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Contains fulltext : 245419.pdf (Publisher’s version ) (Open Access) BACKGROUND: There has been growing interest in young people living with dementia. Future research requires consensus on the terminology and operational definition of this group. OBJECTIVE: The purpose of this integrative review was to explore and include all operational definitions used to define dementia at a young age. METHODS: On August 14, 2020, the PubMed, Embase, Cinahl, and PsycInfo databases were searched for empirical and theoretical literature using Google. Various terms to describe and define 'dementia' and 'at a young age' were used to collect literature concerning terminology; age-related aspects, including cut-off ages and criteria; and etiologies of dementia at a young age. RESULTS: The search yielded 6,891 empirical and 4,660 theoretical publications, resulting in the inclusion of 89 publications, including 36 publications containing an explicit discussion and 53 publications as confirmation. 'Young-onset dementia' was the most commonly used term of seven identified terms, in the last two decades. The age of 65 years at symptom onset was used most frequently when considering a total of six upper age limits and four criteria to define a cut-off age. Eight lower age limits and an option for subdivision based on age were included. We identified 251 different etiologies and 27 categories of etiologies. CONCLUSION: Despite relative consensus on the term young-onset dementia and an age at symptom onset being used as a cut-off criterion, much is still unclear concerning possible etiologies of dementia at a young age. In the current study, controversies were detected for discussion in an international consensus study. more...

While chronic thromboembolic pulmonary hypertension (CTEPH) results from macroscopic and microscopic obstruction of the pulmonary vascular bed, the function of the right ventricle (RV) and increased RV afterload are the main determinants of its symptoms and prognosis. In this review, we assess RV function in patients diagnosed with CTEPH with a focus on the contributions of RV afterload and dysfunction to the pathogenesis of this disease. We will also discuss changes in RV function and geometry in response to treatment, including medical therapy, pulmonary endarterectomy, and balloon pulmonary angioplasty. ispartof: JOURNAL OF CLINICAL MEDICINE vol:12 issue:1 ispartof: location:Switzerland status: published more...

Objective Medullary thyroid cancer (MTC) originates from parafollicular cells (C cell) and produces calcitonin (CT). Basal serum CT was used in the diagnosis and treatment of MTC. If basal CT level is 100 pg/ml or higher, it is likely to have MTC, but if basal CT level is below 10 pg/ml, the probability of developing thyroid disease is low. In cases with basal CT level between 10-100 pg/ml, pentagastrin-stimulated (PS) CT level is studied to evaluate MTC and C cell hyperplasia (CHH). This study aimed to determine cut-off value for basal and PS peak CT level for diagnosis of MTC. Patients-methods We retrospectively reviewed files of patients presented to endocrine outpatient clinic of Ege University, Medicine School, between 2010 and 2019, 176 patients with basal CT level of 10-100 pg/ml and patients with PS test were included to the study. Findings The ROC analysis was used to determine cut-off value for basal CT that can discriminate cases with MTC and those with nodular goiter. Cut-off value for basal CT was calculated as 46.5 pg/ml (specificity; 100 %, sensitivity; 74 %). In the ROC analysis for peak PS CT, cut-off value was calculated as 285 pg/ml (specificity:100 %; sensitivity:82 %). When peak CT level was > 290 pg/ml in PS test, both specificity and sensitivity for MTC were determined as 100 %. The PS peak CT level > 285 pg/ml was significant for MTC diagnosis while level of 117-274 pg/ml was significant for CHH. Conclusion In this study, cut-off value was calculated as 46.5 pg/ml for basal CT whereas 285 pg/ml for PS peak CT in the diagnosis of preoperative MTC. Key words: Medullary thyroid cancer, C cell hyperplasia, Calcitonin, Pentagastrin, Cut-off. more...

PURPOSE The preoperative distinction between uterine leiomyoma (LM) and leiomyosarcoma (LMS) is difficult, which may result in dissemination of an unexpected malignancy during surgery for a presumed benign lesion. An assay based on circulating tumor DNA (ctDNA) could help in the preoperative distinction between LM and LMS. This study addresses the feasibility of applying the two most frequently used approaches for detection of ctDNA: profiling of copy number alterations (CNAs) and point mutations in the plasma of patients with LM. PATIENTS AND METHODS By shallow whole-genome sequencing, we prospectively examined whether LM-derived ctDNA could be detected in plasma specimens of 12 patients. Plasma levels of lactate dehydrogenase, a marker suggested for the distinction between LM and LMS by prior studies, were also determined. We also profiled 36 LM tumor specimens by exome sequencing to develop a panel for targeted detection of point mutations in ctDNA of patients with LM. RESULTS We identified tumor-derived CNAs in the plasma DNA of 50% (six of 12) of patients with LM. The lactate dehydrogenase levels did not allow for an accurate distinction between patients with LM and patients with LMS. We identified only two recurrently mutated genes in LM tumors ( MED12 and ACLY). CONCLUSION Our results show that LMs do shed DNA into the circulation, which provides an opportunity for the development of ctDNA-based testing to distinguish LM from LMS. Although we could not design an LM-specific panel for ctDNA profiling, we propose that the detection of CNAs or point mutations in selected tumor suppressor genes in ctDNA may favor a diagnosis of LMS, since these genes are not affected in LM. more...

Rationale In Parkinson’s disease (PD), spatial covariance analysis of 18F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP by applying spatial covariance analysis to PD cohorts from the Netherlands (NL), Italy (IT), and Spain (SP). Methods The PDRPNL was previously identified (17 controls, 19 PD) and its expression was determined in 19 healthy controls and 20 PD patients from the Netherlands. The PDRPIT was identified in 20 controls and 20 “de-novo” PD patients from an Italian cohort. A further 24 controls and 18 “de-novo” Italian patients were used for validation. The PDRPSP was identified in 19 controls and 19 PD patients from a Spanish cohort with late-stage PD. Thirty Spanish PD patients were used for validation. Patterns of the three centers were visually compared and then cross-validated. Furthermore, PDRP expression was determined in 8 patients with multiple system atrophy. Results A PDRP could be identified in each cohort. Each PDRP was characterized by relative hypermetabolism in the thalamus, putamen/pallidum, pons, cerebellum, and motor cortex. These changes co-varied with variable degrees of hypometabolism in posterior parietal, occipital, and frontal cortices. Frontal hypometabolism was less pronounced in “de-novo” PD subjects (Italian cohort). Occipital hypometabolism was more pronounced in late-stage PD subjects (Spanish cohort). PDRPIT, PDRPNL, and PDRPSP were significantly expressed in PD patients compared with controls in validation cohorts from the same center (P < 0.0001), and maintained significance on cross-validation (P < 0.005). PDRP expression was absent in MSA. Conclusion The PDRP is a reproducible disease characteristic across PD populations and scanning platforms globally. Further study is needed to identify the topography of specific PD subtypes, and to identify and correct for center-specific effects. more...

Contains fulltext : 220920.pdf (Publisher’s version ) (Open Access) Patients with myocardial infarction and non-obstructive coronary arteries (MINOCA), defined as angiographic stenosis

Objectives: To assess the diagnostic accuracy of unenhanced computed tomography (CT) attenuation values to exclude a pheochromocytoma in the diagnostic work-up of patients with an adrenal incidentaloma and to model the associated difference in diagnostic costs. Methods: The MEDLINE and Embase databases were searched from indexing to September 27, 2018, and studies reporting the proportion of pheochromocytomas on either side of the 10-Hounsfield unit (HU) threshold on unenhanced CT were included. The pooled proportion of pheochromocytomas with an attenuation value greater than 10 HU was determined, as were the modeled financial costs of the current and alternative diagnostic approaches. Results: Of 2957 studies identified, 31 were included (N=1167 pheochromocytomas). Overall risk of bias was low. Heterogeneity was not observed between studies (Q=11.5, P=.99, I-2=0%). The pooled proportion of patients with attenuation values greater than 10 HU was 0.990 (95% CI, 0.984-0.995). The modeled financial costs using the new diagnostic approach were (sic)55 (similar to$63) lower per patient. Conclusion: Pheochromocytomas can be reliably ruled out in the case of an adrenal lesion with an unenhanced CT attenuation value of 10 HU or less. Therefore, determination of metanephrine levels can be restricted to adrenal tumors with an unenhanced CT attenuation value greater than 10 HU. Implementing this novel diagnostic strategy is cost-saving. (C) 2019 Mayo Foundation for Medical Education and Research more...

Autoimmune bullous diseases are a group of chronic inflammatory disorders caused by autoantibodies targeted against structural proteins of the desmosomal and hemidesmosomal plaques in the skin and mucosa, leading to intra-epithelial or subepithelial blistering. The oral mucosa is frequently affected in these diseases, in particular, in mucous membrane pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus. The clinical symptoms are heterogeneous and may present with erythema, blisters, erosions, and ulcers localized anywhere on the oral mucosa, and lead to severe complaints for the patients including pain, dysphagia, and foetor. Therefore, a quick and proper diagnosis with adequate treatment is needed. Clinical presentations of autoimmune bullous diseases often overlap and diagnosis cannot be made based on clinical features alone. Immunodiagnostic tests are of great importance in differentiating between the different diseases. Direct immunofluorescence microscopy shows depositions of autoantibodies along the epithelial basement membrane zone in mucous membrane pemphigoid subtypes, or depositions on the epithelial cell surface in pemphigus variants. Additional immunoserological tests are useful to discriminate between the different subtypes of pemphigoid, and are essential to differentiate between pemphigus and paraneoplastic pemphigus. This review gives an overview of the clinical characteristics of oral lesions and the diagnostic procedures in autoimmune blistering diseases, and provides a diagnostic algorithm for daily practice. more...

In this paper, the structural and functional imaging changes associated with sporadic and genetic Parkinson’s disease and atypical Parkinsonian variants are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed, and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression is debated. Imaging changes associated with nonmotor complications of PD are presented. The similarities and differences in imaging findings in Lewy body dementia, Parkinson’s disease dementia, and Alzheimer’s disease are discussed. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-020-00994-4. more...

BackgroundOvarian cancer is the sixth most common cancer in UK women and can be difficult to diagnose, particularly in the early stages. Risk-scoring can help to guide referral to specialist centres.ObjectivesTo assess the clinical and cost-effectiveness of risk scores to guide referral decisions for women with suspected ovarian cancer in secondary care.MethodsTwenty-one databases, including MEDLINE and EMBASE, were searched from inception to November 2016. Review methods followed published guidelines. The meta-analysis using weighted averages and random-effects modelling was used to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). The cost-effectiveness analysis considered the long-term costs and quality-adjusted life-years (QALYs) associated with different risk-scoring methods, and subsequent care pathways. Modelling comprised a decision tree and a Markov model. The decision tree was used to model short-term outcomes and the Markov model was used to estimate the long-term costs and QALYs associated with treatment and progression.ResultsFifty-one diagnostic cohort studies were included in the systematic review. The Risk of Ovarian Malignancy Algorithm (ROMA) score did not offer any advantage over the Risk of Malignancy Index 1 (RMI 1). Patients with borderline tumours or non-ovarian primaries appeared to account for disproportionately high numbers of false-negative, low-risk ROMA scores. (Confidential information has been removed.) To achieve similar levels of sensitivity to the Assessment of Different NEoplasias in the adneXa (ADNEX) model and the International Ovarian Tumour Analysis (IOTA) group’s simple ultrasound rules, a very low RMI 1 decision threshold (25) would be needed; the summary sensitivity and specificity estimates for the RMI 1 at this threshold were 94.9% (95% CI 91.5% to 97.2%) and 51.1% (95% CI 47.0% to 55.2%), respectively. In the base-case analysis, RMI 1 (threshold of 250) was the least effective [16.926 life-years (LYs), 13.820 QALYs] and the second cheapest (£5669). The IOTA group’s simple ultrasound rules (inconclusive, assumed to be malignant) were the cheapest (£5667) and the second most effective [16.954 LYs, 13.841 QALYs], dominating RMI 1. The ADNEX model (threshold of 10%), costing £5699, was the most effective (16.957 LYs, 13.843 QALYs), and compared with the IOTA group’s simple ultrasound rules, resulted in an incremental cost-effectiveness ratio of £15,304 per QALY gained. At thresholds of up to £15,304 per QALY gained, the IOTA group’s simple ultrasound rules are cost-effective; the ADNEX model (threshold of 10%) is cost-effective for higher thresholds.LimitationsInformation on the downstream clinical consequences of risk-scoring was limited.ConclusionsBoth the ADNEX model and the IOTA group’s simple ultrasound rules may offer increased sensitivity relative to current practice (RMI 1); that is, more women with malignant tumours would be referred to a specialist multidisciplinary team, although more women with benign tumours would also be referred. The cost-effectiveness model supports prioritisation of sensitivity over specificity. Further research is needed on the clinical consequences of risk-scoring.Study registrationThis study is registered as PROSPERO CRD42016053326.Funding detailsThe National Institute for Health Research Health Technology Assessment programme. more...

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal malignancies of the gastrointestinal tract. Most GISTs harbor a c-KIT (80%) or a PDGFR alpha (10%) mutation that leads to constitutive activation of the tyrosine kinase receptor. Response to treatment with tyrosine kinase inhibitors (TKIs) is dependent on mutational status of the tumor. The most common mutation in PDGFR alpha, D842V, is known to be imatinib resistant. Almost all other PDGFR alpha mutations are imatinib sensitive. We describe two patients with a PDGFR alpha exon 18 mutated GIST responding to treatment with TKIs. One of these patients has a p.M844_S847 deletion, not previously described in relation with TKI treatment response. Mutations in circulating tumor DNA were detectable with digital droplet PCR in serial plasma samples taken during treatment and correlated with treatment response of both patients. Computer 3D-modeling of the PDGFR alpha kinase domain of these two variants revealed no direct interference in imatinib or sunitinib binding and no effect in its activity in contrast to the reported structure of the imatinib resistant D842V mutation. An overview is given of the literature regarding the evidence of patients with different PDGFR alpha mutated GISTs on response to TKIs. The findings emphasize the use of mutational analysis in GIST to provide patients personalized treatment. Detection of mutations in plasma is feasible and can provide real-time information concerning treatment response. We suggest to register GIST patients with these uncommon mutations in a prospective international database to understand the tumor biology and obtain more evidence of such mutations to predict treatment response. more...

Human cysticercosis (CC) is a parasitic zoonosis caused by the larval stage (cyst) of the Taenia solium. Cysts can establish in the human central nervous system (neurocysticercosis, NCC) and other organs and tissues; they also develop in pigs, the natural intermediate host. Human taeniosis may be caused by T. solium, Taenia saginata and Taenia asiatica tapeworms; these infections are usually asymptomatic, but show a significant relevance as they perpetuate the parasites' life cycle, and, in the case of T. solium, they are the origin of (N)CC. In European Union (EU) member states and associated countries, the occurrence of autochthonous T. solium cases is debated, and imported cases have significantly increased lately; the status of T. asiatica has been never reported, whereas T. saginata is prevalent and causes an economic impact due to condemned carcasses. Based on their effects on the EU society, the specific diagnosis of these pathologies is relevant for their prevention and control. The aims of this study were to know the diagnostic tests used in European laboratories for human taeniosis/cysticercosis by means of a questionnaire, to determine potential gaps in their detection, and to obtain preliminary data on the number of diagnosed taeniosis/CC cases. The present work was finding by the European Union, Cooperation in Science and Technology (COST) Actions, COST Action TD1302 “European Network on Taeniosis/Cysticercosis”. Sí more...

Positron emission tomography with the radiotracer F-18-fluoro-2-deoxy-D-glucose (FDG) plays an important role in the evaluation of bone pathology. However, FDG is not a cancer-specific agent, and knowledge of the differential diagnosis of benign FDG-avid bone alterations that may resemble malignancy is important for correct patient management, including the avoidance of unnecessary additional invasive tests such as bone biopsy. This review summarizes and illustrates the spectrum of benign bone conditions that may be FDG-avid and mimic malignancy, including osteomyelitis, bone lesions due to benign systemic diseases (Brown tumor, Erdheim-Chester disease, Gaucher disease, gout and other types of arthritis, Langerhans cell histiocytosis, and sarcoidosis), benign primary bone lesions (bone cysts, chondroblastoma, chondromyxoid fibroma, desmoplastic fibroma, enchondroma, giant cell tumor and granuloma, hemangioma, nonossifying fibroma, and osteoid osteoma and osteoblastoma), and a group of miscellaneous benign bone conditions (post bone marrow biopsy or harvest status, bone marrow hyperplasia, fibrous dysplasia, fractures, osteonecrosis, Paget disease of bone, particle disease, and Schmorl nodes). Several ancillary clinical and imaging findings may be helpful in discriminating benign from malignant FDGavid bone lesions. However, this distinction is sometimes difficult or even impossible, and tissue acquisition will be required to establish the final diagnosis. (C) 2017 Elsevier Inc. All rights reserved. more...

Diabetes insipidus (DI) is a disorder characterized by excretion of large amounts of hypotonic urine. Central DI results from a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, whereas nephrogenic DI results from resistance to AVP in the kidneys. Central and nephrogenic DI are usually acquired, but genetic causes must be evaluated, especially if symptoms occur in early childhood. Central or nephrogenic DI must be differentiated from primary polydipsia, which involves excessive intake of large amounts of water despite normal AVP secretion and action. Primary polydipsia is most common in psychiatric patients and health enthusiasts but the polydipsia in a small subgroup of patients seems to be due to an abnormally low thirst threshold, a condition termed dipsogenic DI. Distinguishing between the different types of DI can be challenging and is done either by a water deprivation test or by hypertonic saline stimulation together with copeptin (or AVP) measurement. Furthermore, a detailed medical history, physical examination and imaging studies are needed to ensure an accurate DI diagnosis. Treatment of DI or primary polydipsia depends on the underlying aetiology and differs in central DI, nephrogenic DI and primary polydipsia. more...

Pancreatic cystic lesions can be benign, premalignant or malignant. The recent increase in detection and tremendous clinical variability of pancreatic cysts has presented a significant therapeutic challenge to physicians. Mucinous cystic neoplasms are of particular interest given their known malignant potential. This review article provides a brief but comprehensive review of premalignant pancreatic cystic lesions with advanced endoscopic ultrasound (EUS) management approaches. A comprehensive literature search was performed using PubMed, Cochrane, OVID and EMBASE databases. Preneoplastic pancreatic cystic lesions include mucinous cystadenoma and intraductal papillary mucinous neoplasm. The 2012 International Sendai Guidelines guide physicians in their management of pancreatic cystic lesions. Some of the advanced EUS management techniques include ethanol ablation, chemotherapeutic (paclitaxel) ablation, radiofrequency ablation and cryotherapy. In future, EUS-guided injections of drug-eluting beads and neodymium:yttrium aluminum agent laser ablation is predicted to be an integral part of EUS-guided management techniques. In summary, International Sendai Consensus Guidelines should be used to make a decision regarding management of pancreatic cystic lesions. Advanced EUS techniques are proving extremely beneficial in management, especially in those patients who are at high surgical risk. more...

Tumors of adrenal and thyroid glands have been associated with vascular invasions&mdash, so-called tumor thrombi, both in humans and dogs. The detection and characterization of venous thrombi is an important diagnostic step in patients with primary tumors for both surgical planning and prognosis. The aim of this study was to describe the use of contrast-enhanced ultrasonography (CEUS) for the characterization of tumor thrombi. Dogs with tumor thrombus who underwent bi-dimensional ultrasound (B-mode US) and CEUS were included. Seven dogs were enrolled in this retrospective case series. On B-mode US, all thrombi were visualized, and vascular distension and thrombus-tumor continuity were seen in three and two cases, respectively. On color Doppler examination, all thrombi were identified, seemed non-occlusive and only two presented vascularity. On CEUS, arterial-phase enhancement and washout in the venous phase were observed in all cases. Non-enhancing areas were identified in the tumor thrombi most likely representing non-vascularized tissue that could potentially be embolized in the lungs after fragmentation of the tumor thrombi. On the basis of these preliminary study, CEUS appeared to be useful for the characterization of malignant intravascular invasion. more...

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤.03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P, This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología—del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00400 and CB16/12/00489), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI13/02196), Asociación Española Contra el Cáncer (GCB120981SAN and Accelerator Award), the Black Swan Research Initiative of the International Myeloma Foundation, and the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT). more...

BACKGROUND: 18F-FDG brain PET measures metabolic changes in neurodegenerative disorders and may discriminate between different diseases even at an early stage. The objective of this study was to classify patients with amyotrophic lateral sclerosis (ALS) and Parkinson plus syndromes (PP). To this end, different approaches were evaluated using generalized linear models and corresponding glucose metabolic brain patterns. Besides direct classification, healthy controls were also included to generate disease-specific metabolic brain patterns and to perform a classification using disease expression scores. METHODS: ALS patients (n = 70) and PP patients (n = 33: 20 PSP, 3 CBD, and 10 MSA) were available from an existing database of patients with neuromuscular and movement disorders while age-matched healthy controls (n = 29) were selected from a prospective study. To generate both disease-discriminative (direct classification) and disease-specific (classification versus controls) metabolic brain patterns, data were spatially normalized and a principal component analysis (PCA) was performed prior to classification using either logistic regression (PCA-LR) or a support vector machine (PCA-SVM). Furthermore, a direct SVM approach was considered. To compare the three different approaches, Pearson correlations (r) between pattern expression scores and metabolic brain patterns were evaluated, while pairs of ALS- and PP-specific pattern expression scores were compared using the RV coefficient. RESULTS: Classification between ALS and PP resulted in a sensitivity and specificity ≥ 0.82 for both direct classification and classification according to disease-specific pattern expression scores. PCA-LR, PCA-SVM, and SVM generated very similar metabolic brain patterns with voxelwise correlations ≥ 0.66, while all patterns allowed straightforward identification of ALS- and PP-specific brain regions of hyper- and hypometabolism. Moreover, pattern expression scores were highly correlated among different classifiers with a mean r of 0.94 while a RV coefficient ≥ 0.91 was found between pairs of ALS- and PP-specific pattern expression scores. CONCLUSION: We demonstrated that a classification between ALS and PP using expression scores of an ALS and PP metabolic brain pattern leads to a similar and high prediction accuracy as direct classification between ALS and PP. Classification performance and disease-specific metabolic patterns, which could support visual reading and improve insight in brain pathology, were very related for different classifiers. ispartof: EJNMMI RESEARCH vol:8 issue:1 ispartof: location:Germany status: published more...

Background: Detection of anti-neutrophil cytoplasmic antibodies (ANCA) is important for the diagnosis of the ANCA-associated vasculitides (AAV). For AAV, especially ANCA directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are most relevant. ANCA with less well-defined specificities may, however, also be detected in other inflammatory and non-inflammatory conditions. Methods: A questionnaire, initiated by the European Autoimmunity Standardisation Initiative (EASI), was used to gather information on methods and testing algorithms used for ANCA in clinical laboratories of 12 European countries (EASI survey). Results: Four hundred and twenty-nine responses were included in the EASI survey analysis which revealed differences within countries and between countries. Laboratories overall were poor in adherence to international consensus on ANCA testing. Substantial variation was observed with respect to the use of ANCA indirect immunofluorescence (IIF) in the algorithm, application of distinct methods for MPO- and PR3-ANCA, the daily availability of new ANCA results, and interpretation of test results. Conclusions: Awareness of these differences may stimulate further harmonization and standardization of ANCA testing. This may be promoted by an update of the international ANCA consensus and the introduction of international standards. more...

Objective: To investigate the diagnostic value of dual-phase apparent diffusion coefficient (ADC) compared to traditional ADC values in quantitative diffusion-weighted imaging (DWI) for differentiating between benign and malignant breast masses. Materials and Methods: Diffusion-weighted images of pathologically confirmed 88 benign and 85 malignant lesions acquired using a 3.0T MR scanner were analyzed. Small region-of-interests focusing on the highest signal intensity of lesions were used. Lesion ADC estimates were obtained separately from all b-value images (ADC; b=50, 400 and 800s/mm(2)), lower b-value images (ADC low; b=50 and 400s/mm2) and higher b-value images (ADC(high); b=400 and 800s/mm(2)). A set of dual-phase ADC (dpADC) models were constructed using ADC low, ADC high and a perfusion influence factor ranging from 0 to 1. Results: Strong positive correlation is observable between ADC and all dpADCs (rho=0.80-1.00). Differences in ADC and dpADCs between the benign and the malignant lesions are all significant (p more...

Neuropathic pain is clinically described as pain caused by a lesion or disease of the somatosensory nervous system. The aim of this study was to assess the validity of the Dutch version of the DN4, in a cross-sectional multicentre design, as a screening tool for detecting a neuropathic pain component in a large consecutive, not pre-stratified on basis of the target outcome, population of patients with chronic pain. Patients' pain was classified by two independent (pain-) physicians as the gold standard. The analysis was initially performed on the outcomes of those patients (n = 228 out of 291) in whom both physicians agreed in their pain classification. Compared to the gold standard the DN4 had a sensitivity of 75% and specificity of 76%. The DN4-symptoms (seven interview items) solely resulted in a sensitivity of 70% and a specificity of 67%. For the DN4-signs (three examination items) it was respectively 75% and 75%. In conclusion, because it seems that the DN4 helps to identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way, a comprehensive (physical-) examination by the physician is still obligate. more...

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors found in the gastrointestinal (GI) tract, with the stomach being the most common site. They represent a distinct group of GI tumors originating from the interstitial cells of Cajal and are characterized by gain-of-function mutations of KIT. KIT oncoprotein serves as both diagnostic and therapeutic targets. Prognosis is related to size, mitotic activity, and site of the tumor. Asymptomatic, small endoscopic ultrasonography (EUS)-suspected GISTs are increasingly encountered with the wide availability of endoscopic/endosonographic examination. The majority of small GISTs are biologically indolent, albeit possibly harboring c-KIT gene mutations. An ongoing controversy exists regarding the management and surveillance policy for small gastric GISTs. A number of reports on the management of GISTs have been published, not confidently addressing the issue of gastric GISTs of small size. This work provides an overview on the current state of management considerations, specifically focusing on small EUS-suspected gastric GISTs, which are increasingly encountered by clinicians. more...

(11)C-methionine (MET) is the most popular amino acid tracer used in PET imaging of brain tumours. Because of its characteristics, MET PET provides a high detection rate of brain tumours and good lesion delineation. This review focuses on the role of MET PET in imaging cerebral gliomas. The Introduction provides a clinical overview of what is important in primary brain tumours, recurrent brain tumours and brain metastases. The indications for radiotherapy and the results and problems arising after chemoradiotherapy in relation to imaging (pseudoprogression or radionecrosis) are discussed. The working mechanism, scan interpretation and quantification possibilities of MET PET are then explained. A literature overview is given of the role of MET PET in primary gliomas (diagnostic accuracy, grading, prognosis, assessment of tumour extent, biopsy and radiotherapy planning), in brain metastases, and in the differentiation between tumour recurrence and radiation necrosis. Finally, MET PET is compared to other nuclear imaging possibilities in brain tumour imaging. more...

Contains fulltext : 88443.pdf (Publisher’s version ) (Closed access) It is often very difficult to confidently distinguish benign and malignant Spitz lesions, and a diagnosis of Spitz tumor of unknown malignant potential (STUMP) is rendered. To address this problem, we performed molecular genetic analysis in a large group of Spitz tumors (93 Spitz nevi and 77 STUMPs) and identified a subgroup of 24 lesions harboring a HRAS mutation. This subgroup lay predominantly in the dermis, had a relatively low cellularity, showed desmoplasia (with single cells interspersed between the collagen bundles), and had an infiltrating base. In 7 of these 24 cases (29%) melanoma had been the initial diagnosis, or an important differential diagnostic consideration, mainly based on the presence of multiple or deeply located mitotic figures, especially in adult patients. In our series none of the patients with the HRAS-mutated lesions developed recurrences or metastases (mean and median follow-up: 10.5 y). This was in accordance with the literature: review showed that no HRAS mutations had so far been reported in Spitzoid melanomas. We therefore conclude that HRAS mutation analysis may be a useful diagnostic tool to help differentiate between Spitz nevus and Spitzoid melanoma, thereby reducing the frequency of overdiagnosis of melanoma, and to help predict the biological behavior of a STUMP. Moreover, this might be a first step toward a more reproducible classification of Spitz tumors combining histological and genetic data. 01 oktober 2010 more...

With a drive towards minimally invasive surgery, endoscopic submucosal dissection (ESD) is now gaining popularity. In a number of East Asian countries, ESD is now the treatment of choice for early non-metastatic gastric cancer, but the outcomes of ESD for colorectal lesions are unclear. The present review summarizes the mid-term outcomes of colorectal ESD including complication and recurrence rates. A systematic literature search was done in May 2014, identifying 20 publications reporting the outcomes of colorectal ESD which were included in this review. En-bloc resection rates, complete (R0) resection rates, endoscopic clearance rates, complication and recurrences rates were analyzed. Statistical pooling was done to calculate weighted means using random effects modeling. Twenty studies reporting the outcomes of 3060 colorectal ESD procedures were reported. Overall weighted en-bloc resection rate was 89% (95% CI: 83-94%), R0 resection rate 76% (95% CI: 69-83%), endoscopic clearance rate 94% (95% CI: 90-97%) and recurrence rate 1% (95% CI: 0.5-2%). Studies that followed up patients for over 1 year were found to have an en-bloc resection rate of 91% (95% CI: 86-96%), R0 resection rate of 81% (95% CI: 75-88%), endoscopic clearance rate 93% (95% CI: 90-97%) and recurrence rate of 0.8% (95% CI: 0.4-1%). Colorectal ESD can be carried out effectively and safely with a 1% recurrence rate. Further studies with longer follow-up periods are required to determine whether colorectal ESD is a viable alternative to conventional surgical therapy. more...

Contains fulltext : 154200.pdf (Publisher’s version ) (Closed access) Various ancillary investigations can assist clinicians in the differential diagnosis of patients with parkinsonism. It is unknown which test offers greatest diagnostic value in clinical practice. We included 156 consecutive patients with parkinsonism, but with an initially uncertain diagnosis. At baseline, all patients underwent extensive clinical testing and the following ancillary investigations: brain magnetic resonance imaging (MRI); (123)I-iodobenzamide single photon-emission computed tomography (IBZM-SPECT); analysis of cerebrospinal fluid (CSF); and anal sphincter electromyography (EMG). The final diagnosis was established after 3-year follow-up by two movement disorder specialists, according to international consensus criteria. We determined the diagnostic value by comparing the baseline clinical parameters and ancillary studies with the final diagnosis. Out of a potential 138 parameters, univariate analysis identified 35 parameters that discriminated Parkinson's disease (PD, n = 62) and atypical parkinsonism (AP, n = 94), with AUC of 0.55-0.81. Stepwise logistic regression showed that the combination of tandem gait, axial UPDRS subscore, slow saccadic eye movements and dysphagia yielded an AUC of 0.93, adjusted for optimism. The combination of tandem gait and axial UDPRS subscore yielded an AUC of 0.90. None of the ancillary investigations alone or in combination with clinical testing improved this clinically based diagnostic accuracy, not even in a subgroup of patients with the greatest diagnostic uncertainty at baseline. Our study demonstrates that a comprehensive set of clinical tests provides good accuracy to differentiate PD from AP. Our results also suggest that routine MRI, IBZM-SPECT, CSF analysis and anal sphincter EMG do not improve this diagnostic accuracy. Future work should evaluate the possible diagnostic value of more advanced diagnostic tests. more...

Pulmonary-renal syndrome is a potentially life-threatening combination of pulmonary hemorrhage and acute renal failure. Several pathological entities can cause this syndrome. This review discusses the diagnostic strategy required to initiate appropriate therapy. Rapid serological testing and appropriate interpretation can be of great additive diagnostic value. Also discussed are the pathogenesis, therapy, and outcome of anti-glomerular basement membrane disease, one of the pathological entities that can cause pulmonary-renal syndrome. more...

Contains fulltext : 88280.pdf (Publisher’s version ) (Open Access) In this study we investigated the cerebrospinal fluid (CSF) levels of neurofilament light (NFL) and heavy chain (NFHp35), total tau (t-tau), and glial fibrillary acidic protein (GFAP) to detect disease specific profiles in sporadic Creutzfeldt Jakob disease (sCJD) patients and Alzheimer's disease (AD) patients. CSF levels of NFL, NFHp35, t-tau, and GFAP of 23 sCJD patients and 55 AD patients were analyzed and compared to non-demented controls. Median NFL, NFHp35, GFAP, and t-tau levels were significantly increased in sCJD patients and AD patients versus controls (p < 0.0001 in all). NFL, NFHp35, and t-tau levels were significantly increased in sCJD patients versus AD patients (p < 0.005), but GFAP concentrations did not differ between sCJD and AD. The results suggest that neuroaxonal damage, reflected by higher CSF levels of NFL, NFHp35, and t-tau, is more pronounced in the pathophysiology of sCJD than in AD. The comparable CSF GFAP concentrations suggest that astroglial damage or astrocytosis is equally pronounced in the pathophysiology of AD and sCJD. Prospective studies are needed to determine whether NFL and NFHp35 may be additional tools in the differential diagnosis of rapidly progressive dementias. more...

Phenylketonuria (PKU) was the first inherited metabolic disease in which treatment was found to prevent clinical features of the disorder; dietary management was established almost 60 years ago. The institution of a low-phenylalanine (Phe) diet in the first few weeks of life was made possible by Guthrie neonatal screening, which further increased effectiveness of therapy. Indeed, neonatal diagnosis of PKU followed by institution of a low-Phe diet has been a remarkable success in preventing the devastating brain damage associated with untreated PKU. Nevertheless, significant difficulties exist in caring for PKU patients, including problems with adhering to the prescribed dietary regimen and the presence of neurocognitive deficits despite therapy, During the past few years, several ideas for new treatment strategies have emerged. This review aims to address these treatment strategies based on theoretical considerations of the biochemistry and pathogenesis of PKU. Recent times have seen the introduction of a wide array of novel treatments currently in clinical use, including more palatable medical foods, glycomacropeptide, large neutral amino acids, and tetrahydrobiopterin. Human trials are underway using an enzymatic therapeutic approach, while preclinical work continues in the fields of gene and cellular therapy. These therapeutic strategies propose to treat PKU at various levels, including nutritional intake, gut, liver, and blood-brain barrier, and have the potential to further improve outcome in PKU. (C) 2009 Elsevier Inc. All rights reserved. more...

Meta-iodbenzylguanidine scintigraphy (MIBG scintigraphy) shows reduced uptake in idiopathic Parkinson's disease (IPD), idiopathic REM sleep behavior disorder (IRBD) and Lewy body dementia (LBD), but not in other parkinsonian or dementia syndromes. We retrospectively reevaluated 50 patients. Concordance rate between last clinical diagnosis and scintigraphy diagnosis was only given in two-thirds of the patients. Confounding factors were: decreasing heart/mediastinum ratio (HMR) with progressive age, higher HMR in women and possibly interference with antihypertensive medication. Standardization of the methods and precise clinical guidelines are warranted for better clinical use. more...

Cyclic Cushing’s syndrome (CS) is a rare disorder, characterized by repeated episodes of cortisol excess interspersed by periods of normal cortisol secretion. The so-called cycles of hypercortisolism can occur regularly or irregularly with intercyclic phases ranging from days to years. To formally diagnose cyclic CS, three peaks and two troughs of cortisol production should be demonstrated. Our review of 65 reported cases demonstrates that cyclic CS originates in 54% of cases from a pituitary corticotroph adenoma, in 26% from an ectopic ACTH-producing tumour and in about 11% from an adrenal tumour, the remainder being unclassified. The pathophysiology of cyclic CS is largely unknown. The majority of patients with cyclic CS have clinical signs of CS, which can be either fluctuating or permanent. In a minority of patients, clinical signs of CS are absent. The fluctuating clinical picture and discrepant biochemical findings make cyclic CS extremely hard to diagnose. Clinicians should therefore be aware of this clinical entity and actively search for it in all patients with suspected CS but normal biochemistry or vice versa. Frequent measurements of urinary cortisol or salivary cortisol levels are a reliable and convenient screening tool for suspected cyclic CS. Cortisol stimulation or suppression tests may give spurious results owing to spontaneous falls or rises in serum cortisol at the time of testing. When cyclic CS is biochemically confirmed, further imaging and laboratory studies are guided by the presence or absence of ACTH dependency. In cases of suspected ectopic ACTH production, specific biochemical testing for carcinoids or neuroendocrine tumours is required, including measurements of serotonin in platelets and/or urine, chromogranin A and calcitonin. more...

Spontaneous hyperadrenocorticism in dogs is known to be the result of excessive secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland or excessive autonomous glucocorticoid secretion by an adrenocortical tumor. Here, we report on an 8-year-old German shepherd dog in which ACTH-dependent hyperadrenocorticism was a result of ectopic ACTH secretion and could be related to an abdominal neuroendocrine tumor. Hyperadrenocorticism was diagnosed on the basis of the history, clinical signs, and elevated urinary corticoid/creatinine ratios (UCCRs; 236 and 350 x 10(-6); reference range more...

Early discrimination between benign and malignant pleural diseases is vital for the treatment and prognosis of a patient. Imaging is traditionally performed with CT or MRI, with an accuracy of 50%-75%. PET has proven to be superior as a diagnostic tool in several malignancies. In this prospective study, PET results in patients with pleural abnormalities on CT were compared with histologic results. Methods: Eligible patients had pleural thickening on CT and were medically fit for surgical diagnostic procedures. All patients underwent PET. Qualitative assessment led to a PET score of 1 (definitely normal), 2 (probably normal), 3 (probably abnormal), or 4 (definitely abnormal). PET scores of 1 or 2 indicated a negative finding, whereas PET scores of 3 or 4 indicated a positive PET finding. Pathologic verification techniques included thoracocentesis, thoracoscopy, or open pleural biopsy at thoracotomy. Results: Thirty-two patients were enrolled, 19 with malignant and 13 with benign pleural disease. PET was true positive in 18 and true negative in 12 patients, with an accuracy and negative predictive value of 94% and 92%, respectively. PET was false negative in a patient with a slowly growing malignant solitary fibrous tumor and false positive in a patient with infectious pleuritis. Median standardized uptake values calculated for 7 patients with malignant and benign pleural diseases were 6.28 and 1.69, respectively. Patients with a PET score of 1 or 2 survived significantly longer than patients with a PET score of 3 or 4. Conclusion: Qualitative assessment of pleural thickening with PET accurately discriminates between malignant and benign pleural thickening, with a high accuracy and negative predictive value. more...

BackgroundInterstitial lung diseases (ILD), such as idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP), and chronic obstructive pulmonary disease (COPD) are severe, progressive pulmonary disorders with a poor prognosis. Prompt and accurate diagnosis is important to enable patients to receive appropriate care at the earliest possible stage to delay disease progression and prolong survival. Artificial intelligence-assisted lung auscultation and ultrasound (LUS) could constitute an alternative to conventional, subjective, operator-related methods for the accurate and earlier diagnosis of these diseases. This protocol describes the standardised collection of digitally-acquired lung sounds and LUS images of adult outpatients with IPF, NSIP or COPD and a deep learning diagnostic and severity-stratification approach.MethodsA total of 120 consecutive patients (>= 18 years) meeting international criteria for IPF, NSIP or COPD and 40 age-matched controls will be recruited in a Swiss pulmonology outpatient clinic, starting from August 2022. At inclusion, demographic and clinical data will be collected. Lung auscultation will be recorded with a digital stethoscope at 10 thoracic sites in each patient and LUS images using a standard point-of-care device will be acquired at the same sites. A deep learning algorithm (DeepBreath) using convolutional neural networks, long short-term memory models, and transformer architectures will be trained on these audio recordings and LUS images to derive an automated diagnostic tool. The primary outcome is the diagnosis of ILD versus control subjects or COPD. Secondary outcomes are the clinical, functional and radiological characteristics of IPF, NSIP and COPD diagnosis. Quality of life will be measured with dedicated questionnaires. Based on previous work to distinguish normal and pathological lung sounds, we estimate to achieve convergence with an area under the receiver operating characteristic curve of > 80% using 40 patients in each category, yielding a sample size calculation of 80 ILD (40 IPF, 40 NSIP), 40 COPD, and 40 controls.DiscussionThis approach has a broad potential to better guide care management by exploring the synergistic value of several point-of-care-tests for the automated detection and differential diagnosis of ILD and COPD and to estimate severity.Trial registration Registration: August 8, 2022. ClinicalTrials.gov Identifier: NCT05318599. more...

Introduction Dopaminergic scintigraphic imaging is a cornerstone to support the diagnosis in dementia with Lewy bodies. To clarify the current state of knowledge on this imaging modality and its impact on clinical diagnosis, we performed an updated systematic review of the literature. Methods This systematic review was carried out according to PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published through June 2022 was performed using the following search algorithm: (a) "Lewy body" [TI] OR "Lewy bodies" [TI] and (b) ("DaTscan" OR "ioflupane" OR "123ip" OR "123?ip" OR "123 ip" OR "123i-FP-CIT" OR "FPCIT" OR "FP-CIT" OR "beta?CIT" OR "beta CIT" OR "CIT?SPECT" OR "CIT SPECT" OR "Dat?scan*" OR "dat scan*" OR "dat?spect*" OR "SPECT"). Risk of bias and applicability concerns of the studies were evaluated using the QUADAS-2 tool. Results We performed a qualitative analysis of 59 studies. Of the 59 studies, 19 (32%) addressed the diagnostic performance of dopamine transporter imaging, 15 (25%) assessed the identification of dementia with Lewy bodies in the spectrum of Lewy body disease and 18 (31%) investigated the role of functional dopaminergic imaging in distinguishing dementia with Lewy bodies from other dementias. Dopamine transporter loss was correlated with clinical outcomes in 19 studies (32%) and with other functional imaging modalities in 15 studies (25%). Heterogeneous technical aspects were found among the studies through the use of various radioligands, the more prevalent being the [123I]N‑ω‑fluoropropyl‑2β‑carbomethoxy‑3β‑(4‑iodophenyl) nortropane (123I-FP-CIT) in 54 studies (91.5%). Image analysis used visual analysis (9 studies, 15%), semi-quantitative analysis (29 studies, 49%), or a combination of both (16 studies, 27%). Conclusion Our systematic review confirms the major role of dopaminergic scintigraphic imaging in the assessment of dementia with Lewy bodies. Early diagnosis could be facilitated by identifying the prodromes of dementia with Lewy bodies using dopaminergic scintigraphic imaging coupled with emphasis on clinical neuropsychiatric symptoms. Most published studies use a semi-quantitative analytical assessment of tracer uptake, while there are no studies using quantitative analytical methods to measure dopamine transporter loss. The superiority of a purely quantitative approach to assess dopaminergic transmission more accurately needs to be further clarified. more...