Renin inhibition with aliskiren: where are we now, and where are we going?

With the development of aliskiren, blockade of the renin-angiotensin-aldosterone system (RAAS) at the level of the interaction of renin with a substrate has become a clinical reality. This review covers the specific features of the first agent likely to achieve widespread clinical exposure, aliskiren. The potential of renin inhibition must be viewed in the context of the remarkable efficacy of both angiotensin-converting enzyme (ACE) inhibition and angiotensin receptor blockers (ARBs). The implications of blockade of the renin system at its rate-limiting step are reviewed, with the therapeutic implications for both the renin inhibitor employed alone or the renin inhibitor combined with an ACE inhibitor or ARB. The relevant and necessary studies are ongoing.     

Validation of whole‐body against conventional magnetic resonance imaging for scoring acute inflammatory lesions in the sacroiliac joints of patients with spondylarthritis

Objective

To compare the performance of whole‐body magnetic resonance imaging (MRI) versus conventional MRI in assessing acute inflammatory lesions of the sacroiliac (SI) joints in patients with established and active spondylarthritis (SpA) using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. This study is validating whole‐body MRI against the current MRI standard for assessing active inflammatory lesions of the SI joints in patients with SpA.

Methods

Thirty‐two SpA patients with clinically active disease (Bath Ankylosing Spondylitis Disease Activity Index score ≥4) fulfilling the modified New York criteria were scanned by whole‐body and conventional MRI of the SI joints. The MRIs were scored independently in random order by 3 readers blinded to patient identity. Active inflammatory lesions of the SI joints were recorded on a Web‐based SPARCC index. Pearson's correlation coefficients were used to compare scores for whole‐body and conventional MRI for each reader, whereas intraclass correlation coefficients (ICCs) were used to compare interobserver reliability.

Results

The Pearson's correlation coefficients between whole‐body and conventional MRI per rater were 0.94, 0.87, and 0.93. The mean sum scores for conventional versus whole‐body MRI were statistically significantly higher for all 3 readers, although all patients showing inflammatory lesions on conventional MRI also demonstrated them on whole‐body MRI. The ICCs(2,1) were 0.69, 0.78, and 0.95 for conventional MRI, and 0.79, 0.85, and 0.96 for whole‐body MRI for the 3 possible reader pairs.

Conclusion

Whole‐body and conventional MRI scores show a strong correlation and comparable reliability for the detection of inflammatory lesions of the SI joints.     

Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells

The Ca(2+)-binding proteins parvalbumin (PV) and calbindin D-28k (CB) are key players in the intracellular Ca(2+)-buffering in specific cells including neurons and have profound effects on spatiotemporal aspects of Ca(2+) transients. The previously observed increase in mitochondrial volume density in fast-twitch muscle of PV-/- mice is viewed as a specific compensation mechanism to maintain Ca(2+) homeostasis. Since cerebellar Purkinje cells (PC) are characterized by high expression levels of the Ca(2+) buffers PV and CB, the question was raised, whether homeostatic mechanisms are induced in PC lacking these buffers. Mitochondrial volume density, i.e. relative mitochondrial mass was increased by 40% in the soma of PV-/- PC. Upregulation of mitochondrial volume density was not homogenous throughout the soma, but was selectively restricted to a peripheral region of 1.5 microm width underneath the plasma membrane. Accompanied was a decreased surface of subplasmalemmal smooth endoplasmic reticulum (sPL-sER) in a shell of 0.5 microm thickness underneath the plasma membrane. These alterations were specific for the absence of the "slow-onset" buffer PV, since in CB-/- mice neither changes in peripheral mitochondria nor in sPL-sER were observed. This implicates that the morphological alterations are aimed to specifically substitute the function of the slow buffer PV. We propose a novel concept that homeostatic mechanisms of components involved in Ca(2+) homeostasis do not always occur at the level of similar or closely related molecules. Rather the cell attempts to restore spatiotemporal aspects of Ca(2+) signals prevailing in the undisturbed (wildtype) situation by subtly fine tuning existing components involved in the regulation of Ca(2+) fluxes.     

Identification of intervention categories for physical therapy, based on the international classification of functioning, disability and health: a Delphi exercise

BACKGROUND AND PURPOSE: Disability or limitations in human functioning are universal experiences that concern all people. Physical therapists aim to improve functioning and prevent disability. With the approval of the new International Classification of Functioning, Disability and Health (ICF), we can now rely on a globally recognized framework and classification to be used in different health care situations by all health care professionals in multidisciplinary teams. The objective of this study was to identify ICF categories that describe the most relevant and common patient problems managed by physical therapists in acute, rehabilitation, and community health care situations taking into account 3 major groups of health conditions: musculoskeletal, neurological, and internal. SUBJECTS: The subjects were physical therapists who were identified as possible participants by the heads of physical therapy departments who were members of the Swiss Association of Physical Therapy Department Heads or who were recruited from the membership of the Swiss Association of Physiotherapy. METHODS: A consensus-building, 3-round, electronic-mail survey with 9 groups of physical therapists was conducted using the Delphi technique. RESULTS: Two hundred sixty-three physical therapists participated in at least one round of the Delphi exercise. They had consensus levels of 80% or higher for categories in all ICF components (Body Functions, Body Structures, Activities and Participation, and Environmental Factors 1 and 2). DISCUSSION AND CONCLUSION: This study is a first step toward identifying a list of intervention categories relevant for physical therapy according to the ICF. The ICF, designed as a common language for multidisciplinary use, is also a very helpful framework for defining the core competence for the physical therapy profession.     

Quality assessment of cardiovascular magnetic resonance in the setting of the European CMR registry: description and validation of standardized criteria

Background

Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in cardiovascular medicine. However, insufficient image quality may compromise its diagnostic accuracy. We aimed to describe and validate standardized criteria to evaluate a) cine steady-state free precession (SSFP), b) late gadolinium enhancement (LGE), and c) stress first-pass perfusion images. These criteria will serve for quality assessment in the setting of the Euro-CMR registry.

Methods

Thirty-five qualitative criteria were defined (scores 0–3) with lower scores indicating better image quality. In addition, quantitative parameters were measured yielding 2 additional quality criteria, i.e. signal-to-noise ratio (SNR) of non-infarcted myocardium (as a measure of correct signal nulling of healthy myocardium) for LGE and % signal increase during contrast medium first-pass for perfusion images. These qualitative and quantitative criteria were assessed in a total of 90 patients (60 patients scanned at our own institution at 1.5T (n=30) and 3T (n=30) and in 30 patients randomly chosen from the Euro-CMR registry examined at 1.5T). Analyses were performed by 2 SCMR level-3 experts, 1 trained study nurse, and 1 trained medical student.

Results

The global quality score was 6.7±4.6 (n=90, mean of 4 observers, maximum possible score 64), range 6.4-6.9 (p=0.76 between observers). It ranged from 4.0-4.3 for 1.5T (p=0.96 between observers), from 5.9-6.9 for 3T (p=0.33 between observers), and from 8.6-10.3 for the Euro-CMR cases (p=0.40 between observers). The inter- (n=4) and intra-observer (n=2) agreement for the global quality score, i.e. the percentage of assignments to the same quality tertile ranged from 80% to 88% and from 90% to 98%, respectively. The agreement for the quantitative assessment for LGE images (scores 0–2 for SNR <2, 2–5, >5, respectively) ranged from 78-84% for the entire population, and 70-93% at 1.5T, 64-88% at 3T, and 72-90% for the Euro-CMR cases. The agreement for perfusion images (scores 0–2 for %SI increase >200%, 100%-200%,<100%, respectively) ranged from 81-91% for the entire population, and 76-100% at 1.5T, 67-96% at 3T, and 62-90% for the Euro-CMR registry cases. The intra-class correlation coefficient for the global quality score was 0.83.

Conclusions

The described criteria for the assessment of CMR image quality are robust with a good inter- and intra-observer agreement. Further research is needed to define the impact of image quality on the diagnostic and prognostic yield of CMR studies.