ADVANCED GLYCATION END PRODUCTS IN RENAL FAILURE: AN OVERVIEW

The article aims to present an overview of the existing knowledge on advanced glycation end products (AGE). They are moieties that bind to proteins, but also lipids and nuclear acids. AGE are formed during glycation and oxidative stress. Accumulation of AGE occurs especially in diabetes and chronic renal failure and plays a major pathogenetic role. The deleterious effects of AGE result from cross‐linking of proteins and activation of the receptor for advanced glycation end products. AGE accumulation can be noninvasively assessed by the skin autofluorescence reader. In diabetics, the skin autofluorescence predicts cardiac mortality and the occurrence of macro‐ and microvascular complications. In patients on haemodialysis, skin autofluorescence is highly elevated and predicts mortality. After renal transplantation AGE accumulation is lower than during haemodialysis, but still remains elevated and is a strong risk factor for chronic renal transplant dysfunction. Some of the potential methods to intervene with AGE accumulation are discussed in this article.     

1 + 1 = 3? The systematic development of a theoretical and evidence-based tailored multimedia intervention to improve medication adherence

Objective

To describe the development of a theoretical and evidence-based tailored multimedia intervention to improve medication intake behavior in patients with inflammatory bowel disease (IBD). The intervention integrates interpersonal and technology-mediated strategies with the expectation that this will work synergistically.

Methods

The development followed the Medical Research Council's framework. Three literature reviews and three pre-tests among 84 IBD patients and eight nurses were conducted to guide the development of the intervention. A feasibility study was carried out among four nurses and 29 patients.

Results

The components include: (1) an online preparatory assessment (OPA); (2) tailored interpersonal communication; and (3) tailored text messaging. To support the development, the feasibility was tested. Results indicated that the OPA was comprehensive and could be a helpful tool for both patients and nurses to prepare for the consultation. The training was evaluated as being instructive and applicable with a mean mark of 8.5. Of the developed messages, 65.6% received positive evaluations and were used in the intervention.

Conclusion

By applying the framework, we were able to describe the logic behind the development of a tailored multimedia intervention to improve medication intake behavior.

Practice implications

This study could serve as a guide for the development of other health interventions.     

Timing-Invariant CT Angiography Derived from CT Perfusion Imaging in Acute Stroke: A Diagnostic Performance Study

BACKGROUND AND PURPOSE:Timing-invariant (or delay-insensitive) CT angiography derived from CT perfusion data may obviate a separate cranial CTA in acute stroke, thus enhancing patient safety by reducing total examination time, radiation dose, and volume of contrast material. We assessed the diagnostic accuracy of timing-invariant CTA for detecting intracranial artery occlusion in acute ischemic stroke, to examine whether standard CTA can be omitted.MATERIALS AND METHODS:Patients with suspected ischemic stroke were prospectively enrolled and underwent CTA and CTP imaging at admission. Timing-invariant CTA was derived from the CTP data. Five neuroradiologic observers assessed all images for the presence and location of intracranial artery occlusion in a blinded and randomized manner. Sensitivity and specificity of timing-invariant CTA and standard CTA were calculated by using an independent expert panel as the reference standard. Interrater agreement was determined by using κ statistics.RESULTS:We included 108 patients with 47 vessel occlusions. Overall, standard CTA and timing-invariant CTA provided similar high diagnostic accuracy for occlusion detection with a sensitivity of 96% (95% CI, 90%–100%) and a specificity of 100% (99%–100%) for standard CTA and a sensitivity of 98% (95% CI, 94%–100%) and a specificity of 100% (95% CI, 100%–100%) for timing-invariant CTA. For proximal large-vessel occlusions, defined as occlusions of the ICA, basilar artery, and M1, the sensitivity and specificity were 100% (95% CI, 100%–100%) for both techniques. Interrater agreement was good for both techniques (mean κ value, 0.75 and 0.76).CONCLUSIONS:Timing-invariant CTA derived from CTP data provides diagnostic accuracy similar to that of standard CTA for the detection of artery occlusions in acute stroke.

Stroke imaging research currently focuses on prediction of patient outcome and identifying patients who are suitable for neurointerventional treatment.^1,2 For these purposes, advanced stroke imaging protocols typically add CT perfusion imaging or diffusion-weighted MR imaging to the traditional work-up, consisting of noncontrast CT and CT angiography.^2,3 Noncontrast CT is used to differentiate hemorrhagic stroke from ischemic stroke and to assess early signs of ischemia. CTA is used to localize arterial occlusions and to identify proximal large-vessel occlusions that may be suitable for endovascular treatment. CT perfusion imaging and DWI are used to assess the extent and severity of hypoperfusion and particularly increase the sensitivity of imaging in the early stages of ischemic stroke.⁴ The practical advantages of CT perfusion imaging are that it is widely available and does not delay treatment decisions because it is fast and most patients already undergo CT scanning.³Currently, CTA can be derived from CT perfusion data. Such an approach allows the enhancement of patient safety by reducing the total scanning time, radiation dose, and amount of contrast material needed.⁵ In CT perfusion imaging, multiple scans after intravenous injection of contrast material are obtained with time, generating a 4D dataset, which is used to derive cerebral perfusion maps such as the cerebral blood flow, cerebral blood volume, and arrival times. When imaging is performed on a CT scanner with large spatial coverage, however, this 4D data can also be used to provide CT angiographic information, referred to as 4D-CTA or dynamic CTA. Previous studies have assessed whether 4D-CTA can be used for detection of vascular occlusion in a stroke setting but found that image quality was moderate and diagnostic performance for stroke assessment was limited because large-vessel occlusions may be missed.^5–8 Recently, a different approach to obtain CTA from CT perfusion source data was presented that combines the whole 4D-CTA dataset into 1 high-quality 3D-CTA dataset by displaying maximum contrast enhancement with time.⁵ This technique is referred to as “timing-invariant CTA” because it is insensitive to delayed contrast arrival and was shown to provide similar-to-superior image quality compared with standard CTA.⁵The aim of our study was to test the diagnostic performance of timing-invariant CTA for stroke evaluation, to assess whether standard CTA can be omitted when CT perfusion imaging has been performed.     

Skin Advanced Glycation End Product Accumulation Is Poorly Reflected by Glycemic Control in Type 2 Diabetic Patients (ZODIAC-9)

Background

Glycemic memory can be reflected by tissue accumulation of advanced glycation end products (AGEs). In type 1 diabetes mellitus (T1DM) patients, hemoglobin A1c (HbA1c) levels over various time periods poorly predicted the accumulation of different AGEs in skin biopsies. Our aim was to investigate whether HbA1c assessments can predict the change in skin AGEs during time in type 2 diabetes mellitus (T2DM).

Methods

We included 452 T2DM patients participating in a shared-care setting, who are screened annually for HbA1c and diabetic complications. Baseline and follow-up levels of skin AGEs were assessed with a validated noninvasive autofluorescence (AF) method, which is based on the fluorescence characteristics of certain AGEs.

Results

Our study population had a mean age of 65 years and 54% were female. After a mean follow-up duration of 3.3 years, linear regression analyses showed weak relationships among different assessments of HbA1c (baseline, maximum, mean, and variance of HbA1c) and skin AF at follow-up. Baseline skin AF and age were predictors of skin AF at follow-up, but diabetes duration, smoking, and creatinine were of less or no predictive value for skin AF at follow-up.

Conclusions

In our T2DM population, integrated HbA1c assessments over years poorly predict the change in skin AGE level measured by skin AF. These findings agree with results in patients with T1DM. This suggests either the need for longer exposure to glucose disturbances to change tissue AGEs or other mechanisms, such as oxidative stress, leading to AGE accumulation.     

Commentary: Periodontitis and Rheumatoid Arthritis: What Do We Know?

Background: Currently, in the field of rheumatology, there is much attention given towards the possible causality between periodontitis and rheumatoid arthritis (RA), specifically regarding the role of Porphyromonas gingivalis (Pg). This bacterium is unique, having a citrullinating enzyme. Antibodies against citrullinated proteins are rather specific for RA. Methods: Because causality is ultimately tested in longitudinal cohort studies which currently do not exist for periodontitis and RA, this commentary applied Bradford Hill criteria on the existing literature to assess causality as the most likely interpretation of this association. Conclusions: From an epidemiologic point of view, patients with RA have a higher incidence of periodontal disease than individuals without RA. In addition, there is a dose‐response pattern in the association between the severity of periodontitis and RA disease activity. There are indications that periodontitis precedes RA, but there is no evidence yet available to show that Pg plays a direct role in this temporal relationship. The role of the unique characteristic of citrullination by Pg remains unexplained. However, in animal models, citrullination by Pg plays a distinct role in the development and aggravation of experimental arthritis. Although the role of Pg in RA remains speculative, a causative role for periodontitis as a chronic inflammatory disease caused by infectious agents in RA seems biologically plausible.