Zimmer Biomet (United States)

The Pto gene in tomato confers resistance to races of Pseudomonas syringae pv. tomato that carry the avirulence gene avrPto. A yeast artificial chromosome clone that spans the Pto region was identified and used to probe a leaf complementary DNA (cDNA) library. A cDNA clone was isolated that represents a gene family, at least six members of which genetically cosegregate with Pto. When susceptible tomato plants were transformed with a cDNA from this family, they were resistant to the pathogen. Analysis of the amino acid sequence revealed similarity to serine-threonine protein kinases, suggesting a role for Pto in a signal transduction pathway.

MOTIVATION: In genomic studies, thousands of features are collected on relatively few samples. One of the goals of these studies is to build classifiers to predict the outcome of future observations. There are three inherent steps to this process: feature selection, model selection and prediction assessment. With a focus on prediction assessment, we compare several methods for estimating the 'true' prediction error of a prediction model in the presence of feature selection. RESULTS: For small studies where features are selected from thousands of candidates, the resubstitution and simple split-sample estimates are seriously biased. In these small samples, leave-one-out cross-validation (LOOCV), 10-fold cross-validation (CV) and the .632+ bootstrap have the smallest bias for diagonal discriminant analysis, nearest neighbor and classification trees. LOOCV and 10-fold CV have the smallest bias for linear discriminant analysis. Additionally, LOOCV, 5- and 10-fold CV, and the .632+ bootstrap have the lowest mean square error. The .632+ bootstrap is quite biased in small sample sizes with strong signal-to-noise ratios. Differences in performance among resampling methods are reduced as the number of specimens available increase. SUPPLEMENTARY INFORMATION: A complete compilation of results and R code for simulations and analyses are available in Molinaro et al. (2005) (http://linus.nci.nih.gov/brb/TechReport.htm).

Two thousand eight hundred thirty-seven cases of carcinoid tumor from files at the National Cancer Institute were analyzed statistically. Tumors were found in the lung, ovary, and biliary and gastrointestinal tracts. Most were in the appendix, rectum, and ileum. Age-adjusted incidence rates were higher for black males, except for lung carcinoids. Carcinoids showed several differences from other kinds of tumor, including a low age for appendiceal and lung cases and low male/female and black/white ratios in the lung. Percentages of concurrent neoplasms and multiple carcinoids were low compared to other series. Five-year relative survival rates ranged from 99% (appendix) to 33% (sigmoid colon). Survival for colon cases was not so low as expected on the basis of the high rate of metastasis. Some appendiceal carcinoids were metastatic and may have killed 1 patient. Findings are compared with other studies.

Growth factors released from activated platelets initiate and modulate wound healing in both soft and hard tissues. A recent strategy to promote the wound-healing cascade is to prepare an autologous platelet concentrate suspended in plasma, also known as platelet-rich plasma, that contains growth factors and administer it to wound sites. The purpose of this study was to quantitate platelet number and growth factors released from a prepared platelet concentrate. Whole blood was drawn from 10 healthy patients undergoing cosmetic surgery and concentrated into platelet-rich plasma. Platelet counts on whole blood and platelet-rich plasma were determined using a Cell-Dyn 3200. Platelet-derived growth factor-BB, transforming growth factor-beta1, vascular endothelial growth factor, endothelial growth factor, and insulin-like growth factor-1 were measured in the platelet-rich plasma using the enzyme-linked immunosorbent assay method. In addition, platelet activation during the concentration procedure was analyzed by measuring P selectin values in blood serum. An 8-fold increase in platelet concentration was found in the platelet-rich plasma compared with that of whole blood (baseline whole blood, 197 +/- 42 x 10 platelets/microl; platelet concentrate, 1600 +/- 330 x 10 platelets/microl). The concentration of growth factors also increased with increasing platelet number. However, growth factor concentration varied from patient to patient. On average for the whole blood as compared with platelet-rich plasma, the platelet-derived growth factor-BB concentration increased from 3.3 +/- 0.9 ng/ml to 17 +/- 8 ng/ml, transforming growth factor-beta1 concentration increased from 35 +/- 8 ng/ml to 120 +/- 42 ng/ml, vascular endothelial growth factor concentration increased from 155 +/- 110 pg/ml to 955 +/- 1030 pg/ml, and endothelial growth factor concentration increased from 129 +/- 61 pg/ml to 470 +/- 320 pg/ml. No increase was found for insulin-like growth factor-1. In addition, no increase in platelet activation occurred during the concentration procedure as determined by the platelet surface receptor P selectin (45 +/- 16 pg/ml to 52 +/- 11 pg/ml, p = 0.65). In conclusion, a variety of potentially therapeutic growth factors were detected and released from the platelets in significant levels in platelet-rich plasma preparations. Sufficient concentrates and release of these growth factors through autologous platelet gels may be capable of expediting wound healing in a variety of as yet undetermined specific wound applications.

CONTEXT: Psychiatric disorders and substance use during pregnancy are associated with adverse outcomes for mothers and their offspring. Information about the epidemiology of these conditions in this population is lacking. OBJECTIVE: To examine sociodemographic correlates, rates of DSM-IV Axis I psychiatric disorders, substance use, and treatment seeking among past-year pregnant and postpartum women in the United States. DESIGN: National survey. SETTING: Face-to-face interviews conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. PARTICIPANTS: A total of 43 093 respondents were interviewed, of whom 14 549 were women 18 to 50 years old with known past-year pregnancy status. MAIN OUTCOME MEASURES: Prevalence of 12-month DSM-IV Axis I psychiatric disorders, substance use, and treatment seeking. RESULTS: Past-year pregnant and postpartum women had significantly lower rates of alcohol use disorders and any substance use, except illicit drug use, than nonpregnant women. In addition, currently pregnant women had a lower risk of having any mood disorder than nonpregnant women. The only exception was the significantly higher prevalence of major depressive disorder in postpartum than in nonpregnant women. Age, marital status, health status, stressful life events, and history of traumatic experiences were all significantly associated with higher risk of psychiatric disorders in pregnant and postpartum women. Lifetime and past-year treatment-seeking rates for any psychiatric disorder were significantly lower among past-year pregnant than nonpregnant women with psychiatric disorders. Most women with a current psychiatric disorder did not receive any mental health care in the 12 months prior to the survey regardless of pregnancy status. CONCLUSIONS: Pregnancy per se is not associated with increased risk of the most prevalent mental disorders, although the risk of major depressive disorder may be increased during the postpartum period. Groups of pregnant women with particularly high prevalence of psychiatric disorders were identified. Low rates of maternal mental health care underscore the need to improve recognition and delivery of treatment for mental disorders occurring during pregnancy and the postpartum period.

Following individuals sampled in a large-scale health survey for the development of diseases and/or death offers the opportunity to assess the prognostic significance of various risk factors. The proportional hazards regression model, which allows for the control of covariates, is frequently used for the analysis of such data. The authors discuss the appropriate time-scale for such regression models, and they recommend that age rather than time since the baseline survey (time-on-study) be used. Additionally, with age as the time-scale, control for calendar-period and/or birth cohort effects can be achieved by stratifying the model on birth cohort. Because, as discussed by the authors, many published analyses have used regression models with time-on-study as the time-scale, it is important to assess the magnitude of the error incurred from this type of incorrect modeling. The authors provide simple conditions for when incorrect use of time-on-study as the time-scale will nevertheless yield approximately unbiased proportional hazards regression coefficients. Examples are given using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Followup Study. Additional issues concerning the analysis of longitudinal follow-up of survey data are briefly discussed.

(1944). Application of the Logistic Function to Bio-Assay. Journal of the American Statistical Association: Vol. 39, No. 227, pp. 357-365.

MOTIVATION: Genetic recombination and, in particular, genetic shuffling are at odds with sequence comparison by alignment, which assumes conservation of contiguity between homologous segments. A variety of theoretical foundations are being used to derive alignment-free methods that overcome this limitation. The formulation of alternative metrics for dissimilarity between sequences and their algorithmic implementations are reviewed. RESULTS: The overwhelming majority of work on alignment-free sequence has taken place in the past two decades, with most reports published in the past 5 years. Two main categories of methods have been proposed-methods based on word (oligomer) frequency, and methods that do not require resolving the sequence with fixed word length segments. The first category is based on the statistics of word frequency, on the distances defined in a Cartesian space defined by the frequency vectors, and on the information content of frequency distribution. The second category includes the use of Kolmogorov complexity and Chaos Theory. Despite their low visibility, alignment-free metrics are in fact already widely used as pre-selection filters for alignment-based querying of large applications. Recent work is furthering their usage as a scale-independent methodology that is capable of recognizing homology when loss of contiguity is beyond the possibility of alignment. AVAILABILITY: Most of the alignment-free algorithms reviewed were implemented in MATLAB code and are available at http://bioinformatics.musc.edu/resources.html

AIMS: Sodium-glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-like physiologic effects, we compared dapagliflozin and hydrochlorothiazide (HCTZ) effects on 24-h blood pressure (BP), body weight, plasma volume and glomerular filtration rate (GFR). METHODS: In this randomized, placebo-controlled, double-blind trial, 75 subjects with type 2 diabetes were assigned placebo, dapagliflozin 10 mg/day, or HCTZ 25 mg/day. Changes from baseline BP, body weight, plasma volume and GFR were assessed after 12 weeks of treatment. RESULTS: Subjects' mean age was 56 years, type 2 diabetes mellitus (T2DM) duration 6.3 years, and haemoglobin A1c (HbA1c) 7.5%. Treatment with placebo, dapagliflozin or HCTZ resulted in changes from baseline in 24-h ambulatory mean systolic blood pressure (SBP) of -0.9 (95%CI -4.2, +2.4), -3.3 (95%CI -6.8, +0.2), and -6.6 (95%CI -9.9, -3.2) mmHg, respectively at week 12, adjusted for baseline SBP. Body weight decreased with dapagliflozin and HCTZ. In a sub-study plasma volume appeared to decrease with dapagliflozin but did not change with placebo or HCTZ treatment. Dapagliflozin induced a greater reduction in GFR (-10.8%; 95%CI -14.6, -6.7) relative to placebo (-2.9%; 95% CI -6.9, +1.2) or HCTZ (-3.4%; 95%CI -7.3, +0.6). CONCLUSIONS: Dapagliflozin-induced SGLT2 inhibition for 12 weeks is associated with reductions in 24-h BP, body weight, GFR and possibly plasma volume. Cumulatively, these effects suggest that dapagliflozin may have a diuretic-like capacity to lower BP in addition to beneficial effects on glycaemic control.

Longitudinal studies have a prominent role in psychiatric research; however, statistical methods for analyzing these data are rarely commensurate with the effort involved in their acquisition. Frequently the majority of data are discarded and a simple end-point analysis is performed. In other cases, so called repeated-measures analysis of variance procedures are used with little regard to their restrictive and often unrealistic assumptions and the effect of missing data on the statistical properties of their estimates. We explored the unique features of longitudinal psychiatric data from both statistical and conceptual perspectives. We used a family of statistical models termed random regression models that provide a more realistic approach to analysis of longitudinal psychiatric data. Random regression models provide solutions to commonly observed problems of missing data, serial correlation, time-varying covariates, and irregular measurement occasions, and they accommodate systematic person-specific deviations from the average time trend. Properties of these models were compared with traditional approaches at a conceptual level. The approach was then illustrated in a new analysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program dataset, which investigated two forms of psychotherapy, pharmacotherapy with clinical management, and a placebo with clinical management control. Results indicated that both person-specific effects and serial correlation play major roles in the longitudinal psychiatric response process. Ignoring either of these effects produces misleading estimates of uncertainty that form the basis of statistical tests of hypotheses.

In Brief The present guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in postoperative nausea and vomiting (PONV) under the auspices of The Society of Ambulatory Anesthesia. The panel critically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. In brief, these guidelines identify risk factors for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic monotherapy and combination therapy regimens for PONV prophylaxis; recommend approaches for treatment of PONV when it occurs; and provide an algorithm for the management of individuals at increased risk for PONV. IMPLICATIONS: Evidence-based guidelines developed by an international multidisciplinary panel of experts and endorsed by Society for Ambulatory Anesthesia for the management of postoperative nausea and vomiting.

In Brief Objective: The purpose of this study was to describe the natural history, identify risk factors, and determine outcomes for the development of postoperative delirium in the elderly. Background: Postoperative delirium is a common and deleterious complication in geriatric patients. Methods: Subjects older than 50 years scheduled for an operation requiring a postoperative intensive care unit admission were recruited. After preoperative informed written consent, enrolled subjects had baseline cognitive and functional assessments. Postoperatively, subjects were assessed daily for delirium using the confusion assessment method-intensive care unit. Patients were also followed for outcomes. Results: During the study period, 144 patients were enrolled before major abdominal (40%), thoracic (53%), or vascular (7%) operations. The overall incidence of delirium was 44% (64/144). The average time to onset of delirium was 2.1 ± 0.9 days and the mean duration of delirium was 4.0 ± 5.1 days. Several preoperative variables were associated with an increased risk of delirium including older age (P < 0.001), hypoalbuminemia (P < 0.001), impaired functional status (P < 0.001), pre-existing dementia (P < 0.001), and pre-existing comorbidities (P < 0.001). In a multivariable logistic regression model, pre-existing dementia remains the strongest risk factor for the development of postoperative delirium. Worse outcomes, including increased length of stay (P < 0.001), postdischarge institutionalization (P < 0.001), and 6 month mortality (P = 0.001), occurred in subjects who developed delirium. Conclusions: In the current study, delirium occurred in 44% of elderly patients after a major operation. Pre-existing cognitive dysfunction was the strongest predictor of the development of postoperative delirium. Outcomes, including an increased rate of 6 month mortality, were worse in patients who developed postoperative delirium. The purpose of this study was to describe the natural history, identify risk factors, and determine the outcomes for the development of postoperative delirium in the elderly. Delirium occurred in 44% of subjects, and pre-existing cognitive dysfunction was the strongest predictor of postoperative delirium. Outcomes, including a higher rate of 6 month mortality, were worse in subjects who developed postoperative delirium.

OBJECTIVE: To describe the time between treatment for choroidal melanoma and first diagnosis of metastatic disease, sites of metastasis, treatments for metastasis, and time between diagnosis of metastasis and death. DESIGN: Prospective, longitudinal follow-up of patients diagnosed with choroidal melanoma who were enrolled in 2 randomized trials conducted by the Collaborative Ocular Melanoma Study Group. METHODS: Systemic and laboratory evaluations were performed during follow-up according to a standard protocol for 2320 patients enrolled in the Collaborative Ocular Melanoma Study trials without evidence of melanoma metastasis or other primary cancer at baseline. RESULTS: Seven hundred thirty-nine patients were diagnosed with at least 1 site of metastasis during follow-up after treatment for choroidal melanoma. Five- and 10-year cumulative metastasis rates were 25% (95% confidence interval, 23%-27%) and 34% (95% confidence interval, 32%-37%), respectively. Liver was the most common site (89%). The death rate following the report of melanoma metastasis was 80% at 1 year (95% confidence interval, 77%-83%) and 92% at 2 years (95% confidence interval, 89%-94%). Overall survival after metastasis did not vary by baseline size of primary tumor nor treatment for metastasis (when known). Long-term survival after diagnosis of metastasis was uncommon; only 8 patients survived 5 or more years. CONCLUSION: Metastasis rate increased significantly with increasing primary tumor dimensions at time of patient enrollment. Prognosis after metastatic disease remains poor. Effective methods are needed to prevent, diagnose, and treat metastasis from choroidal melanoma.

The method of calculating the exact likelihood function of a stationary autoregressive moving average (ARMA) time series based on Akaike's Markovian representation and using Kalman recursive estimation is reviewed. This state space approach involves matrices and vectors with dimensions equal to Max (p, q + 1) where p is the order of the autoregression and q is the order of the moving average, rather than matrices with dimensions equal to the number of observations. A key to the calculation of the exact likelihood function is the proper calculation of the initial state covariance matrix. The inclusion of observational error into the model is discussed as is the extension to missing observations. The use of a nonlinear optimization program gives the maximum likelihood estimates of the parameters and allows for model identification based on Akaike's Information Criterion (AIC). An example is presented fitting models to western United States drought data.

Serum lipids (total cholesterol and triglycerides) and lipoprotein cholesterol fractions (low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, and high density lipoprotein (HDL) cholesterol) have been measured approximately every 3 years on children and young adults since 1973-1974 in Bogalusa, Louisiana, a community of approximately 22,000 individuals, one-third of whom are black and two-thirds of whom are white. A total of 1,586 children were examined both at baseline (1973-1974) and at the most recent survey (1984-1986), providing 12 years of follow-up. The decreases in levels noted during puberty for total cholesterol and LDL cholesterol, primarily for boys, were followed by a rise until age 26 years. HDL cholesterol levels, particularly for white boys, continued to drop after age 14 years, yielding increasingly high LDL cholesterol/HDL cholesterol ratios. Tracking, as measured by both correlation coefficients and persistence at extreme quartiles, was evident for all of the lipids and lipoproteins. The 12-year correlation coefficients were greatest for LDL cholesterol and no trend in the magnitude of the correlation coefficients with age was noted. Tracking for HDL cholesterol was better after age 9 years, particularly for white males. Approximately 50% of those children who had total cholesterol levels or LDL cholesterol levels above the 75th percentile at baseline remained elevated 12 years later. For HDL cholesterol, a trend with age was noted for white boys: 42% of those aged 9-14 years in the lower most quartile persisted in this rank 12 years later. The best predictor of follow-up lipid or lipoprotein level was baseline level. The next best predictor was increase in weight as defined by weight/height, an index of obesity. That serum lipid and lipoprotein levels continue to track from childhood into young adulthood points to the necessity of measurement early in life and, where indicated, the introduction of preventive and interventional programs aimed at developing healthy lifestyles.

Cytomegalovirus is a major viral pathogen in patients who undergo renal transplantation, and cytomegalovirus disease is difficult to treat. We therefore conducted a randomized, placebo-controlled, double-blind trial of acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts from cadavers. Acyclovir was given orally in doses of 800 to 3200 mg per day, according to the patients' estimated level of renal function. Patients took the first dose of either acyclovir or placebo six hours before transplantation and continued to take the assigned medication for 12 weeks. Of 118 patients enrolled in the study, 104 completed at least 30 days on the study medication and were included in our analysis of the results. During the first year after transplantation, 4 of 53 patients (7.5 percent) in the acyclovir group had symptomatic cytomegalovirus disease, as compared with 15 of 51 (29 percent) in the placebo group (P = 0.002). There was a single case of cytomegalovirus pneumonia in the acyclovir group, as compared with nine in the placebo group. The greatest prophylactic benefit of acyclovir was observed among seronegative patients who had received a kidney from a seropositive donor; only one of six such patients in the acyclovir group had cytomegalovirus disease, as compared with all seven in the placebo group. Acyclovir decreased the incidence of documented cytomegalovirus infection (with or without symptomatic disease) to 36 percent from 61 percent among the patients who received the placebo (P = 0.011). Among the patients who received acyclovir, the rates of recovery of virus from the blood and urine were significantly reduced, but the rate of viral shedding from the pharynx was not significantly different from that in the placebo group. There were no differences between the groups in the frequency of adverse events or in the rate of survival of either grafts or patients. We conclude that the oral administration of acyclovir, beginning before the transplantation of a renal allograft from a cadaver, reduces the rate of cytomegalovirus infection and disease without affecting the survival rate of either grafts or patients.

Quantitative trait loci (QTLs) have been mapped to small intervals along the chromosomes of tomato (Lycopersicon esculentum), by a method we call substitution mapping. The size of the interval to which a QTL can be mapped is determined primarily by the number and spacing of previously mapped genetic markers in the region surrounding the QTL. We demonstrate the method using tomato genotypes carrying chromosomal segments from Lycopersicon chmielewskii, a wild relative of tomato with high soluble solids concentration but small fruit and low yield. Different L. chmielewskii chromosomal segments carrying a common restriction fragment length polymorphism were identified, and their regions of overlap determined using all available genetic markers. The effect of these chromosomal segments on soluble solids concentration, fruit mass, yield, and pH, was determined in the field. Many overlapping chromosomal segments had very different phenotypic effects, indicating QTLs affecting the phenotype(s) to lie in intervals of as little as 3 cM by which the segments differed. Some associations between different traits were attributed to close linkage between two or more QTLs, rather than pleiotropic effects of a single QTL: in such cases, recombination should separate desirable QTLs from genes with undesirable effects. The prominence of such trait associations in wide crosses appears partly due to infrequent reciprocal recombination between heterozygous chromosomal segments flanked by homozygous regions. Substitution mapping is particularly applicable to gene introgression from wild to domestic species, and generally useful in narrowing the gap between linkage mapping and physical mapping of QTLs.

A set of 194 F7 lines derived from a subspecific rice cross showing strong F1 heterosis was backcrossed to the two parents. The materials (388 BC1F7 lines, 194 F8 lines, two parents, F1) were phenotyped for 12 quantitative traits. A total of 37 significant QTLs (LOD > or = 2.0) was detected through 141 RFLP markers in the BC1F7 populations. Twenty-seven (73%) quantitative trait loci (QTLs) were detected in only one of the BC1F7 populations. In 82% of these cases, the heterozygotes were superior to the respective homozygotes. The remaining 10 (27%) QTLs were detected in both BC1F7 populations, and the heterozygote had a phenotype falling between those of the two homozygotes and in no instances were the heterozygotes found to be superior to both homozygotes. These results suggest that dominance complementation is the major genetic basis of heterosis in rice. This conclusion was strengthened by the finding that there was no correlation between most traits and overall genome heterozygosity and that there were some recombinant inbred lines in the F8 population having phenotypic values superior to the F1 for all of the traits evaluated--a result not expected if overdominance was a major contributor to heterosis. Digenic epistasis was not evident.

BACKGROUND: In a clinical study evaluating the functioning of mobility-limited elders, muscle power accounted for more of the variation in function than strength did. There was also evidence that the power-function relationship may be described as curvilinear. However, these findings have never been confirmed in a representative population. METHODS: An analysis was conducted using data from the InCHIANTI study, a population-based cohort of 1032 adults living in Italy. To assess the relationships between impairments in power and strength and mobility performance, we created separate multivariate linear and log-transformed regression models as well as separate logistic regression models. RESULTS: Subjects were age > or = 65 years, predominantly female (54%), with a mean age of 74.2 years, and most had mild-moderate mobility limitations (Short Physical Performance Battery score 10.5 +/- 2.1). Though leg extension power and isometric hip extension strength were closely associated, in several separate multivariate linear regression models, leg power consistently explained more of the variance than strength did in several measures of physical performance. Differences were even larger when observed in curvilinear models of power and strength. Using separate multivariate logistic regression models to examine the odds ratios for mobility limitations in persons with low muscle power versus high muscle power, and in persons with low muscle strength versus high muscle strength, we found that both factors influenced risk for mobility limitations, but low power was associated with a 2-3-fold greater likelihood than low strength. CONCLUSION: These findings identified muscle power to be a more influential proximal determinant of physical performance than impairments in strength and emphasized muscle power as an important determinant of mobility skills in older adults.

BACKGROUND: Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and can be used to assess prognosis in heart failure and after myocardial infarction. Heart involvement is the most important prognostic factor and causes death in almost all patients with light-chain amyloidosis (AL). We investigated the prognostic value of NT-proBNP and its utility in monitoring amyloid heart dysfunction. METHODS AND RESULTS: NT-proBNP was quantified at diagnosis in 152 consecutive patients seen at the coordinating center of the Italian Amyloidosis Study Group (Pavia) from 1999 throughout 2001. Heart involvement was estimated on the basis of clinical signs, electrocardiography, and echocardiography. NT-proBNP concentrations differed in patients with (n=90, 59%) and without (n=62, 41%) heart involvement (median: 507.8 pmol/L versus 22.1 pmol/L, P=10(-7)). The best cutoff for heart involvement was at 152 pmol/L (sensitivity: 93.33%, specificity: 90.16%, accuracy: 92.05%) and distinguished two groups with different survival (P<0.001). The Cox multivariate model including NT-proBNP was better than models including echocardiographic and clinical signs of heart involvement. NT-proBNP appeared to be more sensitive than conventional echocardiographic parameters in detecting clinical improvement or worsening of amyloid cardiomyopathy during follow-up. CONCLUSIONS: NT-proBNP appeared to be the most sensitive index of myocardial dysfunction and the most powerful prognostic determinant in AL amyloidosis. It adds prognostic information for newly diagnosed patients and can be useful in designing therapeutic strategies and monitoring response. NT-proBNP is a sensitive marker of heart toxicity caused by amyloidogenic light chains.