It Takes a Village: Multimodality Imaging of Cardiac Amyloidosis

Cardiac amyloidosis (CA) is the buildup and infiltration of amyloid plaque in cardiac muscle. An underdiagnosed form of restrictive cardiomyopathy, CA can rapidly progress into heart failure. CA is evaluated using a multimodality approach that includes echocardiography, cardiac magnetic imaging, and nuclear imaging. Echocardiography remains an essential first-line modality that raises suspicion for CA and establishes functional baselines. Cardiac magnetic imaging provides additional incremental value via high-resolution imaging, robust functional assessment, and superior tissue characterization, all of which enable a more comprehensive investigation of CA. Cardiac scintigraphy has eliminated the need for invasive diagnostic approaches and helps differentiate CA subtypes. Positron emission tomography is the first modality introducing targeted amyloid binding tracers that allow for precise burden quantification, early detection, and disease monitoring. In this review, we highlight the role of several cardiac imaging techniques in the evaluation of CA.     

Surrogacy Beyond Prognosis: The Importance of “Trial-Level” Surrogacy

Many candidate surrogate endpoints are currently assessed using a 2-level statistical approach, which consists in checking whether (1) the potential surrogate is associated with the final endpoint in individual patients and (2) the effect of treatment on the surrogate can be used to reliably predict the effect of treatment on the final endpoint. In some situations, condition (1) is fulfilled but condition (2) is not. We use concepts of causal inference to explain this apparently paradoxical situation, illustrating this review with 2 contrasting examples in operable breast cancer: the example of pathological complete response (pCR) and that of disease-free survival (DFS). In a previous meta-analysis, pCR has been shown to be a strong and independent prognostic factor for event-free survival (EFS) and overall survival (OS) after neoadjuvant treatment of operable breast cancer. Yet, in randomized trials, the effects of experimental treatments on pCR have not translated into predictable effects on EFS or OS, making pCR an “individual-level” surrogate, but not a “trial-level” surrogate. In contrast, DFS has been shown to be an acceptable surrogate for OS at both the individual and trial levels in early, HER2-positive breast cancer. The distinction between the prognostic and predictive roles of a tentative surrogate, not always made in the literature, avoids unnecessary confusion and allows better understanding of what it takes to validate a surrogate endpoint that is truly able to replace a final endpoint.

Many candidate surrogate endpoints are currently assessed using a two-level statistical approach. This article explores tentative surrogates versus actual outcomes, focusing on the “surrogate paradox”.

Implications for PracticeThe distinction between the prognostic and predictive roles of a tentative surrogate, not always made in the literature, avoids unnecessary confusion and allows better understanding of what it takes to validate a surrogate endpoint that is truly able to replace a final endpoint.     

Experimentally designed chemometric models for the assay of toxic adulterants in turmeric powder

Turmeric is an indispensable culinary spice in different cultures and a principal component in traditional remedies. Toxic metanil yellow (MY), acid orange 7 (AO) and lead chromate (LCM) are deliberately added to adulterate turmeric powder. This work compares the ability of multivariate chemometric models with those of artificial intelligent networks to enhance the selectivity of spectral data for the rapid assay of these three adulterants in turmeric powder. Using a custom experimental design, we provide a data-driven optimization for the sensitive parameters of the partial least squares model (PLS), artificial neural network (ANN) and genetic algorithm (GA). The optimized models are validated using sets of genuine turmeric samples from five different geographical regions spiked with standard adulterant concentrations. The optimized GA-PLS and GA-ANN models reduce the root mean square error of prediction by 18.4%, 31.1% and 55.3% and 25.0%, 69.9% and 88.4% for MY, AO and LCM, respectively.

Turmeric is an indispensable culinary spice in different cultures and a principal component in traditional remedies.     

基于肝药酶CYP3A4、SULT2A1和UGT1A1探究京尼平的代谢解毒路径（英文）

栀子主要药效成分京尼平具有明显的肝毒性,限制了京尼平以及栀子的应用和开发。本文主要以人源性Hepa RG肝细胞为研究对象,基于肝脏主要代谢解毒酶CYP3A4、SULT2A1和UGT1A1探究介导京尼平代谢解毒的具体路径。结果表明, CYP3A4、SULT2A1和UGT1A1协同介导了京尼平于肝脏的代谢解毒,且CYP3A4是起决定因素的限速酶;其最主要代谢解毒路径为:CYP3A4-SULT2A1/UGT1A1,即:京尼平进入肝细胞后,首先经CYP3A4代谢为毒性减轻的I相代谢产物,再经II相代谢酶SULT2A21和UGT1A1代谢为毒性进一步减轻的代谢产物。本研究的结果初步阐明了京尼平的肝代谢解毒路径,为今后京尼平及栀子的合理使用及研发提供了依据,也为将来京尼平以及中药栀子和含栀子的中药组方配伍解毒的研究奠定了基础。     

Prevalence and Correlates of Physical-mental Multimorbidity in Outpatient Children From a Pediatric Hospital in Canada

ObjectiveThe aim of this study was to estimate the six-month prevalence of mental illness in children with chronic physical illness (multimorbidity), examine agreement between parent and child reports of multimorbidity, and identify factors associated with child multimorbidity.MethodThe sample included 263 children aged 2–16 years with a physician-diagnosed chronic physical illness recruited from the outpatient clinics at a pediatric hospital. Children were categorized by physical illness according to the International Statistical Classification of Diseases and Related Health Problems (ICD)-10. Parent and child-reported six-month mental illness was based on the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID).ResultsOverall, 101 (38%) of children had a parent-reported mental illness; 29 (25%) children self-reported mental illness. There were no differences in prevalence across ICD-10 classifications. Parent-child agreement on the MINI-KID was low (κ = 0.18), ranging from κ = 0.24 for specific phobia to κ = 0.03 for attention-deficit hyperactivity. From logistic regression modeling (odds ratio [OR] and 95% confidence interval), factors associated with multimorbidity were: child age (OR = 1.16 [1.04, 1.31]), male (OR = 3.76 [1.54, 9.22]), ≥$90,000 household income (OR = 2.57 [1.08, 6.22]), parental symptoms of depression (OR = 1.09 [1.03, 1.14]), and child disability (OR = 1.21 [1.13, 1.30]). Similar results were obtained when modeling number of mental illnesses.ConclusionsFindings suggest that six-month multimorbidity is common and similar across different physical illnesses. Level of disability is a robust, potentially modifiable correlate of multimorbidity that can be assessed routinely by health professionals in the pediatric setting to initiate early mental health intervention to reduce the incidence of multimorbidity in children.     

Durability of Fibre Reinforced Polymers in Exposure to Dual Environment of Seawater Sea Sand Concrete and Seawater

The consequence of exposure to the dual environment of seawater sea sand concrete (SWSSC) on the inner surface and seawater (SW) on the outer surface on the durability of fibre reinforced plastic (FRP) confining tubes has received very limited research attention. The durability of FRPs fabricated with different fibre types was investigated for the application of SWSSC filled tubes and SWSSC-filled double-skin tubes exposed to the external environment of SW. The colour and shininess of carbon-fibre-reinforced polymer (CFRP) surfaces generally stayed unchanged even after 6 months of exposure to the dual environment, whereas basalt-fibre-reinforced polymer (BFRP) and glass-fibre-reinforced polymer (GFRP) tubes suffered degradation. The degradation led to a ~20–30% increase in pH; however, the pH increase in the external SW was more pronounced when the internal solution was SWSSC. The extent of degradation was greater in BFRP that in GFRP. The investigation also included a specialised investigation of the degradation at the fibre–matrix interface by fracturing specimens in liquid nitrogen.     

Ankle Evaluation in Active Rheumatoid Arthritis by Ultrasound: A Cross-Sectional Study

Ankle joint evaluation is underestimated in many clinical and sonographic scores used for evaluation and follow-up of rheumatoid arthritis (RA) patients. Agreement on examination parameters is poor among sonographic scores that include the ankle joint. More effort is needed to detect the value of ankle joint examination in RA and assessment of ultrasonographic signs according to frequency, disease duration and activity. The objective of this study was to use ultrasound (US) to detect ankle involvement in active RA and to compare findings with disease duration, disease activity and assessment of ankle bone erosion. A total of 63 RA patients with active disease and 20 controls were included in the study. The tibiotalar and talonavicular joints were examined by US for synovitis and/or effusion in gray-scale and power Doppler modes. The anterior, lateral and posterior ankle tendons were examined for tenosynovitis and tendinosis. Mean age was 35.1?±?8.3 y, mean disease duration was 22.7?±?9.6?mo and the mean 28-joint Disease Activity Score–erythrocyte sedimentation rate was 3.05?±?0.66. Ankle involvement was seen in 28 patients (44.4%). The most frequent pathologies detected were tenosynovitis (30.2%), followed by synovitis (18.3%), erosion (8.7%) and tendinosis (4%). The earliest sonographic signs were tenosynovitis, followed by synovitis, erosion and tendinosis. The right ankle exhibited greater involvement than the left ankle, which was significant with respect to erosions (p?=?0.009). The most common tendon affected by tenosynovitis was the tibialis anterior (22.2%), followed by the tibialis posterior (20.6%). Tenosynovitis, especially of the tibialis anterior and posterior, tibiotalar synovitis and erosions should be considered in future US ankle scores for the assessment of RA.