Genetic variation, C-reactive protein levels, and incidence of diabetes

C-reactive protein (CRP) has been shown to be associated with type 2 diabetes, but whether CRP has a causal role is not yet clear. We examined the association in the Rotterdam Study, a population-based prospective cohort study. The association of baseline serum CRP and incident diabetes during follow-up was investigated, and a meta-analysis was conducted on the BMI-adjusted relation of CRP and diabetes. Furthermore, the association of CRP haplotypes with serum CRP and risk of diabetes was assessed. The age- and sex-adjusted hazard ratio for diabetes was 1.41 (95% CI 1.29-1.54) per 1 SD increase in natural logarithm of CRP, and it was 1.88, 2.16, and 2.83 for the second, third, and fourth quartiles of CRP, respectively, compared with the first quartile. The risk estimates attenuated but remained statistically significant after additional adjustment for obesity indexes, which agreed with the results of the meta-analysis. The most common genetic haplotype was associated with a significantly lower CRP level compared with the three other haplotypes. The risk of diabetes was significantly higher in the haplotype with the highest serum CRP level compared with the most common haplotype (OR 1.45, 95% CI 1.08-1.96). These findings support the hypothesis that serum CRP enhances the development of diabetes.     

Image-guided vascular neurosurgery based on three-dimensional rotational angiography. Technical note

Three-dimensional rotational angiography is capable of exquisite visualization of cerebral blood vessels and their pathophysiology. Unfortunately, images obtained using this modality typically show a small region of interest without exterior landmarks to allow patient-to-image registration, precluding their use for neuronavigation purposes. The aim of this study was to find an alternative technique to enable 3D rotational angiography-guided vascular neurosurgery. Three-dimensional rotational angiograms were obtained in an angiographic suite with direct navigation capabilities. After image acquisition, a navigated pointer was used to touch fiducial positions on the patient's head. These positions were located outside the image volume but could nevertheless be transformed into image coordinates and stored in the navigation system. Prior to surgery, the data set was transferred to the navigation system in the operating room, and the same fiducial positions were touched again to complete the patient-to-image registration. This technique was tested on a Perspex phantom representing the cerebral vascular tree and on two patients with an intracranial aneurysm. In both the phantom and patients, the neuronavigation system provided 3D images representing the vascular tree in its correct orientation, that is, the orientation seen by the neurosurgeon through the microscope. In one patient, tissue shift was clearly observed without significant changes in the orientation of the structures. Results in this study demonstrate the feasibility of using 3D rotational angiography data sets for neuronavigation purposes. Determining the benefit of this type of navigation should be the subject of future studies.     

Predictive Value of Four Kallikrein Markers for Pathologically Insignificant Compared With Aggressive Prostate Cancer in Radical Prostatectomy Specimens: Results From the European Randomized Study of Screening for Prostate Cancer Section Rotterdam

Background

Treatment decisions can be difficult in men with low-risk prostate cancer (PCa).

Objective

To evaluate the ability of a panel of four kallikrein markers in blood—total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2—to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries.

Design, setting, and participants

The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA ≥3.0 ng/ml and were treated with RP between 1994 and 2004.

Outcome measurements and statistical analysis

We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3–T4, extracapsular extension, tumor volume >0.5 cm³, or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood.

Results and limitations

A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p < 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model.

Conclusions

Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment.     

Replacement of the aortic root for acute prosthetic valve endocarditis: prosthetic composite versus aortic allograft root replacement

OBJECTIVE: Aortic root replacement for prosthetic aortic valve endocarditis with accompanying destruction of the aortic root is a well-established surgical intervention. However, there is still no consensus whether prosthetic material or allogeneic material should be used. Here we report on our experience with prosthetic composite and aortic allograft root replacement in such patients during a 10-year interval. METHODS: From 1991 through 2001, 29 patients with prosthetic aortic valve endocarditis combined with aortic root destruction underwent reoperation at our institution. Sixteen patients received aortic root replacement with a cryopreserved aortic root allograft (group A) and 13 with a prosthetic composite graft (group B). The interval between the initial operation and reoperation was 29 months (range, 5-168 months) in group A and 55 months (range, 7-248 months) in group B. RESULTS: Hospital mortality was 18.5% (n = 5 patients, 3 in group A and 2 in group B). Median follow-up was 21 months (range, 1-48 months) for group A and 34 months (range, 1-152 months) for group B (P >.2). Survival at 1 and 5 years was 81% +/- 10% and 81% +/- 10% in group A and 85% +/- 10% and 85% +/- 10% in group B, respectively. No patient underwent reoperation for recurrent prosthetic aortic valve endocarditis. CONCLUSIONS: Our results indicate that excellent long-term results can be achieved regardless of the material used for aortic root replacement in patients with prosthetic aortic valve endocarditis.     

A chronic-constriction injury of the sciatic nerve reduces bilaterally the responsiveness to formalin in rats: a behavioral and hormonal evaluation

Application of four loose ligatures to the sciatic nerve of a rat (chronic constriction injury [CCI]) induces clear hypersensitivity to non-noxious stimulation and chemical irritants. However, in this study, an injection of formalin in the hind paw of a rat with CCI-induced mononeuropathy resulted in an ipsilateral decreased flinching and licking or biting behavior in both phases of the formalin testing. The effect was independent of the formalin concentration used. This altered behavior was accompanied with smaller plasma levels of adrenocorticotrope hormone and corticosterone compared with sham and non-operated animals. Formalin injection in the contralateral nonligated hind paw of CCI rats also reduced the licking or biting behavior as compared with sham-operated and non-operated control animals only in the second phase of the formalin test. Thus, CCI reduces the pain reactivity and hypothalamic-pituitary-adrenal-axis activation to ipsilateral and contralateral formalin injection. Further research should investigate whether the decreased pain reactivity by CCI is situated at the peripheral, spinal, or supraspinal level or is result of changes in the stress reactivity and coping strategies. IMPLICATIONS: We evaluated the changes in the behavioral reactions and the hormonal effects of a noxious chemical stimulus, i.e., formalin injection in animals with previously induced chronic constriction injury to the sciatic nerve. The effect in animals injected at the ipsilateral and contralateral site, sham-operated and controls, were compared.     

Causes of frequency and nocturia after renal transplantation

OBJECTIVE

To explore the role of bladder capacity, bladder pain, dysfunctional voiding, urgency, urinary tract infections (UTIs), and urinary output as potential causes of frequency and nocturia after renal transplantation.

PATIENTS AND METHODS

Data were gathered from 52 adult renal transplant patients (35 men and 17 women, mean age 49 years), using a written questionnaire, medical records, frequency/volume charts, and urinary cultures. The mean time between transplantation and data collection was 5 months. Structural equation modelling (SEM) was used for the simultaneous assessment of direct and indirect relationships between explanatory variables and voiding frequency.

RESULTS

Frequency and nocturia were found in 54% and 60% of the study population, respectively. Frequency was directly associated with a small bladder capacity, bladder pain, urgency, and a high daytime urine volume, and indirectly by UTIs (via urgency and bladder pain). Nocturia was associated with high nocturnal urine volume, small bladder capacity and dysfunctional voiding. A quarter of the patients had small bladders and another quarter had large bladders, the latter being associated with nocturnal polyuria.

CONCLUSIONS

The presence of frequency, especially when accompanied by bladder pain, might aid the physician to identify patients with small bladders. The presence of nocturia can be the result of a high nocturnal urine volume, which increases the risk of bladder enlargement. Because both abnormal bladder conditions can contribute to graft dysfunction, we recommend a urological follow‐up after renal transplantation, using frequency/volume charts.     

Short Bouts of Intensive Exercise During the Workday Have a Positive Effect on Neuro‐cognitive Performance

Beside its positive impact on physical health, exercise is indicated to positively affect cognitive performance based on a relocation of cortical activity. This study examined the influence of different types of breaks on cognitive performance and related cortical activity in office‐based employees. Breaks were filled with exercise, resting or a usual break and a control condition where employees continued working without any break. Cognitive performance was assessed using the d2‐R test and two commercially available cognitive tasks. Brain cortical activity was recorded using electroencephalography before and after breaks. Individual's mood was analysed using a profile of mood state. Results indicate a positive effect of a 3‐min boxing intervention on cognitive performance, mirrored by a decrease in prefrontal cortex activity. Although perceived psychological state was increased after the usual break, this is reflected in neither cortical activity nor cognitive performance. With respect to the fact that also bike activity resulted an increase in prefrontal alpha‐2 activity, a positive effect of exercise on neuro‐cognitive performance can be stated. Health and economic benefits may result from brief physical activity breaks and help to maintain workplace performance and job satisfaction. Copyright © 2015 John Wiley & Sons, Ltd.     

Alterations in midline cortical thickness and gyrification patterns mapped in children with 22q11.2 deletions

The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome)is a neurogenetic condition associated with visuospatial deficits,as well as elevated rates of attentional disturbance, mood disorder,and psychosis. Previously, we detected pronounced cortical thinningin superior parietal and right parieto-occipital cortices inpatients with this syndrome, regions critical for visuospatialprocessing. Here we applied cortical pattern-matching algorithmsto structural magnetic resonance images obtained from 21 childrenwith confirmed 22q11.2 deletions (ages 8–17) and 13 demographicallymatched comparison subjects, in order to map cortical thicknessacross the medial hemispheric surfaces. In addition, corticalmodels were remeshed in frequency space to compute their surfacecomplexity. Cortical maps revealed a pattern of localized thinningin the ventromedial occipital–temporal cortex, criticalfor visuospatial representation, and the anterior cingulate,a key area for attentional control. However, children with 22q11.2DSshowed significantly increased gyral complexity bilaterallyin occipital cortex. Regional gray matter volumes, particularlyin medial frontal cortex, were strongly correlated with bothverbal and nonverbal cognitive functions. These findings suggestthat aberrant parieto-occipital brain development, as evidencedby both increased complexity and cortical thinning in theseregions, may be a neural substrate for the deficits in visuospatialand numerical understanding characteristic of this syndrome.