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Previously, we described associations between health-related quality of life (HRQOL) and disease-related factors among childhood onset systemic lupus erythematosus (cSLE) patients. Here we determined the relationship between HRQOL, disease activity and damage in a large prospective international cohort of cSLE. We compared HRQOL, disease activity and disease damage across different continents and examined the relationship between children's and parents' assessments of HRQOL. Patients with cSLE and their parents completed HRQOL measures at enrollment and ≽4 follow-up visits. Physicians assessed disease activity and damage. The multinational cohort (n=467) had relatively low disease activity and damage. Patient and parent HRQOL scores were significantly correlated. Asian and European patients had the highest HRQOL, while South and North American patients had lower HRQOL scores. Renal, CNS, skin and musculoskeletal systems exhibited the highest levels of damage. North and South American and Asian patients were more likely to have disease damage and activity scores above median values, compared with Europeans. Asians were more likely to use cyclophosphamide/rituximab. Female gender, high disease activity and damage, non-White ethnicity, and use of cyclophosphamide and/rituximab were related to lower HRQOL. HRQOL domain scores continue to emphasize that SLE has widespread impact on all aspects of children's and parents' lives. [ABSTRACT FROM AUTHOR]

The objective of this study is to classify urban streets into a number of classes and to define the speed ranges of levels of service (LOS) categories in Indian context. In this purpose, average travel speed on street segments is used as the measure of effectiveness, which has been obtained from second-wise speed data collected using Global Positioning System (GPS) receiver. Midsized vehicle (car) was used to collect travel speed data on five urban road corridors comprising of 100 street segments in the city of Mumbai and two major road corridors of Kolkata city in India. Both k-means and k-medoid clustering methods and several cluster validation measures have been employed in the classification of urban streets and LOS categories. It is found that k-medoid clustering is more suitable in Indian context and speed ranges of level of service categories are significantly different from that values mentioned in HCM 2000.

Background: MECP2 variants cause X-chromosome-linked rare developmental syndromes. Typically, the mutation is sporadic, occurs in females and is fatal in men. Accurate genetic and clinical diagnostics are considered essential for the management of symptoms and the development of new treatments. These aims may be difficult to reach before more is known about factors resulting in highly variable clinical pictures among patients carrying the same MECP2 variant. We describe the clinical picture of two brothers carrying the same MECP2 variant and compare them with cases published in the literature., Methods: Most of the MECP2 mutations are known to be de novo mutations, which is why the recurrence of the mutation in the couple's other children is unlikely. Unexpectedly, our routine genetic testing revealed a 23-year-old man (P1) and his younger brother (P2) to carry the same hemizygous pathogenic missense variant c.419C>T, p.(Ala140Val) (transcript NM_004992.3) of MECP2, which was found to be inherited from their presumably asymptomatic mother. Thus, further clinical evaluation and comparison with literature cases was considered necessary., Results: The P1 has a severe syndromic intellectual disorder (ID), whereas his brother has a substantially milder ID predominantly limited to problems in verbal skills. Neither P1 nor his younger brother has been diagnosed with Rett syndrome. The P1 (unlike his younger brother) has several lingual, social and motor difficulties; disruptive behavior was the most difficult symptom to treat. P1's response to several medical and non-medical treatment trials has remained inadequate, thus requiring the patient to be hospitalised for a long time. The literature review revealed that apart from our family, there are five other families with more than one male carrying the same MECP2 p.Ala140Val mutation, such as P1 and P2. The phenotypes of all 24 men from us (n = 2) and others (n = 22) carrying the same, presumably non-lethal mutation show great variability., Conclusions: The p.Ala140Val mutation of MECP2 in males is associated with a rare X-chromosomal developmental disorder with highly variable phenotypes. Further studies are needed to better understand all those influencing factors that can explain phenotypic differences within the same genotype to find optimal medicinal therapies., (© 2025 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Obesity is a major public health crisis. Multi-specific peptides have emerged as promising therapeutic strategies for clinical weight loss. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are endogenous incretins that regulate weight through their receptors (R). AMG 133 (maridebart cafraglutide) is a bispecific molecule engineered by conjugating a fully human monoclonal anti-human GIPR antagonist antibody to two GLP-1 analogue agonist peptides using amino acid linkers. Here, we confirm the GIPR antagonist and GLP-1R agonist activities in cell-based systems and report the ability of AMG 133 to reduce body weight and improve metabolic markers in male obese mice and cynomolgus monkeys. In a phase 1, randomized, double-blind, placebo-controlled clinical study in participants with obesity ( NCT04478708 ), AMG 133 had an acceptable safety and tolerability profile along with pronounced dose-dependent weight loss. In the multiple ascending dose cohorts, weight loss was maintained for up to 150 days after the last dose. These findings support continued clinical evaluation of AMG 133., (© 2024. The Author(s).)

Background: Hypertension (HTN) is a leading cause of cardiovascular diseases and its control is poor. There is heterogeneity in levels of blood pressure control among various population subgroups. The present study was conducted within the framework of the National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases, and Stroke (NPCDCS) in India. It aims to estimate the proportion of optimal blood pressure control and identify factors associated with uncontrolled HTN consequent to initial screening., Materials and Methods: We assembled a cohort of individuals with HTN confirmed in a baseline screening in sixteen urban slum clusters of Bhopal (2017-2018). Sixteen accredited social health activists were trained from within these slums. Individuals with HTN were linked to primary care providers and followed up for the next two years. Obtaining optimal blood pressure control (defined as SBP <140 and DBP <90 mm of Hg) was a key outcome., Results: Of a total of 6174 individuals, 1571 (25.4%) had HTN, of which 813 were previously known and 758 were newly detected during the baseline survey. Two-year follow-up was completed for 1177 (74.9%). Blood pressure was optimally controlled in 301 (26%) at baseline and in 442 (38%) individuals at two years (an absolute increase of 12%; 95% CI 10.2-13.9). Older age, physical inactivity, higher body mass index, and newly diagnosed HTN were significantly associated with uncontrolled blood pressure., Conclusion: We found about six of every ten individuals with HTN were on treatment, and about four were optimally controlled. These findings provide a benchmark for NPCDCS, in terms of achievable goals within short periods of follow-up., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricaemia in surgically 5/6 nephrectomized rats. Three weeks after subtotal nephrectomy or sham operation, the rats were allocated to control diet or 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Then blood, urine and tissue samples were taken, and renal morphology and oxidative stress were examined. Inflammation and fibrosis were evaluated using immunohistochemistry and real-time PCR (RT-PCR). Remnant kidney rats ingesting normal or oxonic acid diet presented with ~60% reduction of creatinine clearance and suppressed plasma renin activity. Oxonic acid diet increased plasma uric acid levels by >80 μmol/L. In remnant kidney rats, moderate hyperuricaemia decreased glomerulosclerosis, tubulointerstitial damage and kidney mast cell count, without influencing the fibrosis marker collagen I messenger RNA (mRNA) content. In both sham-operated and 5/6 nephrectomized rats, the mast cell product 11-epi-prostaglandin-F 2α excretion to the urine and kidney tissue cyclooxygenase-2 (COX-2) levels were decreased. To conclude, hyperuricaemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately elevated plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental renal insufficiency., (© 2022 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored 1,2 . FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10 -11 ) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants., (© 2023. The Author(s).)

Study Question: Can we identify novel variants associated with polycystic ovary syndrome (PCOS) by leveraging the unique population history of Northern Europe?, Summary Answer: We identified three novel genome-wide significant associations with PCOS, with two putative independent causal variants in the checkpoint kinase 2 (CHEK2) gene and a third in myosin X (MYO10)., What Is Known Already: PCOS is a common, complex disorder with unknown aetiology. While previous genome-wide association studies (GWAS) have mapped several loci associated with PCOS, the analysis of populations with unique population history and genetic makeup has the potential to uncover new low-frequency variants with larger effects., Study Design, Size, Duration: A population-based case-control GWAS was carried out., Participants/materials, Setting, Methods: We identified PCOS cases from national registers by ICD codes (ICD-10 E28.2, ICD-9 256.4, or ICD-8 256.90), and all remaining women were considered controls. We then conducted a three-stage case-control GWAS: in the discovery phase, we had a total of 797 cases and 140 558 controls from the FinnGen study. For validation, we used an independent dataset from the Estonian Biobank, including 2812 cases and 89 230 controls. Finally, we performed a joint meta-analysis of 3609 cases and 229 788 controls from both cohorts. Additionally, we reran the association analyses including BMI as a covariate, with 2169 cases and 160 321 controls from both cohorts., Main Results and the Role of Chance: Two out of the three novel genome-wide significant variants associating with PCOS, rs145598156 (P = 3.6×10-8, odds ratio (OR) = 3.01 [2.02-4.50] minor allele frequency (MAF) = 0.005) and rs182075939 (P = 1.9×10-16, OR = 1.69 [1.49-1.91], MAF = 0.04), were found to be enriched in the Finnish and Estonian populations and are tightly linked to a deletion c.1100delC (r2 = 0.95) and a missense I157T (r2 = 0.83) in CHEK2. The third novel association is a common variant near MYO10 (rs9312937, P = 1.7 × 10-8, OR = 1.16 [1.10-1.23], MAF = 0.44). We also replicated four previous reported associations near the genes Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4), DENN Domain Containing 1A (DENND1A), FSH Subunit Beta (FSHB) and Zinc Finger And BTB Domain Containing 16 (ZBTB16). When adding BMI as a covariate only one of the novel variants remained genome-wide significant in the meta-analysis (the EstBB lead signal in CHEK2 rs182075939, P = 1.9×10-16, OR = 1.74 [1.5-2.01]) possibly owing to reduced sample size., Large Scale Data: The age- and BMI-adjusted GWAS meta-analysis summary statistics are available for download from the GWAS Catalog with accession numbers GCST90044902 and GCST90044903., Limitations, Reasons for Caution: The main limitation was the low prevalence of PCOS in registers; however, the ones with the diagnosis most likely represent the most severe cases. Also, BMI data were not available for all (63% for FinnGen, 76% for EstBB), and the biobank setting limited the accessibility of PCOS phenotypes and laboratory values., Wider Implications of the Findings: This study encourages the use of isolated populations to perform genetic association studies for the identification of rare variants contributing to the genetic landscape of complex diseases such as PCOS., Study Funding/competing Interest(s): This work has received funding from the European Union's Horizon 2020 research and innovation programme under the MATER Marie Skłodowska-Curie grant agreement No. 813707 (N.P.-G., T.L., T.P.), the Estonian Research Council grant (PRG687, T.L.), the Academy of Finland grants 315921 (T.P.), 321763 (T.P.), 297338 (J.K.), 307247 (J.K.), 344695 (H.L.), Novo Nordisk Foundation grant NNF17OC0026062 (J.K.), the Sigrid Juselius Foundation project grants (T.L., J.K., T.P.), Finska Läkaresällskapet (H.L.) and Jane and Aatos Erkko Foundation (H.L.). The funders had no role in study design, data collection and analysis, publishing or preparation of the manuscript. The authors declare no conflicts of interest., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Elevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial., Methods: We investigated in a cross-sectional setting the association of PUA with hemodynamics in 606 normotensive and never-medicated hypertensive subjects (295 men, 311 women, age range 19-73 years) without cardiovascular disease or gout. In all except 15 individuals, PUA was within the normal range. Supine hemodynamics were recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis., Results: The mean concentrations of PUA in age, sex and body mass index adjusted quartiles were 234, 278, 314, and 373 µmol/l, respectively. The highest PUA quartile presented with higher aortic to popliteal pulse wave velocity (PWV) than the lowest quartile (8.7 vs. 8.2 m/s, p = 0.026) in analyses additionally adjusted for plasma concentrations of C-reactive protein, low density lipoprotein cholesterol, triglycerides, and mean aortic blood pressure. No differences in radial and aortic blood pressure, wave reflections, heart rate, cardiac output, and systemic vascular resistance were observed between the quartiles. In linear regression analysis, PUA was an independent explanatory factor for PWV (β = 0.168, p < 0.001, R 2 of the model 0.591), but not for systolic or diastolic blood pressure. When the regression analysis was performed separately for men and women, PUA was an independent predictor of PWV in both sexes., Conclusions: PUA concentration was independently and directly associated with large arterial stiffness in individuals without cardiovascular disease and PUA levels predominantly within the normal range. Trial registration ClinicalTrials.gov NCT01742702.

Immune checkpoint inhibitor and chimeric antigen receptor T-cell therapies are associated with a unique spectrum of complications termed immune-related adverse events (irAEs). The abdomen is the most frequent site of severe irAEs that require hospitalization with life-threatening consequences. Most abdominal irAEs such as enterocolitis, hepatitis, cholangiopathy, cholecystitis, pancreatitis, adrenalitis, and sarcoid-like reaction are initially detected on imaging such as ultrasonography (US), CT, MRI and fusion 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT during routine surveillance of cancer therapy. Early recognition and diagnosis of irAEs and immediate management with cessation of immune modulator cancer therapy and institution of immunosuppressive therapy are necessary to avert morbidity and mortality. Diagnosis of irAEs is confirmed by tissue sampling or by follow-up imaging demonstrating resolution. Abdominal radiologists reviewing imaging on patients being treated with anti-cancer immunomodulators should be familiar with the imaging manifestations of irAEs.

OBJECTIVE. The purpose of this study is to assess the frequency of atypical response patterns in oncology patients treated with the programmed cell death protein-1 inhibitor nivolumab. MATERIALS AND METHODS. This retrospective study included 254 patients treated with nivolumab alone or in combination, from January 2013 through August 2017. A blinded reader prospectively assessed treatment response. Among 166 patients (65%) who experienced a clinical benefit (defined as stable disease, partial response, or complete response as the best response), four response patterns were identified: pattern 1 is a decrease or less than 20% increase in the sum of the longest dimension (SLD) without a return to below the nadir, pattern 2 is a 10-19% increase in SLD with a return to below the nadir, pattern 3 is a 20% or greater increase in SLD with a return to below the nadir (classic pseudoprogression), and pattern 4 is the development of new lesions with a decrease in SLD lasting through at least two consecutive scans. Patterns 2, 3, and 4 were defined as atypical response patterns. RESULTS. Of 166 patients who experienced a clinical benefit, pattern 1 was seen in 133 (80%), pattern 2 was seen in 15 (9%), pattern 3 was seen in two (1%), and pattern 4 was seen in 16 (10%) patients. Thus, atypical response patterns were seen in 33 (20%) patients who experienced a clinical benefit, including 25 of 91 (27%) taking nivolumab and ipilimumab combined, six of 46 (13%) taking nivolumab alone, and two of 29 (7%) taking a combination of nivolumab and another chemotherapeutic agent ( p = 0.02). CONCLUSION. Although classic pseudoprogression was rare, an atypical response was seen in 20% of patients who experienced a clinical benefit, and a delayed response up to 24 months of therapy may be seen. Radiologists should be aware of these atypical patterns to avoid errors in response assessment.

Objective: A scoring system has been proposed to predict gross residual disease at primary debulking surgery (PDS) for advanced epithelial ovarian cancer. This scoring system has not been assessed in patients undergoing neoadjuvant chemotherapy (NACT). The aim of this study is to assess the reproducibility and prognostic significance of the scoring system when applied to women undergoing NACT followed by interval debulking surgery (IDS)., Methods: A retrospective cohort study was conducted of patients with advanced ovarian cancer who underwent NACT and IDS between 2005 and 2014. Change in tumor burden using computed tomography (CT) at diagnosis (T0) and after initiation of NACT but before IDS (T1) was independently assessed by two radiologists blinded to outcomes using two read criteria: a scoring system utilizing clinical and radiologic criteria and RECIST 1.1. Relationship between CT assessments to surgical outcome, progression free survival (PFS) and overall survival (OS) were evaluated. Reader agreement was measured using Fleiss's kappa (ĸ)., Results: 76 patients were analyzed. Optimal surgical outcome was achieved in 69 (91%) of patients. Median progression free survival was 13.2 months and overall survival was 32.6 months, respectively. Predictive score change from T0 to T1 of >1 (denoting an improvement in disease burden) was associated with optimal cytoreduction (p = 0.02 and 0.01 for readers 1 and 2, respectively). Neither predictive score nor RECIST 1.1 assessment was predictive of OS or PFS. Reader agreement was substantial for predictive score (κ = 0.77) and moderate for RECIST (κ = 0.51) assessments., Conclusions: A change in score before and after neoadjuvant chemotherapy minimizes reader variability and predicts surgical outcome., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors are a new class of cancer therapeutics that have demonstrated striking successes in a rapid series of clinical trials. Consequently, these drugs have dramatically increased in clinical use since being first approved for advanced melanoma in 2011. Current indications in addition to melanoma are non-small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma, and classical Hodgkin lymphoma. A small subset of patients treated with immune checkpoint inhibitors undergoes an atypical treatment response pattern termed pseudoprogression: New or enlarging lesions appear after initiation of therapy, thereby mimicking tumor progression, followed by an eventual decrease in total tumor burden. Traditional response standards applied at the time of initial increase in tumor burden can falsely designate this as treatment failure and could lead to inappropriate termination of therapy. Currently, when new or enlarging lesions are observed with immune checkpoint inhibitors, only follow-up imaging can help distinguish patients with pseudoprogression from the large majority in whom this observation represents true treatment failure. Furthermore, the unique mechanism of immune checkpoint inhibitors can cause a distinct set of adverse events related to autoimmunity, which can be severe or life threatening. Given the central role of imaging in cancer care, radiologists must be knowledgeable about immune checkpoint inhibitors to correctly assess treatment response and expeditiously diagnose treatment-related complications. The authors review the molecular mechanisms and clinical applications of immune checkpoint inhibitors, the current strategy to distinguish pseudoprogression from progression, and the imaging appearances of common immune-related adverse events. © RSNA, 2017.

Background: Recent studies suggest a causal role for increased plasma uric acid in the progression of chronic renal insufficiency (CRI). However, uric acid also functions as an antioxidant with possible beneficial effects., Methods: We investigated the influence of hyperuricemia on mesenteric arterial tone (main and second order branch) and morphology in experimental CRI. Forty-four Sprague-Dawley rats were 5/6 nephrectomized (NX) or Sham-operated and fed 2.0% oxonic acid or control diet for 9 weeks., Results: Oxonic acid feeding elevated plasma uric acid levels 2.4 and 3.6-fold in the NX and Sham groups, respectively. Plasma creatinine and urea were elevated 2-fold and blood pressure increased by 10 mmHg in NX rats, while hyperuricemia did not significantly influence these variables. Right and left ventricular weight, and atrial and B-type natriuretic peptide mRNA content were increased in NX rats, but were not affected by hyperuricemia. In the mesenteric artery, hyperuricemia did not influence vasoconstrictor responses in vitro to norepinephrine or potassium chloride. The small arteries of NX rats featured hypertrophic remodeling independent of uric acid levels: wall to lumen ratio, wall thickness and cross-sectional area were increased without changes in lumen diameter. In the main branch, vasorelaxations to acetylcholine were impaired in NX rats, but were not affected by hyperuricemia. In contrast, relaxations to the large-conductance Ca(2+)-activated K(+)-channel (BKCa) opener NS-1619 were reduced by oxonic acid feeding, whereas responses to nitroprusside were not affected., Conclusions: Experimental hyperuricemia did not influence cardiac load or vascular remodeling, but impaired BKCa -mediated vasorelaxation in experimental CRI.

Background: Rheumatic diseases in children are associated with significant morbidity and poor health-related quality of life (HRQOL). There is no health-related quality of life (HRQOL) scale available specifically for children with less common rheumatic diseases. These diseases share several features with systemic lupus erythematosus (SLE) such as their chronic episodic nature, multi-systemic involvement, and the need for immunosuppressive medications. HRQOL scale developed for pediatric SLE will likely be applicable to children with systemic inflammatory diseases., Findings: We adapted Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY©) to Simple Measure of Impact of Illness in Youngsters (SMILY©-Illness) and had it reviewed by pediatric rheumatologists for its appropriateness and cultural suitability. We tested SMILY©-Illness in patients with inflammatory rheumatic diseases and then translated it into 28 languages. Nineteen children (79% female, n=15) and 17 parents participated. The mean age was 12±4 years, with median disease duration of 21 months (1-172 months). We translated SMILY©-Illness into the following 28 languages: Danish, Dutch, French (France), English (UK), German (Germany), German (Austria), German (Switzerland), Hebrew, Italian, Portuguese (Brazil), Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish (Argentina), Spanish (Mexico), Spanish (Venezuela), Turkish, Afrikaans, Arabic (Saudi Arabia), Arabic (Egypt), Czech, Greek, Hindi, Hungarian, Japanese, Romanian, Serbian and Xhosa., Conclusion: SMILY©-Illness is a brief, easy to administer and score HRQOL scale for children with systemic rheumatic diseases. It is suitable for use across different age groups and literacy levels. SMILY©-Illness with its available translations may be used as useful adjuncts to clinical practice and research.

Purpose: The purposes of this study were to describe the imaging features and metastatic pattern of non-inferior vena cava (IVC) retroperitoneal leiomyosarcomas (non-IVC LMS) and to compare them with those of IVC leiomyosarcomas (IVC LMS) to assess any differences between the 2 groups., Materials and Methods: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, all 56 patients with pathologically confirmed primary retroperitoneal leiomyosarcoma (34 non-IVC LMS and 22 IVC LMS) seen at our tertiary cancer center during a 10-year period were included. All available imaging of primary tumor (18 non-IVC LMS and 19 IVC LMS) and follow-up imaging studies (on all 56 patients) were reviewed in consensus by 2 fellowship-trained oncoradiologists. Imaging features and metastatic spread of non-IVC LMS were described and compared with those of IVC LMS. Continuous variables were compared using the Student t test, binary variables with the Fisher exact test, and survival using the log-rank test., Results: Non-inferior vena cava retroperitoneal leiomyosarcomas had a mean size of 11.3 cm (range, 3.7-27 cm) and most commonly occurred in the perirenal space (16/18). Primary tumors were hyperattenuating to muscle (11/18) and showed heterogeneous enhancement (17/18). Lungs (22/34), peritoneum (18/34), and liver (18/34) were the most common metastatic sites. There was no significant difference between the imaging features and metastatic pattern of non-IVC and IVC LMS. Although non-IVC LMS presented at a more advanced stage (P < 0.002), there was statistically non-significant trend toward better median survival of non-IVC LMS (P = 0.07)., Conclusions: Non-inferior vena cava retroperitoneal leiomyosarcomas are large heterogeneous tumors arising in the perirenal space and frequently metastasize to lungs, peritoneum, and liver. From a radiologist's perspective, non-IVC LMS behave similar to IVC-LMS.

Objective: To describe MRI, MDCT features, and clinical outcome of extremity leiomyosarcomas (LMS)., Materials and Methods: In this IRB-approved, HIPAA-compliant retrospective study, we included 47 patients (23 women, 24 men; mean age: 55.3 years, range: 17-85 years) with pathologically confirmed extremity LMS seen at our adult tertiary cancer center between 2000 and 2012. MRI/MDCT of primary tumors in 23 patients and follow-up in all patients were reviewed by two radiologists in consensus. Clinical data were extracted from electronic medical records., Results: Primary tumors were distributed in bones (6 out of 47), deep soft tissues (24 out of 47), and superficial soft tissues (17 out of 47). On imaging (bone = 4, deep soft tissue = 11, superficial soft tissue = 8), compared with skeletal muscle, they were T1 iso-hypointense and T2 hyperintense. Bone LMS were metaphyseal tumors with cortical destruction (3 out of 4). Deep soft-tissue LMS were large with hemorrhage (7 out of 11) and necrosis (10 out of 11). Superficial soft-tissue LMS were relatively smaller, homogeneously enhancing (6 out of 8) tumors. Distant metastases developed in 32 out of 47 patients (bone LMS [6 out of 6], deep soft-tissue LMS [18 out of 24], superficial soft-tissue LMS [8 out of 17]), commonly to lung (29 out of 47) and bone (14 out of 47). At the time of writing, 22 out of 36 patients (bone LMS [4 out of 6], deep soft-tissue LMS [15 out of 24], superficial soft-tissue LMS [4 out of 17]) have died. There was no statistically significant correlation between metastatic disease and tumor size or grade., Conclusion: Extremity LMS arise in bones and in the deep and superficial soft tissues, frequently metastasize to the lungs, and have a poor prognosis. Superficial LMS tend to have a better prognosis than bone or deep soft-tissue LMS.

Purpose: To compare performance of various tumour response criteria (TRCs) in assessment of regorafenib activity in patients with advanced gastrointestinal stromal tumour (GIST) with prior failure of imatinib and sunitinib., Methods: Twenty participants in a phase II trial received oral regorafenib (median duration 47 weeks; interquartile range (IQR) 24-88) with computed tomography (CT) imaging at baseline and every two months thereafter. Tumour response was prospectively determined on using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, and retrospectively reassessed for comparison per RECIST 1.0, World Health Organization (WHO) and Choi criteria, using the same target lesions. Clinical benefit rate [CBR; complete or partial response (CR or PR) or stable disease (SD)≥16 weeks] and progression-free survival (PFS) were compared between various TRCs using kappa statistics. Performance of TRCs in predicting overall survival (OS) was compared by comparing OS in groups with progression-free intervals less than or greater than 20 weeks by each TRC using c-statistics., Results: PR was more frequent by Choi (90%) than RECIST 1.1, RECIST 1.0 and WHO (20% each), however, CBR was similar between various TRCs (overall CBR 85-90%, 95-100% agreement between all TRC pairs). PFS per RECIST 1.0 was similar to RECIST 1.1 (median 44 weeks versus 58 weeks), and shorter for WHO (median 34 weeks) and Choi (median 24 weeks). With RECIST 1.1, RECIST 1.0 and WHO, there was moderate concordance between PFS and OS (c-statistics 0.596-0.679). Choi criteria had less favourable concordance (c-statistic 0.506)., Conclusions: RECIST 1.1 and WHO performed somewhat better than Choi criteria as TRC for response evaluation in patients with advanced GIST after prior failure on imatinib and sunitinib., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The purpose of this article is to illustrate the imaging findings of typical and atypical metastatic sites of recurrent endometrial carcinoma. Typical sites include local pelvic recurrence, pelvic and para-aortic nodes, peritoneum, and lungs. Atypical sites include extra-abdominal lymph nodes, liver, adrenals, brain, bones and soft tissue. It is important for radiologists to recognize the typical and atypical sites of metastases in patients with recurrent endometrial carcinoma to facilitate earlier diagnosis and treatment.

Objective: The purpose of this study was to evaluate the utilization and role of MRI in the management of myeloid sarcoma in adults., Materials and Methods: A retrospective study of 69 patients with pathologically proven myeloid sarcoma included 25 patients (16 men, nine women; mean age, 55 years; range, 22-78 years) who underwent pretreatment MRI at our institution from January 2001 to October 2011. A total of 71 MRI examinations were evaluated by two radiologists in consensus., Results: A total of 41 sites of involvement of myeloid sarcoma were noted, most commonly bone (13/25, 52%), muscle (7/25, 28%), CNS (6/25, 24%), and head and neck (6/25, 24%). Nineteen sites were noted on MR images obtained for evaluation of a new sign or symptom, most commonly musculoskeletal (11 sites) and CNS (six sites). Fifteen sites were noted on MR images obtained for further evaluation of a previously detected abnormality, most commonly in the abdomen and pelvis (seven sites). Seven lesions were incidentally found on MR images obtained for other myeloid sarcoma-related indications, most commonly in the head and neck (three lesions) and musculoskeletal system (three lesions). The mean size of measurable lesions was 5.6 cm (range, 1-20 cm). Compared with muscle, the lesions were isointense (31/41, 75.6%) or hypointense (10/41, 24.4%) on T1-weighted images and mildly hyperintense (39/41, 95.1%) on T2-weighted images and had homogeneous enhancement (29/38, 76.3%)., Conclusion: In our experience, MRI was most often used for evaluation of bone, muscle, the CNS, and the head and neck region. MRI is useful for evaluation of new musculoskeletal and CNS findings and for further evaluation of known abdominopelvic masses. Incidental findings are often musculoskeletal or in the soft tissues of the head and neck.

Objectives: We hypothesized that the extent of aortic atheroma of the entire thoracic aorta, determined by pre-operative multidetector-row computed tomographic angiography (MDCTA), is associated with long-term mortality following nonaortic cardiothoracic surgery., Background: In patients evaluated for cardiothoracic surgery, presence of severe aortic atheroma is associated with adverse short- and long-term post-operative outcome. However, the relationship between aortic plaque burden and mortality remains unknown., Methods: We reviewed clinical and imaging data from all patients who underwent electrocardiographic-gated contrast-enhanced MDCTA prior to coronary bypass or valvular heart surgery at our institution between 2002 and 2008. MDCTA studies were analyzed for thickness and circumferential extent of aortic atheroma in 5 segments of the thoracic aorta. A semiquantitative total plaque-burden score (TPBS) was calculated by assigning a score of 1 to 3 to plaque thickness and to circumferential plaque extent. When combined, this resulted in a score of 0 to 6 for each of the 5 segments and, hence, an overall score from 0 to 30. The primary end point was all-cause mortality during long-term follow-up., Results: A total of 862 patients (71% men, 67.8 years) were included and followed over a mean period of 25 ± 16 months. The mean TPBS was 8.6 (SD: ±6.0). The TPBS was a statistically significant predictor of mortality (p < 0.0001) while controlling for baseline demographics, cardiovascular risk factors, and type of surgery including reoperative status. The estimated hazard ratio for TPBS was 1.08 (95% confidence interval: 1.045 to 1.12). Other independent predictors of mortality were glomerular filtration rate (p = 0.015), type of surgery (p = 0.007), and peripheral artery disease (p = 0.03)., Conclusions: Extent of thoracic aortic atheroma burden is independently associated with increased long-term mortality in patients following cardiothoracic surgery. Although our data do not provide definitive evidence, they suggest a relationship to the systemic atherosclerotic disease process and, therefore, have important implications for secondary prevention in post-operative rehabilitation programs., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We sought to examine whether contrast-enhanced multidetector row computed tomography (MDCT) allows prediction of X-ray angiographic planes for the root angiogram in the context of transcatheter aortic valve implantation., Background: Understanding of aortic root orientation relative to the body axis is critical for precise positioning of the stent/valve during transcatheter aortic valve implantation., Methods: Forty patients with severe aortic stenosis underwent conventional X-ray angiography and contrast-enhanced MDCT of the aortic root. Oblique MDCT images of the aortic root, corresponding to X-ray angiographic left anterior oblique (LA)/right anterior oblique (RAO) projections, were created. The cranial/caudal angulation was compared between angiographic and reformatted MDCT images. In addition, root diameter measurements were compared., Results: The cranial angulation in the LAO X-ray angiograms (mean LAO: 39+/- 8, n = 38) and matched MDCT images were not significantly different (cranial: 25 +/- 7 vs. 23 +/- 8; p = 0.214). There was a small but significant difference between the caudal angulation in the RAO angiogram (mean RAO: 25 +/- 5, n = 40) and matched CT images (caudal: 21 +/- 9 vs. 29 +/- 10; p = 0.002). The annulus diameter in the LAO projection was not significantly different between X-ray angiography and contrast-enhanced MDCT (2.3 +/- 0.3 vs. 2.4 +/- 0.3; p = 0.052), whereas there was a small but significant difference in the annulus diameter in RAO projections between angiography and MDCT (2.4 +/- 0.3 vs. 2.2 +/- 0.3; p = 0.029)., Conclusions: Pre-procedural contrast-enhanced MDCT imaging of the aortic root allows prediction of X-ray angiographic planes and contributes to planning of the transcatheter aortic valve implantation., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Percutaneous aortic valve insertion is an emerging treatment option for selected patients with severe aortic stenosis and may be done from a transfemoral or transapical approach. Concomitant atherosclerotic peripheral artery disease limits transfemoral access. We evaluated the potential role of multidetector computed tomography in preoperative assessment of vascular anatomy., Methods: Consecutive patients with severe aortic stenosis were included. Contrast-enhanced computed tomographic angiography of the thoracic and abdominal aorta and iliofemoral arteries was performed. Criteria of unfavorable iliofemoral anatomy were defined as a minimal luminal diameter of the common iliac, external iliac, or common femoral arteries of less than 8 mm, presence of greater than 60% circumferential calcification at the external-internal iliac bifurcation, and severe angulation between the common and external iliac arteries (< 90 degrees ). The prevalence of these criteria was evaluated and infrarenal aortic and iliofemoral arterial anatomy was compared in the groups with and without peripheral artery disease for any of these criteria., Results: One hundred patients (79 +/- 9 years, 59% male) were included. A total of 35 (35%) patients had at least one criterion of unsuitable iliofemoral anatomy, including 27 patients with small minimal luminal diameter (<8 mm), 12 patients with severe circumferential calcification at the iliac bifurcation (>60%), and 4 with severe angulation of the iliac arteries (<90 degrees )., Conclusions: Significant atherosclerotic peripheral artery disease is common in the high-risk patient population currently evaluated for percutaneous aortic valve insertion. Computed tomography allows identification of patients with iliofemoral anatomy unfavorable for the transfemoral approach to percutaneous aortic valve insertion.

Objective: Percutaneous aortic valve replacement is an emerging therapy for selected patients with severe aortic stenosis. Preoperative imaging of the aortic root facilitates sizing and deployment of the percutaneous aortic valve replacement device. We compared morphologic characteristics of the aortic root in patients with aortic stenosis versus elderly gender-matched controls using multidetector computed tomography., Methods: Twenty-five consecutive subjects with severe calcific aortic stenosis referred for percutaneous aortic valve replacement and 25 elderly gender-matched controls were scanned on a Siemens Definition Dual Source (Siemens Medical, Forchheim, Germany) multidetector computed tomography scanner. Distances from the valve annulus to the coronary artery ostia and sinotubular junction, dimensions of the aortic root, and characteristics of the valve cusps were determined., Results: Subjects with aortic stenosis had reduced distance from the aortic valve annulus to the inferior margins of the left and right coronary artery ostium and sinotubular junction compared with controls. There were no significant differences in cross-sectional dimensions of the aortic root., Conclusion: The distance from the aortic valve annulus to the coronary artery ostia and sinotubular junction is reduced in patients with aortic stenosis compared with controls. This finding suggests that longitudinal remodeling of the aortic root occurs in calcific aortic stenosis and has implications for the design and deployment of percutaneous aortic valve replacement devices.

A pressure-normalized left ventricular (LV) wall stress (dsigma*/dt(max)) was recently reported as a load-independent index of LV contractility. We hypothesized that this novel contractility index might demonstrate improvement in LV contractile function after surgical ventricular restoration (SVR) using magnetic resonance imaging. A retrospective analysis of magnetic resonance imaging data of 40 patients with ischemic cardiomyopathy who had undergone coronary artery bypass grafting with SVR was performed. LV volumes, ejection fraction, global systolic and diastolic sphericity, and dsigma*/dt(max) were calculated. After SVR, a decrease was found in end-diastolic and end-systolic volume indexes, whereas LV ejection fraction increased from 26% +/- 7% to 31% +/- 10% (p <0.001). LV mass index and peak normalized wall stress were decreased, whereas the sphericity index (SI) at end-diastole increased, indicating that the left ventricle became more spherical after SVR. LV contractility index dsigma*/dt(max) improvement (from 2.69 +/- 0.74 to 3.23 +/- 0.73 s(-1), p <0.001) was associated with shape change as evaluated by the difference in SI between diastole and systole (r = 0.32, p <0.001, preoperative; r = 0.23, p <0.001, postoperative), but not with baseline LV SI. In conclusion, SVR excludes akinetic LV segments and decreases LV wall stress. Despite an increase in sphericity, LV contractility, as determined by dsigma*/dt(max), actually improves. A complex interaction of LV maximal flow rate and LV mass may explain the improvement in LV contractility after SVR. Because dsigma*/dt(max) can be estimated from simple noninvasive measurements, this underscores its clinical utility for assessment of contractile function with therapeutic intervention.