Survival Scoring Research Articles

Biodiversity as insurance for sapling survival in experimental tree plantations

Summary Biodiversity can insure ecosystems against declines in their functioning by increasing the mean level of ecosystem processes and decreasing the spatial or temporal variance of these processes. On this basis, mixing tree species is expected to be an effective management strategy to reduce the risk of planting failure in young plantations. We examined the effects of biodiversity insurance on sapling survival in three tree diversity experiments across Belgium. Based on the survival scoring of 89 254 saplings, planted in 126 plots with up to four‐species mixtures, we tested two hypotheses: (i) variability in plot‐level survival is lower for mixtures compared to monocultures due to compensation among the species (i.e. buffering effect) and (ii) mean survival is higher due to facilitation (i.e. performance‐enhancing effect). Variation in plot‐level survival decreased strongly with diversity, indicating a buffering effect. The risk of severe planting failure was reduced in mixtures because species exhibit different survival rates; therefore, mixing ensures that not all trees in the plantation are equally susceptible to environmental stressors. In contrast, the mean plot‐level survival did not increase with diversity, and thus, an overall performance‐enhancing effect was lacking. However, species‐level analyses did show performance‐enhancing effects, where some species profited from mixing while others did not. Synthesis and applications. We conclude that biodiversity through mixing tree species insures young experimental plantations against planting failure and is therefore highly recommended as a planting management strategy. The risk of large mortality gaps is reduced if tree plantation saplings are mixed at the scale of individual trees or small cells of trees.

A scoring system for predicting the survival prognosis of patients receiving stereotactic body radiation therapy (SBRT) for 1-3 lung metastases.

The main goal of the present study was the development of a survival scoring system for patients treated with stereotactic body radiation therapy (SBRT) for very few lung metastases. Such an instrument would be of value when selecting the optimal dose for individual patients with a limited number of pulmonary lesions. Forty-six patients receiving SBRT for 1-3 lung metastases were retrospectively analyzed. The biologically effective dose plus nine characteristics [gender, age, performance score, interval from tumor diagnosis to SBRT, primary tumor type, additional (extra-pulmonary) metastases, major location of lung metastases, number of pulmonary lesions, and volume treated with SBRT] were evaluated. Characteristics significantly associated with the survival on Cox regression analysis were incorporated in the scoring system. Scoring points were received from 1-year survival rates divided by 10. Sums of these scoring points represented the scores for the individual patients. Survival rates at 1 and 2years were 66 and 56%, respectively. On Cox regression analysis, performance score (p=0.025), the type of primary tumor (p=0.013) and the additional metastases (p=0.032) had a significant impact on survival. Scores for patients ranged from 15 to 25 points. Three groups were designed: 15 points, 16-20 points, and 21-25 points. One-year survival rates were 0, 52, and 83%, respectively (p=0.005); 2-year survival rates were 0, 52, and 66%, respectively. A survival scoring system for patients receiving SBRT for very few lung metastases was developed. This score allowed us to estimate the survival prognosis of these patients and can aid physicians when aiming to choose the optimal SBRT dose for individual patients.

Development of a likelihood of survival scoring system for hospitalized equine neonates using generalized boosted regression modeling.

BackgroundMedical management of critically ill equine neonates (foals) can be expensive and labor intensive. Predicting the odds of foal survival using clinical information could facilitate the decision-making process for owners and clinicians. Numerous prognostic indicators and mathematical models to predict outcome in foals have been published; however, a validated scoring method to predict survival in sick foals has not been reported. The goal of this study was to develop and validate a scoring system that can be used by clinicians to predict likelihood of survival of equine neonates based on clinical data obtained on admission.Methods and ResultsData from 339 hospitalized foals of less than four days of age admitted to three equine hospitals were included to develop the model. Thirty seven variables including historical information, physical examination and laboratory findings were analyzed by generalized boosted regression modeling (GBM) to determine which ones would be included in the survival score. Of these, six variables were retained in the final model. The weight for each variable was calculated using a generalized linear model and the probability of survival for each total score was determined. The highest (7) and the lowest (0) scores represented 97% and 3% probability of survival, respectively. Accuracy of this survival score was validated in a prospective study on data from 283 hospitalized foals from the same three hospitals. Sensitivity, specificity, positive and negative predictive values for the survival score in the prospective population were 96%, 71%, 91%, and 85%, respectively.ConclusionsThe survival score developed in our study was validated in a large number of foals with a wide range of diseases and can be easily implemented using data available in most equine hospitals. GBM was a useful tool to develop the survival score. Further evaluations of this scoring system in field conditions are needed.

A survival score for patients with metastatic spinal cord compression from prostate cancer

This study aimed to develop and validate a survival scoring system for patients with metastatic spinal cord compression (MSCC) from prostate cancer. Of 436 patients, 218 patients were assigned to the test group and 218 patients to the validation group. Eight potential prognostic factors (age, performance status, number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits) plus the fractionation regimen were retrospectively investigated for associations with survival. Factors significant in the multivariate analysis were included in the survival score. The score for each significant prognostic factor was determined by dividing the 6-month survival rate (%) by 10. The total score represented the sum of the scores for each factor. The prognostic groups of the test group were compared to the validation group. In the multivariate analysis of the test group, performance status, ambulatory status, other bone metastases, visceral metastases, and interval from cancer diagnosis to radiotherapy were significantly associated with survival. Total scores including these factors were 20, 21, 22, 24, 26, 28, 29, 30, 31, 32, 33, 35, 37, or 39 points. In the test group, the 6-month survival rates were 6.5% for 20-24 points, 44.6% for 26-33 points, and 95.8% for 35-39 points (p < 0.0001). In the validation group, the 6-month survival rates were 7.4%, 45.4%, and 94.7%, respectively (p < 0.0001). Because the survival rates of the validation group were almost identical to the test group, this score can be considered valid and reproducible.

Xenogeneic immunosuppression of human umbilical cord mesenchymal stem cells in a major histocompatibility complex-mismatched allogeneic acute graft-versus-host disease murine model

Mesenchymal stem cells (MSCs) hold great promise for treating immune disorders owing to their immunoregulatory capacity, but the mechanism remains controversial. As we show here, the mechanism of human umbilical cord mesenchymal stem cell (HUCMSC)-mediated immunosuppression involves TGF-β and indoleamine 2,3-dioxygenase (IDO). In this study, we investigated the influence of xenogeneic HUCMSCs on acute graft-versus-host disease (aGVHD) in murine allogeneic bone marrow transplantation (BMT). In the HUCMSC-treated group, lethally irradiated DBA/2(H-2Kd) mice were adoptively transferred with expanded HUCMSCs, bone marrow (BM), and splenocytes (SCs) from C57BL/6 (H-2Kb) mice. Recipients in the control group were transferred only BM and SCs. The two groups were compared in survival, weight, histopathologic specimens, and aGVHD scoring. In the HUCMSC-treated group, 60% of the mice survived past day 30 after BMT, but in the control group, all mice died within 18 d. The mice treated with HUCMSCs exhibited light symptoms of aGVHD after day 30. The results suggest that xenogeneic HUCMSCs could alleviate aGVHD symptoms and prolong survival after allogeneic BMT. Our study suggests that in vitro expanded HUCMSCs might be used to inhibit severe aGVHD effectively in allogeneic hematopoietic cell transplantation clinically.

Surgery for pathological proximal femoral fractures, excluding femoral head and neck fractures

Pathological femoral head and neck fractures are commonly treated by arthroplasty. Treatment options for the trochanteric region or below are not clearly defined. The purpose of this retrospective, comparative, double-centre study was to analyse survival and influences on outcome according to the surgical technique used to treat pathological proximal femoral fractures, excluding fractures of the femoral head and neck. Fifty-nine patients with 64 fractures were operated up on between 1998 and 2004 in two tertiary referral centres and divided into two groups. One group (S, n = 33) consisted of patients who underwent intramedullary nailing alone, and the other group (R, n = 31) consisted of patients treated by metastatic tissue resection and reconstruction by means of different implants. Median survival was 12.6months with no difference between groups. Surgical complications were higher in the R group (n = 7) vs. the S group (n = 3), with no statistically significant difference. Patients with surgery-related complications had a higher survival rate (p = 0.049), as did patients with mechanical implant failure (p = 0.01). Survival scoring systems did not correlate with actual survival. Resection of metastases in patients with pathological fractures of the proximal femur, excluding femoral head and neck fractures, has no influence on survival. Patients with long postoperative survival prognosis are at risk of implant-related complications.

WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system

AbstractThe impact of WT1 mutations in acute myeloid leukemia (AML) is not completely settled. We aimed to determine the clinical implication of WT1 mutation in 470 de novo non-M3 AML patients and its stability during the clinical course. WT1 mutations were identified in 6.8% of total patients and 8.3% of younger patients with normal karyotype (CN-AML). The WT1 mutation was closely associated with younger age (P < .001), French-American-British M6 subtype (P = .006), and t(7;11)(p15;p15) (P = .003). Multivariate analysis demonstrated that the WT1 mutation was an independent poor prognostic factor for overall survival and relapse-free survival among total patients and the CN-AML group. A scoring system incorporating WT1 mutation, NPM1/FLT3-ITD, CEBPA mutations, and age into survival analysis proved to be very useful to stratify CN-AML patients into different prognostic groups (P < .001). Sequential analyses were performed on 133 patients. WT1 mutations disappeared at complete remission in all WT1-mutated patients studied. At relapse, 3 of the 16 WT1-mutated patients who had paired samples lost the mutation and 2 acquired additional mutations, whereas 3 of 110 WT1-wild patients acquired novel mutations. In conclusion, WT1 mutations are correlated with poor prognosis in AML patients. The mutation status may be changed in some patients during AML progression.

WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system

WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system

Secondary Lymphoid Tissues Are Not Required for the Induction of GVHD Following Allogeneic BMT: A Shifting Paradigm for T Cell Allo-Activation.

Allogeneic (allo) bone marrow transplantation (BMT) is the only curative option for many patients with malignant and non-malignant diseases. Acute graft versus host disease (GVHD) is the major complication of allo-BMT and limits the utility of this treatment strategy. The induction of GVHD fundamentally depends upon the activation of donor T cells by host antigen presenting cells (APCs), and the prevailing hypothesis is that these critical interactions occur in secondary lymphoid organs, such as lymph nodes (LN) Peyer's patches (PP), and spleen (SP). We tested this hypothesis by using a well established, MHC disparate, murine SCT system (Balb/c → B6) and homozygous aly/aly (alymphoplasia) mice that are deficient in all LN and PP and heterozygous aly/+ littermate controls. Lethally irradiated, splenectomized, aly/aly mice (LN/PP/SP −/ −) and aly/+ sham mice (LN/PP/SP +/+) received BMT either from syngeneic (aly/aly) or allo (Balb/c) donors. In some experiments, wild-type B6 recipients of B6 or Balb/c BMT served as additional negative and positive GVHD controls respectively. The severity of GVHD was assessed by survival and well-described scoring systems of both clinical and target organ disease. As expected, greater than 95% of syngeneic (syn) BMT recipients survived and were indistinguishable from naïve, un-transplanted controls, whereas LN/PP/SP +/+ mice receiving allo-BMT showed significant signs of GVHD with ~40% mortality by day 49. All LN/PP/SP −/ − allo-BMT recipients also survived, but surprisingly, examination demonstrated that they too developed significant clinical GVHD compared to syn controls (score: 3.2 vs. 0.85) that was comparable in severity to LN/PP/SP +/+ mice (3.1). Moreover, histopathologic analysis demonstrated that LN/PP/SP −/ − allo-BMT recipients developed significantly greater GVHD target tissue damage in the liver, intestinal tract and skin compared to syn controls. In fact, LN/PP/SP −/ − allo-BMT recipients developed more severe hepatic GVHD compared to allo littermate (LN/PP/SP +/+) controls (30.8±1.9 vs. 20.7±2.2; p < 0.01). Similar differences in liver GVHD was also seen between allo groups as early as day 7 (16.0±2.2 vs. 7.3±0.9; p < 0.01). We next tested the ability of host aly/aly and aly/+ APCs to stimulate donor Balb/c T cells in vitro. No differences in proliferation, IFN γ production or CTL generation were detected, thus showing that the allo-stimulatory capacity of host APCs was not different between groups. In order to ascertain what extra-lymphoid host tissues might serve as initial sites for allo-antigen exposure, we examined donor T cell expansion (CD3+), activation (CD69+) and proliferation (CFSE) in the bone marrow compartment 3 days after BMT. We found that in each case, LN/PP/SP −/ − allo-BMT recipients had significantly higher numbers / divisions compared to allo, littermate, (LN/PP/SP +/+) controls. Collectively, these data challenge the paradigm that secondary lymphoid tissues are required for GVHD induction, and suggest that the bone marrow may represent an alternative site for allo-antigen recognition and donor T cell activation.

No Evidence for an Involvement of the P38 and JNK Mitogen-Activated Protein in Inflammatory Bowel Diseases

Involvement of mitogen-activated protein (MAPK) in inflammatory bowel disease (IBD) remains enigmatic. We sought to evaluate the expression and activity of p38 and JNK MAPK in IBD and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and the effects of a p38 inhibitor, SB203580, in TNBS colitis. P38 and JNK were quantified in colonic mucosa of 28 IBD patients and 19 controls and in 77 TNBS or control mice treated or not with SB203580. Colitis severity was assessed by survival, macroscopic and microscopic scoring, and molecular markers. Expression and activity of p38 and JNK were similar in IBD patients and controls and not modified by inflammation. In mice, p38 and JNK expression or activity did not increase following the induction of colitis. SB203580 decreased the p38 activity but displayed no clinical nor biological therapeutic effect. In conclusion, these results minimize the role of p38 and JNK in inflammatory colitis and the interest of p38 as a therapeutic target in IBD.