Stage line diagram: An age‐conditional reference diagram for tracking development

This paper presents a method for calculating stage line diagrams, a novel type of reference diagram useful for tracking developmental processes over time. Potential fields of applications include: dentistry (tooth eruption), oncology (tumor grading, cancer staging), virology (HIV infection and disease staging), psychology (stages of cognitive development), human development (pubertal stages) and chronic diseases (stages of dementia). Transition probabilities between successive stages are modeled as smoothly varying functions of age. Age‐conditional references are calculated from the modeled probabilities by the mid‐P value. It is possible to eliminate the influence of age by calculating standard deviation scores (SDS). The method is applied to the empirical data to produce reference charts on secondary sexual maturation. The mean of the empirical SDS in the reference population is close to zero, whereas the variance depends on age. The stage line diagram provides quick insight into both status (in SDS) and tempo (in SDS/year) of development of an individual child. Other measures (e.g. height SDS, body mass index SDS) from the same child can be added to the chart. Diagrams for sexual maturation are available as a web application at http://vps.stefvanbuuren.nl/puberty . The stage line diagram expresses status and tempo of discrete changes on a continuous scale. Wider application of these measures scores opens up new analytic possibilities. Copyright © 2009 John Wiley & Sons, Ltd.     

Morphometric differences between urothelial cells in voided urine of patients with grade I and grade II bladder tumours

The morphometric differences between the urothelial cells in the voided urine of 24 patients with grade I and grade II bladder tumours were measured. In both wet-fixed Papanicolaou-stained smears as in air-dried Giemsa-stained preparations, the cells in the grade I tumours are larger and have more pronounced anisocytosis and a smaller nucleus to cytoplasm area (N/C) ratio. Although absolute dimensions of cells and nuclei in the two preparatory technique differ significantly, the average N/C ratios are similar. In both methods almost all grade I tumours have average N/C cell size ratios of less than 0.6 and grade II tumours more than 0.6. Morphometrically urothelial cells could not be distinguished from cells exfoliated from grade I bladder tumours. The results indicate that it is feasible to classify bladder tumours using the morphometric values of the exfoliated urothelial cells alone.     

Withholding or starting antibiotic treatment in patients with dementia and pneumonia: prediction of mortality with physicians' judgment of illness severity and with specific prognostic models.

BACKGROUND: To help decision makers plan treatment, the authors assessed clinical predictors of mortality from nursing home-acquired pneumonia in patients with dementia. METHODS: Pneumonia patients treated without (n = 165) or with antibiotics (n = 541) were enrolled in a prospective cohort study in 61 nursing homes. RESULTS: In both groups, clinical judgment of illness severity was a strong predictor for 1-week mortality. Despite large differences in frailty and mortality (83% in untreated patients and 15% in treated patients), separate multivariable logistic models included similar specific predictors. DISCUSSION: Despite profound differences between the 2 independent groups, predictors for short-term mortality were largely similar. We found that, when combined with physicians' clinical judgment, 3 readily assessed predictors (respiratory rate, fluid intake, and eating dependency) helped predict mortality. Our results, if confirmed in an independent population, can help make decision making about antibiotic treatment of pneumonia in patients with dementia more evidence-based.     

Ureteral length in live donor kidney transplantation; Does size matter?

The aim of this study was to evaluate the role of ureteral length on urological complications. Data were retrospective collected from the INEX‐trial database, a RCT to compare the intravesical to the extravesical ureteroneocystostomy. Ureteral length was measured in 198 recipients and used to divide recipients into three categories based on interquartile ranges: short (≤8.5 cm), medium (8.6–10.9 cm) and long ureters (≥11 cm). Urological complications were defined as the number of percutaneous nephrostomy placements (PCN). Fifty recipients fell into the short, 98 into the medium and 50 recipients into the long ureter category. Median follow‐up was 26 (range 2–45) months. There was no significant difference in number of PCN placements between the categories. There were 9 (18%) PCN placements in the short ureter category, 21 (20%) in medium ureter category and 10 (21%) in the long ureter category, P = 0.886. Risk factor analysis for gender, arterial multiplicity and type of ureteroneocystostomy showed no differences in PCN placements between the three ureteral length categories. We conclude that ureteral length alone does not seem to influence the number of urological complications.     

Course of scar quality of donor sites following split skin graft harvesting: Comparison between patients and observers

There exists little to no data on the development of donor‐site scars that remain after split skin graft harvesting. The objectives of this study were to (a) examine changes in characteristics of donor‐site scar quality over time and (b) assess the agreement between patient‐reported and observer‐reported donor‐site scar quality in a burn population. A prospective cohort study was conducted including patients who underwent split skin grafting for their burn injury. Patients and observers completed the Patient and Observer Scar Assessment Scale (POSAS) for the first harvested donor site at 3 and 12 months post‐surgery. This study included 80 patients with a median age of 34 years. At 3 months post‐surgery, the patients scored the POSAS items itch and color as most deviant from normal skin, both improved between 3 and 12 months (3.1 vs 1.5 and 5.0 vs 3.5, respectively [P < .001]). Other scar characteristics did not show significant change over time. The patients' overall opinion score improved from 3.9 to 3.2 (P < .001). Observers rated the items vascularization and pigmentation most severe, only vascularization improved significantly between both time points. Their overall opinion score decreased from 2.7 to 2.3 (P < .001). The inter‐observer agreement between patients and observers was considered poor (ICC < 0.4) at both time points. Results of current study indicate that observers underestimate the impact of donor‐site scars. This has to be kept in mind while guiding therapy and expectations. LEVEL OF EVIDENCE: II, prospective cohort study.     

Variable heavy chain gene analysis of follicular lymphomas: correlation between heavy chain isotype expression and somatic mutation load

The expansion of follicular lymphomas (FLs) resembles, both morphologically and functionally, normal germinal center B-cell growth. The tumor cells proliferate in networks of follicular dendritic cells and are believed to be capable of somatic hypermutation and isotype switching. To investigate the relation between somatic mutation and heavy chain isotype expression, we analyzed the variable heavy (V(H)) chain genes of 30 FL samples of different isotypes. The V(H) genes of the FLs were heavily mutated (29.3 mutations on average). In addition, isotype-switched lymphomas contained more somatic mutations than immunoglobulin M-positive lymphomas (33.8 mutations per V(H) gene versus 23.0, respectively). In all but one of the FLs, the ratios of replacement versus silent mutations in the framework regions were low, independent of the absolute number of somatic mutations and the level of intraclonal variation. Analysis of relapse samples of 4 FLs showed no obvious increase in somatic mutation load in most FLs and a decrease in intraclonal variation in time. In 3 of 4 cases, we obtained evidence for selection of certain subclones, rather than clonal evolution. Our findings question if intraclonal variation is always a reflection of ongoing somatic hypermutation. This may have implications for the concept of antigen-driven lymphomagenesis. (Blood. 2000;95:2922-2929)