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[Statistic evaluation of prognostic risk factors in penetrating keratoplasty using Cox multiple regression model].

Preoperative risk factors that may influence the prognosis in penetrating keratoplasty were statistically analyzed on 698 consecutive eye that had been operated on at the University of Tokyo Hospital. A Cox multiple regression model (proportional hazards models) was constructed with simultaneous consideration of follow-up periods and prognostic factors. Six preoperative risk factors were identified: corneal endothelial damage, the presence of anterior synechiae, glaucoma, older donor age, the area of vascularization, and aphakia or pseudophakia. Simulations of the prognosis were attempted using the significant factors.

Adult↗

Neurodevelopmental abnormalities in preschool children with high perinatal risk. Prognostic value and consequences on education at 8 years of age.

Two groups of 41 children with high perinatal risk were studied. All children of the study group (SG) had neurodevelopmental abnormalities (NDA) at the age of 5 years, without major handicap. The control group (CG) consisted of 41 children matched for sex, neonatal pathology, birthweight, gestational age and socioeconomic status, without NDA at 5 years. In the SG 85.4% of the children had persistent NDA at school age. In the CG 36.6% of the children presented NDA, but less severe than those of the SG. The SG children had more often associated NDA than those of the CG. The outcome of NDA diagnosed at preschool age and the results of psychometric tests are described. Associated NDA or a borderline IQ, with emotional and behavioral problems, have a gloomy school prognosis. 46.3% of the children in the SG had major schooling problems and 12.2% of children in the CG. These results show the possibility to detect children at risk of school achievement problems before school entrance; they might be useful in counselling and preventing behavioral and educational difficulties.

Achievement↗

Prognostic risk factors in patients with interstitial lung disease referred for lung transplantation.

The aim of the study was to identify prognostic factors that would differentiate patients with interstitial lung disease between those with and without a chance to survive until lung transplantation. A retrospective study was performed in patients with interstitial lung disease referred for lung transplantation between September 1999 and April 2005. The analysis included the demographic data, the time from referral to transplantation, the functional tests (FVC, FEV1, FEV1%VC, the PaO(2) at rest and after oxygen supplementation via a nasal catheter), the count of NYHA functional classes, the left ventricular ejection fraction (EF), the distance covered during a 6-min walk test, and the pathogens in the respiratory tract. The patients were divided into two groups: Group 1 - lung transplant candidates who survived until the successful procedure and Group 2 - lung transplant candidates who died while on the waiting list. There were statistical differences between the two groups in PaO2 after supplementation (P=0.005), EF (P=0.002), and the 6-min walk distance (P=0.001). It appears that simple functional tests of the cardiorespiratory system may define survival of patients with interstitial lung disease waiting for lung transplantation.

Adult↗

Prognostic risk factors for graft failure following pancreas transplantation: results of multivariate analysis of data from the International Pancreas Transplant Registry.

A multivariate analysis of prognostic factors for graft failure was performed on patients in the International Pancreas Transplant Registry. The analysis was restricted to the period January 1978 to June 1987 and included 764 patients. All patients had at least 1 year of follow-up. The following variables were studied: transplant year, continent (N. America, Europe, others), type of donor (cadaver, living related mismatched, living related HLA-identical), donor mismatch at the HLA A, B loci, donor mismatch at the DR loci, preservation time, kidney association (pancreas transplant alone, simultaneous pancreas and kidney transplant, pancreas after kidney transplant), whole versus segmental pancreatic transplant, graft duct management technique (polymer injection, enteric drainage, stomach drainage, bladder drainage), and immunosuppression. By stepwise, logistic regression analysis, we found that the following factors were predictive for 1-year graft function: donor mismatch at the DR loci (P = 0.0003), kidney association (P less than 0.0001), type of donor (P = 0.04), and immunosuppression (P = 0.0002). For donor mismatch at the DR loci, we found an odds ratio for success of 2.2 for 0 versus 2 mismatches. The odds for success were 2.9 for simultaneous pancreas and kidney transplant versus pancreas transplant alone. The best results--79% 1-year graft survival--were obtained for the combination of 0 mismatches at the DR loci, pancreas after kidney transplant, living related HLA-identical donor, and the immunosuppressive regimen consisting of cyclosporin, azathioprine, and prednisone. Patients receiving a pancreas transplant alone with 0 mismatches at the DR loci, living related HLA-identical donor, and triple immunosuppressive regimen had a predicted 1-year graft survival of 71%.

Graft Rejection↗

Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis.

BACKGROUND: The purpose of this study was to develop a reliable model to identify clinical Stage I nonseminomatous germ cell tumors (NSGCTs) associated with low risk or high risk for occult retroperitoneal metastasis, so that the model could be used to customize the therapeutic approach for patients with these tumors. The model was to be based on pathohistologic parameters and immunohistochemical expression of proliferation markers, proteases, and adhesion molecules in the primary tumor. METHODS: One hundred forty-nine patients with clinical Stage I NSGCTs underwent retroperitoneal lymphadenectomy and were included in the study. Three to five paraffin embedded, formalin fixed tissue blocks were available from each patient and were analyzed for the following histopathologic features associated with pathologic Stage I or II disease: the presence or absence of vascular invasion (VI), the presence or absence of tunic invasion, and the percentage of each histologic type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D, and E-cadherin was evaluated using a semiquantitative scoring system. Statistical analysis was performed with univariate and multivariate logistic regression models. RESULTS: The percentage of embryonal carcinoma (%EC, P < 0.001) and the presence of VI (P < 0.0001) and tunic invasion (P < 0.002) were the most significant independent risk factors associated with pathologic Stage II disease. A combination of %EC and VI allowed correct prediction of final pathologic stage for 88% of clinical Stage I patients. Cutoff values including both variables identified the correct pathologic stage for 131 of 149 patients (88%). Less than 45% EC and the absence of VI correctly identified pathologic Stage I disease in 91.5% of patients; more than 80% EC and the presence of VI correctly predicted pathologic Stage II in 88%. In univariate analysis, only p53 (P < 0.03) and E-cadherin (P < 0.001) expression were significantly different in the embryonal carcinoma component of pathologic Stage I and II NSGCT. To evaluate prospectively the clinical utility of the new derived cutoff points, the data were applied to 10 consecutive patients with clinical Stage I NSGCT who underwent retroperitoneal lymphadenectomy; pathologic Stage I and II were correctly predicted for 5 of 6 Stage I and 4 of 4 Stage II patients, respectively. CONCLUSIONS: %EC and the presence or absence of VI appear to be reliable prognosticators to identify patients at high risk and low risk for occult retroperitoneal disease. In cases of clinical Stage I NSGCT, p53, bcl-2, MIB-1, cathepsin D, and E-cadherin did not appear to be of prognostic significance. The authors recommend that all patients with clinical Stage I NSGCT have their primary orchiectomy specimens evaluated for %EC and the presence of VI to determine their risk for occult retroperitoneal metastasis.

Antigens, Nuclear↗

Subclassification of diffuse large B-cell lymphomas according to the Kiel classification: distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor.

Among high-grade malignant non-Hodgkin's lymphomas the updated Kiel classification identifies three major B-cell entities: centroblastic (CB), B-immunoblastic (B-IB), and B-large cell anaplastic (Ki-1+) (now termed anaplastic large cell [CD30+], [B-ALC]). The clinical prognostic relevance of this distinction was evaluated in a randomized prospective treatment trial (COP-BLAM/IMVP-16 regimen randomly combined +/- radiotherapy in complete responders) conducted in adult (age 15 to 75) patients with Ann Arbor stage II-IV disease (n = 219) diagnosed by optimal histomorphology (Giemsa staining) and by immunohistochemistry. Overall survival was significantly better in CB lymphoma as compared to B-IB (P = .0002) or B-ALC (P = .046). Relapse-free survival was worse for B-IB (P = .0003) as compared to CB lymphomas. The prognostic differences between CB and B-IB were confirmed by multivariate analyses including the risk factors of the International Index. Overall survival was significantly determined by performance status (P = .0003), serum-LDH (P = .036), and B-IB histology subtype (P = .036). Relapse-free survival was influenced by age (P = .007) and histological subtype (P = .007). Thus, the diagnosis of the CB and B-IB lymphomas by the histological criteria of the Kiel classification was identified as an independent prognostic factor in diffuse large B-cell lymphomas.

Adolescent↗

A scoring system based on the expression of six surface molecules allows the identification of three prognostic risk groups in B-cell chronic lymphocytic leukemia.

We have previously identified 12 surface antigens whose differential expression represented the signature of B-cell chronic lymphocytic leukemia (B-CLL) subsets with different prognosis. In the present study, expression data for these antigens, as determined in 137 B-CLL cases, all with survivals, were utilized to devise a comprehensive immunophenotypic scoring system of prognostic relevance for B-CLL patients. In particular, univariate z score was employed to identify the markers with greater prognostic impact, while maximally selected log-rank statistics were chosen to define the optimal cut-off points capable to split patients into two groups with different survivals. A weighted immunophenotypic scoring system was developed by integrating results from these analyses. Six antigens were selected: three positive prognosticators (CD62L, CD54, CD49c) and three negative prognosticators (CD49d, CD38, CD79b), with cut-off values ranging from 30% to 50% of positive cells. By weighing the expression of each marker according to its statistical power, a complete scoring system, with point values comprised between 0 (complete absence of phenotypic conditions associated with good prognosis) and 9 (all the phenotypic conditions associated with good prognosis fulfilled), allowed to split the whole set of B-CLL patients, into three distinctive prognostic groups (P = 4.78 x 10(-11)) with high- (score 0-3), intermediate- (score 4-6), and low- (score 7-9) risk of death. The three risk groups showed different distribution of cases as for Rai's stages, IgVH mutations, and ZAP-70 expression. The proposed immunophenotypic scoring system may be an additional useful tool in routine diagnostic/prognostic procedures for B-CLL.

ADP-ribosyl Cyclase 1↗

Hypofractionated conformal HDR brachytherapy in hormone naïve men with localized prostate cancer. Is escalation to very high biologically equivalent dose beneficial in all prognostic risk groups?

PURPOSE: To analyze the long-term effect of local dose escalation using conformal hypofractionated high-dose-rate brachytherapy (HDR-BT) boost and pelvic external-beam radiation therapy (EBRT) in hormone-naïve men with localized prostate cancer. PATIENTS AND METHODS: A total of 579 men were consecutively treated with pelvic EBRT and dose escalating HDR-BT since 1986 in two prospective trials: 378 patients at William Beaumont Hospital (1991-2002), and 201 patients at Kiel University (1986-1999). BT optimization was done modulating both, the dwell times and spatial source positions. A short course of neoadjuvant/concurrent androgen deprivation therapy was given to 222 patients. Hormone-naïve patients only (n = 324) with a follow-up > or = 18 months were analyzed. All patients had at least one poor prognostic factor (stage > or = T2b, Gleason Score > or = 7, pretreatment prostate-specific antigen [PSA] > or = 10 ng/ml): any one factor 122 patients, any two factors 122 patients, and three factors 80 patients. This cohort was stratified by equivalent dose (ED): dose level 1, < or = 94 Gy, n = 58, and dose level 2, > 94 Gy, n = 266, assuming an alpha/beta ratio of 1.2. The ASTRO definition for biochemical failure was used. RESULTS: Mean follow-up was 5.3 years (1.5-13.9 years). For all 324 patients, the 5-year biochemical control (BC) rate was 79%. Cancer-specific survival was 98%, and overall survival 90%. Similar analysis by institution demonstrated no difference in outcomes. For the entire cohort of hormone-naïve men, dose escalation to > 94 Gy resulted in a better 5-year BC of 59% versus 85% (p < 0.001). Discriminating by risk group a striking dose escalation effect was seen in the groups with two or three poor prognostic factors (p = 0.022 and < 0.001, respectively). In the group with only one poor prognostic factor, no statistical difference could be detected questioning the need for ED > 94 Gy. CONCLUSION: The results demonstrate that conformal HDR-BT is a successful method for delivering very high radiation dose to the prostate. The ability to escalate dose to ED > 94 Gy was reflected in improved long-term outcomes in terms of BC, significantly for those patients with two or three poor prognostic factors reaching BC rates of 85%.

Actuarial Analysis↗

An image analysis method for assessment of prognostic risk in prostate cancer: a pilot study.

Fully automated computerized image analysis at medium resolution (1 micron per pixel space) was applied in a study of 17 patients with stage D1 prostate cancer. For this pilot study, patients were selected on the basis of very good or very poor outcome. This selection was made in the hope of identifying morphometric features that are useful in prognostic assessment. Nine patients with good outcome were alive after 7 or more years of follow-up and eight patients with poor prognosis were dead of disease in less than 3 years. All patients were treated with 125I seed implantation to the prostate and pelvic lymph node dissection. Hormone therapy was not administered until the time of distant failure. Routine hematoxylin and eosin tissue sections of lymph nodal tissue bearing metastatic neoplasm were used for this analysis. A minimum of eight scenes per case was analysed. Of 50 measured parameters on each cluster, five (gray level distribution, number of cell clusters per scene, bending energy, average cluster area and cluster polarity) were useful to distinguish patients with good outcome from those with a poor outcome. Thirteen of the 17 patients were correctly classified by image analysis (P = 0.044, Fischer's exact test). By comparison, flow cytometry of the identical tissue samples correctly classified 14 of 17 patients (diploid, good outcome; aneuploid, poor outcome; P = 0.009). Only one patient was incorrectly classified by both image analysis and flow cytometry, implying a complementary prognostic role for the two methods. The encouraging result, successful identification of useful morphometric features, justifies a larger study of unselected patients.

DNA↗

Independent prognostic risk factors for patients referred because of suspected acute myocardial infarction without confirmed diagnosis. Prognosis after discharge in relation to medical history and non-invasive investigations.

Variables associated with risk of cardiac events, i.e. acute myocardial infarction (AMI) or cardiac death after discharge, were studied in patients who had been referred to coronary care units because of suspected AMI due to chest pain, but in whom this was not confirmed. The patients were all under 76 years of age, and were followed from 12 to 24 months, median 14 months. The estimated percentage without a cardiac event in 257 patients after one year was 91.3. On the basis of prognostic and clinical importance the analyzed variables included selected aspects of the medical history, electrocardiogram on admission in all 257 patients, subsequent electrocardiogram at rest, exercise test, thallium scintigraphy, chest X-ray, echocardiography, systolic time intervals and Holter monitoring when possible in 217 patients. Multivariate analysis identified combined electrocardiogram at rest and during exercise as the only variable with independent prognostic information. The presence of ST segment deviation, Q-wave, negative T-wave or intraventricular block in the electrocardiogram at rest or an abnormal ST segment response during exercise, increased the hazard of a cardiac event by a factor of 11.8. It is concluded that patients without confirmed AMI are at risk following discharge. These patients should undergo an exercise test and those with an abnormal electrocardiogram at rest and/or during exercise should be followed closely after discharge.

Adult↗

Does nimodipine eliminate arterial hypertension as a prognostic risk factor in subarachnoid haemorrhage?

Several studies have demonstrated an association between arterial hypertension (AH) and an increased morbidity and mortality from both cardiovascular diseases and stroke (including subarachnoid haemorrhage, SAH). Among the functional disturbances implicated in hypertension much interest has been focused on the calcium handling in the vascular smooth muscle cells, and it has been proposed that a defect in the calcium gating mechanisms in the cell membrane is of major importance. Clinical trials have confirmed that calcium antagonists of the dihydropyridine type (nimodipine) are useful in preventing secondary ischaemia after SAH. The purpose of this retrospective study was to determine if the protective effect of nimodipine differs between normotensive and hypertensive patients focused on delayed ischaemia, total morbidity and mortality. In the group (137 patients) without nimodipine treatment 17 out of 31 individuals (55%) with AH had an unfavourable outcome. In the nimodipine group (also 137 patients) four out of 25 individuals (16%) with AH had an unfavourable outcome. In terms of vasospasm and delayed ischaemia only, the difference was even more evident. These results indicate that nimodipine seems to significantly reduce the prognostic difference between normo- and hypertensive individuals with an aneurysmal SAH.

Adolescent↗

Recent evaluation of prognostic risk factors in esophageal atresia--a multicenter review of 223 cases.

In this study, 223 cases of esophageal atresia (Type IIIb: 85.7%; Type II: 5.8%; Type IIIc: 4.0%; Type IIIa: 2.2%; Type IV: 2.2%) from 6 pediatric surgery centers of Austria, were retrospectively examined for the following parameters and their influence on the prognosis: Birth weight (2494.7 +/- 702.0 g), gestation week (range 27-42 weeks; mean 37.3 +/- 3.1 weeks), sex (male: n = 128; female: n = 95), long-gap atresia (> or = 2 cm: n = 33), Tracheomalacia (n = 16), associated malformations (n = 122; cardiac 27.4%, renal 17.9%, skeletal 17.0%, anal: 10.3%, intestinal 9.9%, mediastinal 7.6%, chromosomal 2.2%), preoperative aspiration (n = 92), pneumonia (n = 96), anastomotic insufficiency (n = 45), empyema (n = 5), mediastinitis (n = 8), sepsis (n = 32), other medical complications (n = 122, in 80 infants), other surgical complications (n = 57). The mortality rate was 41.3% overall, from 1975 to 1991; however, it was 25% from 1987 to 1991 and 0% in 1991. A statistically significant correlation was found between prognosis and the following factors: Cardiac malformations (p = 0.0001), medical complications except aspiration and pneumonia (p = 0.0001), empyema (p = 0.0081), mediastinitis (p = 0.0214), and sepsis (p = 0.0295). These 5 significant factors were given different points and a prognostic score was calculated by the addition of these points. This score was predictive for survival in 90.6% of cases and for mortality in 94% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Austria↗

Blood pressure variability as an adverse prognostic risk factor in end-stage renal disease.

BACKGROUND: Prospective and case-control studies show that blood-pressure variability is an independent risk factor for severe organ damage and cardiovascular events in hypertensives. We prospectively studied the association between systolic blood pressure variability and cardiovascular mortality and mortality from all causes in end-stage renal disease patients. METHODS AND RESULTS: The subjects were 144 patients (86 men, 58 women; mean age+/-SD, 52+/-13 years) who underwent dialysis in the same dialysis centre and were examined for blood-pressure variability. The study period was 38 months beginning in January 1995, during which six cardiovascular and seven noncardiovascular fatalities occurred. Coefficient of variation in systolic blood pressure in 1994, as an indicator of systolic blood pressure variability, ranged from 7.8 to 14.6%. Cumulative incidence of death from all causes was related to coefficient of variation in systolic blood pressure. The difference between the maximum and minimum systolic blood pressure (deltaSBP) in 1994 ranged from 44 to 146 mmHg (mean+/-SD, 78+/-13 mmHg) and correlated significantly with coefficient of variation in systolic blood pressure (r = 0.65, P<0.0001). Cox regression analysis was used to identify the independent predictors for mortality. The hazard ratio for death from all causes increased 1.63 times per 1% increase in coefficient of variation in systolic blood pressure (hazard ratio; 95% confidence interval: 1.63; 1.05-2.53) and 1.03 times per 1 mmHg increase in deltaSBP (1.08; 1.03-1.14). CONCLUSION: These results suggest that systolic blood pressure variability may be a significant prognostic factor in end-stage renal disease.

Adult↗

The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors.

B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade III-negative (P = .012), estrogen receptor-negative (P = .036), and progesterone receptor-negative (P = .040) patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule.

Adult↗

Low natural killer activity and central nervous system disease as a high-risk prognostic indicator in young patients with hemophagocytic lymphohistiocytosis.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis HLH (FHL) is fatal, unless patients are rescued with hematopoietic stem cell transplantation (SCT). Although the molecular identification of FHL now is possible at least in part from perforin gene study, many cases escape detection or never are tested due to the lack of specific hallmarks, making diagnosis difficult. To the authors' knowledge, it remains to be determined whether persistently low natural killer cell (NK) activity and a high incidence of central nervous system (CNS) disease increase the probability of FHL. METHODS: The authors analyzed 42 HLH patients age < 2 years, 13 of whom developed overt CNS disease and 5 of whom demonstrated persistently deficient NK activity (Group 1). The remaining 24 patients had no CNS disease and had NK activity of moderate decrease to within the normal range (Group 2). RESULTS: In Group 1, CNS symptoms were detected in 6 cases within 1 month and between 4.5-9 months in 6 other patients. In these cases, spotty lesions demonstrating a high T2 signal in the white matter were noted on brain magnetic resonance imaging. The survival was significantly poor for patients in Group 1 unless they were rescued with SCT, which was performed in 5 of the 13 patients with CNS disease and in all 5 patients with persistent NK activity deficiency. SCT was successful in 9 patients, with no CNS sequelae reported after the transplantation. Conversely, the prognosis of the 24 patients in Group 2 was better and only 1 patient required SCT. CONCLUSIONS: Very young HLH patients (age < 2 years) who are at high risk of fatal FHL with persistently deficient NK activity and/or overt CNS disease require appropriate SCT to reverse CNS disease and achieve a complete cure.

Age of Onset↗

Thrombus Metabolism-Based Molecular Subtyping for Prognostic Risk Stratification in Acute Ischemic Stroke: A Preliminary Study.

AIMS: To preliminarily characterize metabolic molecular subtypes of cerebral thromboemboli and evaluate their clinical significance in anterior circulation acute ischemic stroke due to large vessel occlusion (AIS-LVO). METHODS: Untargeted metabolomics was performed on thromboemboli retrieved from 36 patients with anterior circulation AIS-LVO using ultra-performance coupled liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Unsupervised hierarchical clustering was employed to identify distinct metabolic molecular subtypes, and their associations with stroke etiology, radiographic severity, and functional outcomes were analyzed. RESULTS: Two distinct thrombus metabolic molecular subtypes (C1 and C2) were identified based on 12 metabolites significantly associated with both short-term (7-day &#x2206;NIHSS) and long-term (90-day mRS) functional outcomes. The C1 subtype, predominantly cardioembolic, exhibited enhanced lipid metabolism, whereas the C2 subtype, primarily atherothrombotic, demonstrated increased folate metabolism. Patients with C1 thromboemboli presented more severe admission ischemic lesions (as indicated by ASPECTS) and experienced poorer short-term and long-term outcomes. A six-metabolite signature derived from LASSO regression was identified for exploratory discrimination of thrombus metabolic subtypes, etiological subtypes, and 90-day outcomes. CONCLUSION: This preliminary exploratory study identifies two metabolically distinct thrombus molecular subtypes with clinical implications in anterior circulation AIS-LVO, providing a novel basis for risk stratification and personalized secondary prevention and warrants further investigation.

Humans↗

Prognostic risk factors and post mortem findings in cerebral malaria in children.

We have examined the possible risk factors for poor prognosis in cerebral malaria in 61 Nigerian children in an area of high malaria transmission. The level of coma, decerebrate rigidity, hypoglycaemia, and high urea levels were indicators of poor prognosis. Pyrexia, vomiting, and anaemia did not influence prognosis. Post-mortem findings suggest gross cerebral oedema and raised intracranial pressure in 4 of 7 cases with petechial haemorrhages and small focal necrosis (Durck's granuloma).

Adolescent↗