Prediction of Postprandial Glycemic Exposure Utility of fasting and 2-h glucose measurements alone and in combination with assessment of body composition, fitness, and strength

OBJECTIVE —To determine the best predictors of total postprandial glycemic exposure and peak glucose concentrations in nondiabetic humans. RESEARCH DESIGN AND METHODS —Data from 203 nondiabetic volunteers who ingested a carbohydrate-containing mixed meal were analyzed. RESULTS —Fasting glucose and insulin concentrations were poor predictors of postprandial glucose area above basal ( R 2 = ∼0.07, P < 0.001). The correlation was stronger for 2-h glucose concentration ( R 2 = 0.55, P < 0.001) and improved slightly but significantly ( P < 0.001) with the addition of fasting glucose, insulin, age, sex, and body weight to the model ( r 2 = 0.58). The 2-h glucose concentration also predicted the peak glucose concentration ( R 2 = 0.37, P < 0.001) with strength of the prediction increasing ( P < 0.001) modestly with the addition of fasting glucose, insulin, age, sex, and body weight to the model ( R 2 = 0.48, P < 0.001). On the other hand, addition of measures of body function and composition did not improve prediction of total glycemic exposure or peak glucose concentration. CONCLUSIONS —Isolated measures of fasting or 2-h glucose concentrations alone or in combination with more complex measures of body composition and function are poor predictors of postprandial glycemic exposure or peak glucose concentration. This may explain, at least in part, the weak and at times inconsistent relationship between these parameters and cardiovascular risk

Fusion with stem cell makes the hepatocellular carcinoma cells similar to liver tumor-initiating cells

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Combined aberrant expression of E-cadherin and S100A4, but not β-catenin is associated with disease-free survival and overall survival in colorectal cancer patients

BACKGROUND/AIMS: Epithelial-to-mesenchymal transition (EMT) in cancers is related to metastasis, recurrence, and poor prognosis. We evaluated whether EMT-related proteins can act as prognostic biomarkers in colorectal cancer (CRC) patients. METHODS: We evaluated the expression of E-cadherin, β-catenin, and S100A4 by immunohistochemistry (IHC) in 333 CRC tissues from the tumor center and invasive margin. Tumor budding, cell grade, tumor stage, type of tumor growth, peritumoral lymphocyte infiltration (TLI), and perineural- or lymphovascular invasion were evaluated as pathological parameters. mRNA levels of E-cadherin, N-cadherin, β-catenin, and S100A4 from 68 specimens from the same set were analyzed by real time quantitative RT-PCR. RESULTS: Loss of E-cadherin, nuclear β-catenin, and gain of S100A4 were higher in the invasive margin than in the tumor center. Loss of E-cadherin was associated with cell grade, macroscopic type, perineural invasion, and tumor budding, β-catenin with microsatellite instability and tumor site, and S100A4 with growth type, macroscopic type, AJCC stage, lymphovascular invasion, and perineural invasion. The aberrant expression of E-cadherin and S100A4 not β-catenin in the invasive margin was a significant and independent risk factor for disease-free and overall-survival by multivariate analysis, along with AJCC stage and perineural invasion. mRNA levels of β-catenin and S100A4 were correlated with the IHC findings at the tumor invasive margin. E-cadherin and N-cadherin showed a weak inverse correlation. CONCLUSIONS: The combination of loss of E-cadherin and gain of S100A4 in the tumor invasive margin can be used to stratify patients with the same AJCC stage into different survival groups. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/939828962924467

Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production

A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6) to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 µM ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release). Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK), and different mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2) as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A2 formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia

Validation and optimization of AFP-based biomarker panels for early HCC detection in Latin America and Europe

Background: HCC is a major cause of cancer death worldwide. Serum biomarkers such as alpha-fetoprotein (AFP), protein induced by vitamin K absence-II, and the Gender, Age, AFP-L3, AFP, Des-gamma-carboxy prothrombin (GALAD) score have been recommended for HCC surveillance. However, inconsistent recommendations in international guidelines limit their clinical utility.Methods: In this multicenter study, over 2000 patient samples were collected in 6 Latin American and 2 European countries. The performance of the GALAD score was validated in cirrhotic cases, and optimized versions were tested for early-stage HCC and prediagnostic HCC detection.Results: The GALAD score could distinguish between HCC and cirrhosis in Latin American patients with an AUC of 0.76, sensitivity of 70%, and specificity of 83% at the conventional cutoff value of −0.63. In a European cohort, GALAD had an AUC of 0.69, sensitivity of 66%, and specificity of 72%. Optimizing the score in the 2 large multicenter cohorts revealed that AFP-L3 contributed minimally to early-stage HCC detection. Thus, we developed a modified GALAD score without AFP-L3, the ASAP (age, sex, AFP, and protein induced by vitamin K absence-II), which showed promise for early-stage HCC detection upon validation. The ASAP score also identified patients with cirrhosis at high risk for advanced-stage HCC up to 15 months before diagnosis (p &lt; 0.0001) and differentiated HCC from hemangiomas, with a specificity of 100% at 71% sensitivity.Conclusion: Our comprehensive analysis of large sample cohorts validates the GALAD score’s utility in Latin American, Spanish, and Dutch patients for early-stage HCC detection. The optimized GALAD without AFP-L3, the ASAP score, is a good alternative and shows greater promise for HCC prediction

Challenges and opportunities in resuming spirometry services in England post-pandemic with potential to adopt Artificial Intelligence decision support software: a qualitative study

Background: Spirometry services to diagnose and monitor lung disease in primary care are restarting post-pandemic in England, identified as a priority in the NHS Long Term Plan, however evidence regarding best practice is limited.Aims: To explore perspectives on spirometry provision in primary care, and the potential for Artificial Intelligence (AI) decision support software to aid quality and interpretation.Design and Setting: Semi-structured interviews with stakeholders in spirometry services in primary care.Methods: Semi-structured interviews were conducted with key stakeholders in spirometry services across England. Participants were recruited by snowball sampling. Interviews explored the pre-pandemic delivery of spirometry, restarting of services and perceptions of the role of AI. Transcripts were analysed thematically.Results: 28 participants (mean [SD], 21.6 [9.4, range 3-40] years’ clinical experience) were interviewed between April and June 2022. Participants included clinicians (n=25) and commissioners (n=3); eight held regional and/or national respiratory network advisory roles. Four themes were identified: 1) Historical challenges in spirometry provision; 2) Inequity in post-pandemic spirometry provision and challenges to restarting spirometry in primary care; 3) Future delivery closer to patients’ homes by appropriately trained staff; 4) The potential for AI to have supportive roles in spirometry.Conclusion: Stakeholders highlighted historic challenges and the damaging effects of the pandemic contributing to inequity in provision of spirometry, which must be addressed. Overall stakeholders were positive about the potential of AI to support clinicians in quality assessment and interpretation of spirometry. However, it was evident that validation of the software must be sufficiently robust for clinicians and healthcare commissioners to have trust in the process