D-dimer levels in assessing severity and clinical outcome in patients with community-acquired pneumonia. A secondary analysis of a randomised clinical trial

BackgroundD-dimer levels are in several studies elevated in patients with CAP. In this study we assess the use of D-dimer levels and its association with severity assessment and clinical outcome in patients hospitalised with community-acquired pneumonia.MethodsIn a subset of randomised trial patients with community-acquired pneumonia serial D-dimer levels was analysed. CURB-65 scores were calculated at admission.ResultsA total of 147 patients were included. D-dimer levels at admission were higher in patients with severe CAP (2166 ± 1258 versus1630 ± 1197 μg/l, p = 0.03), with clinical failure at day 30 (2228 ± 1512 versus 1594 ± 1078 μg/l, p = 0.02) and with early failure (2499 ± 1817 μg/l versus 1669 ± 1121 μg/l, p = 0.01). Non-survivors had higher D-dimer levels (3025 ± 2105 versus 1680 ± 1128 μg/l, p = 0.05). None of the 16 patients with D-dimer levels < 500 μg/l died. In multivariate analysis D-dimer levels were not associated with clinical outcome. D-dimer levels have poor accuracy for predicting clinical outcome at day 30 (AUC 0.62, 95% CI 0.51–0.73) or 30 day mortality (AUC 0.71 (95% CI 0.51–0.91)). Addition of D-dimer levels to CURB-65 did not increase accuracy. No differences were observed in serial D-dimer levels between patients with clinical success or failure at day 30.ConclusionD-dimer levels are elevated in patients with CAP. Significantly higher D-dimer levels are found in patients with clinical failure and with severe CAP. D-dimer levels as single biomarker or as addition to the CURB-65 have no added value for predicting clinical outcome or mortality. D-dimer levels < 500 μg/l may identify candidates at low risk for complications.     

Trends in adolescent alcohol use: effects of age, sex and cohort on prevalence and heritability

Aims To determine the effect of age, sex and cohort on the prevalence and genetic architecture of adolescent alcohol use (AAU). Design Survey study in participants registered with the Netherlands Twin Register. Setting Twins from the general population. Participants Two cohorts (data collected in 1993 and 2005–08) of twins aged 13–15, 16–17 and 18–21 years. In 1993 and 2005–08 a total of 3269 and 8207 twins, respectively, took part. Measurements Survey data on initiation and frequency of alcohol use and quantity of alcohol consumed. Findings The prevalence of alcohol initiation increased between 1993 and 2005–08 for both males and females. The largest difference was for girls observed at ages 13–15, where the prevalence increased from 59.5% to 72.4%. We also found increases in prevalence across cohorts for quantity of alcohol consumed and non‐significant increases for frequency of alcohol use. From age 16 onwards, boys drank more frequently and larger quantities than girls. Genetic model fitting revealed that the genetic architecture of AAU did not differ between birth cohorts, nor were there differences between boys and girls. Genetic factors explained between 21% and 55% of individual differences in alcohol measures throughout adolescence. Shared environment explained between 17% and 64% of variance in alcohol use, across different age groups and alcohol measures. Conclusions In the Netherlands, the prevalence of alcohol initiation, frequency and quantity has increased in adolescents over a 15‐year period, but there are no changes in the genetic architecture of adolescent alcohol use.     

A randomized phase IIb presurgical study of finasteride vs. low-dose flutamide vs. placebo in men with prostate cancer. Efficacy monitored by karyometry

ObjectivePresurgical, window of opportunity trials have been proposed as a model to assess the activity of preventive and therapeutic interventions in a cost-effective manner in prostate cancer (CaP). The aim of the study was to explore karyometry as a method for monitoring the efficacy of intervention with preventive agents in patients with CaP.Materials and methodsThe material used in this investigation was from the 2F study, i.e., an Italian prospective randomized phase IIb presurgical study of finasteride vs. low-dose flutamide vs. placebo in men with CaP. Image analysis was performed in 16 cases treated with finasteride, 24 with flutamide, and 20 with placebo. For all these cases, CaP and normal looking secretory epithelium were present in the pretreatment biopsies as well as the post-treatment ex-vivo biopsies obtained from the radical prostatectomy specimens.ResultsTo establish a direction of nuclear change from normal to malignancy, i.e., the so-called line of progression, a discriminant function was derived with the normal looking epithelium in the pretreatment biopsies as one endpoint, and the CaP in the pretreatment biopsies as the other. The discriminant function was then applied to the post-treatment groups. The increase in relative nuclear area was the dominant feature. In the placebo group, 15 out of 20 CaP (75%) cases had a higher discriminant function score at the end of study, with a significant increase of the mean score by 90%. The flutamide treated CaP cases had increased discriminant function scores in 19 out of 24 cases (79%) and an increase of the mean score by 43%; the 5 cases with lower scores involved only minor reductions. In contrast, the finasteride treated CaP cases had increased discriminant function scores for 8 out of 16 cases (50%), but the increase in the mean score was by only 8%.ConclusionThis exploratory study establishes that karyometric monitoring can track the results of subtle nuclear changes induced by preventive interventions in men with CaP, thus allowing assessment of agent activity in a cost-effective manner.     

Preparing nursing faculty for baccalaureate-level and graduate-level nursing programs: role preparation for the academy

This article explores the multiple roles expected of nursing faculty teaching in baccalaureate and graduate programs, as well as the preparation required to accomplish those roles. The educational preparation for the challenging roles nurse educators are required to assume is explored, along with suggestions on how to support faculty in their roles to ensure they are both productive and retained in their work. Although the research mission remains an important priority role for faculty today, it can easily overshadow and conflict with the equally compelling faculty roles needed to address the holistic development of the next generation of the profession: teaching; service, and practice. Boyer's dimensions of scholarship are used to suggest a structure for the roles that baccalaureate and graduate faculty in nursing programs need to be prepared to assume: the scholarship of discovery, the scholarship of integration, the scholarship of application, and the scholarship of teaching.     

Management of Urologic Complications in Renal Transplantation: A Single-Center Experience

Introduction

Ureterovesical complications subsequent to renal transplantation are associated with a high morbidity leading to graft loss or even death. In the present study, the management of these complications by using interventional and surgical procedures (native pyeloureterostomy [NPUS]/ureteroureterostomy [NUU] vs ureteroneocystostomy [UNC]) was evaluated retrospectively.

Patients and Methods

Between 1994 and 2012, a total of 780 kidney transplantations (690 deceased and 90 living donors) were performed at our institution. Demographic, clinical, and laboratory data from patients with urologic complications were analyzed and compared.

Results

Fifty patients (6.4%) exhibited ureterovesical complications, and 18 patients (36%) were operated on immediately. In 32 (64%) of 50 patients, an interventional procedure was initially performed, with 21 patients (66%) undergoing operation due to therapy failure. NPUS/NUU and UNC were performed in 26 (66.6%) and 13 (33.3%) patients, respectively. Indications for an operation were ureteral stenosis in 12 patients (30.8%), ureteral necrosis and urine leakage in 19 patients (48.7%), and symptomatic vesicoureteral reflux in 8 patients (20.5%). Long-term results were comparable between all groups.

Conclusions

Surgical revision of ureteral complications should be the standard therapy. NPUS/NUU, UNC, and the successful interventional procedures did not differ significantly in terms of long-term results.     

Oral vitamin D3 supplementation reduces monocyte-derived dendritic cell maturation and cytokine production in Crohn’s disease patients

Background

Low serum vitamin D levels may provoke or aggravate Crohn’s disease (CrD). Vitamin D3 is a well-known immune modulator that affects immune functions in vitro and may prevent CrD flares. Dendritic cells (DC) are key mediators of vitamin D3 effects. In this study, we describe changes in monocyte-derived DC (mo-DC) maturation marker expression and cytokine production following 26 weeks of oral vitamin D3 supplementation in CrD patients.

Methods

Ten CrD patients who had increased serum 25-hydroxy vitamin D levels after oral vitamin D3 and calcium treatment and ten seasonally matched placebo-treated patients were selected for this study. Mo-DC were generated before and after the 26 weeks and induced to mature upon lipopolysaccharide (LPS) stimulation. Maturation marker expression and cytokine production were analysed. Mo-DC function was analysed in a mixed leucocyte reaction (MLR).

Results

Compared with baseline values, LPS-matured mo-DC exhibited reduced expression of CD80 and reduced production of the cytokines IL-10, IL-1β, and IL-6 following 26 weeks of oral vitamin D3 supplementation. Mo-DC performance in an allogeneic MLR was unchanged after vitamin D3 supplementation. Treatment with the placebo did not affect maturation markers, cytokine production, or the MLR.

Conclusions

Vitamin D3 treatment in CrD patients led to hypo-responsive LPS-stimulated mo-DC. This finding indicates that vitamin D3 levels have an impact on the monocytic precursors of mo-DC in vivo and may explain the positive effects of vitamin D3 supplementation on CrD patients. Alternatively, CrD patients with high serum vitamin D3 levels may represent a subgroup with low disease activity.     

Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase.

A point mutation in the gene for human serum cholinesterase was identified that changes Asp-70 to Gly in the atypical form of serum cholinesterase. The mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was found by sequencing a genomic clone and sequencing selected regions of DNA amplified by the polymerase chain reaction. The entire coding sequences for usual and atypical cholinesterases were compared, and no other consistent base differences were found. A polymorphic site near the C terminus of the coded region was detected, but neither allele at this locus segregated consistently with the atypical trait. The nucleotide-209 mutation was detected in all five atypical cholinesterase families examined. There was complete concordance between this mutation and serum cholinesterase phenotypes for all 14 heterozygous and 6 homozygous atypical subjects tested. The mutation causes the loss of a Sau3A1 restriction site; the resulting DNA fragment length polymorphism was verified by electrophoresis of 32P-labeled DNA restriction fragments from usual and atypical subjects. Dot-blot hybridization analysis with a 19-mer allele-specific probe to the DNA amplified by the polymerase chain reaction distinguished between the usual and atypical genotypes. We conclude that the Asp-70----Gly mutation (acidic to neutral amino acid substitution) accounts for reduced affinity of atypical cholinesterase for choline esters and that Asp-70 must be an important component of the anionic site. Heterogeneity in atypical alleles may exist, but the Asp-70 point mutation may represent an appreciable portion of the atypical gene pool.     

Single cell morphology of muscle in patients with chronic muscle pain

In 119 patients referred with suspected fibromyalgia, biopsies from the quadriceps muscle were analyzed for "rubber band" morphology, and isokinetic quadriceps strength was measured. Eighty-four fulfilled the criteria for fibromyalgia, 26 had chronic myofascial pain (CMP) and 9 had other diseases including 5 with concomitant fibromyalgia. Twenty-four CMP patients and 48 fibromyalgia patients were randomly selected to match with regard to sex, age, smoking and drinking habits. "Rubber band" morphology was blindly graded on a biopsy score scale from 0 to 2. A statistically significant difference in biopsy score was found between the two matched groups (P = 0.003); median biopsy score in fibromyalgia was 0.42 and 0.25 in CMP. A cut-off value at 0.33 gave a specificity of 71% and a sensitivity of 63%. Isokinetic muscle strength did not differ in the fibromyalgia and CMP groups and was not related to the biopsy score. "Rubber band" morphology is seen more often in fibromyalgia patients than in CMP patients. The exact genesis of this phenomenon is still unknown but theories connected with the possible pathogenesis of the syndrome are presented.