Today or tomorrow? A retrospective analysis of the clinical indications used to request urgent magnetic resonance imaging of the spine

INTRODUCTION

The finite resources available to National Health Service institutions require clinicians to order investigations that are not readily available appropriately. This is particularly true for the radiological assessment of patients presenting with features pertaining to acute spinal cord dysfunction. Such cases conventionally require urgent magnetic resonance imaging (MRI) which is sometimes performed ‘out-of-hours’. There is evidence to suggest, however, that a high proportion of patients do not have a structural abnormality on MRI to account for their clinical findings, and consequently the majority of scans that are requested urgently are normal. The primary aim of this study was to determine whether any clinical feature(s) could accurately predict the presence of a structural abnormality on MRI. As a secondary objective, the ability of such features to predict the need for spinal surgery was assessed.

PATIENTS AND METHODS

A retrospective analysis of consecutive patients who warranted urgent MRI was conducted. Eighty-one patients were eligible for study. The Fisher’s test was used for statistical analysis of all data. A P-value of less than 0.05 was considered to be significant.

RESULTS

MRI was performed within 24 h of admission in 16 patients, and of these, seven had surgery within 24–48 h. Only two patients were found to have significant neurological compromise. Despite both a history and examination suggesting otherwise, MRI was normal in 10 patients (12%).

CONCLUSIONS

We were unable to elucidate any clinical features that were able to predict the presence of an abnormal MRI. We did find, however, that patients with a combination of both subjective neurological findings and positive neurological signs (P = 0.02), saddle anaesthesia and/or decreased anal tone (P = 0.03) or sciatica (P = 0.02) had pathology on MRI that warranted surgical intervention. The authors recommend that the aforementioned features formulate the basis of guidelines used to request and/or perform MRI urgently since they are highly suggestive of surgical intervention. Conversely, patients who do not exhibit the above examination findings might not require either an urgent or ‘out-of-hours’ scan, but could potentially be investigated less expediently and/or wait until ‘normal working hours’.     

Argument for a Doppler echocardiography during exercise in assessing asymptomatic patients with severe aortic stenosis

Aims: Exercise stress testing (EST) is recommended by guidelines torisk-stratify patients with asymptomatic valvular aortic stenosis(AS), though the role of quantitative exercise-Doppler echocardiographyhas rarely been studied. This prospective study sought to correlatestandard EST results with the haemodynamic measurements madeduring exercise by Doppler echocardiography. Methods and results: We performed rest and semi-supine exercise Doppler echocardiographyin 44 consecutive patients (mean age = 68 ± 12 years)with aortic valve areas 0.6 cm²/m². The effective aortic valvearea (EOA), cardiac output (CO), maximal transvalvular velocity,and pulmonary pressure were monitored over the test. No seriousadverse event was observed. EST was positive in 26 (Group 1)and negative in 18 (Group 2) patients. Baseline echocardiographicmeasurements were similar (EOA 0.77 ± 0.15 vs. 0.78 ±0.14 cm²; CO 5.5 ± 1.6 vs. 5.9 ± 2 L/min) in bothgroups. Exercise-induced changes in CO (+2.9 ± 2 vs.+4.3 ± 1.8 L/min, P = 0.04) and EOA (–0.04 ±0.18 vs. +0.15 ± 0.24 cm², P = 0.015) were significantlygreater in Group 2. A correlation between changes in EOA andchanges in CO during exercise was observed, but significantlyhigher in Group 2 (P = 0.04). Conclusion: In the presence of severe asymptomatic AS, exercise Dopplerechocardiography, assessing the mechanisms behind a positiveEST, appears very promising but further studies with prognosisassessment remain necessary.     

Mitral regurgitation in dilated cardiomyopathy: value of both regional left ventricular contractility and dyssynchrony

Aims: Mitral regurgitation (MR) is common and independently predictsmortality in patients with left ventricular (LV) systolic dysfunction.Its management remains challenging because of the complexityand variety of potential mechanisms implicated. We sought todetermine which LV functional characteristics are the most importantdeterminants of the severity of the MR associated with dilatedcardiomyopathies. Methods and results: We performed echocardiographic studies in 87 consecutive patientswith dilated cardiomyopathy. The degree of MR was quantifiedaccording to guidelines. LV, left atrial and mitral annulusdimensions, mitral valve tenting, estimated filling pressures,regional myocardial contractility, and dyssynchrony (using regionalstrain () analysis) were recorded too. Determinants of significantMR was thus assessed using multivariate models. Mitral regurgitantvolume correlated with mitral annulus diameter (P < 0.001),mitral valve tenting height (P < 0.001), LV volumes (P =0.004), LV ejection fraction, mid-lateral wall peak of (P =0.01), and its delay (P < 0.001). That inter-relation betweenthe mitral annulus, the ventricle shape, contractility, anddyssynchrony was founded in the multivariate analysis. As amatter of fact, the model predicting the best the MR volume(R = 0.78) included: mitral annulus diameter, dyssynchrony,tenting heigh and contractility of the LV mid-lateral wall (measuredby ). Conclusion: The MR of the dilated cardiomyopathy is multifactorial. Ourdata suggest that analysing only LV geometry and mitral orificeis insufficient to correctly describe functional MR determinant.LV contractility and dyssynchrony are essential too.     

Contr?le du rythme sinusal ou contr?le de la fréquence ventriculaire ?

Rhythm control or rate control are the 2 therapeutic strategies for atrial fibrillation (AF) management. Despite strong physiological and epidemiological data to support a rhythm control strategy, the results of the prospective studies, especially AFFIRM and RACE trials, did not demonstrate any superiority of a rhythm control versus a rate control strategy. The AF-CHF trial conducted in heart failure patients led to the same conclusions. In clinical practice, the therapeutic management is only driven by the patient symptoms. For rhythm control, antiarrhythmic drugs are still the first step before considering, in selected patients, ablative techniques. Treatment algorithms proposed in 2006 by the European society of cardiology are the references for patient management, treatment being individually optimized.     

Peroxiredoxin-1 protects estrogen receptor α from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer

Introduction

Peroxiredoxin-1 (PRDX1) is a multifunctional protein, acting as a hydrogen peroxide (H₂O₂) scavenger, molecular chaperone and immune modulator. Although differential PRDX1 expression has been described in many tumors, the potential role of PRDX1 in breast cancer remains highly ambiguous. Using a comprehensive antibody-based proteomics approach, we interrogated PRDX1 protein as a putative biomarker in estrogen receptor (ER)-positive breast cancer.

Methods

An anti-PRDX1 antibody was validated in breast cancer cell lines using immunoblotting, immunohistochemistry and reverse phase protein array (RPPA) technology. PRDX1 protein expression was evaluated in two independent breast cancer cohorts, represented on a screening RPPA (n = 712) and a validation tissue microarray (n = 498). In vitro assays were performed exploring the functional contribution of PRDX1, with oxidative stress conditions mimicked via treatment with H₂O₂, peroxynitrite, or adenanthin, a PRDX1/2 inhibitor.

Results

In ER-positive cases, high PRDX1 protein expression is a biomarker of improved prognosis across both cohorts. In the validation cohort, high PRDX1 expression was an independent predictor of improved relapse-free survival (hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.40 to 0.96, P = 0.032), breast cancer-specific survival (HR = 0.44, 95% CI = 0.24 to 0.79, P = 0.006) and overall survival (HR = 0.61, 95% CI = 0.44 to 0.85, P = 0.004). RPPA screening of cancer signaling proteins showed that ERα protein was upregulated in PRDX1 high tumors. Exogenous H₂O₂ treatment decreased ERα protein levels in ER-positive cells. PRDX1 knockdown further sensitized cells to H₂O₂- and peroxynitrite-mediated effects, whilst PRDX1 overexpression protected against this response. Inhibition of PRDX1/2 antioxidant activity with adenanthin dramatically reduced ERα levels in breast cancer cells.

Conclusions

PRDX1 is shown to be an independent predictor of improved outcomes in ER-positive breast cancer. Through its antioxidant function, PRDX1 may prevent oxidative stress-mediated ERα loss, thereby potentially contributing to maintenance of an ER-positive phenotype in mammary tumors. These results for the first time imply a close connection between biological activity of PRDX1 and regulation of estrogen-mediated signaling in breast cancer.     

Immunoreactive GnRH type I receptors in the mouse and sheep brain

Gonadotropin Releasing Hormone-I (GnRH) has been implicated in an array of functions outside the neuroendocrine reproductive axis. Previous investigations have reported extensive GnRH binding in numerous sites and this has been supported by in situ hybridization studies reporting GnRH receptor mRNA distribution. The present study on mice and sheep supports and extends these earlier investigations by revealing the distribution of cells immunoreactive for the GnRH receptor. In addition to sites previously shown to express GnRH receptors such as the hippocampus, amygdala and the arcuate nucleus, the improved resolution afforded by immunocytochemistry detected cells in the mitral cell lay of the olfactory bulb as well as the central grey of the mesencephalon. In addition, GnRH receptor immunoreactive neurons in the hippocampus and mesencephalon of the sheep were shown to colocalize with estrogen receptor beta. Although GnRH may act at some of these sites to regulate reproductive processes, evidence is accumulating to support an extra-reproductive role for this hypothalamic decapeptide.