Semi-quantitative Approaches Research Articles

Semi-quantitative evaluation of levees risk within the context of hydrology uncertainty

Risk assessment is necessary to understand whether a levee is safe and able to prevent flood invasion. Most previous assessment methods attempted to quantitatively assess the risks posed by hydraulic structures using probabilistic analysis from a research perspective. The kind of method depends on the probability density function of factors but sometimes difficult to determine either a priori or posteriori in practice. On the other hand, current semi-quantitative methods despite the convenience are somewhat subjective in their implementation. This study sought to rectify the shortcomings of previous quantitative and semi-quantitative approaches to assessing the risk of levee failure wherein the uncertainty of risk factors is presented within a semi-quantitative framework, in accordance with ISO assessment procedures. The risk of levee failure discussed in this work is mainly related to overtopping and erosion of its foundation. This study proposed a semi-quantitative approach to maintain the exactness and objectivity of the risk assessment of levees and use Puzih river in Taiwan as a case study. In this study, we tried to add uncertainty facts and developed a risk assessment framework for levee management using a risk map according to our semi-quantitative methods. This study firstly defines the risk and associated factors within the context of government regulations, then implement a series of risk assessment tasks using the widely used hydraulic and sedimentation transport model, HEC-RAS, to simulate the risk of inundation, where hydrological events are used as a proxy for uncertainty. This study considers that consequence of levee failure and compute representative qualitative indices by which to evaluate hazards using a risk map and risk matrix in order to illustrate potential economic losses under given flood scenarios. After gaining the levee assessment results, the risk map is also built which can be applied on the practical engineering works. Our results reveal that the most secure levees along Puzih river should be able to withstand flood events with a 100-year return period; however, the levees in a several areas fail to provide suitable protection. Accordingly, this work developed a risk map and corresponding flood prevention strategies to decrease the risk in specific regions for the consideration of rive management administration.

Synchrotron FTIR investigations of kerogen from Proterozoic organic-walled eukaryotic microfossils.

Fourier transform infrared spectroscopy (FTIR) provides a rapid non-destructive molecular characterization of organic and inorganic material in geological samples. Combination of qualitative and semi-quantitative approaches are routinely used in FTIR study of kerogen and coals. A diversity of descriptors provides straightforward tools to characterize kerogen type, composition and structure. However, only a few of these descriptors are applied in the chemical investigation of Precambrian organic-walled microfossils. Synchrotron radiation-based Fourier transform infrared microspectroscopy (SR-FTIR) permits high spatial resolution investigations of organic matter in a large range of applications in biology, geochemistry and cosmochemistry, but remains rarely applied in Precambrian microfossils studies. Here we show that SR-FTIR spectroscopy combined with an integrative approach of kerogen description is particularly relevant for the study of minute organic-walled microfossils of unknown biological origin. The analyses of five morphospecies from three different Proterozoic formations in northwestern Canada highlight kerogen signatures rich in aromatic, aliphatic and oxygenated moieties. This is evidenced by the combined use of spectrum qualitative descriptions (band assignments and positions) and the calculations of semi-quantitative parameters using intensities and integrated areas of absorption bands (CH2/CH3, R3/2, Al/CC, CO/CC, A factor, C factor). Altogether, this study demonstrates the interest of an integrative approach when investigating the chemistry of organic-walled microfossils with FTIR spectroscopy.

State of the Art in Lung Ultrasound, Shifting from Qualitative to Quantitative Analyses.

Lung ultrasound (LUS) has been increasingly expanding since the 1990s, when the clinical relevance of vertical artifacts was first reported. However, the massive spread of LUS is only recent and is associated with the coronavirus disease 2019 (COVID-19) pandemic, during which semi-quantitative computer-aided techniques were proposed to automatically classify LUS data. In this review, we discuss the state of the art in LUS, from semi-quantitative image analysis approaches to quantitative techniques involving the analysis of radiofrequency data. We also discuss recent in vitro and in silico studies, as well as research on LUS safety. Finally, conclusions are drawn highlighting the potential future of LUS.

Pharmacokinetic modeling of PSMA-targeted nanobubbles for quantification of extravasation and binding in mice models of prostate cancer.

Contrast-enhanced ultrasound (CEUS) by injection of microbubbles (MBs) has shown promise as a cost-effective imaging modality for prostate cancer (PCa) detection. More recently, nanobubbles (NBs) have been proposed as novel ultrasound contrast agents. Unlike MBs, which are intravascular ultrasound contrast agents, the smaller diameter of NBs allows them to cross the vessel wall and target specific receptors on cancer cells such as the prostate-specific membrane antigen (PSMA). It has been demonstrated that PSMA-targeted NBs can bind to the receptors of PCa cells and show a prolonged retention effect in dual-tumor mice models. However, the analysis of the prolonged retention effect has so far been limited to qualitative or semi-quantitative approaches. This work introduces two pharmacokinetics models for quantitative analysis of time-intensity curves (TICs) obtained from the CEUS loops. The first model is based on describing the vascular input by the modified local density random walk (mLDRW) model and independently interprets TICs from each tumor lesion. Differently, the second model is based on the reference-tissue model, previously proposed in the context of nuclear imaging, and describes the binding kinetics of an indicator in a target tissue by using a reference tissue where binding does not occur. Our results show that four estimated parameters, β, , , for the mLDRW-input model, and γ for the reference-based model, were significantly different (p-value <0.05) between free NBs and PSMA-NBs. These parameters estimated by the two models demonstrate different behaviors between PSMA-targeted and free NBs. These promising results encourage further quantitative analysis of targeted NBs for improved cancer diagnostics and characterization.

Methods to Summarize Discrete-Choice Experiments in a Systematic Review: A Scoping Review.

Systematic reviews of discrete-choice experiments (DCEs) are being increasingly conducted. The objective of this scoping review was to identify and describe the methodologies that have been used to summarize results across DCEs. We searched the electronic databases MEDLINE and EMBASE from inception to March 18, 2021, to identify English-language systematic reviews of patient preferences that included at least two DCEs and extracted data on attribute importance. The methods used to summarize results across DCEs were classified into narrative, semi-quantitative, and quantitative (meta-analytic) approaches and compared. Approaches to characterize the extent of preference heterogeneity were also described. From 7362 unique records, we identified 54 eligible reviews from 2010 to Mar 2021, across a broad range of health conditions. Most (83%) used a narrative approach to summarize findings of DCEs, often citing differences in studies as the reason for not formally pooling findings. Semi-quantitative approaches included summarizing the frequency of the most important attributes, the frequency of attribute statistical significance, or tabulated comparisons of attribute importance for each pair of attributes. One review conducted a meta-analysis using the maximum acceptable risk. While reviews often commented on the heterogeneity of patient preferences, few (6%) addressed this systematically across studies. While not commonly used, several semi-quantitative and one quantitative approach for synthesizing results of DCEs were identified, which may be useful for generating summary estimates across DCEs when appropriate. Further work is needed to assess the validity and usefulness of these approaches.

Insights into the role of extracellular DNA in heavy metal adsorption

Extracellular polymeric substances (EPS) participate in heavy metal adsorption in the aquatic environments. Extracellular DNA (eDNA) is an essential component of EPS, but its involvement in metal binding remains ambiguous. Herein, the role of eDNA in Cd(II) and Ni(II) adsorption was described using a combination of semi-quantitative and qualitative approaches. EPS were extracted from Burkholderia sp. MBR-1 and eDNA accounted for 6.9% of the total mass of EPS. The eDNA in the extracted EPS was digested using the DNase II to prepare an eDNA-free EPS sample. Potentiometric titration unveiled that the number of total binding sites of the eDNA-free EPS was 19% lower than the untreated EPS. The Cd(II) and Ni(II) adsorption capacity of the eDNA-free EPS was lower than the untreated EPS at the pH range of 4–7. At pH 7, the results of batch adsorption experiments showed that removing eDNA from EPS resulted in declines of 12.6% and 15.7% in the adsorption capacities for Cd(II) and Ni(II), respectively. Furthermore, Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy unraveled that the phosphoryl groups and purines of eDNA are responsible for Cd(II) and Ni(II) complexation. The results demonstrated that eDNA plays an essential role in heavy metal adsorption.

Dependence of lung ultrasound vertical artifacts on frequency, bandwidth, focus and angle of incidence: An in vitro study.

Lung ultrasound (LUS) is nowadays widely adopted by clinicians to evaluate the state of the lung surface. However, being mainly based on the evaluation of vertical artifacts, whose genesis is still unclear, LUS is affected by qualitative and subjective analyses. Even though semi-quantitative approaches supported by computer aided methods can reduce subjectivity, they do not consider the dependence of vertical artifacts on imaging parameters, and could not be classified as fully quantitative. They are indeed mainly based on scoring LUS images, reconstructed with standard clinical scanners, through the sole evaluation of visual patterns, whose visualization depends on imaging parameters. To develop quantitative techniques is therefore fundamental to understand which parameters influence the vertical artifacts' intensity. In this study, we quantitatively analyzed the dependence of nine vertical artifacts observed in a thorax phantom on four parameters, i.e., center frequency, focal point, bandwidth, and angle of incidence. The results showed how the vertical artifacts are significantly affected by these four parameters, and confirm that the center frequency is the most impactful parameter in artifacts' characterization. These parameters should hence be carefully considered when developing a LUS quantitative approach.

Concordance between quantitative and semi-quantitative analysis of Tc-99m-pyrophosphate scintigraphy for the diagnosis of transthyretin cardiac amyloidosis in patients with HFpEF

Abstract Background Transthyretin (TTR) cardiac amyloidosis (CA) is an underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF). Cardiac scintigraphy with 99mTechnetium-pyrophosphate (99mTc-PYP) is referred as a simple, non-invasive and reliable method in the diagnosis of TTR-CA. American Society of Nuclear Cardiology Practice Points recommends two interpretative approaches: the quantitative heart-to-contralateral lung ratio (H/CL) at 1 hour or the semi-quantitative visual assessment at 3 hours after radiotracer injection. Purpose In this study, we evaluated the concordance between semi-quantitative and quantitative approaches in the diagnosis of TTR CA in patients with HFpEF. Methods This single-center, prospective study included 78 patients who had a diagnosis of HFpEF according to 2016 ESC HF guidelines. 99mTc-PYP cardiac scintigraphy was performed in 43 patients who have ≥2 red flags for TTR-CA including left ventricular hypertrophy (LVH) (wall thickness ≥12 mm), biventricular hypertrophy, sparkling pattern, reduction in longitudinal strain with apical sparing, thickening of the interatrial septum (&amp;gt;6mm), low-voltage, pseudo infarct pattern or atrioventricular block on ECG. In the absence of monoclonal protein in the serum and urine, Grade 2 to 3 myocardial uptake in semi-quantitative analysis at 3 hours or a H/CL ratio of ≥1.5 in quantitative analysis at 1 hour post injection of 99mTc-PYP is considered positive for TTR-CA. Grade 2–3 uptake with a H/CL ratio ≥1.5 or Grade 0–1 uptake with a H/CL ratio &amp;lt;1.5 were considered as concordant results. Grade 2–3 uptake with a H/CL ratio &amp;lt;1.5 or Grade 0–1 uptake with a H/CL ratio ≥1.5 were considered as discordant results. Results Mean age of study population was 68.26±9.97 years. 17 (39.5%) of 43 patients who underwent 99mTc-PYP cardiac scintigraphy showed a Grade 2 or 3 cardiac uptake and in these patients with Grade 2–3 uptake, 11 patients (65%) had a H/CL ratio ≥1.5 (concordant results) and 6 patients (35%) had a H/CL ratio &amp;lt;1.5 (discordant results). 26 (60.5%) of 43 patients showed Grade 0–1 cardiac uptake. All patients (100%) with Grade 0–1 uptake had a H/CL ratio &amp;lt;1.5 and therefore, showed concordant results. Overall, 37 (86%) patients had concordant and 6 (14%) patients had discordant results (Table 1). Conclusion The results of this study showed that although there was a high agreement between semi-quantitative and quantitative analysis of 99mTc-PYP cardiac scintigraphy, 14% of patients have discordant results and need further workup to confirm TTR-CA in patients with HFpEF. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer independent grant.

Unbiased automated quantitation of ROS signals in live retinal neurons of Drosophila using Fiji/ImageJ.

Numerous imaging modules are utilized to study changes that occur during cellular processes. Besides qualitative (immunohistochemical) or semiquantitative (Western blot) approaches, direct quantitation method(s) for detecting and analyzing signal intensities for disease(s) biomarkers are lacking. Thus, there is a need to develop method(s) to quantitate specific signals and eliminate noise during live tissue imaging. An increase in reactive oxygen species (ROS) such assuperoxide (O2•-) radicals results in oxidative damage of biomolecules, which leads to oxidative stress. This can be detected by dihydroethidium staining in live tissue(s), which does not rely on fixation and helps prevent stress on tissues. However, the signal-to-noise ratio is reduced in live tissue staining. We employ the Drosophila eye model of Alzheimer's disease as a proof of concept to quantitate ROS in live tissue by adapting an unbiased method. The method presented here has a potential application for other live tissue fluorescent images.

Targeted Mass Spectrometry-Based Approach for the Determination of Intrinsic Internalization Kinetics of Cell-Surface Membrane Protein Targets.

Successful development of targeted therapeutics aimed at the elimination of diseased cells relies on the target properties and the therapeutics that target them. Currently, target properties have been evaluated through antibody-dependent semiquantitative approaches such as flow cytometry, Western blotting, or microscopy. Since antibodies can alter target properties following binding, antibody-dependent approaches provide at best skewed measurements for target intrinsic properties. To circumvent, here we attempted to develop an antibody-free targeted mass spectrometry-based (ATM) strategy to measure the surface densities and the intrinsic rates (Kint) of CD38 internalization in multiple myeloma cell lines. Using cell-surface biotinylation in conjunction with differential mass tagging to separate inward CD38 molecules from the outbound and nascent ones, the ATM approach revealed diversities in measured CD38 Kint values of 0.239 min-1 S.E. ± 0.076, 0.109 min-1 S.E. ± 0.032, and 0.058 min-1 S.E. ± 0.001 for LP1, NCIH929, and MOLP8 cell lines, respectively. Together with CD38 surface densities, intrinsic Kint values aligned well with the tumor penetration model and supported the outcomes for tumor regression in mouse xenografts upon drug treatment. Additionally, the ATM approach can evaluate molecules with fast Kint as we determined for CTLA4 protein. We believe that the ATM approach has the potential to evaluate diverse cell-surface targets as part of the pharmacological assessment in drug discovery.

Estimation of the net influx rate Ki and the cerebral metabolic rate of glucose MRglc using a single static [18F]FDG PET scan in rats

Since accurate quantification of 2-deoxy-2–18F-fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) requires dynamic acquisition with arterial input function, more practical semi-quantitative (static) approaches are often preferred. However, static standardized uptake values (SUV) are typically biased due to large variations in body weight (BW) occurring over time in animal studies. This study aims to improve static [18F]FDG PET SUV quantification by better accounting for BW variations in rats. We performed dynamic [18F]FDG PET imaging with arterial blood sampling in rats (n = 27) with different BW (range 0.230–0.487 kg). By regressing the area under the curve of the input function divided by injected activity against BW (r2=0.697), we determined a conversion factor f(BW) to be multiplied with SUV and SUVglc to obtain ratSUV and ratSUVglc, providing an improved estimate of the net influx rate Ki (r = 0.758, p<0.0001) and cerebral metabolic rate of glucose MRglc (r = 0.906, p<0.0001), respectively. In conclusion, the proposed ratSUV and ratSUVglc provide a proxy for the Ki and MRglc based on a single static [18F]FDG PET SUV measurement improving clinical significance and translation of rodent studies. Given a defined strain, sex, age, diet, and weight range, this method is applicable for future experiments by converting SUV with the derived f(BW).

Analisis Risiko Pada Rantai Pasok Industri Minuman Siap Saji Jus Buah Dengan Pendekatan SCOR-FMEA

The beverage industry is one of the leading national industries with high growth and a very tight level of competition. The risk supply chain management approach is one of the driving factors for the sustainability of the industrial supply chain. The purpose of this study is to analyze the risk supply chain management to support the sustainability of the beverage industry supply chain in the case of fruit juice beverage products. The data used in this study consisted of primary data and secondary data. Primary data obtained from distributing questionnaires, interviews and field observations. The respondents of this research are the beverage industry supply chain stakeholders. This research combines qualitative and semi-quantitative approaches. Qualitative analysis is conducted to describe activities and risks in the beverage industry supply chain. Risk analysis is carried out using a semi-quantitative approach. The risk evaluation in the supply chain of the fruit juice beverage industry combines the SCOR-FMEA method. The risks that are classified as High and Priority are then analyzed by using the Fishbone Diagram as a reference for formulating risk mitigation strategies for the sustainability of the supply chain for the juice beverage industry.

Regional-scale landslide risk assessment on Mt. Umyeon using risk index estimation

The frequency of landslides and their magnitude are increasing worldwide due to global climate change, causing damage to people and infrastructure. Therefore, landslide risk assessment is urgent. This study developed a novel landslide risk assessment framework to analyze landslide risk on Mt. Umyeon, Republic of Korea. The proposed framework comprises four main procedures: (1) landslide hazard analyses using an ensemble statistical and physical model, (2) analyses of physical vulnerability from a vulnerability curve, (3) analyses of physical vulnerability from a semi-quantitative approach, and (4) risk index calculation using the results from the previous steps via a proposed equation which combines the quantitative and semi-quantitative approaches. To confirm the reliability of the framework, the results of each step were compared to a real landslide event that occurred in July 2011 on Mt. Umyeon. The framework successfully assessed landslide risk in this area. In addition, the landslide risk for different landslide return periods was calculated. This new framework for landslide risk assessment supports reliable decision-making for landslide risk assessment and management.

Approaches to Sequence the HTT CAG Repeat Expansion and Quantify Repeat Length Variation.

Background:Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of the HTT CAG repeat. Affected individuals inherit ≥36 repeats and longer alleles cause earlier onset, greater disease severity and faster disease progression. The HTT CAG repeat is genetically unstable in the soma in a process that preferentially generates somatic expansions, the proportion of which is associated with disease onset, severity and progression. Somatic mosaicism of the HTT CAG repeat has traditionally been assessed by semi-quantitative PCR-electrophoresis approaches that have limitations (e.g., no information about sequence variants). Genotyping-by-sequencing could allow for some of these limitations to be overcome.Objective:To investigate the utility of PCR sequencing to genotype large (>50 CAGs) HD alleles and to quantify the associated somatic mosaicism.Methods:We have applied MiSeq and PacBio sequencing to PCR products of the HTT CAG repeat in transgenic R6/2 mice carrying ∼55, ∼110, ∼255 and ∼470 CAGs. For each of these alleles, we compared the repeat length distributions generated for different tissues at two ages.Results:We were able to sequence the CAG repeat full length in all samples. However, the repeat length distributions for samples with ∼470 CAGs were biased towards shorter repeat lengths.Conclusion:PCR sequencing can be used to sequence all the HD alleles considered, but this approach cannot be used to estimate modal allele size or quantify somatic expansions for alleles ⪢250 CAGs. We review the limitations of PCR sequencing and alternative approaches that may allow the quantification of somatic contractions and very large somatic expansions.

Comparing Data Collection Methods in Phenological Evaluations of Himatanthus drasticus

We present a case study focusing on collection methods and phenological data analyses. Qualitative, semi-quantitative, and quantitative approaches were compared in terms of their efficiencies for describing flowering and fruiting intensities and phenophase synchrony in Himatanthus drasticus growing in a gallery forest in the Chapada Diamantina mountains, Brazil. Our results showed that phenophase intensity and synchrony were respectively each best. Determined using quantitative and qualitative methods We reinforce the importance of clearly defining research aims, as quantitative data collections require considerably greater field efforts than qualitative evaluations, especially concerning forest trees.

Tc-99m-pyrophosphate scintigraphy for the diagnosis of ATTR cardiac amyloidosis: Comparison of quantitative and semi-quantitative approaches

BackgroundATTR cardiac amyloidosis (CA) can be diagnosed with Tc-99m-PYP scintigraphy. There are two recommended interpretative approaches: the quantitative heart-to-contralateral lung ratio (H/CL) at 1 hour and the semi-quantitative visual system at 3 hours. This study’s aim was to compare both approaches and to apply the semi-quantitative method at 1 hour. MethodsTc-99m-PYP scans of 122 consecutive subjects were reviewed using both approaches. On 1 hour planar images, regions of interest were drawn over the heart and contralateral chest to determine H/CL. Myocardial uptake was graded on 1 and 3 hour SPECT images according to the semi-quantitative method. Concordance was examined using kappa statistics. Results31, 10, and 81 studies were positive, negative, and equivocal, respectively, for ATTR-CA using the H/CL approach. Using the grading system, 35, 77, and 10 scans were positive, negative, and equivocal, respectively. The quantitative approach led to a significantly higher proportion of equivocal studies compared to the semi-quantitative approach (P < .0001). These approaches yielded discordant results in 2 subjects; biopsy results were concordant with SPECT grade. 1 and 3 hour SPECT grades provided concordant result in 99% of cases. ConclusionsThe H/CL approach resulted in a high proportion of equivocal studies. Using SPECT imaging, the semi-quantitative approach minimized this proportion and showed high concordance at 1 and 3 hours.

Imaging of OA - From disease modification to clinical utility.

Multiple disease-modifying osteoarthritis drug (DMOAD) trials were done in the last two decades, but no pharmacological agent has yet been approved by regulatory agencies as an effective therapy to date. Given the fact that we have seen the recent discontinuation of several late-stage drug development trials, a careful strategy is needed in formulating a plan for a successful DMOAD trial - including the various roles of imaging. This narrative review article will summarize how imaging is utilized in osteoarthritis from the perspective of disease modification to clinical utility. We will describe how semi-quantitative and quantitative magnetic resonance imaging approaches have been deployed in DMOAD trials. We will then review the utility of musculoskeletal ultrasound in research and clinical settings. Finally, novel hybrid positron emission tomography/MRI techniques and current research using artificial intelligence will be discussed, focusing on original research. Older publications are included for the discussion of the previous DMOAD trials and other relevant topics where deemed appropriate.

Application of a behavioural and biochemical endpoint in ecotoxicity testing with Exaiptasia pallida.

Exaiptasia pallida has been applied as a cnidarian model to assess the toxicity of various contaminants using endpoints related to growth, reproduction and mortality. However, increasingly accepted behavioural and biochemical endpoints are underrepresented in ecotoxicity testing with cnidarian species. The aim of this study was to assess the suitability of tentacle retraction and superoxide dismutase activity as behavioural and biochemical endpoints for ecotoxicity testing with E. pallida. A concentration-dependent, tentacle retraction response was found in sub-lethal toxicity testing for anemones exposed to 1–65 μg L−1 Cu and 2–630 μg L−1 Zn for 24 and 96 h. Semi-quantitative and quantitative approaches to tentacle retraction analysis showed a difference in response sensitivity, however, both methods resulted in similar 24- and 96-h EC50 values for Cu and Zn. Additionally, tentacle retraction analysis provided the benefit of identifying recovery in anemones previously exposed to 359 μg L−1 Zn following a 96-h recovery period. Conversely, no significant difference in superoxide dismutase activity was detected in anemones exposed to the Cu and Zn solutions compared with controls, after either 24- or 96-h exposures. These findings support the ease of application and sensitivity of tentacle retraction as an endpoint in ecotoxicity testing with E. pallida and recommend its suitability for use in acute, sub-lethal toxicity testing. Moreover, evidence of recovery in E. pallida following exposure suggests that recovery should be incorporated into future toxicity assessments.

Randomized phase II trial of modified (m) FOLFOX6 induction chemotherapy with or without aflibercept before standard chemoradiotherapy (CRT) and total mesorectal excision (TME) in patients with high-risk rectal adenocarcinoma (HRRC): Final results of the GEMCAD 1402, and by molecular subtypes.

4102 Background: Neoadjuvant chemotherapy (CT) followed by CRT and TME is a treatment option for clinically staged HRRC. The goal of the GEMCAD 1402 trial was to evaluate the benefit of adding an antiangiogenic drug to the neoadjuvant CT. The analysis of primary endpoint showed a better response rate in the experimental arm (Fernandez-Martos et al. Jama Oncol 2019). Here we present 3-year disease-free survival (DFS) and a retrospective analysis of consensus molecular subtypes by Immunohistochemistry (CMSs-IHQ). Methods: Patients (p) with middle or distal third, mrT3/T4/N2 rectal adenocarcinoma were randomly assigned (2:1), to mFOLFOX6 with (arm 1, n=115) or without Aflibercept (arm 2, n=65) prior to CRT (capecitabine with 50.4 Gy in 28 fractions) and TME. Tissue microarrays from 90 (58 arm1, 32 arm 2) p were stained for nine markers (CDX2, FRMD6, HTR2B, ZEB1, KER, MSH2, MSH6, PMS2 and MLH1) by IHQ using both semiquantitative and quantitative approaches. Cases were classified as CMS1-IHQ1, CMS-IHQ2/3 or CMS-IHQ 4 (immune, epithelial or mesenchymal subtypes). Results: In the intention-to-treat population after a median follow-up time of 38 months, 29 p (25%) in arm 1 had a DFS-related event, as compared with 14 p (21%) in arm 2 (HR 1.2063, 95% confidence interval 0.6374 to 2.2829, P=0.5644. The rate of DFS at three years was 75.2% (95% confidence interval, 66.1% to 82.2%) in arm 1 and 81.5% (95% confidence interval, 69.8% to 89.1%) in arm 2 (P=0.5638 by the exact stratified log-rank test). Overall 0/80/10 p were classified as CMS-IHQ1, CMS-IHQ2/3 or CMS-IHQ4 respectively. The pathological complete response (pCR) rate (ypT0N0) was achieved in 27.5% and 0% in epithelial and mesenchymal subtypes respectively. A trend towards worse survival for the mesenchymal subtype was observed. Conclusions: Adding aflibercept to induction mFOLFOX6 is not associated with an improvement in DFS. Our findings suggest that CMSs-IHQ subtypes could be predictive for pCR with this treatment strategy. Clinical trial information: NCT02340949 .

Diagnostic Accuracy of [11C]PIB Positron Emission Tomography for Detection of Cardiac Amyloidosis

ObjectivesThis dual-site study evaluated the diagnostic accuracy of the method. BackgroundPittsburgh compound ([11C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA). MethodsThe study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min-1) were applied prospectively. ResultsThe diagnostic accuracy of visual inspection of [11C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative [11C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. [11C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as [11C]PIB PET positive. ConclusionsIn a dual-center setting, [11C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were [11C]PIB PET positive, indicating that the method may detect early stages of CA.