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J. Clin. Med., Volume 6, Issue 8 (August 2017) – 6 articles

Cover Story (view full-size image): Cardiovascular disease is predicted to account for >23 million by 2030. There is now consensus that dyslipidaemia induces atherosclerosis. Statins have become the cornerstone for management of dyslipidaemia and have a very good safety profile. Nevertheless, potential risk of an adverse event must be considered when using statin therapy for patients. Statin-associated muscle disease (SAMS) is the most common reason for discontinuation of therapy. Reported incidence varies, ranging between 5% and 29%. Milder disease is common. The more serious form, rhabdomyolysis is rarer, with an incidence of roughly 1 in 10000. The pathophysiology of SAMS is not yet fully understood. Although literature points towards statin-induced mitochondrial dysfunction, exact mechanism is not yet elucidated. This paper details some of the different aetiological hypotheses related to mitochondrial dysfunction put forward in the [...] Read more.

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1337 KiB

Open AccessFeature PaperArticle

Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice

by Alireza Morovat, Gayani Weerasinghe, Victoria Nesbitt, Monika Hofer, Thomas Agnew, Geralrine Quaghebeur, Kate Sergeant, Carl Fratter, Nishan Guha, Mehdi Mirzazadeh and Joanna Poulton

J. Clin. Med. 2017, 6(8), 80; https://doi.org/10.3390/jcm6080080 - 21 Aug 2017

Cited by 59 | Viewed by 7113

Abstract

Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other laboratory findings. Patients’ FGF-21 results were assessed by the use of age-adjusted z-scores based on normalised FGF-21 values from a healthy population. One hundred and fifty five patients were investigated. One hundred and four of these patients had molecular evidence for MD, 27 were deemed to have disorders other than MD (non-MD), and 24 had possible MD. Patients with defects in mitochondrial DNA (mtDNA) maintenance (n = 32) and mtDNA rearrangements (n = 17) had the highest median FGF-21 among the MD group. Other MD patients harbouring mtDNA point mutations (n = 40) or mutations in other autosomal genes (n = 7) and those with partially characterised MD had lower FGF-21 levels. The area under the receiver operating characteristic curve for distinguishing MD from non-MD patients was 0.69. No correlation between FGF-21 and creatinine, creatine kinase, or cardio-skeletal myopathy score was found. FGF-21 was significantly associated with plasma lactate and ocular myopathy. Although FGF-21 was found to have a low sensitivity for detecting MD, at a z-score of 2.8, its specificity was above 90%. We suggest that a high serum concentration of FGF-21 would be clinically useful in MD, especially in adult patients with chronic progressive external ophthalmoplegia, and may enable bypassing muscle biopsy and directly opting for genetic analysis. Availability of its assay has thus modified our diagnostic pathway. Full article

(This article belongs to the Special Issue Current Strategies for the Biochemical Diagnosis and Monitoring of Mitochondrial Disease)

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723 KiB

Open AccessArticle

The Fragility Index in a Cohort of Pediatric Randomized Controlled Trials

by Travis J. Matics, Nadia Khan, Priti Jani and Jason M. Kane

J. Clin. Med. 2017, 6(8), 79; https://doi.org/10.3390/jcm6080079 - 14 Aug 2017

Cited by 45 | Viewed by 5047

Abstract

Data suggest inadequacy of common statistical techniques for reporting outcomes in clinical trials. The Fragility Index can measure how many events the statistical significance hinges on, and may facilitate better interpretation of trial results. This study aimed to assess the Fragility Index in pediatric randomized controlled trials (RCTs) with statistically significant findings published in high-quality medical journals. A Fragility Index was calculated on included trials with dichotomous positive outcomes. Analysis of the relationship between trial characteristics and the Fragility Index was performed. Of the 429 abstracts screened, 17 met the inclusion criteria and underwent analysis. The median Fragility Index was 7 with an interquartile range of 2–11. In 41% of the studies, the number of patients lost to follow-up or withdrawn prior to analysis was equal to or greater than the Fragility Index. There was no correlation between the RCT sample size and the Fragility Index (r = 0.249, p = 0.335) nor the event group size and the Fragility Index (r = 0.250, p = 0.334). There was a strong negative correlation between the original p-value and the Fragility Index (r = −0.700, p = 0.002). The Fragility Index is a calculated metric that may assist in applying clinical relevance to statistically significant outcomes in pediatric randomized controlled trials with dichotomous outcomes. Full article

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Open AccessBrief Report

Impact of Larger Sputum Volume on Xpert^® MTB/RIF Assay Detection of Mycobacterium tuberculosis in Smear-Negative Individuals with Suspected Tuberculosis

by Sharlaa Badal-Faesen, Cynthia Firnhaber, Michelle A. Kendall, Xingye Wu, Beatriz Grinsztejn, Rodrigo Otavio da Silva Escada, Michel Fernandez, Evelyn Hogg, Ian Sanne, Pamela Johnson, David Alland, Gerald H. Mazurek, Debra A. Benator, Anne F. Luetkemeyer, The AIDS Clinical Trials Group A5295 and Tuberculosis Trials Consortium Study 34 Teams

J. Clin. Med. 2017, 6(8), 78; https://doi.org/10.3390/jcm6080078 - 7 Aug 2017

Cited by 8 | Viewed by 5080

Abstract

As a strategy to improve the sensitivity of nucleic acid-based testing in acid-fast bacilli (AFB) negative samples, larger volumes of sputum (5–10 mL) were tested with Xpert^® MTB/RIF from 176 individuals with smear-negative sputum undergoing tuberculosis evaluation. Despite larger volumes, this strategy [...] Read more.

(This article belongs to the Special Issue Tuberculosis Treatment and Management)

680 KiB

Open AccessFeature PaperReview

Ultrasound for Early Detection of Joint Disease in Patients with Hemophilic Arthropathy

by Matteo Nicola Dario Di Minno, Gianluigi Pasta, Sonia Airaldi, Federico Zaottini, Antonio Storino, Ernesto Cimino and Carlo Martinoli

J. Clin. Med. 2017, 6(8), 77; https://doi.org/10.3390/jcm6080077 - 31 Jul 2017

Cited by 37 | Viewed by 11017

Abstract

Joint bleeding represents the most commonly reported type of hemorrhage in patients affected by hemophilia. Although the widespread use of prophylaxis has been able to significantly reduce the onset of arthropathy, it has been shown that a non-negligible percentage of patients develop degenerative changes in their joints despite this type of treatment. Thus, periodic monitoring of the joint status in hemophilia patients has been recommended to identify early arthropathic changes and prevent the development or progression of hemophilic arthropathy. Ultrasound (US) has proven able to detect and quantify the most relevant biomarkers of disease activity (i.e., joint effusion and synovial hypertrophy) and degenerative damages (i.e., osteo-chondral changes) by means of scoring scales of increasing disease severity. In the present review, we have detailed major literature evidence about the use of US to assess joint status in hemophilia patients, focusing on signs of disease activity and degenerative damages. In particular, we have discussed recent evidence about “point-of-care” use patients with hemophilia. Full article

(This article belongs to the Special Issue Outstanding Advances in Hemophilia Therapies)

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276 KiB

Open AccessFeature PaperReview

Long-Term Effects of Pregnancy Complications on Maternal Health: A Review

by Ran Neiger

J. Clin. Med. 2017, 6(8), 76; https://doi.org/10.3390/jcm6080076 - 27 Jul 2017

Cited by 113 | Viewed by 13470

Abstract

Background: Most pregnancy-related medical complications appear to resolve at delivery or shortly thereafter. Common examples are preterm labor, placental abruption, preeclampsia, and gestational diabetes. Women who developed such complications are known to be at increased risk of developing similar complications in future pregnancies. It has recently become evident that these women are at an increased risk of long term medical complications. Methods: A search through scientific publications in English regarding the association of obstetric complications and long-term maternal illness. Results: There is a clear association between various obstetric complications and long-term effects on maternal health. Conclusions: Women with a history of adverse pregnancy outcomes are at increased risk of cardiovascular and metabolic diseases later in life. Data increasingly links maternal vascular, metabolic, and inflammatory complications of pregnancy with an increased risk of vascular disease in later life. Full article

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Open AccessFeature PaperReview

Statins, Muscle Disease and Mitochondria

by Radha Ramachandran and Anthony S. Wierzbicki

J. Clin. Med. 2017, 6(8), 75; https://doi.org/10.3390/jcm6080075 - 25 Jul 2017

Cited by 71 | Viewed by 8067

Abstract

Cardiovascular disease (CVD) accounts for >17 million deaths globally every year, and this figure is predicted to rise to >23 million by 2030. Numerous studies have explored the relationship between cholesterol and CVD and there is now consensus that dyslipidaemia is a causal factor in the pathogenesis of atherosclerosis. Statins have become the cornerstone of the management of dyslipidaemia. Statins have proved to have a very good safety profile. The risk of adverse events is small compared to the benefits. Nevertheless, the potential risk of an adverse event occurring must be considered when prescribing and monitoring statin therapy to individual patients. Statin-associated muscle disease (SAMS) is by far the most studied and the most common reason for discontinuation of therapy. The reported incidence varies greatly, ranging between 5% and 29%. Milder disease is common and the more serious form, rhabdomyolysis is far rarer with an incidence of approximately 1 in 10,000. The pathophysiology of, and mechanisms leading to SAMS, are yet to be fully understood. Literature points towards statin-induced mitochondrial dysfunction as the most likely cause of SAMS. However, the exact processes leading to mitochondrial dysfunction are not yet fully understood. This paper details some of the different aetiological hypotheses put forward, focussing particularly on those related to mitochondrial dysfunction. Full article

(This article belongs to the Special Issue Current Strategies for the Biochemical Diagnosis and Monitoring of Mitochondrial Disease)

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