A Single-Molecule Bioelectronic Portable Array for Early Diagnosis of Pancreatic Cancer Precursors

A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRASmut DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 × 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRASmut, MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma.</p

A Single-Molecule Bioelectronic Portable Array for Early Diagnosis of Pancreatic Cancer Precursors

A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRASmut DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 × 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRASmut, MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma.</p

Total aortic arch endovascular repair using an iliac branch device

A 76-year-old man who 2 years before underwent thoracic endovascular aortic repair for aneurysm of the aortic arch was admitted to our department with dysphonia and dysphagia due to an increasing diameter of aneurysm of the aortic arch because of type Ia endoleak. To obtain an adequate proximal neck for conventional thoracic endovascular aortic repair, the double chimney graft technique was chosen using a hypogastric component of the iliac branch Excluder (W. L. Gore & Associates, Flagstaff, Ariz) for the anonymous trunk. At 1-year follow-up, computed tomography scan showed patent chimney graft and no endoleaks. This is the first report in the literature using a hypogastric branch in the aortic arch

A Single-Molecule Bioelectronic Portable Array for Early Diagnosis of Pancreatic Cancer Precursors

A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRAS(mut) DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 x 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRAS(mut), MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma

Results from the Multicenter Study on Aortoenteric Fistulization After Stent Grafting of the Abdominal Aorta (MAEFISTO)

Objective This study investigated the frequency, clinical features, therapeutic options, and results of aortoenteric fistulas (AEFs) developing after endovascular abdominal aortic repair (EVAR). Methods Eight Italian centers with an EVAR program participated in this retrospective multicenter study and collected data on AEFs that developed after a previous EVAR. Results A total of 3932 patients underwent EVAR between 1997 and 2013 at the participating centers. During the same period, 32 patients presented with an AEF during EVAR follow-up, 21 with original EVAR performed for atherosclerotic aneurysmal disease (ATS group) and 11 with the original EVAR performed for a postsurgical pseudoaneurysm (PSA group). The incidence of AEF development after EVAR was 0.46% in the ATS group and 3.9% in the PSA group. Anastomotic PSA as the indication to EVAR (P\ua0<.0001) and urgent/emergency EVAR (P\ua0=.01) were significantly associated with AEF development. Median time between EVAR and the AEF diagnosis was 32\ua0months (interquartile range, 11-75\ua0months) for the ATS group and 14\ua0months (interquartile range, 10.5-21.5\ua0months) for the PSA group. Among five AEF patients treated conservatively, two (40%) died, at 7 and 15\ua0months, and the remaining three were alive at a median follow-up of 12\ua0months. The AEF was treated surgically in 27 patients, including aortic stent graft explantation in all cases, in situ aortic reconstruction in 14 (52%), and extra-anatomic bypass in 13 (48%). Perioperative mortality was 37% (10 of 27). No additional aortic-related death was recorded in operated-on patients at a median follow-up of 28\ua0months. Conclusions Late AEFs rarely occur during EVAR follow-up, but the risk is significantly increased when EVAR is performed for PSA after previous aortic surgery and EVAR is performed as an emergency. Conservative and surgical treatment of post-EVAR AEF are both associated with high mortality. However, beyond the perioperative period, surgical correction of AEFs appears to be durable at midterm follow-up

Results from the Multicenter Study on Aortoenteric Fistulization After Stent Grafting of the Abdominal Aorta (MAEFISTO).

OBJECTIVE: This study investigated the frequency, clinical features, therapeutic options, and results of aortoenteric fistulas (AEFs) developing after endovascular abdominal aortic repair (EVAR). METHODS: Eight Italian centers with an EVAR program participated in this retrospective multicenter study and collected data on AEFs that developed after a previous EVAR. RESULTS: A total of 3932 patients underwent EVAR between 1997 and 2013 at the participating centers. During the same period, 32 patients presented with an AEF during EVAR follow-up, 21 with original EVAR performed for atherosclerotic aneurysmal disease (ATS group) and 11 with the original EVAR performed for a postsurgical pseudoaneurysm (PSA group). The incidence of AEF development after EVAR was 0.46% in the ATS group and 3.9% in the PSA group. Anastomotic PSA as the indication to EVAR (P &lt; .0001) and urgent/emergency EVAR (P = .01) were significantly associated with AEF development. Median time between EVAR and the AEF diagnosis was 32 months (interquartile range, 11-75 months) for the ATS group and 14 months (interquartile range, 10.5-21.5 months) for the PSA group. Among five AEF patients treated conservatively, two (40%) died, at 7 and 15 months, and the remaining three were alive at a median follow-up of 12 months. The AEF was treated surgically in 27 patients, including aortic stent graft explantation in all cases, in situ aortic reconstruction in 14 (52%), and extra-anatomic bypass in 13 (48%). Perioperative mortality was 37% (10 of 27). No additional aortic-related death was recorded in operated-on patients at a median follow-up of 28 months. CONCLUSIONS: Late AEFs rarely occur during EVAR follow-up, but the risk is significantly increased when EVAR is performed for PSA after previous aortic surgery and EVAR is performed as an emergency. Conservative and surgical treatment of post-EVAR AEF are both associated with high mortality. However, beyond the perioperative period, surgical correction of AEFs appears to be durable at midterm follow-up

Analysis of Clinical Samples of Pancreatic Cyst's Lesions with A Multi‐Analyte Bioelectronic Simot Array Benchmarked Against Ultrasensitive Chemiluminescent Immunoassay

Pancreatic cancer, ranking as the third factor in cancer-related deaths, necessitates enhanced diagnostic measures through early detection. In response, SiMoT-Single-molecule with a large Transistor multiplexing array, achieving a Technology Readiness Level of 5, is proposed for a timely identification of pancreatic cancer precursor cysts and is benchmarked against the commercially available chemiluminescent immunoassay SIMOA (Single molecule array) SP-X System. A cohort of 39 samples, comprising 33 cyst fluids and 6 blood plasma specimens, undergoes detailed examination with both technologies. The SiMoT array targets oncoproteins MUC1 and CD55, and oncogene KRAS, while the SIMOA SP-X planar technology exclusively focuses on MUC1 and CD55. Employing Principal Component Analysis (PCA) for multivariate data processing, the SiMoT array demonstrates effective discrimination of malignant/pre-invasive high-grade or potentially malignant low-grade pancreatic cysts from benign non-mucinous cysts. Conversely, PCA analysis applied to SIMOA assay reveals less effective differentiation ability among the three cyst classes. Notably, SiMoT unique capability of concurrently analyzing protein and genetic markers with the threshold of one single molecule in 0.1 mL positions it as a comprehensive and reliable diagnostic tool. The electronic response generated by the SiMoT array facilitates direct digital data communication, suggesting potential applications in the development of field-deployable liquid biopsy.SiMoT-Single-Molecule with Large Transistor technology simultaneously analyzes protein and genetic markers, achieving a one-molecule threshold in 0.1 mL. Benchmarking against SIMOA chemiluminescent ultrasensitive assay, SiMoT outperforms SIMOA in speed and overall performance. Moreover, SiMoT provides an electronic response, enhancing its suitability for direct digital data communication.imag