Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin.

Transplant-related mortality (TRM) following allo- geneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling (n = 263) or unrelated donors (n = 46) for hematologic disorders between December 1990 and December 1996. Of 27 laboratory tests taken on day +7 after BMT, serum bilirubin (P = 0.02) and BUN (P = 0.007) were found to be independent predictors of TRM in multivariate analysis. The median levels of bilirubin (0.9 mg/dl) and of BUN (21 mg/dl) were then used as a cut-off and a score of 1 was given for values equal/greater than the median. There were 216 patients with scores 0-1 (low risk) on day +7 (bilirubin <0.9 and/or BUN <21) and 93 patients with score 2 (high risk) (bilirubin >/=0.9 and BUN >/=21): the latter had more grade III-IV acute graft-versus-host disease (P = 0.03), slower neutrophil (P = 0.02) and slower platelet engraftment (P = 0.002). The actuarial 5 year TRM is 22% for low risk vs44% for high risk patients (P = 0.0003). For HLA-identical siblings TRM is 20% vs35% (P = 0.01), for unrelated donors it is 20% vs 65% (P = 0.01). Day +7 score was highly predictive of TRM on multivariate analysis (hazard ratio 1.9, P < 0.01), after adjustment for year of transplant (P < 0.00001), unrelated vs sibling donors (P = 0.001), patient age (P = 0.01) and diagnosis (P = 0.01). These results were validated on an independent group of 82 allogeneic BMT recipients in a pediatric Unit who showed an actuarial TRM of 16% for low risk vs 46% for high risk patients (P = 0.002). This study suggests that it may be possible to identify patients with different risks of TRM on day +7 after BMT: high risk patients could be eligible for programs designed to intensify prophylaxis of post-transplant complications.     

Serum procollagen type III is an early and sensitive marker for veno- occlusive disease of the liver in children undergoing bone marrow transplantation

Veno-occlusive disease of the liver (VOD) is a life-threatening complication occurring in patients undergoing bone marrow transplantation (BMT). Although clinical signs and laboratory parameters such as elevation of serum bilirubin often suggest this condition, it would be useful to identify early biochemical markers for VOD. Fibrous alterations in the hepatic venules and small lobular veins occur during development of VOD; these changes are accompanied by the deposition of types I and III collagen in the liver tissue. Since the N- terminal propeptide of type III procollagen (PIIINP) is a sensitive marker of liver and lung fibrosis, we undertook a study to evaluate the usefulness of measurements of serum PIIINP in children with VOD. Seven of the 28 children who underwent BMT, both allogenic and autologous, developed VOD. All seven had an increase of more than 100 ng/mL in the serum PIIINP level, whereas only one of the remaining 21 children not affected by VOD had an increment of PIIINP more than 100 ng/mL (P = .0001). The levels of serum PIIINP were higher in the VOD group during the follow-up period of up to 91 days after BMT. The elevation of PIIINP also occurred at a stage of the disease usually preceding any other laboratory or clinical signs of VOD. Serum concentration of PIIINP thus seems to be of value as an early marker for VOD in children undergoing BMT.     

ATG as part of the conditioning regimen reduces transplant-related mortality (TRM) and improves overall survival after unrelated stem cell transplantation in patients with chronic myelogenous leukemia (CML)

Matched unrelated donor transplants have an increased risk of severe graft-versus-host disease and transplant-related mortality (TRM). ATG has been introduced to decrease GvHD and to facilitate engraftment. We conducted a retrospective analysis of 333 patients with chronic myelogenous leukemia, who were treated with Fresenius ATG (n=145, average=90 mg/kg bw, range 40-90 mg/kg bw) or standard immunosuppression without ATG (n=188). Both groups were comparable regarding distribution of age, sex, HLA-matched vs mismatched donors. ATG Fresenius led to a faster leukocyte engraftment, decreased the incidence of acute GvHD and TRM (P=0.01 and P=0.03) and led to a significant better overall survival (70 vs 57%, P=0.03). We concluded that a prospective randomized study is needed to evaluate the definite role of ATG in hemopoietic stem cell transplantation.     

Serum inter-cellular adhesion molecule 1 is an early marker of diagnosis and prediction of severe acute pancreatitis

AIM: To determine if serum inter-cellular adhesion molecule 1 (ICAM-1) is an early marker of the diagnosis and prediction of severe acute pancreatitis (SAP) within 24 h of onset of pain, and to compare the sensitivity, specificity and prognostic value of this test with those of acute physiology and chronic health evaluation (APACHE) II score and interleukin-6 (IL-6).METHODS: Patients with acute pancreatitis (AP) were divided into two groups according to the Ranson’s criteria: mild acute pancreatitis (MAP) group and SAP group. Serum ICAM-1, APACHE IIand IL-6 levels were detected in all the patients. The sensitivity, specificity and prognostic value of the ICAM-1, APACHE IIscore and IL-6 were evaluated.RESULTS: The ICAM-1 level in 36 patients with SAP within 24 h of onset of pain was increased and was significantly higher than that in the 50 patients with MAP and the 15 healthy volunteers (P < 0.01). The ICAM-1 level (25 ng/mL) was chosen as the optimum cutoff to distinguish SAP from MAP, and the sensitivity, specificity, positive predictive value, negative predictive value (NPV), positive likelihood ratio and negative likelihood ratio were 61.11%, 71.42%, 0.6111, 0.7142, 2.1382 and 0.5445, respectively. The area under the curve demonstrated that the prognostic accuracy of ICAM-1 (0.712) was similar to the APACHE-IIscoring system (0.770) and superior to IL-6 (0.508) in distinguishing SAP from MAP.CONCLUSION: ICAM-1 test is a simple, rapid and reliable method in clinical practice. It is an early marker of diagnosis and prediction of SAP within the first 24 h after onset of pain or on admission. As it has a relatively low NPV and does not allow it to be a stand-alone test for the diagnosis of AP, other conventional diagnostic tests are required.     

Serum keratan sulfate is a promising marker of early articular cartilage breakdown

OBJECTIVES: To find serum markers that may serve as indices for an early diagnosis of degeneration or damage of the articular cartilage. METHODS: Twenty-four healthy volunteers, 19 individuals with knee trauma (KT) and 31 with knee osteoarthritis (OA) were evaluated. KT patients were divided into a group (n = 5) with an injury <2 months old (recent KT) and a group (n = 14) with that >2 months old (old KT). Articular cartilage damage was assessed using either arthroscopy or direct observation. Serum concentrations of hyaluronic acid (HA), cartilage proteoglycan aggrecan turnover epitope (CS846) and cartilage oligomeric protein (COMP) were measured using enzyme-linked immunosorbent assay kits and those of keratan sulfate (KS) and chondroitin-6-sulfate (C6S) using high-performance liquid chromatography. RESULTS: Serum KS in the recent KT group (2095 +/- 594 ng/ml) was significantly higher than that in the old KT group (1373 +/- 418 ng/ml; P = 0.021), and serum COMP in the recent KT group (1572 +/- 182 ng/ml) showed a tendency that was higher than that in the old KT group (1350 +/- 250 ng/ml; P = 0.079). Serum KS in OA patients with Kellgren and Lawrence (KL) grades 0 and I (1456 +/- 334 ng/ml) showed a tendency that was higher than that in OA patients with KL grades II, III and IV (1248 +/- 220 ng/ml; P = 0.084). CONCLUSIONS: The serum concentration of KS correlated with the damage of the articular cartilage and it was significantly increased even at an early stage after the injury.     

Serum biotinidase is a sensitive and specific biochemical marker of hepatic dysfunction: A preliminary report

Biotinidase is an enzyme synthesized predominantly by the liver. Serum activity of this enzyme has been shown to be low in chronic liver disease. In this study, we endeavored to assess the diagnostic value of serum biotinidase as a marker of hepatic biosynthetic function in acute and chronic liver dysfunction. Twenty-three patients with acute liver disease and 46 with chronic liver disease, as diagnosed by clinical examination, laboratory tests, histopathology and tests for viral markers, were inducted into the study. Forty-six healthy volunteers were selected as controls. Serum biotinidase activity was estimated in all the subjects. Biotinidase activity was found to be significantly lower in the serum of patients with acute (4.59 +/- 1.26 IU/L vs 7.56 +/- 0.82 IU/L in controls; P相似文献   

Rel B is an early marker of autoimmune islet inflammation in the biobreeding (BB) rat

Because the development of insulitis and diabetes is predictable in Lyp/Lyp congenic BB rats, we have characterized early islet inflammation in these rats to determine the cell subsets involved in the onset of autoimmune insulitis. Pancreas sections from prediabetic Lyp/Lyp, Lyp/+ and +/+ rats were analyzed by immunohistochemistry. We found W3/25+ cells in the exo- and endocrine tissue from all three genotypes, but intraislet insulitis was never found in Lyp/+ or +/+ rats. The onset of massive, intraislet B- and T-cell infiltration in Lyp/Lyp rats was preceded by Rel B+ cells in and around the islets, followed by ED1+ monocytes/macrophages. Rel B+ cells were more frequent in the parafollicular cortex of pancreatic lymph nodes from Lyp/Lyp than from Lyp/+ and +/+ rats. In the Lyp/Lyp thymus, we found significantly increased expression of IL-12p40 messenger RNA (mRNA; p<0.001), located in the Rel B-protein-rich corticomedullary junction. The NF-KB/Rel B complex specifically transactivates genes involved in antigen presentation in dendritic cells. Rel B+ cells in the islets may therefore mark the onset of autoimmune insulitis and antigen-specific activation of autoreactive T cells in the lymph nodes of diabetes prone Lyp/Lyp BB rats. In the thymus, Rel B+ cells may support the Lyp-dependent development of self-reactive thymocytes by activation of cytokine expression.     

Serum pepsinogens as an early diagnostic marker of H. pylori eradication

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) eradication increases the serum pepsinogen I/ pepsinogen II ratio and the percentage change in pepsinogen I/pepsinogen II ratios is a useful marker of H. pylori eradication. We studied whether the pepsinogen method could be an early diagnostic marker of H. pylori eradication even in patients persistently treated with a proton pump inhibitor. METHODOLOGY: Sixty-two H. pylori-positive patients underwent H. pylori-eradication therapy, followed by treatment with a proton pump inhibitor to cure ulcers. Serum levels of pepsinogen I and pepsinogen II were measured before, at the end of, and at 4 weeks after the eradication therapy. The cut-off values of percentage changes in pepsinogen I/pepsinogen II ratios for the diagnosis of eradication of H. pylori were set in proportion to pepsinogen I/pepsinogen II ratios before eradication in accordance with a previous report. RESULTS: Using the results of 13C-urea breath test as the standard, the sensitivity, specificity and validity of the pepsinogen method were 100.0%, 89.8% and 90.3%, respectively, at 4 weeks after eradication therapy. CONCLUSION: The percentage change in serum pepsinogen I/pepsinogen II ratios is useful as an early diagnostic marker for judgment of H. pylori eradication irrespective of proton pump inhibitor treatment.     

Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis

In a previous retrospective case-control study, hemoconcentration was associated with the development of pancreatic necrosis. The aim of the present study was to determine in a cohort study whether hemoconcentration is a marker for both organ failure and necrotizing pancreatitis. A cohort study was performed on patients admitted with acute pancreatitis from February 1996 to April 1997. Pancreatic necrosis was defined by findings on dynamic contrast-enhanced computed tomography scan or magnetic resonance imaging. Of 128 total patients with acute pancreatitis, 53 underwent computed tomography or magnetic resonance imaging. Eighteen of 53 had necrotizing pancreatitis. Logistic regression identified an admission hematocrit > or = 44% and a failure of admission hematocrit to decrease at 24 hours as the best binary predictors of necrotizing pancreatitis and organ failure. By 24 hours, 17 of 18 patients with necrotizing pancreatitis versus 11 of 35 with interstitial pancreatitis met one or the other criterion for necrosis (p < 0.001). By 24 hours, 13 of 15 with organ failure versus 36 of 104 without organ failure met one or the other criterion (p < 0.001). The negative predictive value by 24 hours was 96% for necrotizing pancreatitis and 97% for organ failure. Hemoconcentration with an admission hematocrit > or = 44% and/or failure of admission hematocrit to decrease at approximately 24 hours was associated with the development of necrotizing pancreatitis and organ failure. Patients who did not experience hemoconcentration were very unlikely to develop pancreatic necrosis or organ failure.     

Plasma semicarbazide-sensitive amine oxidase (SSAO) is an independent prognostic marker for mortality in chronic heart failure.

AIMS: Experimental evidence has suggested that semicarbazide-sensitive amine oxidase is involved in vascular endothelial damage and in the process of atherosclerosis, through the formation of reactive aldehydes, hydrogen peroxide and ammonia from endogenous substrates. Recent evidence indicates that semicarbazide-sensitive amine oxidase may be identical with the vascular adhesion protein-1. In patients with diabetes mellitus and chronic heart failure the plasma activity is raised relative to the severity of the disease. The prognostic value of plasma semicarbazide-sensitive amine oxidase is not known. METHODS AND RESULTS: Plasma semicarbazide-sensitive amine oxidase activity was measured at baseline in patients with moderate to severe chronic heart failure who participated in a large European study (PRIME-II). The 372 patients who took part in a pre-defined substudy in The Netherlands were investigated and a survival follow-up (maximum 5.4 years, mean 3.4 years) was carried out. Within the follow-up period 195 patients died. Plasma semicarbazide-sensitive amine oxidase was higher at baseline in those who died than in the survivors (653+/-258 vs 540+/-242 mU. l(-1), P<0.001). Dividing the patients into two groups according to plasma values above or below the median value of 550 mU. l(-1), semicarbazide-sensitive amine oxidase was found to be a prognostic parameter for survival, both in univariate (P<0.0001) and in multivariate (P=0.0106) analysis. Semicarbazide-sensitive amine oxidase values >550 mU. l(-1)had a 1. 50 (95% CI, 1.10-2.04) times increased risk of death. CONCLUSION: The finding that plasma semicarbazide-sensitive amine oxidase is an independent prognostic marker for mortality in chronic heart failure supports the concept that an elevated plasma semicarbazide-sensitive amine oxidase level has deleterious effects, possibly due to vascular endothelial damage.     

Thrombocytopenia: an early marker of late mortality in type B aortic dissection

Mid-term and long-term mortality after aortic dissection remain high and due to unknown factors. To determine predicting factors at the acute phase associated with mid- and long-term all-cause mortality, patients with type B aortic dissection including intramural hematoma, treated in one referral university center in an area with a population of 4 million, were analyzed over a period of 12 years (from 1996 to 2008). Based on the total population, 77 patients discharged after type B aortic dissection (including 11 intramural hematoma) were recorded as treated with either medical treatment alone (n = 41) or with additional endovascular therapy (n = 36). The mean follow-up period was 50.8 months, with a survival rate of 78 % (17 deaths). Patient history, symptoms, medical treatment, biological parameters, imaging, and intervention during acute phase (more than 150 parameters) were analyzed to identify any relationship with complications and death. Kaplan–Meier survival curve and Cox proportional hazards analyses identified independent predictors of follow-up mortality from any cause. Factors influencing mortality (P < 0.05) were a low systolic blood pressure (SBP) at admission, a thrombocytopenia in the acute period, chronic bronchitis, diameter of ascending aorta, and renin–angiotensin system inhibitor intake. Independent predictors of mortality were chronic bronchitis (P = 0.0022, hazard ratio (HR) 17.5), early thrombocytopenia (P = 0.042, HR 3.5), and admission SBP <120 mmHg (P = 0.0048, HR 7.928). Treated (medical ± endovascular) type B aortic dissection held a worse long-term prognosis, which can be correlated with predicting factors, especially in-hospital thrombocytopenia, and should require closer follow-up     

Serum sclerostin is an independent predictor of mortality in hemodialysis patients

Background

Sclerostin (Scl) has recently emerged as a novel marker of bone remodeling and vascular calcification. However, whether high circulating Scl is also a risk factor for death is not well established. The purpose of this study was to test whether serum Scl would be associated with mortality.

Methods

we measured serum Scl in a hemodialysis patients’ cohort, which was followed during a ten-year period. Competing risk regression models were applied, as during the follow-up, patients were exposed to both events kidney transplant and death.

Results

Ninety-one patients aged 42.3?±?18.8 years (55% of male gender, 15% of diabetes) were included. During the follow-up, 32 patients underwent kidney transplant and 26 patients died. Non-survivals presented higher FGF23, higher Scl and lower creatinine. There was an association between all-cause mortality and higher Scl (HR =?2.2), higher age (HR =?1.04) and presence of diabetes (HR =?2.27), by competing risk analyses. Even including potential markers of mortality, as creatinine, FGF 23, and gender, Scl, age and diabetes remained significantly related to higher mortality.

Conclusion

Serum Scl is an independent predictor of mortality in dialysis patients. However, whether clinical interventions to modulate Scl would be able to improve these patients survival needs to be determined.

     

An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation

We monitored levels of C-reactive protein (CRP) in 96 consecutive adult allogeneic BMT patients (age 15-50 years) transplanted in our unit. Major transplant-related complications (MTC) occurred in 32% of cases and included: hepatic veno-occlusive disease, pneumonitis, severe endothelial leakage syndrome and >II acute GVHD. Transplant-related mortality (TRM) before day 100 post-BMT was 13.5%. Variables included in a stepwise logistic regression model were: gender, age, disease category, donor type, T cell depletion, TBI, use of growth factors, bacteremia, mean CRP-levels >50 mg/l between days 0 and 5 (CRP day 0-5) and >100 mg/l between days 6 and 10 (CRP day 6-10) post-BMT. Only high CRP-levels (for MTC and TRM) (P < 0.001) and donor-type (for TRM) (P= 0.02) were independent risk factors. The estimated probability for MTC was 73% (CRP day 6-10 >100 mg/l) vs 17% (CRP day 6-10 <100 mg/l). Using the same cut-off levels, the probabilities for TRM were 36.5% vs 1% in the identical sibling donor situation and 88% vs 12.5% in other donor-type transplants. We conclude that the degree of systemic inflammation, as reflected by CRP-levels, during the first 5-10 days after BMT identifies patients at risk of MTC and TRM. Our data may be useful in selecting patients for clinical trials involving pre-emptive anti-inflammatory treatment.     

Neutrophil Gelatinase-Associated Lipocalin (NGAL): an early marker for diabetic nephropathy

Neutrophil gelatinase-associated lipoprotein (NGAL) represents a novel biomarker for early identification of acute kidney injury. This study evaluates the usefulness of urine NGAL as a marker for the early detection of diabetic nephropathy. This is a cross-sectional study which involved ninety patients with diabetes mellitus and thirty healthy controls. The diabetic patients were categorized into three groups based on their urine albumin/creatinine ratio (UACR); normoalbuminuria (<3.5?mg/mmol), microalbuminuria (3.5?C35?mg/mmol), macroalbuminuria (>35?mg/mmol). In addition to urine NGAL, HbA1C, serum creatinine, urine albumin/creatinine ratio, serum cystatin C, and urine protein were assessed to determine their correlation with urine NGAL. Data analysis was done by using SPSS and MiniTab. Urine NGAL was elevated in all groups of diabetic patients with respect to controls. It was increased proportionately to the severity of kidney function. It was also elevated in some normoalbuminuria diabetic patients. Analysis of correlation revealed that urine NGAL was not correlated with glycemic indices (HbA1C and fasting blood glucose). However, urine NGAL correlated significantly with cystatin C, serum creatinine, urine albumin/creatinine ratio, and inversely with eGFR. Besides, it is also shown to have a significant correlation with eGFR in advanced kidney disease (eGFR?<?30?ml/min per 1.73?min²). Urine NGAL can be used as a non-invasive tool for the early detection and assessment of the severity of diabetic nephropathy.     

Serum cholinesterase levels of vector control workers in Trinidad, West Indies (1979-1987).

During 1979-1987 studies were carried out in vitro on the serum cholinesterase levels of 46 vector control workers exposed to insecticides on a daily basis but without clinical manifestations of insecticide poisoning. The results were compared with those of a control group of workers who had not been exposed to insecticides at home or at work. Cholinesterase levels of both groups were determined by a standard colorimetric method. Suppressed serum cholinesterase levels were detected in all 46 workers exposed to insecticides, 25 of whom were aged 30-39 years. Four persons from the control group showed suppressed levels of enzyme; one of these had a genetically low level, and the other three were on medication when the low levels were recorded.