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      Coupling magnetic levitation of graphene oxide–protein complexes with blood levels of glucose for early detection of pancreatic adenocarcinoma

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          Abstract

          Introduction

          Pancreatic adenocarcinoma (PDAC) has a poor prognosis since often diagnosed too late. Dyslipidemia and hyperglycemia are considered risk factors, but the presence of the tumor itself can determine the onset of these disorders. Therefore, it is not easy to predict which subjects with diabetes or dyslipidemia will develop or have already developed PDAC. Over the past decade, tests based on the use of nanotechnology, alone or coupled with common laboratory tests (e.g., hemoglobin levels), have proven useful in aiding the diagnosis of PDAC. Tests based on magnetic levitation (MagLev) have demonstrated high diagnostic accuracy in compliance with the REASSURED criteria. Here, we aimed to assess the ability of the MagLev test in detecting PDAC when coupled with the blood levels of glycemia, cholesterol, and triglycerides.

          Methods

          Blood samples from 24 PDAC patients and 22 healthy controls were collected. Human plasma was let to interact with graphene oxide (GO) nanosheets and the emerging coronated systems were put in the MagLev device. Outcomes from Maglev experiments were coupled to glycemia, cholesterol, and triglycerides levels. Linear discriminant analysis (LDA) was carried out to evaluate the classification ability of the test in terms of specificity, sensitivity, and global accuracy. Statistical analysis was performed with Matlab (MathWorks, Natick, MA, USA, Version R2022a) software.

          Results

          The positions of the levitating bands were measured at the starting point (i.e., as soon as the cuvette containing the sample was subjected to the magnetic field). Significant variations in the starting position of levitating nanosystems in controls and PDACs were detected. The combination of the MagLev outcomes with the blood glycemic levels returned the best value of global accuracy (91%) if compared to the coupling with those of cholesterol and triglycerides (global accuracy of ~ 77% and 84%, respectively).

          Conclusion

          If confirmed by further studies on larger cohorts, a multiplexed Maglev-based nanotechnology-enabled blood test could be employed as a screening tool for PDAC in populations with hyperglycemia.

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          Most cited references39

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          REASSURED diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes

          Lack of access to quality diagnostics remains a major contributor to health burden in resource-limited settings. It has been more than 10 years since ASSURED (affordable, sensitive, specific, user-friendly, rapid, equipment-free, delivered) was coined to describe the ideal test to meet the needs of the developing world. Since its initial publication, technological innovations have led to the development of diagnostics that address the ASSURED criteria, but challenges remain. From this perspective, we assess factors contributing to the success and failure of ASSURED diagnostics, lessons learnt in the implementation of ASSURED tests over the past decade, and highlight additional conditions that should be considered in addressing point-of-care needs. With rapid advances in digital technology and mobile health (m-health), future diagnostics should incorporate these elements to give us REASSURED diagnostic systems that can inform disease control strategies in real-time, strengthen the efficiency of health care systems and improve patient outcomes.
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            Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology.

            Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.
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              Model to Determine Risk of Pancreatic Cancer in Patients with New-onset Diabetes

              Background & Aims Of subjects with new-onset diabetes (based on glycemia) over the age of 50 years, approximately 1% are diagnosed with pancreatic cancer within 3 years. We aimed to develop and validate a model to determine risk of pancreatic cancer in individuals with new-onset diabetes. Methods We retrospectively collected data from 4 independent, non-overlapping cohorts of patients (n=1561) with new-onset diabetes (based on glycemia; data collected at date of diagnosis and 12 months before) in the Rochester Epidemiology Project, from January 1, 2000 through December 31, 2015 to create our model. The model weighed scores for the 3 factors identified in the discovery cohort to be most strongly associated with pancreatic cancer (64 patients with pancreatic cancer and 192 with type-2 diabetes): change in weight, change in blood glucose, and age at onset of diabetes. We called our model enriching new-onset diabetes for pancreatic cancer (END-PAC). We validated the locked-down model and cutoff score in an independent population-based cohort of 1096 patients with diabetes; of these 9 patients (.82%) had pancreatic within 3 years of meeting the criteria for new-onset diabetes. Results In the discovery cohort the END-PAC model identified patients who developed pancreatic cancer within 3 years of onset of diabetes with an area under the receiver operating characteristic curve value of 0.87; a score of ≥3 identified patients who developed pancreatic cancer with 80% sensitivity and specificity. In the validation cohort, a score of ≥3 identified 7/9 patients with pancreatic cancer (78%), with 85% specificity; the prevalence of pancreatic cancer in subjects with score of ≥3 (3.6%) was 4.4-fold more than in patients with new-onset diabetes. A high END-PAC score in subjects who did not have pancreatic cancer (false positives) was often due to such factors as recent steroid use or different malignancy. An END-PAC score <0 (in 49% of subjects) meant that patients had an extremely low-risk for pancreatic cancer. An END-PAC score ≥3 identified 75% of subjects in the discovery cohort >6 months before a diagnosis of pancreatic cancer. Conclusions Based on change in weight, change in blood glucose, and age at onset of diabetes, we developed and validated a model to determine risk of pancreatic cancer in patients with new-onset diabetes, based on glycemia (the END-PAC model). An independent, prospective study is needed to further validate this model, which could contribute to early detection of pancreatic cancer.
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                Author and article information

                Journal
                Cancer Nanotechnology
                Cancer Nano
                Springer Science and Business Media LLC
                1868-6958
                1868-6966
                December 2023
                March 01 2023
                December 2023
                : 14
                : 1
                Article
                10.1186/s12645-023-00170-1
                312113bb-6ba5-4ab3-ad89-d94dc8503f97
                © 2023

                https://creativecommons.org/licenses/by/4.0

                https://creativecommons.org/licenses/by/4.0

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