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Background: Our study aims to explore the current utilisation of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the diagnostic pathway of pyrexia of unknown origin (PUO) and associated cost of illness in a large tertiary teaching hospital in Australia., Method: 1257 febrile patients between June 2016 and September 2022 were retrospectively reviewed. There were 57 patients who met the inclusion criteria of "classical PUO", of which FDG-PET/CT was performed in 31 inpatients, 15 outpatients and 11 inpatients did not have an FDG-PET/CT scan. The patient demographics, clinical characteristics and inpatient cost were analysed, together with the diagnostic performance of FDG-PET/CT and impact on clinical management., Result: The mean age, length of stay and total cost of admission were higher for inpatients who received FDG-PET/CT versus those who did not. The median cost per patient-bed-day did not differ between the two groups. Inpatients who received earlier FDG-PET/CTs (≤ 7 days from admission) had shorter length of stays and lower total cost compared to those who received a later scan. A negative FDG-PET/CT scan, demonstrating no serious or life-threatening abnormalities resulted in subsequent discharge from hospital or outpatient clinic in 7/10 (70%) patients. There were 11/40 (28%) scans where ancillary abnormalities were identified, requiring further evaluation., Conclusion: FDG-PET/CT showed high diagnostic accuracy and significant impact on patient management in patients with PUO. FDG-PET/CT performed earlier in admission for PUO was associated with shorter length of stay and lower total cost., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The impact of modern imaging in uncovering the underlying pathology of PMR cannot be understated. Long dismissed as an inflammatory syndrome with links to the large vessel vasculitis giant cell arteritis (GCA), a pathognomonic pattern of musculotendinous inflammation is now attributed to PMR and may be used to confirm its diagnosis. Among the available modalities, 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT is increasingly recognized for its high sensitivity and specificity, as well as added ability to detect concomitant large vessel GCA and exclude other relevant differentials like infection and malignancy. This atlas provides a contemporary depiction of PMR's pathology and outlines how this knowledge translates into a pattern of findings on whole body 18 F-FDG PET/CT that can reliably confirm its diagnosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Imaging is increasingly being used to guide clinical decision-making in patients with giant cell arteritis (GCA). While ultrasound has been rapidly adopted in fast-track clinics worldwide as an alternative to temporal artery biopsy for the diagnosis of cranial disease, whole-body PET/CT is emerging as a potential gold standard test for establishing large vessel involvement. However, many unanswered questions remain about the optimal approach to imaging in GCA. For example, it is uncertain how best to monitor disease activity, given there is frequent discordance between imaging findings and conventional disease activity measures, and imaging changes typically fail to resolve completely with treatment. This chapter addresses the current body of evidence for the use of imaging modalities in GCA across the spectrum of diagnosis, monitoring disease activity, and long-term surveillance for structural changes of aortic dilatation and aneurysm formation and provides suggestions for future research directions., Competing Interests: Declaration of competing interest Author CEO declares advisory board for AbbVie; speaking honoraria from AbbVie, Novartis, and Janssen and Roche; co-investigator on STERLING-PMR trial, funded by NIHR-NHMRC; investigator on AbbVie and Novartis clinical trials. Author MY declares advisory board for BioGen; co-investigator on STERLING-PMR trial, funded by NIHR-NHMRC; financial support from AbbVie, and UCB to attend international conferences, including the BSR and EULAR. Author DFL co-investigator on STERLING-PMR trial, funded by NIHR-NHMRC. Author AMP declares no conflict of interest. Author HIK declares speaking honoraria from AbbVie, and Roche and Jansen; co-investigator on STERLING-PMR trial, funded by NIHR-NHMRC; investigator on AbbVie, Sanofi, and Novartis clinical trials; educational support from Pfizer. Author CLH declares co-investigator on STERLING-PMR trial, funded by NIHR-NHMRC; grant support from Vifor. Author SLM declares consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie and AstraZeneca; investigator on clinical trials for Sanofi, GSK, and Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, and Novartis; chief investigator on STERLING-PMR trial, funded by NIHR-NHMRC; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SLM is supported in part by the NIHR Leeds Biomedical Research Centre. The views expressed in this article are those of the authors and not necessarily those of the NIHR, the NIHR Leeds Biomedical Research Centre, the National Health Service, or the UK Department of Health and Social Care., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: Clinical diagnosis of Alzheimer disease (AD) is only 70% accurate. Reduced cerebral blood flow (CBF) and metabolism in parieto-temporal and posterior cingulate cortex may assist diagnosis. While widely accepted that 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG PET) has superior accuracy to CBF-SPECT for AD, there are very limited head-to-head data from clinically relevant populations and these studies relied on clinical diagnosis as the reference standard., Aims: To compare directly the accuracy of CBF-SPECT and 18 F-FDG PET in patients referred for diagnostic studies in detecting β-amyloid PET confirmed AD., Methods: A total of 126 patients, 56% with mild cognitive impairment and 44% with dementia, completed both CBF-SPECT and 18 F-FDG PET as part of their diagnostic assessment, and subsequently underwent β-amyloid PET for research purposes. Transaxial slices and Neurostat 3D-SSP analyses of 18 F-FDG PET and CBF-SPECT scans were independently reviewed by five nuclear medicine clinicians blinded to all other data. Operators selected the most likely diagnosis and their diagnostic confidence. Accuracy analysis used final diagnosis incorporating β-amyloid PET as the reference standard., Results: Clinicians reported high diagnostic confidence in 83% of 18 F-FDG PET compared to 67% for CBF-SPECT (P = 0.001). All reviewers showed individually higher accuracy using 18 F-FDG PET. Based on majority read, the combined area under the receiver operating characteristic curve in diagnosing AD was 0.71 for 18 F-FDG PET and 0.61 for CBF-SPECT (P = 0.02). The sensitivity of 18 F-FDG PET and CBF-SPECT was 76% versus 43% (P < 0.001), while specificity was 74% versus 83% (P = 0.45)., Conclusions: 18 F-FDG PET is superior to CBF-SPECT in detecting AD among patients referred for the assessment of cognitive impairment., (© 2020 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians.)

Purpose: To evaluate the sensitivity and specificity of PET/CT findings in PMR and generate a diagnostic algorithm utilizing a minimum number of musculoskeletal sites., Methods: Steroid-naïve patients with newly diagnosed PMR (2012 EULAR/ACR classification criteria) were prospectively recruited to undergo whole-body 18 F - FDG PET/CT. Each PMR case was age- and sex-matched to four PET/CT controls. Control scan indication, diagnosis and medical history were extracted from the clinical record. Qualitative and semi-quantitative scoring (maximum standardized uptake value [SUV max ]) of abnormal 18 F-FDG uptake at 21 musculoskeletal sites was undertaken for cases and controls. Results informed the development of a novel PET/CT diagnostic algorithm using a classification and regression trees (CART) method., Results: Thirty-three cases met the inclusion criteria and were matched to 132 controls. Mean age was 68.6 ± 7.4 years for cases compared with 68.2 ± 7.3 for controls, and 54.5% were male. Median CRP was 49 mg/L (32-65) and ESR 41.5 mm/h (24.6-64.4) in the PMR group. The predominant control indication for PET/CT was malignancy (63.6%). Individual musculoskeletal sites proved insufficient for diagnostic purposes. A novel algorithm comprising 18 F-FDG uptake ≥ 2 adjacent to the ischial tuberosities in combination with either abnormalities at the peri-articular shoulder or interspinous bursa achieved a sensitivity of 90.9% and specificity of 92.4% for diagnosing PMR., Conclusions: The presence of abnormal 18 F-FDG uptake adjacent to the ischial tuberosities together with findings at the peri-articular shoulder or interspinous bursa on whole-body PET/CT is highly sensitive and specific for a diagnosis of PMR., Trial Registration: Clinical Trial Registration: Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au , ACTRN1261400696695.

Large vessel vasculitides (LVV) such as giant cell arteritis, Takayasu arteritis and aortitis/periaortitis are characterised by immune-mediated inflammation of medium to large arteries. Clinical disease manifestations can be non-specific and diagnostic imaging plays an important role in the diagnostic pathway. In recent years, FDG PET/CT has proven to be a powerful metabolic tool that can provide a wholed body, non-invasive assessment of vascular inflammation. This review outlines the clinical features of large vessel vasculitis and the closely related entity of polymyalgia rheumatica, summarises the evidence for FDG PET/CT in the assessment of these conditions, and provides guidance for patient preparation, image acquisition and interpretation., (© 2024 Royal Australian and New Zealand College of Radiologists.)

Objectives: To characterize 18F-fluorodeoxyglucose (18F-FDG) uptake on whole-body PET/CT in PMR, and identify its precise anatomic correlate using MRI., Methods: Patients with newly diagnosed PMR according to the 2012 EULAR/ACR classification criteria were prospectively recruited. Participants with GCA were excluded. A whole-body 18F-FDG PET/CT scan was performed in all untreated patients. Qualitative and semiquantitative [standardized uptake value maximum (SUVmax)] scoring of abnormal 18F-FDG uptake was undertaken. MRI of the pelvis, knee and wrist and hand was performed in three representative patients with anatomical correlation of FDG-avid sites carried out using Medview fusion software., Results: Twenty-two patients with PMR were recruited. Their mean age was 68.3 years (s.d. 6.3) and 13/22 were male. On whole-body PET/CT, 18F-FDG uptake adjacent to the ischial tuberosities was observed in 21 participants (95.4%) and recorded the highest mean SUVmax value [3.6 (s.d. 1.7)]. A high frequency of posteromedial knee (61.9%) and wrist and/or hand involvement (66.7%) was also appreciated. MRI of the pelvis revealed high T2 signal surrounding the proximal hamstring tendon origins of both semimembranosus and the conjoint tendon of the semitendinosus and biceps femoris. At the knee, peritendonitis at the distal insertion of the semimembranosus was observed. PET/MRI fusion at the pelvis and knee confirmed semimembranosus peritendonitis as the anatomical correlate of 18F-FDG uptake adjacent to the ischial tuberosities and of posteromedial knee structures., Conclusion: Hamstring peritendonitis is a common and distinctive manifestation of PMR on whole-body PET/CT., Trial Registration: Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au, ACTRN1261400696695., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) can provide unique insights; however, access may be difficult. In this 2-year statewide study of all neurology inpatient admissions, 27.9% (41/147) of PET (any field of view) demonstrated significant abnormalities. At sites without on-site PET access, the proportion of patients receiving PET was lower (P < 0.01), and the time from admission to receiving PET was longer (P = 0.018), as compared to those with on-site access. Investigation of strategies to improve access is warranted., (© 2024 Royal Australasian College of Physicians.)

Large vessel vasculitis, including giant cell arteritis (GCA) and Takayasu arteritis (TAK), are autoimmune diseases primarily affecting the aorta and its branches. GCA is the most common primary vasculitis. Inflammatory changes in the vessel walls can cause serious complications such as amaurosis, stroke, and aortic dissection and rupture. Imaging techniques have become an integral part for the diagnosis and monitoring of large vessel vasculitis, allowing for effective disease monitoring. GCA and TAK exhibit similar patterns of vascular distribution. However, the temporal arteries are never involved in TAK, and axillary arteritis occurs more frequently in GCA. In most centers, ultrasound of the temporal and axillary arteries has replaced temporal artery biopsy as the primary diagnostic tool for GCA. In addition to ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and [ 18 F]-FDG (fluorodeoxyglucose) positron emission tomography-computed tomography (PET) are important, particularly for visualizing the aorta. Moreover, PET-CT is now also capable of assessing the temporal arteries, although it is not yet widely available. In polymyalgia rheumatica (PMR), ultrasound of the shoulder and hip regions is part of the ACR/EULAR classification criteria. MRI allows detailed visualization of additional inflammatory extraarticular manifestations, showing characteristic inflammatory lesions in entheses, tendons, and ligaments. [ 18 F]-FDG-PET-CT also enables the visualization of musculoskeletal inflammation, especially in the shoulder and hip regions, as well as paravertebral areas. Ultrasound can detect subclinical GCA in up to 23% of patients with PMR, which should be treated like GCA. Technological innovations such as new radiotracers and improved MRI imaging could further enhance the diagnosis and monitoring of large vessel vasculitis and PMR, thus playing a crucial role in improving the prognosis through faster initiation of therapy., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: V.S. Schäfer, S.M. Petzinna und W.A. Schmidt geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Polymyalgia rheumatica is one of the most common inflammatory rheumatic conditions in older adults. The disease is characterized by pain and stiffness in the shoulder and pelvic girdle. Polymyalgia rheumatica is almost always observed in adults over the age of 50. The current article aimed to provide explanations for the age preference of polymyalgia rheumatica by reviewing the literature regarding disease etiology and pathogenesis. Potential factors related to the association between polymyalgia rheumatica and aging include immunosenescence/inflammaging, increased risk of infections by aging, endocrinosenescence, and age-related changes in gut microbiota. These factors and their potential contributions to immune-mediated inflammation will be discussed. [ABSTRACT FROM AUTHOR]

Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One of the main transcription factors activated by hypoxia is hypoxiainducible factor (HIF), which regulates the expression of genes involved in various aspects of tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, and cell migration. This can negatively impact patient outcomes by inducing therapeutic resistance. The importance of hypoxia is clearly demonstrated by continued research into finding clinically relevant hypoxia biomarkers, and hypoxia-targeting therapies. One of the problems is the lack of clinically applicable methods of hypoxia detection, and lack of standardisation. Additionally, a lot of the methods of detecting hypoxia do not take into consideration the complexity of the hypoxic tumour microenvironment (TME). Therefore, this needs further elucidation as approximately 50% of solid tumours are hypoxic. The ECM is important component of the hypoxic TME, and is developed by both cancer associated fibroblasts (CAFs) and tumour cells. However, it is important to distinguish the different roles to develop both biomarkers and novel compounds. Fibronectin (FN), collagen (COL) and hyaluronic acid (HA) are important components of the ECM that create ECM fibres. These fibres are crosslinked by specific enzymes including lysyl oxidase (LOX) which regulates the stiffness of tumours and induces fibrosis. This is partially regulated by HIFs. The review highlights the importance of understanding the role of matrix stiffness in different solid tumours as current data shows contradictory results on the impact on therapeutic resistance. The review also indicates that further research is needed into identifying different CAF subtypes and their exact roles; with some showing pro-tumorigenic capacity and others having antitumorigenic roles. This has made it difficult to fully elucidate the role of CAFs within the TME. However, it is clear that this is an important area of research that requires unravelling as current strategies to target CAFs have resulted in worsened prognosis. The role of immune cells within the tumour microenvironment is also discussed as hypoxia has been associated with modulating immune cells to create an anti-tumorigenic environment. Which has led to the development of immunotherapies including PD-L1. These hypoxia-induced changes can confer resistance to conventional therapies, such as chemotherapy, radiotherapy, and immunotherapy. This review summarizes the current knowledge on the impact of hypoxia on the TME and its implications for therapy resistance. It also discusses the potential of hypoxia biomarkers as prognostic and predictive indictors of treatment response, as well as the challenges and opportunities of targeting hypoxia in clinical trials. [ABSTRACT FROM AUTHOR]

The article focuses on the evolving understanding and management of polymyalgia rheumatica (PMR), highlighting advancements in diagnosis, including the use of imaging techniques, and the shift towards incorporating steroid-sparing agents and disease-modifying antirheumatic drugs (DMARDs) in treatment. Topics include the diagnostic work-up for PMR, management approaches for newly diagnosed and relapsing disease, and the potential role of biologic agents in transforming PMR management.

The impact of modern imaging in uncovering the underlying pathology of PMR cannot be understated. Long dismissed as an inflammatory syndrome with links to the large vessel vasculitis giant cell arteritis (GCA), a pathognomonic pattern of musculotendinous inflammation is now attributed to PMR and may be used to confirm its diagnosis. Among the available modalities, 18F-fluorodeoxyglucose (18F-FDG) PET/CT is increasingly recognized for its high sensitivity and specificity, as well as added ability to detect concomitant large vessel GCA and exclude other relevant differentials like infection and malignancy. This atlas provides a contemporary depiction of PMR's pathology and outlines how this knowledge translates into a pattern of findings on whole body 18F-FDG PET/CT that can reliably confirm its diagnosis. [ABSTRACT FROM AUTHOR]

For a searchable version of these abstracts, please visit www.acrabstracts.org. [ABSTRACT FROM AUTHOR]

Purpose: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation., Methods: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year., Results: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%., Conclusion: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy., Trial Registration: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020., (© 2024. The Author(s).)

Purpose: Polymyalgia rheumatica (PMR) can be difficult to diagnose. Whole-body [18F]FDG-PET/CT allows for a comprehensive evaluation of all relevant articular and extra-articular structures affected by PMR. We aimed to summarize current evidence on the diagnostic value of [18F]FDG-PET/CT for a diagnosis of PMR., Methods: PubMed/MEDLINE and the Cochrane Library database were searched from inception through May 31, 2020. Studies containing patients with PMR who underwent [18F]FDG-PET/CT were included. Screening and full-text review were performed by 3 investigators and data extraction by 2 investigators. Risk of bias was examined with the QUADAS-2 tool. Diagnostic test meta-analysis was performed with a bivariate model., Results: Twenty studies were included in the systematic review, of which 9 studies (n = 636 patients) were eligible for meta-analysis. [18F]FDG positivity at the following sites was associated with a diagnosis of PMR: interspinous bursae (positive likelihood ratio (LR+) 4.00; 95% CI 1.84-8.71), hips (LR+ 2.91; 95% CI 2.09-4.05), ischial tuberosities (LR+ 2.86; 95% CI 1.91-4.28), shoulders (LR+ 2.57; 95% CI 1.24-5.32) and sternoclavicular joints (LR+ 2.31; 95% CI 1.33-4.02). Negative likelihood ratios (LR-) for these sites, as well as the greater trochanters, were all less than 0.50. Composite [18F]FDG-PET/CT scores, as reported in 3 studies, provided a pooled LR+ of 3.91 (95% CI 2.42-6.32) and LR- of 0.19 (95% CI 0.10-0.36). Moderate to high heterogeneity was observed across the studies, mainly due to differences in patient selection, scanning procedures and/or interpretation criteria., Conclusion: Significant [18F]FDG uptake at a combination of anatomic sites is informative for a diagnosis of PMR. [18F]FDG-PET/CT might be an important diagnostic tool in patients with suspected PMR. This study also highlights the need for adherence to published procedural recommendations and standardized interpretation criteria for the use of [18F]FDG-PET/CT in PMR.

Neurological diseases can be broadly divided according to causal factors into circulatory system disorders leading to ischemic stroke; degeneration of the nerve cells leading to neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, and immune system disorders; bioelectric activity (epileptic) problems; and genetically determined conditions as well as viral and bacterial infections developing inflammation. Regardless of the cause of neurological diseases, they are usually accompanied by disturbances of the central energy in a completely unexplained mechanism. The brain makes up only 2% of the human body's weight; however, while working, it uses as much as 20% of the energy obtained by the body. The energy requirements of the brain are very high, and regulatory mechanisms in the brain operate to ensure adequate neuronal activity. Therefore, an understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving cooperativity between structural and molecular factors in the central nervous system. This article reviewed selected molecular biomarkers of oxidative stress and energy metabolism disorders such as homocysteine, DNA damage such as 8-oxo2dG, genetic variants, and antioxidants such as glutathione in selected neurological diseases including ischemic stroke, AD, PD, and epilepsy. This review summarizes our and others' recent research on oxidative stress in neurological disorders. In the future, the diagnosis and treatment of neurological diseases may be substantially improved by identifying specific early markers of metabolic and energy disorders. [ABSTRACT FROM AUTHOR]

Polymyalgia rheumatica (PMR) is an inflammatory joint disease in patients over 50 years of age with pain and prolonged morning stiffness in the shoulder and hip girdles and neck. The lack of specific clinical findings, laboratory signs, biomarker and established imaging methods makes it difficult to diagnose patients with this disease. The aim of the systematic review is to present the literature data on the use of imaging methods for early diagnosis, assessment of disease activity and therapeutic response in PMR. At the same time, the advantages, disadvantages and contraindications of each method are considered. A literature search was carried out in PubMed and Scopus up to June 2022. Studies were selected that met the following criteria: (1) English language publications in peer-reviewed journals, (2) cohort or case–control studies and a series of more than five clinical cases, (3) studies of newly diagnosed or suspected PMR patients according to classification criteria or expert opinion, (4) imaging evaluation of articular, extraarticular and vascular impairment in PMR. Out of a total of 1431 publications, 61 articles were selected, which differed in the imaging techniques used: radiography (5), scintigraphy (4), magnetic resonance imaging (14), PET/CT (14) and ultrasound (24). Prevalence of extraarticular involvement (tendons, entheses and bursae) was identified in patients with PMR. In a significant number of cases, subclinical vasculitis of the large vessels was found, confirming the common pathogenetic pathways of the two diseases. The diagnostic, therapeutic and prognostic potential of imaging methods in PMR has been relatively poorly studied and remains to be clarified. [ABSTRACT FROM AUTHOR]

Objectives To evaluate MRI changes to define muscle-lesion specific patterns in patients with antisynthetase syndrome (ASS), and compare them with those in other common idiopathic inflammatory myopathy subtypes. Methods Qualitative and semi-quantitative thigh MRI evaluations were conducted in patients with ASS, DM and immune-mediated necrotizing myopathy (IMNM). Results This study included 51 patients with ASS, 56 with DM and 61 with IMNM. Thigh MRI revealed muscle oedema (62.7%), myofascial oedema (90.2%), subcutaneous-tissue oedema (60.8%) and fatty infiltration of muscles (68.6%) in patients with ASS. Compared with IMNM, ASS and DM were associated with more frequent adductor-muscle relative sparing (40.6% vs 3.6%, P <0.001, and 25.6% vs 3.6%, P <0.001) and subcutaneous-tissue oedema (60.8% vs 23.0%, P <0.001, and 57.1% vs 23.0%, P <0.001). Although ASS and DM exhibited similar oedema patterns, there were certain subtle differences between them. The ASS group was less frequently symmetric (60.6% vs 88.4%, P =0.005, and 60.6% vs 80.0%, P =0.048), but more frequently showed myofascial oedema of the tensor fasciae latae (80.4% vs 48.2%, P <0.001, and 80.4% vs 31.1%, P <0.001) than either the DM or IMNM groups. The receiver operating characteristic curve analysis showed an optimal combination of thigh MRI findings had an area under the curve with 0.893 for diagnosing ASS. Conclusion Thigh MRI in ASS exhibited frequent myofascial oedema. ASS oedema patterns resembled those of DM more than those of IMNM. Bilateral asymmetry, adductor-muscle relative sparing and remarkable myofascial oedema of tensor fasciae latae were the most characteristic ASS imaging findings. [ABSTRACT FROM AUTHOR]

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease affecting people older than 50 years and is 2–3 times more common in women. The most common symptoms are pain and morning stiffness in the shoulder and pelvic girdle and the onset may be acute or develop over a few days to weeks. General symptoms such as fatigue, fever and weight loss may occur, likely driven by systemic IL‐6 signalling. The pathology includes synovial and periarticular inflammation and muscular vasculopathy. A new observation is that PMR may appear as a side effect of cancer treatment with checkpoint inhibitors. The diagnosis of PMR relies mainly on symptoms and signs combined with laboratory markers of inflammation. Imaging modalities including ultrasound, magnetic resonance imaging and positron emission tomography with computed tomography are promising new tools in the investigation of suspected PMR. However, they are still limited by availability, high cost and unclear performance in the diagnostic workup. Glucocorticoid (GC) therapy is effective in PMR, with most patients responding promptly to 15–25 mg prednisolone per day. There are challenges in the management of patients with PMR as relapses do occur and patients with PMR may need to stay on GC for extended periods. This is associated with high rates of GC‐related comorbidities, such as diabetes and osteoporosis, and there are limited data on the use of disease‐modifying antirheumatic drugs and biologics as GC sparing agents. Finally, PMR is associated with giant cell arteritis that may complicate the disease course and require more intense and prolonged treatment. [ABSTRACT FROM AUTHOR]

Creutzfeldt–Jakob disease (CJD) is a rare, uniformly fatal prion disease. Although CJD commonly presents with rapidly progressive dementia, ataxia, and myoclonus, substantial clinicopathological heterogeneity is observed in clinical practice. Unusual and predominantly cognitive clinical manifestations of CJD mimicking common dementia syndromes are known to pose as an obstacle to early diagnosis and prognosis. We report a series of three patients with probable or definite CJD (one male and two females, ages 52, 58 and 68) who presented to our tertiary behavioral neurology clinic at Mayo Clinic Rochester that met criteria for a newly defined progressive dysexecutive syndrome. Glucose hypometabolism patterns assessed by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) strongly resembled those of dysexecutive variant of Alzheimer's disease (dAD). However, magnetic resonance imaging (MRI) demonstrated restricted diffusion in neocortical areas and deep nuclei, while cerebrospinal fluid biomarkers indicated abnormal levels of 14-3-3, total-tau, and prion seeding activity (RT-QuIC), establishing the diagnosis of CJD. Electroencephalogram (EEG) additionally revealed features previously documented in atypical cases of CJD. This series of clinical cases demonstrates that CJD can present with a predominantly dysexecutive syndrome and FDG-PET hypometabolism typically seen in dAD. This prompts for the need to integrate information on clinical course with multimodal imaging and fluid biomarkers to provide a precise etiology for dementia syndromes. This has important clinical implications for the diagnosis and prognosis of CJD in the context of emerging clinical characterization of progressive dysexecutive syndromes in neurodegenerative diseases like dAD. [ABSTRACT FROM AUTHOR]

Objective: To perform a COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN)-based systematic literature review of measurement properties of the Polymyalgia Rheumatica Activity Score (PMR-AS).Methods: PubMed, EMBASE, and CINAHL were broadly searched. English full-text articles, with (quantitative) data on ≥ 5 patients with PMR using the PMR-AS were selected. Seven hypotheses for construct validity and 3 for responsiveness, concerning associations with erythrocyte sedimentation rate, physical function, quality of life, clinical disease states, ultrasound, and treatment response, were formulated. We assessed the structural validity, internal consistency, reliability, and measurement error, or the hypotheses on construct validity or responsiveness of the PMR-AS based on COSMIN criteria.Results: Out of the identified 26 articles that used the PMR-AS, we were able to use 12 articles. Structural validity, internal consistency, construct validity, and responsiveness were assessed in 1, 2, 8, and 3 articles, respectively. Insufficient evidence was found to confirm structural validity and internal consistency. No data were found on reliability or measurement error. Although 60% and 67% of hypotheses tested for construct validity and responsiveness, respectively, were confirmed, there was insufficient evidence to meet criteria for good measurement properties.Conclusion: While there is some promising evidence for construct validity and responsiveness of the PMR-AS, it is lacking for other properties and, overall, falls short of criteria for good measurement properties. Therefore, further research is needed to assess its role in clinical research and care. [ABSTRACT FROM AUTHOR]

2-deoxy-2[18F]fluoro-D-glucose (FDG) PET-CT has revolutionized oncological imaging. The cellular processes that make cancer cells visible on FDG PET-CT also occur in a number of inflammatory cells. Exploiting this phenomenon has led to a growth of evidence supporting the use of FDG PET-CT in a wide range of infective and inflammatory diseases. Rheumatological diseases can affect multiple sites within the musculoskeletal system alongside multi-organ extra-articular disease manifestations. Inflammation is central to these diseases, making FDG PET-CT a logical choice. In this review article we describe the various applications of FDG PET-CT in rheumatological diseases using illustrative examples to highlight the beneficial role of FDG PET-CT in each case. [ABSTRACT FROM AUTHOR]

Objective Recent studies suggest that the knee is frequently involved in PMR. In this study, we aimed to determine whether the US assessment of the shoulder and knee discriminates between PMR and other differential diagnoses and improves the accuracy of the 2012 EULAR/ACR provisional classification criteria for PMR. Methods We consecutively enrolled 81 untreated patients who received a diagnosis of PMR. These patients were divided into two groups based on the final diagnosis made at 1-year follow-up: PMR-definite group (n  = 60) and PMR-mimic group (n  = 21). We also enrolled age/sex-matched untreated RA patients with shoulder pain from an independent cohort (RA group, n  = 60). All patients underwent comprehensive US assessment of the shoulder and knee for synovitis, bursitis, tenosynovitis, tendinitis and ligament inflammation at baseline. Results US scores for tenosynovitis, tendinitis and ligament inflammation better discriminated the PMR-definite group from the PMR-mimic and RA groups than do those for synovitis or bursitis. Among logistic regression models to identify US variables that were associated with the PMR-definite group, the best fitted model included two US variables: the bilateral involvement of the shoulder (long head of biceps, supraspinatus or subscapularis tendon) and the bilateral involvement of the knee (popliteus tendon or medial or lateral collateral ligament). Incorporating these two items into the 2012 EULAR/ACR provisional classification criteria numerically increased the accuracy to classify the PMR-definite group. Conclusion US assessment of the tendon/ligament-related lesions in the shoulder and knee may improve the accuracy of the 2012 EULAR/ACR provisional classification criteria for PMR. [ABSTRACT FROM AUTHOR]

Objectives To compare and validate the diagnostic accuracy of fluorodeoxyglucose (FDG)-PET/CT scores for PMR; and to explore their association with clinical factors. Methods This retrospective study included 39 consecutive patients diagnosed with PMR and 19 PMR comparators. The final clinical diagnosis was established after 6 months follow-up. Patients underwent FDG-PET/CT prior to glucocorticoid treatment. Visual grading of FDG uptake was performed at 30 anatomic sites. Three FDG-PET/CT scores (the Leuven Score, two Besançon Scores) and two algorithms (the Saint-Etienne and Heidelberg Algorithms) were investigated. Receiver operating characteristic (ROC) analysis with area under the curve (AUC) was performed. Diagnostic accuracy was assessed at predefined cut-off points. Results All three FDG-PET/CT scores showed high diagnostic accuracy for a clinical diagnosis of PMR in the ROC analysis (AUC 0.889–0.914). The Leuven Score provided a sensitivity of 89.7% and specificity of 84.2% at its predefined cut-off point. A simplified Leuven Score showed similar diagnostic accuracy to that of the original score. The Besançon Scores showed limited specificity at their predefined cut-off points (i.e. 47.4% and 63.2%), while ROC analysis suggested that substantially higher cut-off points are needed for these scores. The Heidelberg and Saint-Etienne Algorithms demonstrated high sensitivity, but lower specificity (i.e. 78.9% and 42.1%, respectively) for PMR. Female sex and presence of large-vessel vasculitis were associated with lower FDG-PET/CT scores in patients with PMR. Conclusion The Leuven Score showed the highest diagnostic utility for PMR. A modified, concise version of the Leuven Score provided similar diagnostic accuracy to that of the original score. [ABSTRACT FROM AUTHOR]

Immature and chaotic vascular networks with critically increased intervascular distances are characteristic features of malignant tumors. Spatial and temporal heterogeneities of blood flow and associated availabilities of O2, together with limited diffusive O2 transport, and -in some patients- anemia, obligatorily lead to tumor hypoxia (= critically reduced O2 levels) on macro- and microscopic scales. This detrimental condition, recently classified as a key hallmark of malignant growth, acts (a) as a barrier in most antitumor treatments, and (b) leads to malignant progression based on hypoxia-induced changes of the genome, transcriptome, and proteome, and finally to poor patient survival. This knowledge is, to a great extent, based on the systematic detection of tumor hypoxia in the clinical setting since the late 1980s. Precise assessment of the tumor oxygenation status was made possible using minimally invasive polarographic pO2 microsensors in a series of research projects. To assess tumor hypoxia in the clinical setting, it is highly desirable to use technologies with (a) high spatial and temporal resolutions, (b) the capability to judge the severity of tumor hypoxia, (c) to allow mapping of pO2 of the whole tumor mass, and (d) to enable serial investigations in order to verify treatment-related changes in tumor hypoxia. Selection and treatment of cancer patients according to their individual tumor oxygenation/hypoxia status for intensified and/or personalized hypoxia-targeted treatment strategies should be the ultimate goal. [ABSTRACT FROM AUTHOR]

PMR is an inflammatory rheumatic disease of elderly people characterized by pain and stiffness in the neck, shoulder and pelvic girdles. No specific diagnostic confirmatory tests exist and clinical symptoms, as well as increased acute phase reactants, are unspecific. The diagnostic value of imaging including ultrasound, MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with/without CT for PMR is increasingly studied. These techniques, particularly FDG-PET/CT, may help to detect underlying GCA in PMR patients with an incomplete response to glucocorticoids and/or recurrent relapses. Recent imaging studies provide novel insights into the anatomical basis of inflammation in PMR, particularly at hip and spine, which may help to distinguish this disease from other mimicking conditions. In this review, we discuss novel insights into the pathoanatomy of PMR, compare the diagnostic values of different imaging techniques and summarize current data on the role of imaging for monitoring and outcome prediction. [ABSTRACT FROM AUTHOR]

Objective There is currently no diagnostic test for PMR. A characteristic pattern of extracapsular inflammation as assessed by contrast-enhanced MRI (ceMRI) has recently been described in the pelvis of patients with PMR. We aimed to evaluate the performance of inflammatory ceMRI signals at predefined pelvic sites as a diagnostic test for PMR. Methods Pelvic MRI scans of patients with pelvic girdle pain (n  = 120), including 40 patients with an expert diagnosis of PMR and 80 controls with other reasons for pelvic pain were scored by three blinded radiologists, who evaluated the degree of contrast enhancement at 19 predefined tendinous and capsular pelvic structures. Different patterns of involvement were analysed statistically. Results The frequency of bilateral peritendinitis and pericapsulitis including less common sites, such as the proximal origins of the m. rectus femoris and m. adductor longus, differed significantly between PMR cases and controls: 13.4 ± 2.7 vs 4.0 ± 2.3. A cut-off of ≥10 inflamed sites discriminated well between groups (sensitivity 95.8%, specificity 97.1%). Bilateral inflammation of the insertion of the proximal m. rectus femoris or adductor longus tendons together with ≥3 other bilaterally inflamed sites performed even better (sensitivity 100%, specificity 97.5%). Conclusion This study confirms that a distinctive MRI pattern of pelvic inflammation (bilateral peritendinitis and pericapsulitis and the proximal origins of the m. rectus femoris and m. adductor longus) is characteristic for PMR. The high sensitivity and specificity of the set of anatomical sites evaluated suggests their clinical usefulness as a confirmatory diagnostic test. [ABSTRACT FROM AUTHOR]

Background: Hypoxia can induce radiation resistance and is an independent prognostic marker for outcome in head and neck cancer. As 18F-FMISO (FMISO), a hypoxia tracer for PET, is far less common than 18F-FDG (FDG) and two separate PET scans result in doubled cost and radiation exposure to the patient, we aimed to predict hypoxia from FDG PET with new techniques of voxel based analysis and texture analysis. Methods: Thirty-eight patients with head-and-neck cancer underwent consecutive FDG and FMISO PET scans before any treatment. ROIs enclosing the primary cancer were compared in a voxel-by-voxel manner between FDG and FMISO PET. Tumour hypoxia was defined as the volume with a tumour-to-muscle ratio (TMR) > 1.25 in the FMISO PET and hypermetabolic volume was defined as >50% SUVmax in the FDG PET. The concordance rate was defined as percentage of voxels within the tumour which were both hypermetabolic and hypoxic. 38 different texture analysis (TA) parameters were computed based on the ROIs and correlated with presence of hypoxia. Results: Within the hypoxic tumour regions, the FDG uptake was twice as high as in the non-hypoxic tumour regions (SUVmean 10.9 vs. 5.4; p<0.001). A moderate correlation between FDG and FMISO uptake was found by a voxel-by-voxel comparison (r = 0.664 p<0.001). The average concordance rate was 25% (± 22%). Entropy was the TA parameter showing the highest correlation with hypoxia (r = 0.524 p<0.001). Conclusion: FDG uptake was higher in hypoxic tumour regions than in non-hypoxic regions as expected by tumour biology. A moderate correlation between FDG and FMISO PET was found by voxel-based analysis. TA yielded similar results in FDG and FMISO PET. However, it may not be possible to predict tumour hypoxia even with the help of texture analysis. [ABSTRACT FROM AUTHOR]

Abstract: Polymyalgia rheumatica is the most common inflammatory rheumatic disease in elderly people, usually develops in patients older than 50 years, more frequently in females. An emerging imaging tool in the diagnostic workup of this condition is whole-body PET/CT, which allows an overall assessment of the articular and extra-articular structures involved., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The article presents the list of the authors including the Ackermann U.; Akamatsu G.; and the Akhurst T.

Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers. [ABSTRACT FROM AUTHOR]

Introduction For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non-small cell lung cancer ( NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside (18 F- FAZA) positron emission tomography ( PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation. Methods Patients with stage IIIA-IIIB NSCLC underwent 18 F- FAZA PET scans and 18F-2-deoxyglucose ( FDG)- PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60 Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival ( DFS). Results Seventeen patients underwent pre-treatment 18 F- FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes ( P = 0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia ( P = 0.38). Eight patients with baseline hypoxia had post treatment 18F- FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P = 0.42). Conclusions Intra-lesional hypoxia, as detected by 18 F- FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC. [ABSTRACT FROM AUTHOR]

Aim 18Fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) is an established part of staging in a wide variety of malignancies. Incidental abnormal uptake of 18FDG of unknown significance is frequently encountered. Therefore, we investigated patients with abnormal colonic uptake of 18FDG, determined by PET/CT images, using colonoscopy. Method The radiology reports of all patients referred to a tertiary referral centre for a PET/CT scan were reviewed retrospectively. Patients with abnormal colonic uptake of 18FDG were identified and the PET/CT findings were correlated with colonoscopic findings. Results Of 555 consecutive patients identified over a 26-month period, 53 had abnormal colonic uptake of 18FDG, as determined by PET/CT images. Twenty-nine were not investigated following discussion in a specialist multidisciplinary (MDT) meeting, according to local protocol. Twenty out of 24 patients investigated by endoscopy had a colonic lesion correlating to the site identified on the PET/CT image: 16 patients had tubulovillous adenomas (nine of which were > 10 mm), two had invasive adenocarcinomas, two had diverticular disease and one had collagenous colitis; no colonic lesion was detected in three. These findings were incidental and not related to the primary diagnosis for which the scan was being performed. Accordingly, a positive predictive value of 83% is associated with the finding of abnormal uptake of 18FDG on PET/CT images. Conclusion Incidental abnormal colonic uptake of 18FDG, determined by a PET/CT scan requires definitive colonic investigation in patients suitable for further treatment because significant colonic pathology is frequently identified. The benefit of this approach should be discussed in specialist MDT meetings and tailored to each patient; however, national guidelines for management are required. [ABSTRACT FROM AUTHOR]

The article presents a study investigating the clinical significance F-fluoro-2-dexoy-D-glucose (FDG)-positive incidental intraabdominal findings on positron emission tomography (PET) for lung cancer during work-up of pulmonary nodules. It is found that FDG intraabdominal findings PET imaging may represent clinically significant pathology, especially if the lesion is located in the colon, but it also need to be further investigated by colonoscopy. It also includes information on several risk factors of cancer and their lung cancer staging.

Oxygen supply and diffusion into tissues are necessary for survival. The oxygen partial pressure (pO), which is a key component of the physiological state of an organ, results from the balance between oxygen delivery and its consumption. In mammals, oxygen is transported by red blood cells circulating in a well-organized vasculature. Oxygen delivery is dependent on the metabolic requirements and functional status of each organ. Consequently, in a physiological condition, organ and tissue are characterized by their own unique 'tissue normoxia' or 'physioxia' status. Tissue oxygenation is severely disturbed during pathological conditions such as cancer, diabetes, coronary heart disease, stroke, etc., which are associated with decrease in pO, i.e. 'hypoxia'. In this review, we present an array of methods currently used for assessing tissue oxygenation. We show that hypoxia is marked during tumour development and has strong consequences for oxygenation and its influence upon chemotherapy efficiency. Then we compare this to physiological pO values of human organs. Finally we evaluate consequences of physioxia on cell activity and its molecular modulations. More importantly we emphasize the discrepancy between in vivo and in vitro tissue and cells oxygen status which can have detrimental effects on experimental outcome. It appears that the values corresponding to the physioxia are ranging between 11% and 1% O whereas current in vitro experimentations are usually performed in 19.95% O, an artificial context as far as oxygen balance is concerned. It is important to realize that most of the experiments performed in so-called normoxia might be dangerously misleading. [ABSTRACT FROM AUTHOR]

Background and Aim: Renal cell carcinoma (RCC) is the 13th most common cancer worldwide and accounts for 4% of all adult malignancies. Herein the state of the art and recent advances in cross-sectional radiological imaging applied to RCC are reviewed, including ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography. Methods: Literature search of peer-reviewed papers published by October 2010. Results: In front of more conventional and widespread imaging tools, such as ultrasonography and computed tomography, an array of newer and attractive radiological modalities are under investigation and show promise to improve our ability to noninvasively detect renal tumors and its recurrences, accurately assess the extent of the disease, and reliably evaluate treatment response, particularly in the era of antiangiogenetic therapy. Conclusions: Recent major advances in radiological imaging techniques have considerably improved our ability to diagnose, stage and follow-up RCC. Further studies are needed to evaluate the potential of most recent and still investigational imaging tools. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: We present a review of radionuclide imaging of tumour vascular physiology as it relates to angiogenesis. We focus on clinical trials in human subjects using PET and SPECT to evaluate tumour physiology, in particular blood flow and hypoxia. Methods: A systematic review of literature based on MEDLINE searches updated in February 2010 was performed. Results: Twenty-nine studies were identified for review: 14 dealt with O-water PET perfusion imaging, while 8 dealt with F-fluoromisonidazole PET hypoxia imaging. Five used SPECT methods. The studies varied widely in technical quality and reporting of methods. Conclusions: A subset of radionuclide methods offers accurate quantitative scientific observations on tumour vascular physiology of relevance to angiogenesis and its treatment. The relationship between cellular processes of angiogenesis and changing physiological function remains poorly defined. The promise of quantitative functional imaging at high specificity and low administered dose sustains interest in radionuclide methods. [ABSTRACT FROM AUTHOR]

In 2007, 1179 papers were published that involved the application of optical biosensors. Reported developments in instrument hardware, assay design, and immobilization chemistry continue to improve the technology's throughput, sensitivity, and utility. Compared to recent years, the widest range of platforms, both traditional format and array-based, were used. However, as in the past, we found a disappointingly low percentage of well-executed experiments and thoughtful data interpretation. We are alarmed by the high frequency of suboptimal data and over-interpreted results in the literature. Fortunately, learning to visually recognize good-and more importantly, bad-data is easy. Using examples from the literature, we outline several features of biosensor responses that indicate experimental artifacts versus actual binding events. Our goal is to have everyone, from benchtop scientists to project managers and manuscript reviewers, become astute judges of biosensor results using nothing more than their eyes. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]