCAACATACCA/TGATCCGCTTCCT-3'.     

The effect of immunization with herpes simplex virus glycoprotein D fused with interleukin-2 against murine herpetic keratitis

PURPOSE: To evaluate the preventive effect of vaccination using fusion protein (gD-IL-2) consisting of herpes simplex virus type 1 (HSV-1) glycoprotein D (gD), and human interleukin-2 (IL-2), and plasmid DNA encoding gD-IL-2 against murine herpetic keratitis. METHODS: Plasmid containing gD-IL-2 (pHDLneo1) was constructed, and gD-IL-2 peptide was purified. BALB/c mice were injected hypodermally or subconjunctivally twice with 1 microg/0.1 mL of gD-IL-2 peptide, or subconjunctivally twice with 90 microg/0.05 mL of gD-IL-2 plasmid DNA. Neutralizing antibody titer and delayed-type hypersensitivity (DTH) against HSV-1 were measured. Immunized mice were challenged with CHR3 strain of HSV-1 into the cornea. Clinical manifestations of the epithelial and stromal keratitis were scored. RESULTS: Stromal keratitis was inhibited in gD-IL-2 peptide- or DNA-immunized mice; however, epithelial keratitis was not. It was confirmed that plasmid gD-IL-2 elicited significant virus neutralizing titer in sera and DTH response. CONCLUSION: Vaccination with gD-IL-2 was effective against murine herpetic keratitis.     

Hemodialysis raises oxidative stress through carbon-centered radicals despite improved biocompatibility

Leukocyte activation and the resulting oxidative stress induced by bioincompatible materials during hemodialysis impact the prognosis of patients. Despite multiple advances in hemodialysis dialyzers, the prognosis of hemodialysis patients with complications deeply related to oxidative stress, such as diabetes mellitus, remains poor. Thus, we re-evaluated the effects of hemodialysis on multiple reactive oxygen species using electron spin resonance-based methods for further improvement of biocompatibility in hemodialysis. We enrolled 31 patients in a stable condition undergoing hemodialysis using high-flux polysulfone dialyzers. The effects of hemodialysis on reactive oxygen species were evaluated by two methods: MULTIS, which evaluates serum scavenging activities against multiple hydrophilic reactive oxygen species, and i-STrap, which detects lipophilic carbon-center radicals. Similar to previous studies, we found that serum hydroxyl radical scavenging activity significantly improved after hemodialysis. Unlike previous studies, we discovered that scavenging activity against alkoxyl radical was significantly reduced after hemodialysis. Moreover, patients with diabetes mellitus showed a decrease in serum scavenging activity against alkyl peroxyl radicals and an increase in lipophilic carbon-center radicals after hemodialysis. These results suggest that despite extensive improvements in dialyzer membranes, the forms of reactive oxygen species that can be eliminated during dialysis are limited, and multiple reactive oxygen species still remain at increased levels during hemodialysis.     

Interleukin-3 in cooperation with transforming growth factor beta induces granulocyte macrophage colony stimulating factor independent differentiation of human CD34+ hematopoietic progenitor cells into dendritic cells with features of Langerhans cells

Recently, we have reported that M-CSF in cooperation with TGF-beta1 can induce Langerhans cell (LC) development from hematopoietic progenitor cells (HPCs) without GM-CSF. In the present study, we examined whether TGF-beta1 changes the differentiation of HPCs induced by IL-3 towards LC development. We cultured HPCs in a serum-free medium in the presence of IL-3 and a combination cytokines including Flt3L, SCF, and TNF-alpha with or without TGF-beta1. DCs induced by the IL-3 culture (IL-3 DCs) did not significantly differ from those induced by the GM-CSF culture (GM-CSF DCs). Namely, both expressed CDla, F-cadherin, and Langerin in the presence of TGF-beta1 and stimulated allogeneic T cells at a similar magnitude. In contrast to GM-CSF DCs, IL-3 DCs lacked the expression of Birbeck granules (BGs) in spite of their expression of Langerin. When we compared the expression of Langerin between these two DCs, however, it became clear that both Langerin protein and mRNA were significantly lower in IL-3 DCs than in GM-CSF DCs. These studies again demonstrated the ability of TGF-beta1 to polarize the differentiation of HPCs induced by IL-3 towards LC development, although IL-3 DCs were unable to form BGs partly because of their poor ability to induce Langerin.     

Characterization of cutaneous infiltrates in MRL/lpr mice monitored from onset to the full development of lupus erythematosus-like skin lesions.

The skin is a primary site injured in lupus erythematosus (LE), but it is still controversial whether the injury is due to cells of the mononuclear infiltrate and which immunocompetent cells play the major role in the development of cutaneous LE. To better characterize the role of immunocompetent cells, we performed an immunohistochemical examination of these cells in LE-like skin lesions in MRL/Mp-lpr/lpr (MRL/lpr) mice. Skin lesions in 60 female MRL/lpr mice were monitored from onset to full development. Skin specimens from each stage were stained for epidermal Ia+ Langerhans cells (Ia(+)-LC), for Thy-1+ dendritic epidermal cells (Thy-1+DEC), and for the phenotype of the mononuclear cell infiltrates. The numbers of Ia(+)-LC and Thy-1+DEC were decreased markedly in the skin lesions at the later stage. However, the numbers of Ia(+)-LC were increased significantly in the central portion of lesions at an early stage and in the peripheral portion of lesions later. L3T4+ cells were predominant, and the L3T4/Lyt-2 ratio was high in dermal infiltrates at an early stage. With advancing stage, the L3T4/Lyt-2 ratio gradually decreased in dermal infiltrates, whereas the Thy-1.2/Lyt-2 ratio in lymph nodes was reversed. L3T4+ cells were especially predominant in dermal infiltrates under the epidermis with increased numbers of Ia(+)-LC. This immunohistochemical analysis of a mouse model of cutaneous LE revealed changes in immunocompetent cell populations with the evolution of skin lesions, and we conclude that Ia(+)-LC and Thy-1+DEC, as well as L3T4+ and Lyt-2+ cells, may play pathogenic roles in the development of skin lesions.     

Cord blood CD34+ cells differentiate into dermal dendritic cells in co-culture with cutaneous fibroblasts or stromal cells

The skin is a unique organ that contains two different subsets of dendritic cells, i.e., Langerhans cells and dermal dendritic cells. Our hypothesis is that cutaneous fibroblasts may affect the development of these dendritic cells. We cocultured cord blood CD34+ hematopoietic progenitor cells with several human cutaneous fibroblast cell lines without any exogenous cytokines for 3 wk. In this culture, hematopoietic progenitor cells increased in number from 20.1 +/- 2.4 times, and produced aggregates of cells with dendritic processes. They were composed of 54.9 +/- 3.2% HLA-DR+ CD14+ CD1a-- cells and 13.8 +/- 3.6% HLA-DR+ CD1a+ cells, which also expressed CD11b and CD11c. There were significant numbers of factor XIIIa+ cells in the culture, whereas no Lag+ or E-cadherin+ cells were detected, and they were potent stimulators in allogeneic T cell activation. There was a significant difference in the ability to induce CD1a+ cells among different human cutaneous fibroblast cell lines. These CD1a+ cells lacked the expression of CD80, CD86, or CD83. In addition, half of them still expressed CD14. When these dendritic cells were cultured with tumor necrosis factor-alpha, however, they became mature dendritic cells with augmented expression of CD86 and CD83 and with increased allogeneic T cell stimulation. The subsequent experiment using a dividing chamber, enzyme-linked immunosorbent assay for granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, and the blocking studies with antibodies for these cytokines suggested that both the presence of direct contact between hematopoietic progenitor cells and human cutaneous fibroblast cell lines and macrophage colony-stimulating factor produced by human cutaneous fibroblast cell lines are required for their maximum growth and differentiation into CD1a+ dendritic cells, whereas macrophage colony-stimulating factor was solely responsible for their differentiation. These data suggest that cutaneous fibroblasts support the differentiation of dermal dendritic cells in addition to that of monocytes from hematopoietic progenitor cells by their direct contact with hematopoietic progenitor cells and by their macrophage colony-stimulating factor production.     

Macrophage colony-stimulating factor in cooperation with transforming growth factor-beta1 induces the differentiation of CD34+ hematopoietic progenitor cells into Langerhans cells under serum-free conditions without granulocyte-macrophage colony-stimulating factor

Macrophage colony-stimulating factor has not been considered as a factor responsible for dendritic cell or Langerhans cell development from hematopoietic progenitor cells. In this study, we examined whether macrophage colony-stimulating factor could be used instead of granulocyte-macrophage colony-stimulating factor for the in vitro development of Langerhans cells from hematopoietic progenitor cells. We replaced granulocyte-macrophage colony-stimulating factor with macrophage colony-stimulating factor from a serum-free culture containing granulocyte-macrophage colony-stimulating factor, stem cell factor, Flt3 ligand, tumor necrosis factor-alpha, and transforming growth factor-beta1. This serum-free culture medium containing macrophage colony-stimulating factor, but not granulocyte-macrophage colony-stimulating factor (macrophage colony-stimulating factor culture), could induce CD1a+ Birbeck granule+ Langerin+ E-cadherin+ factor-like XIIIa Langerhans cells. As a control, the culture of hematopoietic progenitor cells in this culture medium depleted of macrophage colony-stimulating factor or transforming growth factor-beta1 resulted in far fewer or null CD1a+ cells, respectively. Macrophage colony-stimulating factor increased the number of CD1a+ cells in a concentration-dependent fashion. These macrophage colony-stimulating factor-induced Langerhans cells were different from granulocyte-macrophage colony-stimulating factor-induced Langerhans cells in their decreased expression of CD11c and their immature phenotype. The decreased expression of CD11c, however, was recovered by culturing them with granulocyte-macrophage colony-stimulating factor, while they acquired a mature phenotype qby granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, interleukin-1alpha, or lipo-polysaccharide. Macrophage colony-stimulating factor-induced Langerhans cells could stimulate allogeneic T cells. Interestingly, we could keep the growth and immature phenotypes of macrophage colony-stimulating factor-induced Langerhans cells for at least 28 d of culture. These studies demonstrated that macrophage colony-stimulating factor in cooperation with transforming growth factor-beta1 could induce Langerhans cell development from hematopoietic progenitor cells in vitro without granulocyte-macrophage colony-stimulating factor, which suggests the possibility that macrophage colony-stimulating factor plays a part in the Langerhans cell development in vivo. In addition, the culture using macrophage colony-stimulating factor presents a novel culture system to enable a large-scale and long-term culture of immature Langerhans cells.