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Nomogram for Doppler echocardiographic assessment of mitral stenosis in atrial fibrillation.

Non-invasive assessment of the stenotic mitral valve area is often difficult when the mitral stenosis is associated with atrial fibrillation. In this study, 16 patients with mitral stenosis and atrial fibrillation were evaluated by transthoracic Doppler echocardiography. The mitral valve area calculated by the pressure half-time method was 1.65 +/- 0.73 cm2. The enddiastolic mitral gradient was obtained from the enddiastolic forward mitral flow velocity by application of the simplified Bernoulli equation. For each patient there was a linear relationship between the enddiastolic mitral gradient and the corresponding RR interval. The slope and intercept of this relationship were significantly correlated with the mitral valve area. From the regression equations describing these correlations we established a nomogram ascertaining mitral valve area from enddiastolic mitral gradient and corresponding heart rate. This nomogram was helpful in the non-invasive assessment of stenotic mitral valve area in the presence of atrial fibrillation.

Aged↗

Obesity, weight gain, and risk of biochemical failure among prostate cancer patients following prostatectomy.

PURPOSE: Several lines of evidence suggest that diet and weight gain may be important environmental factors implicated in prostate carcinogenesis, especially in tumor progression. The purpose of this study was to evaluate obesity at different ages in a well-characterized cohort of prostate cancer patients treated with prostatectomy and to develop a prognostic model that incorporates body mass index (BMI) as a measure of obesity. EXPERIMENTAL DESIGN: We carried out a prospective study of 526 patients registered at the M.D. Anderson Cancer Center from 1992 to 2001. Kaplan-Meier and Cox proportional hazard analyses were done. RESULTS: During an average follow-up of 54 months, 97 (18%) post-prostatectomy patients experienced biochemical failure. Patients who were obese (BMI > or = 30 kg/m2) at diagnosis had a higher rate of biochemical failure than nonobese men (P = 0.07). Those obese at 40 years had an even greater rate of biochemical failure (P = 0.001). Higher BMI at diagnosis [hazard ratio (HR), 1.07; P = 0.01] and Gleason score = 7(4 + 3) and > or =8 (HR, 3.9; P = 0.03 and HR, 10.0; P < or = 0.001, respectively) remained significant independent predictors of biochemical failure in multivariate analysis. Men who gained weight at the greatest rate (>1.5 kg/y) between 25 years and diagnosis progressed significantly sooner (mean time, 17 months) than those who exhibited a slower weight gain (mean time, 39 months; P(trend) = 0.005). The inclusion of obesity to the clinical nomogram improved performance. CONCLUSIONS: Our findings validate the importance for a role of obesity in prostate cancer progression and suggest a link to the biological basis of prostate cancer progression that can be therapeutically exploited.

Adult↗

Site specific predictors of positive margins at radical prostatectomy: an argument for risk based modification of technique.

PURPOSE: We identify patients at high risk for positive bladder neck, apical or posterior margins who may benefit from technical modifications, such as excision of the bladder neck or wide excision of the neurovascular bundles. MATERIALS AND METHODS: We studied 242 patients with clinically localized prostate cancer undergoing radical prostatectomy with or without neoadjuvant androgen deprivation therapy between June 1992 and August 1997 who had a sextant biopsy available for review. Multivariate logistic regression analysis was used to develop models for prediction of positive bladder neck, apical, and right and left posterior margins based on clinical parameters. From these models patients at low and high risk for positive margins were identified. RESULTS: The incidence of positive margins was 36% with 69% solitary sites. Patients with a prostate specific antigen of greater than 10 ng./ml. had a higher incidence (16%) of positive bladder neck margins. Patients with 3 or more positive cores who did not receive neoadjuvant androgen deprivation therapy had a higher incidence (24%) of positive apical margins. A nomogram incorporating pretreatment serum prostate specific antigen, number of ipsilateral positive cores and whether androgen deprivation therapy was used identified patients at high risk for positive posterior margins. CONCLUSIONS: The nomograms presented identify patients at high risk for positive margins at various sites who may benefit from modification of surgical technique based on risk.

Adenocarcinoma↗

Using the percentage of biopsy cores positive for cancer, pretreatment PSA, and highest biopsy Gleason sum to predict pathologic stage after radical prostatectomy: the Center for Prostate Disease Research nomograms.

OBJECTIVES: To develop probability nomograms to predict pathologic outcome at the time of radical prostatectomy (RP) on the basis of established prognostic factors and prostate biopsy quantitative histology. METHODS: Using information from the database of the Center for Prostate Disease Research (CPDR), univariate and multivariate analyses were performed on 1510 men who had undergone transrectal ultrasound and biopsy for diagnosis and had radical prostatectomy as primary therapy, with variables of age, race, clinical stage, pretreatment prostate-specific antigen (PSA), biopsy Gleason sum, and percentage of biopsy cores positive for cancer (total number of cores positive for cancer divided by the total number of cores obtained). The percentages of biopsy cores positive were grouped as less than 30%, 30% to 59%, and greater than or equal to 60%. The three most significant variables were used to develop probability nomograms for pathologic stage. RESULTS: PSA, biopsy Gleason sum, and percentage of cores positive were the three most significant independent predictors of pathologic stage. The assigned percentage of biopsy core-positive subgroups along with pretreatment PSA and highest Gleason sum were used to develop probability nomograms for pathologic stage. CONCLUSIONS: Pretreatment PSA, highest biopsy Gleason sum, and the percentage of cores positive for cancer are the most significant predictors for pathologic stage after radical prostatectomy. On the basis of these findings, CPDR probability nomograms were developed to predict pathologic outcome at the time of RP.

Adult↗

[Computer-assisted monitoring reflecting interrelation of parameters of oxygen transport and lipid peroxidation].

Correctness of a real-time graphic image was checked by a multi-system integral nomogram showing changes in the condition of certain homeostasis parameters with regard for a condition of systemic oxygen transport. Concentrations of TB-active products and of medium-weight molecules were examined at the moment of finding the integral dot of oxygen transport to different quadrants of the nomogram obtained on the basis of blood samples taken from 286 obstetric and gynecological patients. Correctness and timeliness of real-time nomograms' images as well as occurrence of hypo- and hyperoxic conditions as a response to changing parameters of systemic oxygen transport were proven.

Adult↗

Pharmacokinetics of vancomycin in normal subjects and in patients with reduced renal function.

Recent novel clinical applications of vancomycin have stimulated reinvestigations of the pharmacologic properties of this drug. Absorption from the gastrointestinal tract is negligible, and oral administration is appropriate only for patients with certain staphylococcal and clostridial diarrheas. After intravenous administration (the intramuscular route being painful), vancomycin is excreted by glomerular filtration, with virtually total recovery in the urine. Distribution is consistent with a three-compartment open pharmacokinetic model. Serum half-life values are usually greater than 8 min in the distribution phase, 30 min to 1.5 hr in the intermediate phase, and between 5 and 11 hr in the elimination phase. The level of binding to human serum proteins is 55%. Since the relation between the vancomycin clearance and the creatinine clearance (but not the level of creatinine in serum) is linear in both normal and impaired renal function, a nomogram has been prepared that delineates dosages that will produce a mean steady-state concentration in serum of 15 micrograms/ml. Vancomycin penetrates well into pericardial, pleural, synovial, and ascitic fluid in humans, but concentrations in cerebrospinal fluid after parenteral administration may be insufficient for the successful treatment of certain cases of meningitis.

Administration, Oral↗

Stiffness of systemic arteries in patients with myocardial infarction. A noninvasive method to predict severity of coronary atherosclerosis.

The static elastic properties of arterial tree (abdominal aorta and common carotid artery) were studied in 19 normal subjects and in 49 patients with myocardial infarction with an ultrasonic phase-locked echo-tracking system that allows continuous transcutaneous measurement of the arterial diameter. The stiffness index beta, which represented the mechanical properties in the arterial wall, was calculated from the relation between systemic blood pressure and the diameter of the artery. Patients with myocardial infarction underwent coronary angiography in their convalescent period to determine involved vessels. In 11 patients, coronary artery was patent; 15 patients had one-vessel disease, 12 had two-vessel disease, and the remaining 11 patients had three-vessel disease. In normal subjects, increasing age was associated with an increase in arterial stiffness. An average value of the stiffness index of the abdominal aorta was 8.58 +/- 3.02 (mean +/- SD) and that of common carotid artery was 9.17 +/- 2.22. In patients with three-vessel disease, these values were significantly higher (22.37 +/- 4.29 in abdominal aorta and 13.17 +/- 4.56 in common carotid artery) than those in normal subjects. Stiffness index of patients with two- or one-vessel disease was also increased but lower than those in patients with three-vessel disease (p less than 0.05). Forty-four of 49 patients with infarction had an arterial stiffness index of abdominal aorta higher than the 95% confidence limits of the normal data (p less than 0.05). Twenty-eight patients were outside the nomogram of common carotid artery (p less than 0.05). The mechanical properties of these elastic arteries provided sufficiently reliable information on changes caused by atherosclerosis.

Adult↗

Patient-oriented performance measures of diagnostic tests. 3. U-Factor.

When a clinician is faced with the problem of deciding whether to order a specific diagnostic test, the ideal information would be the utility of the "perform test" branch of the decision tree versus the utility of the "do not perform test" branch. This difference in utility is termed the Expected Utility of the Test ( EUT ). We propose a new performance measure of a test called the U-Factor (UF) which is related to EUT by a simple formula. UF depends on the prior probability of disease and on the decision thresholds at which one would be indifferent between any two immediately subsequent management options, and can be presented as a two-dimensional nomogram. UF is useful as a computational aid in a formal decision analysis, and may be useful as an informal measure of the value of a diagnostic test when a formal analysis is not feasible.

Costs and Cost Analysis↗

Nomogram for estimating creatinine clearance.

Several methods have been published for estimating creatinine clearance from serum creatinine concentrations. Such estimates of creatinine clearance are widely used for dosage adjustments of drugs which are primarily eliminated through the kidneys in patients with reduced renal function. Most of these methods involve the use of equations, requiring a few steps of calculations. A simple and easy-to-use nomogram is presented for estimating creatinine clearance from serum creatinine concentration, plus the age, sex, and bodyweight of the individual patient. This nomogram is based on the linear relationship between creatinine clearance and the reciprocal value of the serum creatinine concentration, where the slope of this relationship is determined by the rate of creatinine production. The rate of creatinine production, however, is related to age, sex, and bodyweight. These physical characteristics are therefore used to scale the slopes of the relationships between creatinine clearance and serum creatinine concentration. The validity of the nomogram was tested in 50 consecutive hospitalised patients for which creatinine clearance was measured. There was an excellent correlation (r = 0.903) between predicted and observed creatinine clearance values.

Creatinine↗

[Can nomograms derived in the U.S. applied to German patients? A study about the validation of preoperative nomograms predicting the risk of recurrence after radical prostatectomy].

In patients suffering from prostate cancer, preoperative nomograms, which predict the risk of recurrence may provide a helpful tool in regard to the counselling and planning of an appropriate therapy. The best known nomograms were published by the Baylor College of Medicine, Houston and the Harvard Medical School, Boston. We investigated these nomograms derived in the U.S. when applied to German patients. Data from 1003 patients who underwent radical prostatectomy at the University-Hospital Hamburg were used for validation. Nomogram predictions of the probability for 2-years (Harvard nomogram) and 5-years (Kattan nomogram) freedom from PSA recurrence were compared with actual follow-up recurrence data using areas under the receiver-operating-characteristic curves (AUC). The recurrence free survival after 2 and 5 years was 78% and 58%, respectively. The AUC of the Harvard nomogram predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction of 0.83. Thereby, the Kattan nomogram showed a significant higher predictive accuracy (p=0.0274). For that reason preoperative nomograms derived in the U.S. can be applied to german patients. However, we would recommend the utilization of the Kattan nomogram due to its higher predictive accuracy.

Biomarkers, Tumor↗

A blood-gas nomogram of the chick fetus: blood flow distribution between the chorioallantois and fetus.

This paper presents equations for quantifying the relationships between the O2 and CO2 concentrations and tensions in the blood of the 18-day chick fetus. A blood-gas nomogram showing these relationships is presented. Starting with the reported chorioallantoic artery and vein gas tensions and using the blood-gas equations, the range of embryonic arterial and venous gas tensions as well as the distribution of the cardiac output and the degree of mixing between the chorioallantoic and embryonic circulations are explored. It is concluded that at least 65% of the blood in the chorioallantoic artery consists of blood of embryonic mixed venous composition. A model of the blood flow distribution is proposed in which chorioallantoic and embryonic flows are equal, with 70% of the blood returning from the tissues of the embryo going to the chorioallantois and vice versa.

Allantois↗

Integrated multi-omics identification of m6A-SNP-related diagnostic biomarkers in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) lacks reliable and minimally invasive biomarkers for early diagnosis. m6A-associated single-nucleotide polymorphisms (m6A-SNPs) may influence RNA methylation and gene expression, offering opportunities to identify clinically relevant diagnostic markers. METHODS: We integrated eQTLGen cis-eQTL data, RMVar m6A-SNP annotations, and ALS transcriptomic datasets to identify m6A-SNP-related genes. Random Forest and LASSO regression were combined to screen robust diagnostic markers. A nomogram was constructed and validated using independent cohorts. Immune infiltration, predicted m6A modification sites, and potential RBP-SNP interactions were assessed. Peripheral blood samples from ALS patients were used for exploratory validation of gene expression and global m6A levels. RESULTS: We identified 109 ALS-associated m6A-SNP-related genes with cis-eQTL signals and narrowed these to seven candidate diagnostic markers (TMED5, OXR1, BRI3, FEM1C, SUZ12, EIF2AK4, and TJAP1). The seven-gene model outperformed the individual markers in the training cohort and retained moderate discrimination in the independent validation cohort. ALS samples showed differences in inferred immune-cell composition, including monocytes, neutrophils, and T-cell subsets. The selected SNP loci were located near predicted m6A sites and annotated RBP-binding regions. Exploratory clinical validation showed significant upregulation of FEM1C and SUZ12 at both mRNA and protein levels, accompanied by reduced global m6A modification. CONCLUSIONS: Through multi-omics integration and exploratory clinical validation, this study identifies m6A-SNP-related candidate markers associated with ALS. The findings support further evaluation of m6A-related signatures for ALS discrimination and molecular characterization, while larger independent cohorts and additional calibration are required before clinical application.

Humans↗

Nomograms of the Goldman equation.

Solutions of the Goldman equations for sodium and potassium ions are displayed in nomograms which allow one to determine which values of the variables in the equation (including the activity of the Na/K pump) are compatible with possible steady states of a cell. The nomograms are particularly suited for the study of relative changes of the cell parameters when one or more of them are altered and the cell undergoes a transition from one steady state to another. Special diagrams are presented for finding the changes of the slope conductance (determined at a clamp potential of -80 mV) associated with such transitions. Separate diagrams are given for the cationic component conductance, (gNa + gK), and the anionic component conductance, gCl. The application of the nomograms is illustrated by the exemplary solution of a problem taken from muscle physiology. Further applications of the nomograms are indicated and the limitations of the method are described. The effects of differing activity coefficients in the intra- and extracellular spaces, as well as the contribution of the electrogenic Na/K pump current to the resting potential are discussed.

Cell Physiological Phenomena↗

Experience with a once-daily dosing program of aminoglycosides in critically ill patients.

BACKGROUND: As aminoglycosides show concentration-dependent killing, once-daily aminoglycoside (ODA) regimens have been instituted. Data on experience with ODA regimens in critically ill patients are limited. OBJECTIVES: 1) To evaluate the ODA-program in critically ill patients; 2) to describe the pharmacokinetics of aminoglycosides (gentamicin and tobramycin); and 3) to assess the incidence of nephrotoxicity associated with an ODA regimen in this specific of group patients. DESIGN: A prospective, descriptive study. SETTING: Eighteen-bed surgical and 12-bed medical intensive care unit in a referral centre. PATIENTS: Eighty-nine critically ill patients with a suspected or confirmed infection for which gentamicin or tobramycin was indicated and a creatinine clearance > 30 ml/min were monitored. One hundred and nine pharmacokinetic profiles were gathered. INTERVENTIONS: A first dose of 7 mg/kg/24 h of gentamicin or tobramycin was given to every patient independent of renal function. Subsequent doses were chosen on the basis of the pharmacokinetic results of the first dose. MEASUREMENTS: Serum samples were collected 1 h and 6 h after start of the aminoglycoside infusion. All samples were assayed by using immunofluorescence. Pharmacokinetic parameters were estimated using a one-compartment model. RESULTS: The volume of distribution of aminoglycosides was significantly higher in critical ill patients with septic shock than in those without. Consequently, the maximum concentration reached was significantly lower in patients with septic shock. In P. aeruginosa infections the mean (SD) estimated Cmax/MIC ratio was 10.3 (3.3). In n = 17 (49%) of the patients treated > 24 h ( n = 35), a dose adjustment or lengthening of interval was necessary. The recommended dosing interval based on the Hartford Hospital nomogram and one-serum concentration at 6 h was correct in only 62% of all cases. Signs of renal impairment occurred in n = 12 (14%) of the patients; in all survivors renal function recovered completely and no haemofiltration was needed. CONCLUSIONS: An ODA-regimen of 7 mg/kg produced Cmax/MIC ratios > 10 in the majority of critically ill patients in our population. Septic shock and renal dysfunction caused an aberrant pharmacokinetic profile of aminoglycosides in these patients. Therefore, individual therapeutic drug monitoring is warranted. Signs of renal impairment were common in the presence of shock, but appeared to be reversible.

Adult↗

Separate contribution of ventricular pumping and load impedance on ventricular power output.

The heart is a rather special type of fluid pump in the sense that it is an organic pump. In this paper, however, it is postulated that the heart behaves like any other mechanical pump whose power output may assume, for a primary change in load, values bounded by two limits which are power output values obtained had the pump been a pressure generator and a flow generator respectively. A power output value outside the limits would imply a definite alteration in ventricular pump function concomitant with the load change. A nomogram to illustrate the proposal is included. The hypothesis may be developed into a powerful tool for assessing the pumping capability of the left ventricle, and this has significant clinical and physiological implications.

Animals↗

Natural history of prostatism: urinary flow rates in a community-based study.

Urinary flow rates were measured in a randomly selected community sample of more than 2,000 men 40 to 79 years old with no history of prostate surgery, prostate cancer or certain other diseases known to interfere with normal voiding. Peak urinary flow rates decreased from a median of 20.3 ml. per second in men 40 to 44 years old to 11.5 ml. per second for men 75 to 79 years old, while voided volumes decreased from a median of 355.5 to 222.5 ml. for the same age ranges. Peak flow rates of less than 10 ml. per second were found in 6% of the men aged 40 to 44 years, increasing to 35% among men aged 75 to 79 years. Urological standards for peak urinary flow rate should be based on community data, and should account for age and voided volume. Our study may serve as the starting point for the development of community-based flow rate normal ranges. Nomograms are given to permit estimating flow rate percentiles as a function of age and voided volume.

Adult↗

A clinical nomogram for predicting long-term survival in advanced colorectal cancer.

From our prospectively accrued database of patients with gastrointestinal cancer, 1057 patients with advanced colorectal cancer were identified with the aim of determining predictive factors for survival of greater than 2 years and to use this information to develop a predictive nomogram. Patient's baseline characteristics, type and number of chemotherapy regimens received, and response to chemotherapy were assessed by univariate and multivariate logistic regression comparing those who survived greater than or less than 2 years. A total of 161 (15.2%) patients survived more than 2 years, so-called long survivors (LS). In multivariate analysis, positive predictive factors for LS were: good performance status (PS), normal serum carcinoembryonic antigen (CEA), rectal primary, Dukes' stage A-B, well or moderate differentiation, two or less disease sites, response to chemotherapy and treatment used protracted venous infusion (PVI) 5-fluorouracil (5-FU) in first-line chemotherapy, and the increasing number of chemotherapy treatments received. From these PS, CEA, number of sites and response to first-line chemotherapy were used to develop a nomogram capable of predicting the probability of survival beyond 2 years for an individual patient. This large study confirmed the relevance of known prognostic factors in metastatic colorectal cancer and demonstrated the importance of response to chemotherapy as an independent factor to predict LS. By combining these, we developed a nomogram which provides information which is likely to prove useful in the management of patients with advanced colorectal cancer.

Adolescent↗

Cholesterol Metabolism-related Characteristics Predict Therapeutic Response and Survival in Esophageal Cancer.

INTRODUCTION: Cholesterol homeostasis has been identified as an essential downstream pathway of mutations in TP53. Esophageal cancer is one of the most prevalent malignancies exhibiting the mutation. OBJECTIVES: To explore the significance of cholesterol metabolism-related characteristics in tumor phenotype and treatment outcomes of esophageal cancer. METHODS: We established a cholesterol metabolism-related gene set (CMGs) and performed Lasso-Cox analysis to identify prognostic signatures. Nomogram-based risk scores and clinical stages afterwards were constructed and evaluated. We simultaneously identified two metabolic subtypes based on the distinct features of the CMGs. We annotated the functional and pathway characteristics of differentially expressed genes between the clusters and compared the differences in clinical and immune characteristics. Finally, we assessed the prognostic value of signatures in the GSE53625 and two clinical cohorts using whole-exon sequencing and multiplex immunofluorescence. RESULTS: Our study identified five cholesterol prognosis-related genes (CRGs) that demonstrated superior prognostic efficacy in the training set compared to clinical staging, validated in independent public databases and two clinical cohorts. According to the different expression patterns of the signatures, patients were divided into two subtypes. The C1 group demonstrated poorer overall survival, response to immunotherapy, and downregulation of the p53 pathway. In the immune correlation analysis, we found that the risk score based on 5-signature model was significantly positively correlated with the abundance of suppressive immune cells and the immune checkpoints. Finally, we explored the impact of expression and genomic polymorphism of the signatures on the prognosis at the pan-cancer level. CONCLUSIONS: Our findings underscore the distinct expression patterns of CRGs in esophageal cancer. These signatures are efficient to serve as prognostic indicators and assess the effectiveness of immunotherapy. They may also represent promising targets in other TP53 mutant malignancies.

Humans↗