MRI in Neuromuscular Diseases: An Emerging Diagnostic Tool and Biomarker for Prognosis and Efficacy

There is an unmet need to identify biomarkers sensitive to change in rare, slowly progressive neuromuscular diseases. Quantitative magnetic resonance imaging (MRI) of muscle may offer this opportunity, as it is noninvasive and can be carried out almost independent of patient cooperation and disease severity. Muscle fat content correlates with muscle function in neuromuscular diseases, and changes in fat content precede changes in function, which suggests that muscle MRI is a strong biomarker candidate to predict prognosis and treatment efficacy. In this paper, we review the evidence suggesting that muscle MRI may be an important biomarker for diagnosis and to monitor change in disease severity. ANN NEUROL 2020;88:669–681     

The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest

Introduction

Early prognostication after successful cardiopulmonary resuscitation is difficult, and there is a need for novel methods to estimate the extent of brain injury and predict outcome. In this study, we evaluated the impact of the cardiac arrest syndrome on the plasma levels of selected tissue-specific microRNAs (miRNAs) and assessed their ability to prognosticate death and neurological disability.

Methods

We included 65 patients treated with hypothermia after cardiac arrest in the study. Blood samples were obtained at 24 hours and at 48 hours. For miRNA-screening purposes, custom quantitative polymerase chain reaction (qPCR) panels were first used. Thereafter individual miRNAs were assessed at 48 hours with qPCR. miRNAs that successfully predicted prognosis at 48 hours were further analysed at 24 hours. Outcomes were measured according to the Cerebral Performance Category (CPC) score at 6 months after cardiac arrest and stratified into good (CPC score 1 or 2) or poor (CPC scores 3 to 5).

Results

At 48 hours, miR-146a, miR-122, miR-208b, miR-21, miR-9 and miR-128 did not differ between the good and poor neurological outcome groups. In contrast, miR-124 was significantly elevated in patients with poor outcomes compared with those with favourable outcomes (P < 0.0001) at 24 hours and 48 hours after cardiac arrest. Analysis of receiver operating characteristic curves at 24 and 48 hours after cardiac arrest showed areas under the curve of 0.87 (95% confidence interval (CI) = 0.79 to 0.96) and 0.89 (95% CI = 0.80 to 0.97), respectively.

Conclusions

The brain-enriched miRNA miR-124 is a promising novel biomarker for prediction of neurological prognosis following cardiac arrest.     

MR imaging of the breast in patients with invasive lobular carcinoma

OBJECTIVE: Our objective was to assess the usefulness of MR imaging in patients diagnosed with invasive lobular carcinoma of the breast. MATERIALS AND METHODS: Between July 1993 and September 1999, 32 women (33 cases) diagnosed with pure invasive lobular carcinoma of the breast underwent contrast-enhanced MR imaging examination. One woman was excluded because of lack of follow-up. Correlation was made between the mammographic and sonographic findings, the MR imaging findings, and the final pathology results for the remaining 32 cases. RESULTS: In 18 women who did not undergo excisional biopsy before the MR imaging, MR imaging showed more extensive tumor burden or the detection of the primary lesion that was occult on conventional imaging in seven (38.9%) of 18 women. In nine (50%) of 18 women, MR imaging performed equally as well as mammography and sonography. In one case (5.6%), MR imaging and mammography underestimated disease extent. In another patient (5.6%), MR imaging overestimated tumor burden, although mammography failed to show the cancer. In 14 patients who had excisional biopsy before the MR imaging, residual tumor was shown in eight women (57.1%) with extensive tumor or additional separate foci in five of the eight patients. In two cases (14.3%) that were interpreted as equivocal, residual tumor was shown in both cases on reexcision. In three cases (21.4%), the MR imaging was interpreted as negative, but microscopic tumor was shown around seroma on reexcision. False-positive enhancement was seen in one case (7.1%). CONCLUSION: MR imaging showed more extensive tumor than conventional imaging and affected the clinical management in 16 (50%) of 32 patients with invasive lobular carcinoma.     

Fatigue after myocardial infarction: Relationships with indices of emotional distress,and sociodemographic and clinical variables

Alsén P, Brink E, Brändström Y, Karlson BW, Persson L‐O. International Journal of Nursing Practice 2010; 16 : 326–334
Fatigue after myocardial infarction: Relationships with indices of emotional distress, and sociodemographic and clinical variables Fatigue and depressive symptoms are relatively common among patients recovering from myocardial infarction (MI). The symptoms of depression and fatigue overlap. The present study aimed at identifying patient fatigue and at examining the incidence of fatigue, particularly without coexisting depression, after MI. The sample comprised 204 consecutive patients who had completed the questionnaires Hospital Anxiety and Depression Scale and the Multidimensional Fatigue Inventory–20 after MI (1 week and 4 months). The results showed that fatigue had decreased after 4 months compared with the time of MI onset. Compared with the general population, patients reported significantly higher levels of fatigue. Furthermore, fatigue was associated with depression, but 33% of the sample reported fatigue without coexisting depression after 4 months. In order to prevent or treat patients' symptoms of fatigue after MI, the concepts of fatigue and depression should be assessed separately so as to exclude overlapping effects.     

Saving lives versus life‐years in rural Bangladesh: an ethical preferences approach

Using a random sample of individuals in rural Bangladesh, this paper investigates people's ethical preferences regarding relative values of lives when it comes to saving lives of individuals of different ages. By assuming that an individual has preferences concerning different states of the world, and that these preferences can be described by an individual social welfare function, the individuals' preferences for life‐saving programs are elicited using a pair‐wise choice experiment involving different life‐saving programs. In the analyses, we calculate the social marginal rates of substitution between saved lives of people of different ages. We also test whether people have preferences for saving more life‐years rather than only saving lives. In particular, we test and compare the two hypotheses that only lives matter and that only life‐years matter. The results indicate that the value of a saved life decreases rapidly with age and that people have strong preferences for saving life‐years rather than lives per se. Overall, the results clearly show the importance of the number of life‐years saved in the valuation of life. Copyright © 2010 John Wiley & Sons, Ltd.     

Should plasma from female donors be avoided? A population‐based cohort study of plasma recipients in Sweden from 1990 through 2002

BACKGROUND: Plasma from female donors has been implicated in the sometimes fatal complication known as transfusion‐related acute lung injury. In studies of patients in intensive care units, worsened gas exchange of the lungs has also been attributed to female plasma. Despite a lack of population‐based evidence, policies have already been introduced to exclude female donor plasma. STUDY DESIGN AND METHODS: Short‐term mortality after plasma transfusion was investigated using data from the Scandinavian Donations and Transfusions (SCANDAT) database. A cohort of 92,565 patients in 30 Swedish hospitals were followed for 14 days after their first plasma transfusion. The relative risk (RR) of death in recipients of female plasma compared to recipients of only male plasma was estimated from Poisson regression. RESULTS: Recipients had median age 70 years, received a mean of 4.4 plasma units, and had an overall 14‐day mortality of 8.43%. Sixty‐eight percent were exposed to female plasma, with a 14‐day mortality of 8.85% compared to 7.53% in the nonexposed group. After adjustment for potential confounding factors, the RRs were 1.16 (confidence interval [CI], 1.06‐1.27) and 1.32 (CI, 1.17‐1.49) for those receiving 3 to 4 and 5 or more units of female plasma, respectively. Risk estimates were increased in an analysis of deaths with a concomitant discharge diagnosis involving the respiratory or circulatory system or an adverse reaction. CONCLUSIONS: This large population‐based cohort study of unselected patients suggests that transfusion of plasma from female donors confers a short‐term survival disadvantage on recipients.     

In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass

IntroductionThe positron emission tomography (PET) tracer 9-[¹⁸F]fluoroethyl-(+)-dihydrotetrabenazine ([¹⁸F]-FE-(+)-DTBZ) is a potential candidate for quantifying beta-cell mass in vivo. The purpose was to investigate in vitro and in vivo utility of this tracer for the assessment of beta-cell mass.MethodsThree pigs were intravenously administered [¹⁸F]-FE-(+)-DTBZ and examined by PET/computed tomography. Binding parameters were estimated by kinetic modeling. In vitro k_D and B_max were determined by saturation binding studies of endocrine and exocrine human tissue homogenates. In vitro pancreatic uptake was determined by tissue autoradiography with pancreases from patients with types 1 (T1DM) and 2 diabetes mellitus (T2DM) and healthy controls.Results[¹⁸F]-FE-(+)-DTBZ had a k_D of 3.5±1.0 nM, a B_max of 382±108 fmol/mg protein and a specificity of 89±1.8% in islet homogenates. The total exocrine uptake was lower and 65% was nondisplaceable. No uptake difference was observed in pancreatic tissue slices from patients with T1DM, T2DM or healthy controls. The in vivo porcine pancreatic uptake reached a peak of standardized uptake value (SUV) of 2.8 with a low distribution volume ratio in all animals. Moderate to high tracer uptake was identified in the bile system and in bone.Conclusions[¹⁸F]-FE-(+)-DTBZ binds to vesicular monoamine transporter 2 (VMAT2) with high specificity in pure islet tissue in vitro. However, there is high nondisplaceable binding to exocrine tissue. In addition, in vivo tracer metabolism and dehalogenation result in severe underestimation of porcine pancreatic VMAT2 expression and BCM. The results do not support [¹⁸F]-FE-(+)-DTBZ as a suitable tracer for in vivo beta-cell imaging.