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Diagnostics, Volume 8, Issue 2 (June 2018)

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Editorial

Jump to: Research, Review, Other

Open AccessEditorial The Art of Caring in the Treatment of Thoracic Outlet Syndrome
Diagnostics 2018, 8(2), 35; https://doi.org/10.3390/diagnostics8020035 (registering DOI)
Received: 17 April 2018 / Revised: 15 May 2018 / Accepted: 15 May 2018 / Published: 19 May 2018
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Abstract
Those who diagnose and treat patients with thoracic outlet syndrome, especially those patients
with neurogenic thoracic outlet syndrome, have a practice, which needs to include many modalities to
diagnose, treat, and intervene to improve their quality of life for the present and for
[...] Read more.
Those who diagnose and treat patients with thoracic outlet syndrome, especially those patients
with neurogenic thoracic outlet syndrome, have a practice, which needs to include many modalities to
diagnose, treat, and intervene to improve their quality of life for the present and for the future.[...] Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Thoracic Outlet Syndrome)

Research

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Open AccessArticle Optimization of Stress-Based Microfluidic Testing for Methicillin Resistance in Staphylococcus aureus Strains
Diagnostics 2018, 8(2), 24; https://doi.org/10.3390/diagnostics8020024
Received: 29 March 2018 / Revised: 11 April 2018 / Accepted: 11 April 2018 / Published: 17 April 2018
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Abstract
The rapid evolution of antibiotic resistance in bacterial pathogens is driving the development of innovative, rapid antibiotic susceptibility testing (AST) tools as a way to provide more targeted and timely antibiotic treatment. We have previously presented a stress-based microfluidic method for the rapid
[...] Read more.
The rapid evolution of antibiotic resistance in bacterial pathogens is driving the development of innovative, rapid antibiotic susceptibility testing (AST) tools as a way to provide more targeted and timely antibiotic treatment. We have previously presented a stress-based microfluidic method for the rapid determination of antibiotic susceptibility in methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). In this method, stress is used to potentiate the action of antibiotics, and cell death is measured as a proxy for susceptibility. The method allows antibiotic susceptibility to be determined within an hour from the start of the antibiotic introduction. However, the relatively low dynamic range of the signal (2–10% cell response) even with high antibiotic concentrations (10–50 µg/mL) left room for the method’s optimization. We have conducted studies in which we varied the flow patterns, the media composition, and the antibiotic concentration to increase the cell death response and concordantly decrease the required antibiotic concentration down to 1–3 µg/mL, in accordance with the Clinical and Laboratory Standards Institute’s (CLSI) guidelines for AST breakpoint concentrations. Full article
(This article belongs to the Section In Vitro Diagnostics)
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Open AccessArticle Angiogenesis PET Tracer Uptake (68Ga-NODAGA-E[(cRGDyK)]2) in Induced Myocardial Infarction and Stromal Cell Treatment in Minipigs
Diagnostics 2018, 8(2), 33; https://doi.org/10.3390/diagnostics8020033
Received: 9 April 2018 / Revised: 4 May 2018 / Accepted: 14 May 2018 / Published: 16 May 2018
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Abstract
Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αv
[...] Read more.
Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82Rubidium (82Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUVmean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUVmean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUVmean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated. Full article
(This article belongs to the Section Medical Imaging)
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Open AccessArticle Diagnosing Breast Cancer with Microwave Technology: remaining challenges and potential solutions with machine learning
Diagnostics 2018, 8(2), 36; https://doi.org/10.3390/diagnostics8020036 (registering DOI)
Received: 14 April 2018 / Revised: 15 May 2018 / Accepted: 16 May 2018 / Published: 19 May 2018
PDF Full-text (744 KB)
Abstract
Currently, breast cancer often requires invasive biopsies for diagnosis, motivating researchers to design and develop non-invasive and automated diagnosis systems. Recent microwave breast imaging studies have shown how backscattered signals carry relevant information about the shape of a tumour, and tumour shape is
[...] Read more.
Currently, breast cancer often requires invasive biopsies for diagnosis, motivating researchers to design and develop non-invasive and automated diagnosis systems. Recent microwave breast imaging studies have shown how backscattered signals carry relevant information about the shape of a tumour, and tumour shape is often used with current imaging modalities to assess malignancy. This paper presents a comprehensive analysis of microwave breast diagnosis systems which use machine learning to learn characteristics of benign and malignant tumours. The state-of-the-art, the main challenges still to overcome and potential solutions are outlined. Specifically, this work investigates the benefit of signal pre-processing on diagnostic performance, and proposes a new set of extracted features that capture the tumour shape information embedded in a signal. This work also investigates if a relationship exists between the antenna topology in a microwave system and diagnostic performance. Finally, a careful machine learning validation methodology is implemented to guarantee the robustness of the results and the accuracy of performance evaluation. Full article

Review

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Open AccessReview Synthesized Mammography: Clinical Evidence, Appearance, and Implementation
Diagnostics 2018, 8(2), 22; https://doi.org/10.3390/diagnostics8020022
Received: 30 December 2017 / Revised: 31 March 2018 / Accepted: 2 April 2018 / Published: 4 April 2018
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Abstract
Digital breast tomosynthesis (DBT) has improved conventional mammography by increasing cancer detection while reducing recall rates. However, these benefits come at the cost of increased radiation dose. Synthesized mammography (s2D) has been developed to provide the advantages of DBT with nearly half the
[...] Read more.
Digital breast tomosynthesis (DBT) has improved conventional mammography by increasing cancer detection while reducing recall rates. However, these benefits come at the cost of increased radiation dose. Synthesized mammography (s2D) has been developed to provide the advantages of DBT with nearly half the radiation dose. Since its F.D.A. approval, multiple studies have evaluated the clinical performance of s2D. In clinical practice, s2D images are not identical to conventional 2D images and are designed for interpretation with DBT as a complement. This article reviews the present literature to assess whether s2D is a practical alternative to conventional 2D, addresses the differences in mammographic appearance of findings, and provides suggestions for implementation into clinical practice. Full article
(This article belongs to the Special Issue Breast Imaging)
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Open AccessReview Percutaneous, Imaging-Guided Biopsy of Bone Metastases
Diagnostics 2018, 8(2), 25; https://doi.org/10.3390/diagnostics8020025
Received: 20 January 2018 / Revised: 10 April 2018 / Accepted: 16 April 2018 / Published: 18 April 2018
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Abstract
Approximately 70% of cancer patients will eventually develop bone metastases. Spine, due to the abundance of red marrow in the vertebral bodies and the communication of deep thoracic-pelvic veins with valve-less vertebral venous plexuses, is the most common site of osseous metastatic disease.
[...] Read more.
Approximately 70% of cancer patients will eventually develop bone metastases. Spine, due to the abundance of red marrow in the vertebral bodies and the communication of deep thoracic-pelvic veins with valve-less vertebral venous plexuses, is the most common site of osseous metastatic disease. Open biopsies run the risk of destabilizing an already diseased spinal or peripheral skeleton segment. Percutaneous biopsies obviate such issues and provide immediate confirmation of correct needle location in the area of interest. Indications for percutaneous bone biopsy include lesion characterization, optimal treatment and tumor recurrence identification, as well as tumor response and recurrence rate prediction. Predicting recurrence in curative cases could help in treatment stratification, identification, and validation of new targets. The overall accuracy of percutaneous biopsy is 90–95%; higher positive recovery rates govern biopsy of osteolytic lesions. The rate of complications for percutaneous biopsy approaches is <5%. The purpose of this review is to provide information about performing bone biopsy and what to expect from it as well as choosing the appropriate imaging guidance. Additionally, factors governing the appropriate needle trajectory that would likely give the greatest diagnostic yield and choice of the most appropriate biopsy system and type of anesthesia will be addressed. Full article
(This article belongs to the Special Issue Imaging of Bone Metastases in Oncology)
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Open AccessReview Aneuploid CTC and CEC
Diagnostics 2018, 8(2), 26; https://doi.org/10.3390/diagnostics8020026
Received: 11 March 2018 / Revised: 16 April 2018 / Accepted: 17 April 2018 / Published: 18 April 2018
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Abstract
Conventional circulating tumor cell (CTC) detection technologies are restricted to large tumor cells (> white blood cells (WBCs)), or those unique carcinoma cells with double positive expression of surface epithelial cell adhesion molecule (EpCAM) for isolation, and intracellular structural protein cytokeratins (CKs) for
[...] Read more.
Conventional circulating tumor cell (CTC) detection technologies are restricted to large tumor cells (> white blood cells (WBCs)), or those unique carcinoma cells with double positive expression of surface epithelial cell adhesion molecule (EpCAM) for isolation, and intracellular structural protein cytokeratins (CKs) for identification. With respect to detecting the full spectrum of highly heterogeneous circulating rare cells (CRCs), including CTCs and circulating endothelial cells (CECs), it is imperative to develop a strategy systematically coordinating all tri-elements of nucleic acids, biomarker proteins, and cellular morphology, to effectively enrich and comprehensively identify CRCs. Accordingly, a novel strategy integrating subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), independent of cell size variation and free of hypotonic damage as well as anti-EpCAM perturbing, has been demonstrated to enable in situ phenotyping multi-protein expression, karyotyping chromosome aneuploidy, and detecting cytogenetic rearrangements of the ALK gene in non-hematologic CRCs. Symbolic non-synonymous single nucleotide variants (SNVs) of both the TP53 gene (P33R) in each single aneuploid CTCs, and the cyclin-dependent kinase inhibitor 2A (CDKN2A) tumor suppressor gene in each examined aneuploid CECs, were identified for the first time across patients with diverse carcinomas. Comprehensive co-detecting observable aneuploid CTCs and CECs by SE-iFISH, along with applicable genomic and/or proteomic single cell molecular profiling, are anticipated to facilitate elucidating how those disparate categories of aneuploid CTCs and CECs cross-talk and functionally interplay with tumor angiogenesis, therapeutic drug resistance, tumor progression, and cancer metastasis. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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Open AccessReview Fine Needle Aspiration Cytology for Neck Masses in Childhood. An Illustrative Approach
Diagnostics 2018, 8(2), 28; https://doi.org/10.3390/diagnostics8020028
Received: 29 January 2018 / Revised: 16 April 2018 / Accepted: 19 April 2018 / Published: 22 April 2018
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Abstract
The primary indication of fine-needle aspiration cytology of the head and neck region is a thyroid nodule or a mass located in the cervical area or the head. Although a thyroid nodule may raise the suspicion of malignancy, less than one in 20
[...] Read more.
The primary indication of fine-needle aspiration cytology of the head and neck region is a thyroid nodule or a mass located in the cervical area or the head. Although a thyroid nodule may raise the suspicion of malignancy, less than one in 20 cases results in a carcinoma. In addition, the list of differential diagnoses is quite different according to the age of the patient. A number of benign lesions, such as branchial cysts, sialadenosis, and sialoadenitis are often seen in childhood and youth. The malignant lesions that are on the top of the list of a pediatric mass of the head and neck (H&N) region include rhabdomyosarcoma, neuroblastoma, and papillary carcinoma of the thyroid gland. This critical review of the diagnostic features of a pediatric mass of the H&N region is accompanied by panels of several cytology features that may be of help to the cytopathologist and clinician. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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Open AccessReview Sialidosis: A Review of Morphology and Molecular Biology of a Rare Pediatric Disorder
Diagnostics 2018, 8(2), 29; https://doi.org/10.3390/diagnostics8020029
Received: 23 February 2018 / Revised: 22 April 2018 / Accepted: 22 April 2018 / Published: 25 April 2018
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Abstract
Sialidosis (MIM 256550) is a rare, autosomal recessive inherited disorder, caused by α-N-acetyl neuraminidase deficiency resulting from a mutation in the neuraminidase gene (NEU1), located on 6p21.33. This genetic alteration leads to abnormal intracellular accumulation as well as urinary
[...] Read more.
Sialidosis (MIM 256550) is a rare, autosomal recessive inherited disorder, caused by α-N-acetyl neuraminidase deficiency resulting from a mutation in the neuraminidase gene (NEU1), located on 6p21.33. This genetic alteration leads to abnormal intracellular accumulation as well as urinary excretion of sialyloligosaccharides. A definitive diagnosis is made after the identification of a mutation in the NEU1 gene. So far, 40 mutations of NEU1 have been reported. An association exists between the impact of the individual mutations and the severity of clinical presentation of sialidosis. According to the clinical symptoms, sialidosis has been divided into two subtypes with different ages of onset and severity, including sialidosis type I (normomorphic or mild form) and sialidosis type II (dysmorphic or severe form). Sialidosis II is further subdivided into (i) congenital; (ii) infantile; and (iii) juvenile. Despite being uncommon, sialidosis has enormous clinical relevance due to its debilitating character. A complete understanding of the underlying pathology remains a challenge, which in turn limits the development of effective therapeutic strategies. Furthermore, in the last few years, some atypical cases of sialidosis have been reported as well. We herein attempt to combine and discuss the underlying molecular biology, the clinical features, and the morphological patterns of sialidosis type I and II. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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Open AccessReview Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis
Diagnostics 2018, 8(2), 30; https://doi.org/10.3390/diagnostics8020030
Received: 1 April 2018 / Revised: 24 April 2018 / Accepted: 24 April 2018 / Published: 28 April 2018
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Abstract
The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a
[...] Read more.
The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and the resulting lessons learned about CTC and metastasis biology. We will also discuss how the use of clinically-relevant CTC technologies such as the CellSearch® and Parsortix™ platforms for preclinical CTC studies can serve to enhance the study of cancer biology, new biomarkers, and novel therapies from the bench to the bedside. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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Open AccessReview Cancer Diagnosis Using a Liquid Biopsy: Challenges and Expectations
Diagnostics 2018, 8(2), 31; https://doi.org/10.3390/diagnostics8020031
Received: 15 April 2018 / Revised: 4 May 2018 / Accepted: 7 May 2018 / Published: 9 May 2018
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Abstract
The field of cancer diagnostics has recently been impacted by new and exciting developments in the area of liquid biopsy. A liquid biopsy is a minimally invasive alternative to surgical biopsies of solid tissues, typically achieved through the withdrawal of a blood sample
[...] Read more.
The field of cancer diagnostics has recently been impacted by new and exciting developments in the area of liquid biopsy. A liquid biopsy is a minimally invasive alternative to surgical biopsies of solid tissues, typically achieved through the withdrawal of a blood sample or other body fluids, allowing the interrogation of tumor-derived material including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) fragments that are present at a given time point. In this short review, we discuss a few studies that summarize the state-of-the-art in the liquid biopsy field from a diagnostic perspective, and speculate on current challenges and expectations of implementing liquid biopsy testing for cancer diagnosis and monitoring in the clinical setting. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
Open AccessReview The Clinical Relevance of Methods for Handling Inconclusive Medical Test Results: Quantification of Uncertainty in Medical Decision-Making and Screening
Diagnostics 2018, 8(2), 32; https://doi.org/10.3390/diagnostics8020032
Received: 6 March 2018 / Revised: 4 May 2018 / Accepted: 7 May 2018 / Published: 9 May 2018
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Abstract
Background: although the existence of inconclusive medical test results or bio-markers is widely recognized, there are indications that this inherent diagnostic uncertainty is sometimes ignored. This paper discusses three methods for defining and determining inconclusive medical test results, which use different definitions and
[...] Read more.
Background: although the existence of inconclusive medical test results or bio-markers is widely recognized, there are indications that this inherent diagnostic uncertainty is sometimes ignored. This paper discusses three methods for defining and determining inconclusive medical test results, which use different definitions and differ in clinical relevance. Methods: the TG-ROC (two graphs receiver operating characteristics) method is the easiest to use, while the grey zone method and the uncertain interval method require more extensive calculations. Results: this paper discusses the technical details of the methods, as well as advantages and disadvantages for their clinical use. TG-ROC and the grey zone method can help in the acquisition of high rates of diagnostic certainty, but can exclude large groups. The uncertain interval method can prevent decisions that are the most uncertain, invalid and unreliable, while excluding smaller groups. Conclusions: the identification of uncertain test scores is relevant, because these scores indicate the need to obtain better information or to await further developments. The methods presented help to determine inconclusive test scores and can help to reduce erroneous decisions. However, further research and development is desirable. Full article
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Other

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Open AccessOpinion Perspective on Cancer Therapeutics Utilizing Analysis of Circulating Tumor Cells
Diagnostics 2018, 8(2), 23; https://doi.org/10.3390/diagnostics8020023
Received: 19 March 2018 / Revised: 3 April 2018 / Accepted: 9 April 2018 / Published: 11 April 2018
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Abstract
Various methods are available for cancer screening, and the methods are performed depending on the origin site of cancer. Among these methods, biopsy followed by medical imaging is the most common. After cancer progression is determined, an optimal treatment—such as surgery, chemotherapy, and/or
[...] Read more.
Various methods are available for cancer screening, and the methods are performed depending on the origin site of cancer. Among these methods, biopsy followed by medical imaging is the most common. After cancer progression is determined, an optimal treatment—such as surgery, chemotherapy, and/or radiation therapy—is selected. A new assay has been developed that detects circulating tumor cells (CTCs). Tracking changes in CTCs may reveal important tumoral sensitivity information or resistance patterns to specific regimens and prompt changes in therapy on a personalized basis. Characterization of CTCs at the DNA, RNA, and protein levels is important for gaining insight for clinical applications. A small number of CTCs can be analyzed to obtain genome information such as the progression of cancer including metastasis, even in a single cluster. Although many clinical studies, particularly CTC enumeration and detection of specific oncogene expression, have increased the success rate of diagnosis and predicting prognosis, there is no consensus regarding the technical approaches and various aspects of the methodology, making it difficult to standardize optimal methods for CTC analysis. However, ongoing technological advances are currently being achieved and large-scale clinical studies are being conducted. Applying CTC analysis in the clinic would be very useful for advancing diagnosis, prognosis prediction, and therapeutics. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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Open AccessInteresting Images Concomitant Polymyalgia Rheumatica and Large-Vessel Vasculitis Visualized on 18F-FDG PET/CT
Diagnostics 2018, 8(2), 27; https://doi.org/10.3390/diagnostics8020027
Received: 10 April 2018 / Revised: 19 April 2018 / Accepted: 20 April 2018 / Published: 22 April 2018
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Abstract
Polymyalgia rheumatica (PMR) and large-vessel vasculitis (LVV) are related rheumatic diseases which are occasionally present concomitantly. PMR is characterized by synovitis and bursitis. In LVV, inflammation of the blood vessel wall is seen. Both disorders can be difficult to diagnose since patients often
[...] Read more.
Polymyalgia rheumatica (PMR) and large-vessel vasculitis (LVV) are related rheumatic diseases which are occasionally present concomitantly. PMR is characterized by synovitis and bursitis. In LVV, inflammation of the blood vessel wall is seen. Both disorders can be difficult to diagnose since patients often present non-specific symptoms and results of blood tests. The non-specific symptoms cannot always be distinguished from symptoms indicating an occult malignancy. We present a case of PMR and LVV in a Scandinavian man visualized on [18F]-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) with the presentation of typically affected sites of joints and arteries and with the same imaging modality ruling out occult malignancy. Full article
(This article belongs to the Section Medical Imaging)
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Open AccessCommentary Dutch Health Council Advisory Report on Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: Taking the Wrong Turn
Diagnostics 2018, 8(2), 34; https://doi.org/10.3390/diagnostics8020034
Received: 16 April 2018 / Revised: 11 May 2018 / Accepted: 15 May 2018 / Published: 16 May 2018
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Abstract
Recently, the Dutch Health Council published their advisory report on Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) which is meant to determine the medical policy with regard to ME in the Netherlands. The Health Council briefly discusses several diagnostic criteria and proposes to use
[...] Read more.
Recently, the Dutch Health Council published their advisory report on Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) which is meant to determine the medical policy with regard to ME in the Netherlands. The Health Council briefly discusses several diagnostic criteria and proposes to use new diagnostic criteria for “ME/CFS” in research and clinical practice in the future. The advisory report then summarizes organic abnormalities observed in the last decades and concludes that “ME/CFS” is a “serious, chronic, multisystem disease”. According to the Health Council there are no curative treatments for “ME/CFS”, due to lack of knowledge, but specific medication could bring symptomatic relief. The Health Council recommends conducting more research, to (re)educate medical professionals about “ME/CFS”, to appoint three academic expertise centres, which will install a care network for patients, and to fairly judge the limitations (disability) of patients when they apply for a disability income, medical aid and care. The advisory report was welcomed by many patients, because it puts an end to the dominance of the (bio)psychosocial explanatory model and seems to offer a perspective of improving the situation of patients. However, the starting point of the advisory report, a new definition of “ME/CFS”, will have serious (long-lasting) consequences for patients and researchers. Full article
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