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Shaping quality in cardiovascular magnetic resonance: a comparative study of segmentation approaches by trainees and experts
Get PDFBackground: Cardiovascular magnetic resonance (CMR) is an established cardiovascular imaging (CVI) technique. Deficits in training limit the widespread use of CMR. This study analyzed the influence of CVI experience on segmentation, to define quality standards for teaching and supervision. Methods: Four CMR experts determined left ventricular (LV) and right ventricular (RV) gold-standard contours in end-systole (ES) and enddiastole (ED), by consensus. After a brief teaching session, readers independently performed segmentations. Readers were classified as beginners (no previous experience in CVI), intermediates (previous experience in CVI, but not in CMR), or experts (extensive experience in CVI including CMR). Results were compared, and the cause of deviation was analyzed, using metrics such as the Dice similarity coefficient (DSC). Results: A total of 46 readers (19 beginners, 21 intermediates, 6 experts) performed image analysis. Using the DSC, we found significant differences in endocardial LV ED contours (median [interquartile range]: beginners, 92.9% [91.9%-93.5%]); intermediates, 93.5% (93.0%-94.1%); experts, 93.9% (93.1%-94.3%); P ¼ 0.043) and in myocardial contours (beginners, 79.0% (75.0%-80.9%); intermediates, 80.9% (78.0%-82.4%); experts, 85.0% (79.8%-86.5%); p ¼ 0.001). Experts had higher DSC scores for the right ventricle (ES: beginners, 83.8% (81.3%-85.8%); intermediates, 81.7% (79.6%-85.6%); experts, 89.0% (86.6%-89.8%); P ¼ 0.003; ED: beginners, 89.2% (88.1%90.3%); intermediates, 88.6% (87.9%-89.2%); experts, 91.6% (89.8%93.3%); P ¼ 0.002). The disagreements were not traceable in absolute volume and function (P for all > 0.2). Sources of disagreement were related mainly to handling of basal slices. Conclusions: After a brief standardized teaching session, beginners and intermediates performed chamber quantification consistent with that of experts. Differences, especially in LV mass and RV segmentations, warrant continuous training, ideally accompanied by automatic methods for quality assurance
Sex differences in children and adolescents with hypertrophic cardiomyopathy
Get PDFBACKGROUND: Sex differences have been described in adults with hypertrophic cardiomyopathy (HCM), but it is unknown if similar differences exist in childhood-onset disease. OBJECTIVES: This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of children with HCM. METHODS: An international retrospective cohort of patients diagnosed with nonsyndromic HCM ≤16 years was formed. Sex differences in baseline characteristics and clinical outcomes were investigated. Primary outcome was all-cause mortality or cardiac transplantation. Secondary outcomes include major arrhythmic cardiac event and heart failure event. RESULTS: Of 1,433 patients diagnosed at a median age of 11 years (IQR: 6-14), 471 (33.0%) were female. Although there were no sex differences in phenotype in preadolescent patients (<12 years), adolescent female patients were more likely to have heart failure symptoms (n = 53 [31.9%] vs n = 86 [22.5%]; P = 0.019). Adolescent female patients had larger left atrial size (1.4 z-score [±2.3] vs 2.1 z-score [±2.5]; P = 0.0056) but there was no difference in degree of hypertrophy or proportion with obstructive disease. Over a median follow-up of 5.3 years (IQR: 2.9, 8.0) annual incidence of all-cause mortality or cardiac transplantation, major arrhythmic cardiac event or heart failure events did not vary by sex. CONCLUSIONS: Young female patients with HCM are more likely to experience heart failure symptoms and have echocardiographic features of diastolic impairment. Despite differences in phenotype, outcomes during childhood and young adulthood are not different. Further studies are required to explore the underlying mechanisms for these observed differences
Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development
Get PDFBats are the only mammals capable of self-powered flight, an evolutionary innovation based on the transformation of forelimbs into wings. The bat wing is characterized by an extreme elongation of the second to fifth digits with a wing membrane called the chiropatagium connecting them. Here we investigated the developmental and cellular origin of this structure by comparing bat and mouse limbs using omics tools and single-cell analyses. Despite the substantial morphological differences between the species, we observed an overall conservation of cell populations and gene expression patterns including interdigital apoptosis. Single-cell analyses of micro-dissected embryonic chiropatagium identified a specific fibroblast population, independent of apoptosis-associated interdigital cells, as the origin of this tissue. These distal cells express a conserved gene programme including the transcription factors MEIS2 and TBX3, which are commonly known to specify and pattern the early proximal limb. Transgenic ectopic expression of MEIS2 and TBX3 in mouse distal limb cells resulted in the activation of genes expressed during wing development and phenotypic changes related to wing morphology, such as the fusion of digits. Our results elucidate fundamental molecular mechanisms of bat wing development and illustrate how drastic morphological changes can be achieved through repurposing of existing developmental programmes during evolution
Management and burden of disease in people with myelin oligodendrocyte glycoprotein antibody-associated disease: data from an international, cross-sectional survey
Get PDFBACKGROUND: There are challenges in the diagnosis of myelin-oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and a current lack of targeted treatments. This study investigated the disease management and burden of MOGAD in a real-world setting. METHODS: Data were derived from the Adelphi MOGAD Disease Specific Programme (DSP)™, a cross-sectional survey of neurologists and their consulting patients with MOGAD, conducted in Europe and the United States in 2022. Neurologists reported on patient demographics, clinical characteristics, disease management history, treatments prescribed and burden of disease. Patients voluntarily reported on their perceptions on burden of disease. All analyses were descriptive. RESULTS: Overall, 74 neurologists provided data for 268 consecutively consulting patients with MOGAD, of whom 66 completed voluntary questionnaires. Sixty four percent of patients received a preliminary/alternative diagnoses, and patients underwent a median (Q1, Q3) of 12.0 (9.0; 19.0) blood tests, assessments and/or scans to confirm MOGAD diagnosis. The median (interquartile range, Q1, Q3) physician-reported time from symptom onset to preliminary/alternative diagnosis was 19.0 (0.0; 59.0) days, and from symptom onset to definitive diagnosis 64.0 (31.0; 150.2) days. At time of the survey, 91.8% and 83.5% of patients were prescribed acute and maintenance treatment, respectively. Symptomatic burden remained moderately high, with patients reporting quality of life (QoL) and work productivity impairments. CONCLUSION: Patients with MOGAD may suffer from challenges in diagnosis, and disease management remains suboptimal, with burden to patients affecting their QoL and ability to work. Both the diagnosis and treatment of MOGAD should continue to be the subject of further research
Clinical and echocardiographic phenotype of cardiac wasting in patients with advanced cancer
Get PDFAIMS: Cardiac wasting-associated cardiomyopathy in patients with advanced cancer is characterized by loss of left ventricular (LV) mass and independently associated with poor prognosis. Better understanding of this very prevalent cardiomyopathy is urgently needed. METHODS AND RESULTS: Overall, 398 patients with active, mostly advanced cancer without significant cardiovascular disease (mean LV ejection fraction [LVEF] 64.3 ± 0.2%) or active infection were prospectively examined (mean age 60 ± 1 years, 50% women, body mass index 25.0 ± 0.2 kg/m, 26% cachectic). Patients were categorized and compared by quartiles of LV mass/height. LVEF, global longitudinal strain (GLS), and anticancer therapy naive status were similar across quartiles. Patients in Q1 (lowest LV mass quartile) were younger, more likely cachectic, had lower: BMI, 10-step stair-climbing power, tricuspid annular plane systolic excursion (TAPSE), stroke volume, cardiac output, and higher heart rate. In repeat follow-up assessments after 140 ± 8 days (n = 143), LVEF, TAPSE, LV mass, left atrial volume, and GLS were found reduced (all p ≤ 0.002). Only in those with above-median LV mass at baseline, cardiac output and heart rate increased during follow-up - in those with below-median LV mass, mitral E/A decreased. CONCLUSIONS: Patients with advanced cancer with low LV mass have a distinct phenotype characterized by lower cardiac chamber volumes, stroke volume, and cardiac output, but normal LVEF and GLS that may be the distinct feature of cardiac wasting-associated cardiomyopathy
Immune cell membrane protrusions as sensory organelles
Get PDFImmune cells possess a remarkable set of complementary surface protrusions, such as microvilli, podosomes, filopodia, and lamellipodia, which play pivotal roles in the sensing of and responding to varied environmental cues. These dynamic structures maximize the surface area–to–volume ratio of immune cells, which in turn enhances cell–cell and cell–matrix interactions, while generating pulling and pushing forces, allowing immune cells to integrate biochemical and physical cues from their surroundings. This review discusses recent insights into the structures and dynamics of different protrusions, the molecular machinery behind mechanosensing, the differential role of protrusions for different subsets of immune cells, and the cutting-edge technology that has advanced our understanding of those protrusions
Prevalence of the central vein sign on susceptibility-weighted imaging in people with pediatric-onset multiple sclerosis
Get PDFBACKGROUND AND OBJECTIVES: iven the high sensitivity but only moderate specificity of current diagnostic criteria for multiple sclerosis (MS), novel diagnostic biomarkers for pediatric-onset MS (POMS) are highly warranted. The central vein sign (CVS) is a such promising MRI biomarker candidate that has been shown to distinguish MS from other neuroimmunologic diseases with high specificity. The aim of this study was to assess the prevalence of the CVS in POMS under real-world conditions by analyzing T2-hyperintense lesions using 1.5T susceptibility-weighted imaging (SWI). METHODS: We retrospectively reviewed clinical MRI scans acquired at 1.5T in patients with POMS based on International Paediatric Multiple Sclerosis Study Group criteria and 2017 McDonald criteria at first clinical presentation. Each examination included (1) fluid-attenuated inversion recovery in sagittal, axial, or coronal plane and (2) SWI sequences obtained in the axial plane. Lesions with diameters >3 mm were assessed for CVS according to the North American Imaging in Multiple Sclerosis Cooperative criteria, and Select6* criteria were applied in every patient by 2 experienced raters. RESULTS: We assessed 31 POMS patients (mean age 13.8 ± 2.6 years; 81% female) with 4 children initially diagnosed as patients with radiologically isolated syndrome (RIS). In total, 535 of 605 T2-hyperintense cerebral lesions were assessable for CVS evaluation, corresponding to a median number of 14 (IQR: 6–21], range 2–57) lesions per patient adequate for CVS assessment. Most lesions were characterized as periventricular (n = 201 [37.6%]), while 20 cortical lesions (3.7%) were detected. The median individual CVS percentage per patient was 75% (IQR: 70%–82%). All POMS patients exhibited a CVS percentage above 40% and fulfilled Select6* criteria, including those investigated at the time of RIS. DISCUSSION: CVS was frequently observed in T2-hyperintense lesions of patients with POMS, consistent with the proposed MS-specific Select6* criteria and above the 40% cutoff, despite the use of heterogeneous MRI protocols at 1.5T under real-world clinical conditions. SWI at 1.5T may therefore hold the potential to increase the specificity of MS diagnostic criteria also in pediatric patients
Extracellular domain of the Fap2 autotransporter adhesin from Fusobacterium nucleatum ATCC23726
No full textThe postdoc paradox: a career without a path
No full textLike characters in Waiting for Godot, postdocs stand still: trained, ready and full of promise, caught in an endless wait for something that may never come