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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]

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]

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]

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]

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]

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. [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]

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 18F−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 [SUVmax]) of abnormal 18F-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 18F-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 18F-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 [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]

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]

An author index for the April 2014 issue of the "Internal Medicine Journal" is presented.

An author index for the September 2012 issue of the "Internal Medicine Journal" is presented.

Background: We investigated the prognostic predictive value of the combination of fluorodeoxyglucose (FDG)- and fluoromisonidazole (FMISO)-PET in patients with non-small cell lung carcinoma (NSCLC) treated with stereotactic body radiation therapy (SBRT). Patients and methods: We prospectively examined patients with pathologically proven NSCLC; all underwent FDG and FMISO PET/CT scans before SBRT. PET images were acquired using a whole-body time-of-flight PET-CT scanner with respiratory gating. We classified them into recurrent and non-recurrent groups based on their clinical follow-ups and compared the groups' tumor diameters and PET parameters (i.e., maximum of the standardized uptake value (SUVmax), metabolic tumor volume, tumor-to-muscle ratio, and tumor-to-blood ratio). We performed univariate analysis to evaluate the impact of the PET variables on the patients' progression-free survival (PFS). We divided the patients by thresholds of FDG SUVmax and FMISO SUVmax obtained from receiver operating characteristic analysis for assessment of recurrence rate and PFS. Results: Thirty-two NSCLC patients (19 male and 13 females; median age, 83 years) were enrolled. All received SBRT. At the study endpoint, 23 patients (71.9%) were non-recurrent and nine patients (28.1%) had recurrent disease. Significant between-group differences were observed in tumor diameter and all the PET parameters, demonstrating that those were significant predictors of the recurrence in all patients. In the 22 patients with tumors > 2 cm, tumor diameter and FDG SUVmax were not significant predictors. Thirty-two patients were divided into three patterns from the thresholds of FDG SUVmax (6.81) and FMISO SUVmax (1.89); A, low FDG and low FMISO (n = 14); B, high FDG and low FMISO (n = 8); C, high FDG and high FMISO (n = 10). No pattern A patient experienced tumor recurrence, whereas two pattern B patients (25%) and seven pattern C patients (70%) exhibited recurrence. A Kaplan-Meier analysis of all patients revealed a significant difference in PFS between patterns A and B (p = 0.013) and between patterns A and C (p < 0.001). In the tumors > 2 cm patients, significant differences in PFS were demonstrated between pattern A and C patients (p = 0.002). Conclusion: The combination of FDG- and FMISO-PET can identify patients with a baseline risk of recurrence and indicate whether additional therapy might be performed to improve survival. [ABSTRACT FROM AUTHOR]

Background: This study investigated the noninvasive assessment of tumor vascularization with clinical F-18-fluorodeoxyglucose positron emission tomography/computed tomography and contrast-enhanced computed tomography ([18F]FDG-PET/CT and CE-CT) in experimental human xenograft tumors with modifiable vascularization and compared results to histology. Tumor xenografts with modifiable vascularization were established in 71 athymic nude rats by subcutaneous transplantation of human non-small-cell lung cancer (NSCLC) cells. Four different groups were transplanted with two different tumor cell lines (either A549 or H1299) alone or tumors co-transplanted with rat glomerular endothelial (RGE) cells, the latter to increase vascularization. Tumors were assessed noninvasively by [18F]FDG PET/CT and contrast-enhanced CT (CE-CT) using clinical scanners. This was followed by histological examinations evaluating tumor vasculature (CD-31 and intravascular fluorescent beads). Results: In both tumor lines (A549 and H1299), co-transplantation of RGE cells resulted in faster growth rates [maximal tumor diameter of 20 mm after 22 (± 1.2) as compared to 45 (± 1.8) days, p < 0.001], higher microvessel density (MVD) determined histologically after CD-31 staining [171.4 (± 18.9) as compared to 110.8 (± 11) vessels per mm2, p = 0.002], and higher perfusion as indicated by the number of beads [1.3 (± 0.1) as compared to 1.1 (± 0.04) beads per field of view, p = 0.001]. In [18F]FDG-PET/CT, co-transplanted tumors revealed significantly higher standardized uptake values [SUVmax, 2.8 (± 0.2) as compared to 1.1 (± 0.1), p < 0.001] and larger metabolic active volumes [2.4 (± 0.2) as compared to 0.4 (± 0.2) cm3, p < 0.001] than non-co-transplanted tumors. There were significant correlations for vascularization parameters derived from histology and [18F]FDG PET/CT [beads and SUVmax, r = 0.353, p = 0.005; CD-31 and SUVmax, r = 0.294, p = 0.036] as well as between CE-CT and [18F]FDG PET/CT [contrast enhancement and SUVmax, r = 0.63, p < 0.001; vital CT tumor volume and metabolic PET tumor volume, r = 0.919, p < 0.001]. Conclusions: In this study, a human xenograft tumor model with modifiable vascularization implementable for imaging, pharmacological, and radiation therapy studies was successfully established. Both [18F]FDG-PET/CT and CE-CT are capable to detect parameters closely connected to the degree of tumor vascularization, thus they can help to evaluate vascularization in tumors noninvasively. [18F]FDG-PET may be considered for characterization of tumors beyond pure glucose metabolism and have much greater contribution to diagnostics in oncology. [ABSTRACT FROM AUTHOR]